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Sample records for restricted ketogenic diet

  1. THE NEUROPROTECTIVE PROPERTIES OF CALORIE RESTRICTION, THE KETOGENIC DIET, AND KETONE BODIES

    PubMed Central

    Maalouf, Marwan A.; Rho, Jong M.; Mattson, Mark P.

    2008-01-01

    The therapeutic potential of calorie restriction and the ketogenic diet have been repeatedly demonstrated in clinical settings and in various animal models of neurological disease. The underlying mechanisms involve an improvement in mitochondrial function, a decrease in the expression of apoptotic factors and an increase in the activity of neurotrophic factors. Clinical applications of ketogenic diets have been significantly hampered however by poor tolerability and potentially serious side-effects. Recent research aimed at identifying a mediator that can reproduce the neuroprotective effects of calorie restriction with less demanding changes to dietary intake suggests that ketone bodies might represent an appropriate candidate. Ketone bodies protect neurons against multiple types of neuronal injury and the underlying mechanisms are similar to those of calorie restriction and of the ketogenic diet. The present review describes the neuroprotective effects of calorie restriction, the ketogenic diet and ketone bodies and compare the molecular mechanisms of action of these interventions. PMID:18845187

  2. Improvement in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets.

    PubMed

    Mantis, John G; Fritz, Christie L; Marsh, Jeremy; Heinrichs, Stephen C; Seyfried, Thomas N

    2009-06-01

    Rett syndrome (RTT) is a rare X-linked autistic-spectrum neurological disorder associated with impaired energy metabolism, seizure susceptibility, progressive social behavioral regression, and motor impairment primarily in young girls. The objective of this study was to examine the influence of restricted diets, including a ketogenic diet (KD) and a standard rodent chow diet (SD), on behavior in male Mecp2(308/y) mice, a model of RTT. The KD is a high-fat, low-carbohydrate diet that has anticonvulsant efficacy in children with intractable epilepsy and may be therapeutic in children with RTT. Following an 11-day pretrial period, adult wild-type and mutant Rett mice were separated into groups that were fed either an SD in unrestricted or restricted amounts or a ketogenic diet (KetoCal) in restricted amounts for a total of 30 days. The restricted diets were administered to reduce mouse body weight by 20-23% compared to the body weight of each mouse before the initiation of the diet. All mice were subjected to a battery of behavioral tests to determine the influence of the diet on the RTT phenotype. We found that performance in tests of motor behavior and anxiety was significantly worse in male RTT mice compared to wild-type mice and that restriction of either the KD or the SD improved motor behavior and reduced anxiety. We conclude that although both restricted diets increased the tendency of Rett mice to explore a novel environment, the beneficial effects of the KD were due more to calorie restriction than to the composition of the diet. Our findings suggest that calorically restricted diets could be effective in reducing the anxiety and in improving motor behavior in girls with RTT.

  3. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

    PubMed Central

    Zhou, Weihua; Mukherjee, Purna; Kiebish, Michael A; Markis, William T; Mantis, John G; Seyfried, Thomas N

    2007-01-01

    Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A) and a human malignant glioma (U87-MG). Methods Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal® was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal® on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet. Results KetoCal® administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal® diet reduced plasma glucose levels while elevating plasma ketone body (β-hydroxybutyrate) levels. Tumor microvessel density was less in the calorically restricted KetoCal® groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, β-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, was lower in the

  4. Epigenetic mechanisms underlying lifespan and age-related effects of dietary restriction and the ketogenic diet.

    PubMed

    Moreno, Cesar L; Mobbs, Charles V

    2016-11-22

    Aging constitutes the central risk factor for major diseases including many forms of cancer, neurodegeneration, and cardiovascular diseases. The aging process is characterized by both global and tissue-specific changes in gene expression across taxonomically diverse species. While aging has historically been thought to entail cell-autonomous, even stochastic changes, recent evidence suggests that modulation of this process can be hierarchal, wherein manipulations of nutrient-sensing neurons (e.g., in the hypothalamus) produce peripheral effects that may modulate the aging process itself. The most robust intervention extending lifespan, plausibly impinging on the aging process, involves different modalities of dietary restriction (DR). Lifespan extension by DR is associated with broad protection against diseases (natural and engineered). Here we review potential epigenetic processes that may link lifespan to age-related diseases, particularly in the context of DR and (other) ketogenic diets, focusing on brain and hypothalamic mechanisms.

  5. Ketogenic diet in Rett syndrome.

    PubMed

    Liebhaber, Gisela Maria; Riemann, Edith; Baumeister, Friedrich Albert Matthias

    2003-01-01

    Treatment of Rett syndrome with the ketogenic diet has been reported only once and showed positive effects on seizure frequency and behavior. We report a patient with Rett syndrome who was treated with the ketogenic diet for 4 years. The diet was initiated at the age of 8 years owing to the patient's refractory epilepsy and led to a 70% reduction in seizures. Treatment with the ketogenic diet was also associated with improvements in contact and behavior. Diagnosis of Rett syndrome was confirmed by molecular detection of the Ser134Cys mutation in the MECP2 gene, which has previously been described only in classic Rett syndrome. This observation demonstrates that the ketogenic diet has a positive effect on Rett syndrome.

  6. Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma metabolites and lipids in C57BL/6J mice

    PubMed Central

    2014-01-01

    Background Diet therapies including calorie restriction, ketogenic diets, and fish-oil supplementation have been used to improve health and to treat a variety of neurological and non-neurological diseases. Methods We investigated the effects of three diets on circulating plasma metabolites (glucose and β-hydroxybutyrate), hormones (insulin and adiponectin), and lipids over a 32-day period in C57BL/6J mice. The diets evaluated included a standard rodent diet (SD), a ketogenic diet (KD), and a standard rodent diet supplemented with fish-oil (FO). Each diet was administered in either unrestricted (UR) or restricted (R) amounts to reduce body weight by 20%. Results The KD-UR increased body weight and glucose levels and promoted a hyperlipidemic profile, whereas the FO-UR decreased body weight and glucose levels and promoted a normolipidemic profile, compared to the SD-UR. When administered in restricted amounts, all three diets produced a similar plasma metabolite profile, which included decreased glucose levels and a normolipidemic profile. Linear regression analysis showed that circulating glucose most strongly predicted body weight and triglyceride levels, whereas calorie intake moderately predicted glucose levels and strongly predicted ketone body levels. Conclusions These results suggest that biomarkers of health can be improved when diets are consumed in restricted amounts, regardless of macronutrient composition. PMID:24910707

  7. Should the ketogenic diet be considered for enhancing fertility?

    PubMed

    Kulak, D; Polotsky, A J

    2013-01-01

    The ketogenic diet was first developed in the 1920s as a treatment for epilepsy in an attempt to create a prolonged physiologic starvation state. Since that time, the diet has been found to have other therapeutic effects, most of which are neurologic. Other diets, mostly based on the principals of caloric restriction, have been shown to improve fertility in certain populations. We explore the data, both clinical and laboratory, for potential fertility enhancing benefits of the ketogenic diet, beyond just caloric restriction or weight loss.

  8. Epilepsy characteristics and psychosocial factors associated with ketogenic diet success.

    PubMed

    McNamara, Nancy A; Carbone, Loretta A; Shellhaas, Renée A

    2013-10-01

    The ketogenic diet is an effective therapy for childhood epilepsy, but its important impacts on families could affect successful treatment. We assessed medical and psychosocial factors associated with successful ketogenic diet treatment. A total of 23 families of patients treated with ketogenic diet completed questionnaires (30% response), including inquiries about challenges to successful dietary treatments and validated family functioning scales. Of these, 14 were considered successful (diet discontinued once the child was seizure-free or continued as clinically indicated). Family-identified challenges were food preparation time (n = 11) and that the diet was too restrictive (n = 9). Neither Medicaid insurance nor family functioning scale scores were significantly associated with successful treatment. Lower seizure frequency prior to ketogenic diet initiation (P = .02) and postdiet seizure improvement (P = .01) were associated with increased odds of success. Effective ketogenic diet treatment is dictated both by psychosocial and epilepsy-related influences. A focus on understanding the psychosocial issues may help to improve families' experiences and success with the ketogenic diet.

  9. The ketogenic diet and other dietary treatments for refractory epilepsy in children.

    PubMed

    Sharma, Suvasini; Jain, Puneet

    2014-07-01

    The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed.

  10. Clinical efficacy of the ketogenic diet.

    PubMed

    Vining, E P

    1999-12-01

    The ketogenic diet is an effective alternative therapy used to control intractable seizures. It was originally described in 1921 as a way to duplicate and prolong the beneficial effects that fasting appeared to have on seizure control. It involves consuming a calorie-restricted diet in which the fat:carbohydrate + protein ratio ranges from 2:1 to 5:1. Recent prospective studies in children demonstrate that about 50% of children will continue on the diet for at least a year, with 40-50% of those starting the diet having a >50% reduction in seizures after 12 months. When the diet is discontinued it is usually due to lack of efficacy. The diet is a radical medical therapy and nutritional well-being is a constant concern. Renal stones have occurred in 5-8% of children on the diet; lipids are elevated, but the significance of this is not known. The mechanism of action of the diet remains unknown, and it is difficult to assess which biochemical parameters should be monitored as adjustments are made to the diet.

  11. The ketogenic diet in Dravet syndrome.

    PubMed

    Laux, Linda; Blackford, Robyn

    2013-08-01

    Dravet syndrome is an infantile epilepsy syndrome with intractable pleomorphic seizures, cognitive impairment, and a number of comorbidities including ataxia/gait abnormalities and behavioral issues. Antiseizure medications are only partially effective in controlling seizures. Secondary to the intractable epilepsy, patients are often on multiple antiseizure medications with significant accumulative neurotoxic side effects. Specifically for Dravet syndrome, the medical literature includes both laboratory and clinical research that supports the use of the ketogenic diet. In addition, a review of the children with Dravet syndrome who were treated with the ketogenic diet at our center was undertaken. Thirteen of the 20 children (65%) with Dravet syndrome treated with the ketogenic diet experienced a greater than 50% reduction in seizure frequency. The ketogenic diet is a good alternative to medication for seizure management in children with Dravet syndrome.

  12. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    PubMed Central

    Damiani, Ernesto; Bosco, Gerardo

    2014-01-01

    An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review. PMID:25101284

  13. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.

    PubMed

    Rieger, Johannes; Bähr, Oliver; Maurer, Gabriele D; Hattingen, Elke; Franz, Kea; Brucker, Daniel; Walenta, Stefan; Kämmerer, Ulrike; Coy, Johannes F; Weller, Michael; Steinbach, Joachim P

    2014-06-01

    Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.

  14. Ketogenic diets, mitochondria, and neurological diseases

    PubMed Central

    Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

    2014-01-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

  15. Ketogenic diets, mitochondria, and neurological diseases.

    PubMed

    Gano, Lindsey B; Patel, Manisha; Rho, Jong M

    2014-11-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate "classic KD", as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD.

  16. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

    ERIC Educational Resources Information Center

    Villeneuve, Nathalie; Pinton, Florence; Bahi-Buisson, Nadia; Dulac, Olivier; Chiron, Catherine; Nabbout, Rima

    2009-01-01

    Aim: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method: From the 70 patients who received the ketogenic diet during a 3-year period at…

  17. Treatment of diabetes and diabetic complications with a ketogenic diet.

    PubMed

    Mobbs, Charles V; Mastaitis, Jason; Isoda, Fumiko; Poplawski, Michal

    2013-08-01

    Accumulating evidence suggests that low-carbohydrate, high-fat diets are safe and effective to reduce glycemia in diabetic patients without producing significant cardiovascular risks. Most of these studies have been carried out specifically restricting carbohydrates, which tends to lead to increased protein intake, thus reducing the ketosis. However, diets that limit protein as well as carbohydrates, entailing a composition very high in fat, appear even more effective to reduce glucose and whole-body glucose metabolism in humans. In animal models, low-carbohydrate, high-protein diets do not produce ketosis or reduce glycemia but rather cause obesity. However, limiting both protein and carbohydrates as in a classic ketogenic diet remarkably reduces blood glucose in animal models of type 1 and type 2 diabetes and reverses diabetic nephropathy. Future studies should assess if ketogenic diets would be effective to reverse diabetic complications in humans.

  18. Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies

    PubMed Central

    Mantis, John G; Centeno, Nicole A; Todorova, Mariana T; McGowan, Richard; Seyfried, Thomas N

    2004-01-01

    Background The high fat, low carbohydrate ketogenic diet (KD) was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR) inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted (SD-UR) or restricted (SD-R), and either a KD unrestricted (KD-UR) or restricted (KD-R). All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once/week over a nine-week treatment period. Results Body weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p < 0.001) reduced in the SD-R and KD-R groups. Plasma β-hydroxybutyrate levels were significantly (p < 0.001) increased in the SD-R and KD-R groups compared to their respective UR groups. Seizure susceptibility remained high in both UR-fed groups throughout the study, but was significantly reduced after three weeks in both R-fed groups. Conclusions The results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone

  19. The Ketogenic Diet and Potassium Channel Function

    DTIC Science & Technology

    2014-10-01

    1 AWARD NUMBER: W81XWH-13-1-0463 TITLE: The Ketogenic Diet and Potassium Channel Function...Diet and Potassium Channel Function 5b. GRANT NUMBER W81XWH-13-1-0463 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Geoffrey Murphy 5d. PROJECT...regulates neuronal excitability by influencing potassium channel activity via the auxiliary potassium channel subunit Kvβ2. To test this hypothesis we

  20. The effects of ketogenic diet on oxidative stress and antioxidative capacity markers of Taekwondo athletes.

    PubMed

    Rhyu, Hyun-Seung; Cho, Su-Youn; Roh, Hee-Tae

    2014-12-01

    The purpose of this study was to investigate the effects of the ketogenic diet through 3 weeks on oxidative stress and antioxidative capacity markers in Taekwondo athletes. The participants selected for this research were 18 high school taekwondo contestants aged 15-18 who had at least 5 yr of career as contestant. The subjects were randomly assigned to the ketogenic diet (KD) group and the Non ketogenic diet (NDK) group. Body composition and oxidative stress and antioxidative capacity markers (LDH, MDA, ROS, HDL, and SOD) were analysed before and after 3 weeks of ketogenic diet. No significant difference was found between the groups in body composition, ROS and SOD level. The KD group showed an elevated HDL level and NKD group showed an elevated LDH and MDA level after ketogenic diet by 3 weeks. This result suggests that weight loss by 3 weeks of calorie restriction and exercise can cause oxidative stress, and that ketogenic diet can be effective for preventing it. It could also be inferred that ketogenic diet can be effective for increasing blood antioxidative capacity.

  1. The Ketogenic Diet: A Practical Guide for Pediatricians.

    PubMed

    Luat, Aimee F; Coyle, Leigh; Kamat, Deepak

    2016-12-01

    The ketogenic diet is an effective treatment for drug-resistant epilepsies in children. In addition, it is the first-line treatment for some metabolic disorders, such as glucose transporter 1 deficiency syndrome. This article discusses the proposed mechanisms of a ketogenic diet's antiseizure action, its clinical indications, and its contraindications. The steps involved in ketogenic diet initiation, monitoring, and management of its side effects are also discussed. This review provides general pediatricians with the necessary skills to provide comprehensive care of children using the ketogenic diet and counsel their families and caregivers. [Pediatr Ann. 2016;45(12):e446-e450.].

  2. [The ketogenic diet: an underappreciated therapeutic option?].

    PubMed

    Paoli, A; Canato, M; Toniolo, L; Bargossi, A M; Neri, M; Mediati, M; Alesso, D; Sanna, G; Grimaldi, K A; Fazzari, A L; Bianco, A

    2011-01-01

    Obesity is reaching epidemic proportions in Western countries and is a strong risk factor for cardiovascular disease. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Although there is a common agreement about the concept that exercise and diet are two key factors for the control of body weight, the ideal amount and type of exercise and also the ideal diet for weight control are still under debate. A widely accepted nutritional regime is the Mediterranean diet that has evident health benefits although less attention has been paid to see if the effects are due to other lifestyle factors which may contribute to the health benefits perhaps as much as specific food choices. There are several other options available to the physician that may produce good weight loss results in the short/medium term and also for maintenance of the goal achieved. One of these strategies is the ketogenic diet or VLCKD (very low carbohydrate ketogenic diet) that has been widely studied in recent years. Most studies show that this diet has a solid physiological and biochemical basis which is able to induce effective weight loss and improvement of several parameters of cardiovascular risk. This review discusses the physiological basis of VLCKD and the main applications together with its strengths and weaknesses compared to common dietary recommendations.

  3. Purines and neuronal excitability: links to the ketogenic diet.

    PubMed

    Masino, S A; Kawamura, M; Ruskin, D N; Geiger, J D; Boison, D

    2012-07-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A(1)Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms.

  4. Purines and Neuronal Excitability: Links to the Ketogenic Diet

    PubMed Central

    Masino, SA; Kawamura, M; Ruskin, DN; Geiger, JD; Boison, D

    2011-01-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms. PMID:21880467

  5. Risk factors for urolithiasis in children on the ketogenic diet.

    PubMed

    Furth, S L; Casey, J C; Pyzik, P L; Neu, A M; Docimo, S G; Vining, E P; Freeman, J M; Fivush, B A

    2000-11-01

    Kidney stones have been associated with use of the ketogenic diet in children with refractory seizure disorders. We performed a case-control study examining risk factors for the development of stones on the ketogenic diet, and prospectively followed children initiating the ketogenic diet to evaluate the incidence of urolithiasis. Clinical characteristics of 18 children presenting with stones (8 uric acid stones, 6 mixed calcium/uric acid stones, 1 calcium oxalate/phosphate stone, 3 stones not evaluated) were compared with characteristics of non-stone-forming children initiating the ketogenic diet at Johns Hopkins since July 1996. Since July 1996, 112 children initiating the ketogenic diet have been followed for development of stones. Follow-up times on the diet range from 2 months to 2.5 years. Of 112 children, 6 have developed stones (3 uric acid, 3 mixed calcium/uric acid stones) (0.8 children developing stones/ 100 patient-months at risk). Comparisons of children presenting with stones on the ketogenic diet with characteristics of the entire cohort initiating the ketogenic diet suggest younger age at diet initiation and hypercalciuria are risk factors for the development of stones. Prospective evaluation of children initiating the ketogenic diet revealed that almost 40% of patients had elevated fasting urine calcium: creatinine ratios at baseline; this increased to 75% after 6 months on the diet. Median urine pH was 5.5 at diet initiation, and remained at 6.0 thereafter. In a subset of patients tested, urinary citrate excretion fell from a mean of 252 mg/24 h pre diet initiation to 52 mg/24 h while on the diet. Uric acid excretion remained normal. Patients maintained on the ketogenic diet often have evidence of hypercalciuria, acid urine, and low urinary citrate excretion. In conjunction with low fluid intake, these patients are at high risk for both uric acid and calcium stone formation.

  6. Ketogenic diet for obesity: friend or foe?

    PubMed

    Paoli, Antonio

    2014-02-19

    Obesity is reaching epidemic proportions and is a strong risk factor for a number of cardiovascular and metabolic disorders such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, and also certain types of cancers. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Genetic predisposition in combination with inactive lifestyles and high caloric intake leads to excessive weight gain. Even though there may be agreement about the concept that lifestyle changes affecting dietary habits and physical activity are essential to promote weight loss and weight control, the ideal amount and type of exercise and also the ideal diet are still under debate. For many years, nutritional intervention studies have been focused on reducing dietary fat with little positive results over the long-term. One of the most studied strategies in the recent years for weight loss is the ketogenic diet. Many studies have shown that this kind of nutritional approach has a solid physiological and biochemical basis and is able to induce effective weight loss along with improvement in several cardiovascular risk parameters. This review discusses the physiological basis of ketogenic diets and the rationale for their use in obesity, discussing the strengths and the weaknesses of these diets together with cautions that should be used in obese patients.

  7. Ketogenic Diet for Obesity: Friend or Foe?

    PubMed Central

    Paoli, Antonio

    2014-01-01

    Obesity is reaching epidemic proportions and is a strong risk factor for a number of cardiovascular and metabolic disorders such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, and also certain types of cancers. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Genetic predisposition in combination with inactive lifestyles and high caloric intake leads to excessive weight gain. Even though there may be agreement about the concept that lifestyle changes affecting dietary habits and physical activity are essential to promote weight loss and weight control, the ideal amount and type of exercise and also the ideal diet are still under debate. For many years, nutritional intervention studies have been focused on reducing dietary fat with little positive results over the long-term. One of the most studied strategies in the recent years for weight loss is the ketogenic diet. Many studies have shown that this kind of nutritional approach has a solid physiological and biochemical basis and is able to induce effective weight loss along with improvement in several cardiovascular risk parameters. This review discusses the physiological basis of ketogenic diets and the rationale for their use in obesity, discussing the strengths and the weaknesses of these diets together with cautions that should be used in obese patients. PMID:24557522

  8. [Ketogenic diet--an alternative therapy for epilepsy in adults].

    PubMed

    Schiff, Y; Lerman-Sagie, T

    1998-04-01

    The ketogenic diet is an accepted alternative for children with intractable generalized or multi-focal seizures not amenable to surgery. It is not commonly used in adults because of the impression that the diet is less effective after childhood, when it is more difficult both to achieve ketosis and to change dietary habits. We present a 20-year-old man with intractable epilepsy since early childhood who is being treated with great success by a medium-chain triglyceride ketogenic diet. It has not only controlled the seizures but has also improved quality of life. We recommend a therapeutic trial of the ketogenic diet in intractable epilepsy for all ages.

  9. Glut1 deficiency syndrome and novel ketogenic diets.

    PubMed

    Klepper, Joerg; Leiendecker, Baerbel

    2013-08-01

    The classical ketogenic diet has been used for refractory childhood epilepsy for decades. It is also the treatment of choice for disorders of brain energy metabolism, such as Glut1 deficiency syndrome. Novel ketogenic diets such as the modified Atkins diet and the low glycemic index treatment have significantly improved the therapeutic options for dietary treatment. Benefits of these novel diets are increased palatability, practicability, and thus compliance-at the expense of lower ketosis. As high ketones appear essential to meet the brain energy deficit caused by Glut1 deficiency syndrome, the use of novel ketogenic diets in this entity may be limited. This article discusses the current data on novel ketogenic diets and the implications on the use of these diets in regard to Glut1 deficiency syndrome.

  10. Ketogenic diet improves core symptoms of autism in BTBR mice.

    PubMed

    Ruskin, David N; Svedova, Julia; Cote, Jessica L; Sandau, Ursula; Rho, Jong M; Kawamura, Masahito; Boison, Detlev; Masino, Susan A

    2013-01-01

    Autism spectrum disorders share three core symptoms: impaired sociability, repetitive behaviors and communication deficits. Incidence is rising, and current treatments are inadequate. Seizures are a common comorbidity, and since the 1920's a high-fat, low-carbohydrate ketogenic diet has been used to treat epilepsy. Evidence suggests the ketogenic diet and analogous metabolic approaches may benefit diverse neurological disorders. Here we show that a ketogenic diet improves autistic behaviors in the BTBR mouse. Juvenile BTBR mice were fed standard or ketogenic diet for three weeks and tested for sociability, self-directed repetitive behavior, and communication. In separate experiments, spontaneous intrahippocampal EEGs and tests of seizure susceptibility (6 Hz corneal stimulation, flurothyl, SKF83822, pentylenetetrazole) were compared between BTBR and control (C57Bl/6) mice. Ketogenic diet-fed BTBR mice showed increased sociability in a three-chamber test, decreased self-directed repetitive behavior, and improved social communication of a food preference. Although seizures are a common comorbidity with autism, BTBR mice fed a standard diet exhibit neither spontaneous seizures nor abnormal EEG, and have increased seizure susceptibility in just one of four tests. Thus, behavioral improvements are dissociable from any antiseizure effect. Our results suggest that a ketogenic diet improves multiple autistic behaviors in the BTBR mouse model. Therefore, ketogenic diets or analogous metabolic strategies may offer novel opportunities to improve core behavioral symptoms of autism spectrum disorders.

  11. An Update on the Ketogenic Diet, 2012

    PubMed Central

    Halevy, Ayelet; Peleg-Weiss, Lilach; Cohen, Roni; Shuper, Avinoam

    2012-01-01

    The ketogenic diet has been in use for the last 90 years, and its role in the treatment of epilepsy in the pediatric population has been gaining recognition. It can be helpful in many types of epilepsies, even the more severe ones, and has a beneficial effect on the child’s alertness and cognition, which can be impaired by both the condition and the medications needed for controlling it. Parental compliance is good in spite of the inconveniences inherent in following the diet. The significant advancements in understanding the nature of the diet are in better defining when its use is contraindicated and in validating its application in severe epilepsies in infancy, such as infantile spasms. Although most neurologists do not consider it as being the preferred first-line therapy, it is often a reasonable option when two medications have already failed. PMID:23908829

  12. Cardiac complications in pediatric patients on the ketogenic diet.

    PubMed

    Best, T H; Franz, D N; Gilbert, D L; Nelson, D P; Epstein, M R

    2000-06-27

    Cardiac complications of the ketogenic diet, in the absence of selenium deficiency, have not been reported. Twenty patients on the ketogenic diet at one institution were investigated. Prolonged QT interval (QTc) was found in 3 patients (15%). There was a significant correlation between prolonged QTc and both low serum bicarbonate and high beta-hydroxybutyrate. In addition, three patients had evidence of cardiac chamber enlargement. One patient with severe dilated cardiomyopathy and prolonged QTc normalized when the diet was discontinued.

  13. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis.

    PubMed

    Gibson, A A; Seimon, R V; Lee, C M Y; Ayre, J; Franklin, J; Markovic, T P; Caterson, I D; Sainsbury, A

    2015-01-01

    Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.

  14. Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet.

    PubMed

    Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich

    2016-04-01

    High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone.

  15. Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy.

    PubMed

    Lima, Patricia Azevedo de; Sampaio, Leticia Pereira de Brito; Damasceno, Nágila Raquel Teixeira

    2014-12-01

    A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat) for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed.

  16. The implementation and maintenance of the Ketogenic Diet in children.

    PubMed

    Casey, J C; McGrogan, J; Pillas, D; Pyzik, P; Freeman, J; Vining, E P

    1999-10-01

    The Ketogenic Diet is an effective treatment for epilepsy in children. At Johns Hopkins Hospital more than 400 children have been placed on the Ketogenic Diet. The implementation and maintenance of this treatment require significant collaboration between the family and Epilepsy Team. During initiation of the diet, in the hospital, parents attend classes on the history and mechanism of the diet, preparation of meals, psychological issues, complications and the management of childhood illnesses on the ketogenic diet. Many factors are considered in calculating a ketogenic formula. Age, weight, height and activity level are the obvious factors. However, secondary medical diagnoses, medications, neurological deficits, feeding issues and psychological issues are additional factors that affect the formulation of an optimal ketogenic prescription. Once this prescription has been formulated and implemented, many patients require fine-tuning of their ketogenic diets to get the best antiepileptic results while promoting growth. We believe that our success in sustaining this treatment is related to our fine-tuning and management practices.

  17. Renal stone associated with the ketogenic diet in a 5-year old girl with intractable epilepsy.

    PubMed

    Choi, Ji Na; Song, Ji Eun; Shin, Jae Il; Kim, Heung Dong; Kim, Myung Joon; Lee, Jae Seung

    2010-05-01

    In this paper, we report on a 5-year-old girl who developed a renal stone while following the ketogenic diet to treat refractory seizure disorder. Three months after initiating the ketogenic diet, she developed severe abdominal pain and vomiting. The spot urine calcium-to-creatinine (Ca/Cr) ratio and 24-hour urine evaluation showed hypercalciuria. Computed tomography (CT) imaging revealed a stone in the right ureteropelvic junction, resulting in hydronephrosis of the right kidney. The renal stone disappeared 5 days after conservative treatment; the patient's microscopic hematuria resolved concurrently. In light of this case report, we recommend regularly monitoring the urine Ca/Cr ratio with ultrasonography for further development of renal stones in patients following the ketogenic diet. If these patients exhibit evidence of symptomatic hypercalciuria or cyristalluria, liberalization of fluid restriction and urine alkalization using oral potassium citrate should be considered.

  18. Methionine and choline regulate the metabolic phenotype of a ketogenic diet.

    PubMed

    Pissios, Pavlos; Hong, Shangyu; Kennedy, Adam Richard; Prasad, Deepthi; Liu, Fen-Fen; Maratos-Flier, Eleftheria

    2013-01-01

    Low-carbohydrate ketogenic diets are commonly used as weight loss alternatives to low-fat diets, however the physiological and molecular adaptations to these diets are not completely understood. It is assumed that the metabolic phenotype of the ketogenic diet (KD) is caused by the absence of carbohydrate and high fat content, however in rodents the protein content of KD affects weight gain and ketosis. In this study we examined the role of methionine and choline in mediating the metabolic effects of KD. We have found that choline was more effective than methionine in decreasing the liver steatosis of KD-fed mice. On the other hand, methionine supplementation was more effective than choline in restoring weight gain and normalizing the expression of several fatty acid and inflammatory genes in the liver of KD-fed mice. Our results indicate that choline and methionine restriction rather than carbohydrate restriction underlies many of the metabolic effects of KD.

  19. Introduction of a ketogenic diet in young infants.

    PubMed

    Klepper, J; Leiendecker, B; Bredahl, R; Athanassopoulos, S; Heinen, F; Gertsen, E; Flörcken, A; Metz, A; Voit, T

    2002-10-01

    The ketogenic diet is a rational treatment for pyruvate dehydrogenase complex deficiency (McKusick 312170) and GLUT1 deficiency syndrome (McKusick 138140). An increasing number of patients are diagnosed in early infancy, but few data are available on the introduction of a ketogenic diet in this age group. GLUT1 deficiency syndrome was suspected in four infants presenting with seizures and unexplained hypoglycorrhachia. A ketogenic diet was introduced at 6-28 weeks of age. Ketosis was initiated by fasting, monitored by bedside blood glucose and 3-hydroxybutyrate determinations, and was maintained successfully using supplemented carbohydrate-free infant formula and emulgated triglycerides. All patients developed ketosis within 24 h. 3-Hydroxybutyrate concentrations available at the bedside correlated inversely with the base excess. At glucose levels < or = 40 mg/dl patients remained asymptomatic in the presence of ketones. The ketogenic formula was tolerated well, parental compliance was good, and all patients remained seizure-free on the diet. GLUT1 deficiency was confirmed in two patients; the diet was discontinued in the other two patients. In one infant, failure to thrive on medium-chain triglycerides was effectively reversed using long-chain triglycerides. Urine dipstick analyses failed to detect ketosis in another infant. Adverse effects of the diet were limited to renal stones in one patient. The ketogenic diet can be introduced and maintained successfully in young infants using long-chain fat emulsion. Monitoring 3-hydroxybutyrate at the bedside was useful for metabolic control and superior to urine dipstick analysis. Seizure control was effective and adverse effects were limited, but evaluation of the long-term effects of the ketogenic diet in this age group must await ongoing studies.

  20. Mitochondria: The ketogenic diet--A metabolism-based therapy.

    PubMed

    Vidali, Silvia; Aminzadeh, Sepideh; Lambert, Bridget; Rutherford, Tricia; Sperl, Wolfgang; Kofler, Barbara; Feichtinger, René G

    2015-06-01

    Mitochondria are the energy-producing organelles of the cell, generating ATP via oxidative phosphorylation mainly by using pyruvate derived from glycolytic processing of glucose. Ketone bodies generated by fatty acid oxidation can serve as alternative metabolites for aerobic energy production. The ketogenic diet, which is high in fat and low in carbohydrates, mimics the metabolic state of starvation, forcing the body to utilize fat as its primary source of energy. The ketogenic diet is used therapeutically for pharmacoresistant epilepsy and for "rare diseases" of glucose metabolism (glucose transporter type 1 and pyruvate dehydrogenase deficiency). As metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells; there is increasing evidence that the ketogenic diet may also be beneficial as an adjuvant cancer therapy by potentiating the antitumor effect of chemotherapy and radiation treatment. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.

  1. Alternative diets to the classical ketogenic diet--can we be more liberal?

    PubMed

    Miranda, Maria J; Turner, Zahava; Magrath, Gwyneth

    2012-07-01

    The ketogenic diet (KD), a high-fat, adequate protein, low-carbohydrate diet has been used since 1921 for the treatment of severe medically refractory epilepsy. In the past 15 years, the use of the KD has expanded enormously and a huge amount of clinical evidence of its efficacy is available. The classical KD is however restrictive and therefore alternative more liberal varieties of the classical KD have been developed within the last 8 years. The purpose of this report is to summarise the principles and evidence of effectiveness of the alternative ketogenic diets: Medium Chain Triglyceride (MCT)-KD, modified Atkins diet (MAD) and low glycaemic index treatment (LGIT), compared to the classical KD. The clinical evidence to date suggests that the more liberal versions of the classical KD such as MCT KD, MAD and LGIT have an efficacy close to the classical KD; however, no RCT data are available for MAD and LGIT. This evidence suggests that factors such as age, epilepsy type, lifestyle and resources are important factors in deciding which diet we should start a patient on. This report intends to summarise guidelines based on the evidence available.

  2. Ketogenic diet alters dopaminergic activity in the mouse cortex.

    PubMed

    Church, William H; Adams, Ryan E; Wyss, Livia S

    2014-06-13

    The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity.

  3. Ketogenic diet in the treatment of refractory epilepsy in childhood.

    PubMed

    Hassan, A M; Keene, D L; Whiting, S E; Jacob, P J; Champagne, J R; Humphreys, P

    1999-08-01

    There has been renewed interest in the ketogenic diet in the treatment of medically refractory seizure disorders in childhood. This article reports the results of a retrospective chart review of 52 patients who were treated with the ketogenic diet. The vast majority (49 of 52) were treated with the classic 4:1 diet. Seizure control improved in 67.3% of patients with complete abolition of seizures in six. Adverse reactions were uncommon and included the development of renal stones, gall bladder stones, and hypoproteinemia in one patient each. Routine biochemical screening during the diet did not identify or prevent adverse events. The authors' experiences with the diet emphasize the need for close ongoing medical and dietary supervision.

  4. The Ketogenic Diet and Sport: A Possible Marriage?

    PubMed

    Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A

    2015-07-01

    The ketogenic diet (KD) is used widely as a weight loss strategy and, more rarely, as therapy for some diseases. In many sports, weight control is often necessary (boxing, weightlifting, wrestling, etc.), but the KD usually is not considered. Our hypothesis is that KD might be used to achieve fat loss without affecting strength/power performance negatively.

  5. Peroxisome proliferator-activated receptor alpha and the ketogenic diet.

    PubMed

    Cullingford, Tim

    2008-11-01

    Peroxisome proliferator-activated receptor alpha (PPARalpha) is a drug/fatty acid-activated trans cription factor involved in the starvation response, and is thus relevant to the ketogenic diet (KD). This article summarizes research indicating the role of PPARalpha in central and peripheral nervous system function with particular reference to downstream targets relevant to anticonvulsant action.

  6. The ketogenic diet upregulates expression of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in rat brain.

    PubMed

    Cullingford, Tim E; Eagles, Douglas A; Sato, Hitoshi

    2002-04-01

    The ketogenic diet is a clinically and experimentally effective anti-epileptic treatment whose molecular mechanism(s) of action remain to be elucidated. As a first step in defining its effects on regulation of fatty acid oxidation and ketogenesis at the genetic level, we have administered to rats: (1) a calorie-restricted ketogenic diet (KCR); (2) a calorie-restricted normal diet (NCR); or (3) a normal diet ad libitum (NAL). We have used RNase protection to co-assay diet-induced changes in abundance of the mRNA encoding the critical enzyme of ketogenesis from acetyl-CoA namely mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) in liver and brain, together with mRNAs encoding three other key enzymes of fatty acid oxidation. We demonstrate that NCR-fed rats exhibit a significant 2-fold increase in liver mHS mRNA compared to NAL-fed rats, and that KCR-fed rats exhibit a significant 2-fold increase in both liver and brain mHS mRNA compared to NAL-fed rats. Our results demonstrate, for the first time, the effect of a ketogenic diet on gene expression in brain, and suggest possible anti-epileptic mechanisms for future investigation.

  7. Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats.

    PubMed

    Fukushima, Atsushi; Ogura, Yuji; Furuta, Miyako; Kakehashi, Chiaki; Funabashi, Toshiya; Akema, Tatsuo

    2015-10-05

    A ketogenic diet was recently shown to reduce glutamate accumulation in synaptic vesicles, decreasing glutamate transmission. We questioned whether a ketogenic diet affects hippocampal function, as glutamate transmission is critically involved in visuospatial ability. In the present study, male Wistar rats were maintained on a ketogenic diet containing 10% protein and 90% fat with complements for 3 weeks to change their energy expenditure from glucose-dependent to fat-dependent. Control rats were fed a diet containing 10% protein, 10% fat, and 80% carbohydrates. The fat-dependent energy expenditure induced by the ketogenic diet led to decreased body weight and increased blood ketone production, though the rats in the two groups consumed the same number of calories. The ketogenic diet did not alter food preferences for the control or high-fat diet containing 10% protein, 45% fat, and 45% carbohydrates. Anxiety in the open field was not altered by ingestion the ketogenic diet. However, rats fed the ketogenic diet performed better in the Y-maze test than rats fed the control diet. No difference was observed between the two groups in the Morris water maze test. Finally, Western blot revealed that the hippocampal expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit 1 (GluR1) was significantly increased in mice fed a ketogenic diet. These results suggest that hippocampal function is not impaired by a ketogenic diet and we speculate that the fat-dependent energy expenditure does not impair visuospatial ability.

  8. Kidney stones and the ketogenic diet: risk factors and prevention.

    PubMed

    Sampath, Amitha; Kossoff, Eric H; Furth, Susan L; Pyzik, Paula L; Vining, Eileen P G

    2007-04-01

    A cohort study was performed of children started on the ketogenic diet for intractable epilepsy from 2000 to 2005 (n = 195). Children who developed kidney stones were compared with those without in terms of demographics, urine laboratory markers, and intervention with urine alkalinization (potassium citrate). Thirteen children (6.7%) developed kidney stones. The use of oral potassium citrate significantly decreased the prevalence of stones (3.2% vs 10.0%, P = .049) and increased the mean time on the ketogenic diet before a stone was first noted (260 vs 149 patient-months, P = .29). The prevalence of kidney stones did not correlate with younger age or use of carbonic anhydrate inhibitors (eg, topiramate or zonisamide) but trended toward higher correlation with the presence of hypercalciuria (92% vs 71%, P = .08). No child stopped the diet due to stones; in fact, the total diet duration was longer (median 26 vs 12 months, P < .001). Kidney stones continue to occur in approximately 1 in 20 children on the ketogenic diet, and no statistically significant risk factors were identified in this cohort. As oral potassium citrate was preventative, prospective studies using this medication empirically are warranted.

  9. Ketogenic diet does not change NKCC1 and KCC2 expression in rat hippocampus.

    PubMed

    Gómez-Lira, Gisela; Mendoza-Torreblanca, Julieta Griselda; Granados-Rojas, Leticia

    2011-09-01

    In control rats, we examined the effects of ketogenic diet on NKCC1 and KCC2 expression levels in hippocampus. Neither the number of NKCC1 immunoreactive cells nor the intensity of labeling of KCC2 was found to modify in hippocampus of the rats after ketogenic diet treatment. These results indicate that ketogenic diet by itself does not modify the expression of these cation chloride cotransporters.

  10. Ketogenic diet sensitizes glucose control of hippocampal excitability1

    PubMed Central

    Kawamura, Masahito; Ruskin, David N.; Geiger, Jonathan D.; Boison, Detlev; Masino, Susan A.

    2014-01-01

    A high-fat low-carbohydrate ketogenic diet (KD) is an effective treatment for refractory epilepsy, yet myriad metabolic effects in vivo have not been reconciled clearly with neuronal effects. A KD limits blood glucose and produces ketone bodies from β-oxidation of lipids. Studies have explored changes in ketone bodies and/or glucose in the effects of the KD, and glucose is increasingly implicated in neurological conditions. To examine the interaction between altered glucose and the neural effects of a KD, we fed rats and mice a KD and restricted glucose in vitro while examining the seizure-prone CA3 region of acute hippocampal slices. Slices from KD-fed animals were sensitive to small physiological changes in glucose, and showed reduced excitability and seizure propensity. Similar to clinical observations, reduced excitability depended on maintaining reduced glucose. Enhanced glucose sensitivity and reduced excitability were absent in slices obtained from KD-fed mice lacking adenosine A1 receptors (A1Rs); in slices from normal animals effects of the KD could be reversed with blockers of pannexin-1 channels, A1Rs, or KATP channels. Overall, these studies reveal that a KD sensitizes glucose-based regulation of excitability via purinergic mechanisms in the hippocampus and thus link key metabolic and direct neural effects of the KD. PMID:25170119

  11. Ketosis, ketogenic diet and food intake control: a complex relationship

    PubMed Central

    Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M.; Mangar, Devanand

    2015-01-01

    Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture. PMID:25698989

  12. Mouse models: the ketogenic diet and polyunsaturated fatty acids.

    PubMed

    Borges, Karin

    2008-11-01

    Literature on the anticonvulsant effects of the ketogenic diet (KD) in mouse seizure models is summarized. Recent data show that a KD balanced in vitamin, mineral, and antioxidant content is anticonvulsant in mice, confirming that the KD's effect in mice can be attributed to the composition of the diet and not other dietary factors. Given that the anticonvulsant mechanism of the KD is still unknown, the anticonvulsant profile of the diet in different seizure models may help to decipher this mechanism. The implications of the findings that the KD is anticonvulsant in electrical seizure models are indicated. Further, the potential involvement of polyunsaturated fatty acids (PUFA) in the KD's anticonvulsant mechanism is discussed.

  13. Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure.

    PubMed

    Selfridge, J Eva; Wilkins, Heather M; E, Lezi; Carl, Steven M; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H

    2015-04-01

    Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain's aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated.

  14. Clinical experience of ketogenic diet on children with refractory epilepsy.

    PubMed

    Mak, S C; Chi, C S; Wan, C J

    1999-01-01

    Thirteen children with refractory epilepsy received a ketogenic diet (medium chain triglyceride oil diet) as an alternative therapy since September 1997. Their seizure patterns included (1) generalized tonic-clonic seizures, (2) myoclonic seizures, (3) generalized tonic + atonic seizures, (4) complex partial seizures, (5) generalized clonic + atonic + myoclonic seizures, (6) head nodding + myoclonic + gelastic seizures, and (7) generalized tonic-clonic + myoclonic + atonic seizures. Major concerns emphasized on the efficacy and side effects of the diet. Clinical observation one month after the diet revealed that 53.8% of the patients had a > 75% reduction in seizure frequency and 76.9% of the patients had a > 50% reduction in seizure frequency. Six patients had some degrees of improvement in cognitive function and/ or school performances. The most common side effects were body weight loss (n = 6) and diarrhea (n = 5). Others included bad temper (n = 1), abdominal cramps (n = 2), nausea (n = 2), bad body smell (n = 1), and renal stones (n = 1). Even after discontinuation of the diet, 61.5% of patients still had a > 50% reduction in seizure frequency. We concluded that the ketogenic diet deserves a trial in children with refractory epilepsy.

  15. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    PubMed Central

    2011-01-01

    Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently

  16. A high-fat, ketogenic diet induces a unique metabolic state in mice.

    PubMed

    Kennedy, Adam R; Pissios, Pavlos; Otu, Hasan; Roberson, Russell; Xue, Bingzhong; Asakura, Kenji; Furukawa, Noburu; Marino, Frank E; Liu, Fen-Fen; Kahn, Barbara B; Libermann, Towia A; Maratos-Flier, Eleftheria

    2007-06-01

    Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.

  17. The ketogenic diet in children with Glut1 deficiency syndrome and epilepsy.

    PubMed

    Rauchenzauner, Markus; Klepper, Jörg; Leiendecker, Bärbel; Luef, Gerhard; Rostasy, Kevin; Ebenbichler, Christoph

    2008-11-01

    The effects of a long-term ketogenic diet in children with Glut1 deficiency syndrome on metabolism are unknown. Our results indicate a characteristic effect of a long-term ketogenic diet on glucose and lipid homeostasis in Glut1 deficiency syndrome. Although serum lipids and apolipoproteins reflect a proatherogenic lipoprotein profile, adipocytokine constellation is not indicative of enhanced cardiovascular risk.

  18. Development and evaluation of a ketogenic diet program.

    PubMed

    MacCracken, K A; Scalisi, J C

    1999-12-01

    Use of the ketogenic diet for seizure control in children with epilepsy has seen a recent resurgence. Little cost-benefit analysis of this therapy has been published. Lack of diet standardization and method for evaluation of diet efficacy makes the decision to implement this diet therapy problematic for dietetics practitioners. In 1995, a 3-year trial ketogenic diet program was implemented; the decision on whether to continue the program depended on patient outcomes and financial implications to the institution. The program initiation process involved development of a protocol encompassing inpatient and outpatient care, patient/caregiver education materials, and a parent/caregiver satisfaction survey for evaluation of subjective responses to therapy. The program was researched and developed by registered dietitians and required approximately 55 hours of labor over a period of 5 months. Nutrition management averaged 16 hours per patient. Available cost data revealed 83% reimbursement of hospital charges and 99% reimbursement of inpatient costs. Seizure reduction and/or improved behavior occurred in 6 of 11 (55%) patients. Although program development and patient-care management was labor intensive, results have been encouraging based on reduction in seizures and behavioral improvements in patients and parent/caregiver satisfaction.

  19. How do you keto? Survey of North American pediatric ketogenic diet centers.

    PubMed

    Jung, Da Eun; Joshi, Sucheta M; Berg, Anne T

    2015-06-01

    We surveyed ketogenic diet centers in North America about their practices surrounding the ketogenic diet. An internet survey was disseminated via REDCap(©) to North American ketogenic diet centers identified from the Charlie Foundation and Ketocal(©) websites. Fifty-six centers responded. In addition to physicians, nurses and dieticians, ketogenic teams included social workers (39%), feeding specialists (14%), educational liaisons (4%), psychologists (5%), and pharmacists (36%). A child attending school (2%), non-English speaking family (19%), single-parent family (0%), and oral feeding (6%) were rarely considered barriers. Overall, the diet was considered the first or second (0%), third or fourth (67%), fifth or sixth (29%), and last resort treatment (4%) by centers. It was considered the first or second treatment for GLUT1 disease (86%) and third or fourth for Dravet (63%), West (71%), and Doose (65%) syndromes. Ketogenic diet is no longer a last resort option. Traditional barriers do not influence its use.

  20. Neuronal-glial interactions in rats fed a ketogenic diet.

    PubMed

    Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula

    2006-01-01

    Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative

  1. The influence of the ketogenic diet on the elemental and biochemical compositions of the hippocampal formation.

    PubMed

    Chwiej, Joanna; Skoczen, Agnieszka; Matusiak, Katarzyna; Janeczko, Krzysztof; Patulska, Agnieszka; Sandt, Christophe; Simon, Rolf; Ciarach, Malgorzata; Setkowicz, Zuzanna

    2015-08-01

    A growing body of evidence demonstrates that dietary therapies, mainly the ketogenic diet, may be highly effective in the reduction of epileptic seizures. All of them share the common characteristic of restricting carbohydrate intake to shift the predominant caloric source of the diet to fat. Catabolism of fats results in the production of ketone bodies which become alternate energy substrates to glucose. Although many mechanisms by which ketone bodies yield its anticonvulsant effect are proposed, the relationships between the brain metabolism of the ketone bodies and their neuroprotective and antiepileptogenic action still remain to be discerned. In the study, X-ray fluorescence microscopy and FTIR microspectroscopy were used to follow ketogenic diet-induced changes in the elemental and biochemical compositions of rat hippocampal formation tissue. The use of synchrotron sources of X-rays and infrared allowed us to examine changes in the accumulation and distribution of selected elements (P, S, K, Ca, Fe, Cu, Zn, and Se) and biomolecules (proteins, lipids, ketone bodies, etc.) with the micrometer spatial resolution. The comparison of rats fed with the ketogenic diet and rats fed with the standard laboratory diet showed changes in the hippocampal accumulation of P, K, Ca, and Zn. The relations obtained for Ca (increased level in CA3, DG, and its internal area) and Zn (decreased areal density in CA3 and DG) were analogous to those that we previously observed for rats in the acute phase of pilocarpine-induced seizures. Biochemical analysis of tissues taken from ketogenic diet-fed rats demonstrated increased intensity of absorption band occurring at 1740 cm(-1), which was probably the result of elevated accumulation of ketone bodies. Moreover, higher absolute and relative (3012 cm(-1)/2924 cm(-1), 3012 cm(-1)/lipid massif, and 3012 cm(-1)/amide I) intensity of the 3012-cm(-1) band resulting from increased unsaturated fatty acids content was found after the treatment

  2. Effect of short-term ketogenic diet on redox status of human blood.

    PubMed

    Nazarewicz, Rafal R; Ziolkowski, Wieslaw; Vaccaro, Patrick S; Ghafourifar, Pedram

    2007-12-01

    The present study investigated the effect of a ketogenic diet on the blood redox status of healthy female subjects. Twenty healthy females with mean body mass index of 21.45 +/- 2.05 kg/m(2) were provided a low-carbohydrate (55 +/- 6 g; 13% total energy), high-fat (138 +/- 16 g; 74% total energy), calorie-restricted (-465 +/- 115 kcal/d) diet. The followings were tested prior to and after 14 days consumption of the diet: Whole body, body weight and total body fat; blood, complete blood count, red blood cells, white blood cells, hemoglobin, and hematocrit; plasma, 3-beta-hydroxybutyrate, total antioxidative status, and uric acid; red blood cells, total sulfhydryl content, malondialdehyde, superoxide dismutase activity, and catalase activity. After 14 days, weight loss was significant whereas no changes were detected in body fat. No alterations were observed in blood count or morphology. 3-beta-hydroxybutyrate, total antioxidative status, uric acid, and sulfhydryl content were significantly increased. There were no alterations in malondialdehyde, or superoxide dismutase or catalase activity. The present study demonstrates that 14 days of a ketogenic diet elevates blood antioxidative capacity and does not induce oxidative stress in healthy subjects.

  3. Antiepileptic popular ketogenic diet: emerging twists in an ancient story.

    PubMed

    Vamecq, Joseph; Vallée, Louis; Lesage, Florian; Gressens, Pierre; Stables, James P

    2005-01-01

    The antiepileptic activity associated with ketogenic diets (KD) have been known for some time. First reports date back to the Middle Ages and even Biblical times where KD was achieved by fasting (i.e. "water diet") [see Swink, T.D., Vining, E.P.G., Freeman, J.M., 1997. The ketogenic diet: 1997. Adv. Pediatr. 44, 297-329, and references therein]. In the early 20th century, changes in the design of the KD were introduced, shifting the so-called "water diet" to a high-fat diet. Initial clinical evaluations undertaken between the 1920s and 1940s were enthusiastic, but the popularity of the KD was retrograded upon clinical introduction of phenytoin and subsequently other antiepileptic drugs. Today, despite a pharmacological arsenal targeting cerebral receptors and specific events in seizure initiation and development, about 30-40% patients are still refractory to available medications. Thus, the KD has been re-introduced in recent years as an alternative therapy, averring to be efficacious against some instances of resistant or intractable epilepsy. Despite a long historical background and enlarged clinical use, identification of the underlying anticonvulsant mechanisms associated with this nonpharmacological approach is still in stagnation. The present review is an attempt to encourage current research orientation through well-based and directed proposals for putative emerging candidates mediating KD anticonvulsant mechanisms. The reader is provided with a special emphasis on ATP-sensitive and recently cloned two-pore (or tandem) domain potassium channels, as well as several emerging conceptual views and advances such as nuclear receptors, uncoupling proteins and gap junctions that the authors speculate may contribute to understanding the basic mechanisms linked to the KD.

  4. Fat-Free Mass Changes During Ketogenic Diets and the Potential Role of Resistance Training.

    PubMed

    Tinsley, Grant M; Willoughby, Darryn S

    2016-02-01

    Low-carbohydrate and very-low-carbohydrate diets are often used as weight-loss strategies by exercising individuals and athletes. Very-low-carbohydrate diets can lead to a state of ketosis, in which the concentration of blood ketones (acetoacetate, 3-β-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and activity of ketogenic enzymes. A potential concern of these ketogenic diets, as with other weight-loss diets, is the potential loss of fat-free mass (e.g., skeletal muscle). On examination of the literature, the majority of studies report decreases in fat-free mass in individuals following a ketogenic diet. However, some confounding factors exist, such as the use of aggressive weight-loss diets and potential concerns with fat-free mass measurement. A limited number of studies have examined combining resistance training with ketogenic diets, and further research is needed to determine whether resistance training can effectively slow or stop the loss of fat-free mass typically seen in individuals following a ketogenic diet. Mechanisms underlying the effects of a ketogenic diet on fat-free mass and the results of implementing exercise interventions in combination with this diet should also be examined.

  5. Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss

    PubMed Central

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés; Alonso-Moraga, Ángeles

    2008-01-01

    Background Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine. Methods A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 ± 2.22 and 38.48 ± 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat (≥30 ml/day), moderate red wine intake (200–400 ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's t test. Results There was an extremely significant (p < 0.0001) reduction in body weight (108.62 kg→ 94.48 kg), body mass index (36.46 kg/m2→31.76 kg/m2), systolic blood pressure (125.71 mmHg→109.05 mmHg), diastolic blood pressure (84.52 mmHg→ 75.24 mmHg), total cholesterol (208.24 mg/dl→186.62 mg/dl), triacylglicerols (218.67 mg/dl→113.90 mg/dl) and glucose (109.81 mg/dl→ 93.33 mg/dl). There was a significant (p = 0.0167) reduction in LDLc (114.52 mg/dl→105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl→54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction). Conclusion The

  6. High-fat and ketogenic diets in amyotrophic lateral sclerosis.

    PubMed

    Paganoni, Sabrina; Wills, Anne-Marie

    2013-08-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials.

  7. A ketogenic diet reduces long-term potentiation in the dentate gyrus of freely behaving rats.

    PubMed

    Koranda, Jessica L; Ruskin, David N; Masino, Susan A; Blaise, J Harry

    2011-08-01

    Ketogenic diets are very low in carbohydrates and can reduce epileptic seizures significantly. This dietary therapy is particularly effective in pediatric and drug-resistant epilepsy. Hypothesized anticonvulsant mechanisms of ketogenic diets focus on increased inhibition and/or decreased excitability/excitation. Either of these consequences might not only reduce seizures, but also could affect normal brain function and synaptic plasticity. Here, we characterized effects of a ketogenic diet on hippocampal long-term potentiation, a widely studied form of synaptic plasticity. Adult male rats were placed on a control or ketogenic diet for 3 wk before recording. To maintain the most physiological conditions possible, we assessed synaptic transmission and plasticity using chronic in vivo recordings in freely behaving animals. Rats underwent stereotaxic surgery to chronically implant a recording electrode in the hippocampal dentate gyrus and a stimulating electrode in the perforant path; they recovered for 1 wk. After habituation and stable baseline recording, 5-Hz theta-burst stimulation was delivered to induce long-term potentiation. All animals showed successful plasticity, demonstrating that potentiation was not blocked by the ketogenic diet. Compared with rats fed a control diet, rats fed a ketogenic diet demonstrated significantly diminished long-term potentiation. This decreased potentiation lasted for at least 48 h. Reduced potentiation in ketogenic diet-fed rats is consistent with a general increase in neuronal inhibition (or decrease in excitability) and decreased seizure susceptibility. A better understanding of the effects of ketogenic diets on synaptic plasticity and learning is important, as diet-based therapy is often prescribed to children with epilepsy.

  8. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men.

    PubMed

    Sharman, Matthew J; Kraemer, William J; Love, Dawn M; Avery, Neva G; Gómez, Ana L; Scheett, Timothy P; Volek, Jeff S

    2002-07-01

    Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). This study examined the effects of a 6-wk ketogenic diet on fasting and postprandial serum biomarkers in 20 normal-weight, normolipidemic men. Twelve men switched from their habitual diet (17% protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein, 8% carbohydrate and 61% fat) and eight control subjects consumed their habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet. Fasting serum total and LDL cholesterol and oxidized LDL were unaffected and HDL cholesterol tended to increase with the ketogenic diet (+11.5%; P = 0.066). In subjects with a predominance of small LDL particles pattern B, there were significant increases in mean and peak LDL particle diameter and the percentage of LDL-1 after the ketogenic diet. There were no significant changes in blood lipids in the control group. To our knowledge this is the first study to document the effects of a ketogenic diet on fasting and postprandial CVD biomarkers independent of weight loss. The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia.

  9. Lipid and fatty acid profiles in rats consuming different high-fat ketogenic diets.

    PubMed

    Dell, C A; Likhodii, S S; Musa, K; Ryan, M A; Burnham, W M; Cunnane, S C

    2001-04-01

    High-fat ketogenic diets are used to treat intractable seizures in children, but little is known of the mechanism by which these diets work or whether fats rich in n-3 polyunsaturates might be beneficial. Tissue lipid and fatty acid profiles were determined in rats consuming very high fat (80 weight%), low-carbohydrate ketogenic diets containing either medium-chain triglyceride, flaxseed oil, butter, or an equal combination of these three fat sources. Ketogenic diets containing butter markedly raised liver triglyceride but had no effect on plasma cholesterol. Unlike the other fats, flaxseed oil in the ketogenic diet did not raise brain cholesterol. Brain total and free fatty acid profiles remained similar in all groups, but there was an increase in the proportion of arachidonate in brain total lipids in the medium-chain triglyceride group, while the two groups consuming flaxseed oil had significantly lower arachidonate in brain, liver, and plasma. The very high dietary intake of alpha-linolenate in the flaxseed group did not change docosahexaenoate levels in the brain. Our previous report based on these diets showed that although ketosis is higher in rats consuming a ketogenic diet based on medium-chain triglyceride oil, seizure resistance in the pentylenetetrazol model is not clearly related to the degree of ketosis achieved. In combination with our present data from the same seizure study, it appears that ketogenic diets with widely differing effects on tissue lipids and fatty acid profiles can confer a similar amount of seizure protection.

  10. Recommendations for the clinical management of children with refractory epilepsy receiving the ketogenic diet.

    PubMed

    Alberti, María J; Agustinho, Ariela; Argumedo, Laura; Armeno, Marisa; Blanco, Virginia; Bouquet, Cecilia; Cabrera, Analía; Caraballo, Roberto; Caramuta, Luciana; Cresta, Araceli; de Grandis, Elizabeth S; De Martini, Martha G; Diez, Cecilia; Dlugoszewski, Corina; Escobal, Nidia; Ferrero, Hilario; Galicchio, Santiago; Gambarini, Victoria; Gamboni, Beatriz; Guisande, Silvina; Hassan, Amal; Matarrese, Pablo; Mestre, Graciela; Pesce, Laura; Ríos, Viviana; Sosa, Patricia; Vaccarezza, María; Viollaz, Rocío; Panico, Luis

    2016-02-01

    The ketogenic diet, a non-drug treatment with proven effectiveness, has been the most commonly used therapy in the past decade for the management of refractory epilepsy in the pediatric population. Compared to adding a new drug to a pre-existing treatment, the ketogenic diet is highly effective and reduces the number of seizures by 50-90% in approximately 45-60% of children after six months of treatment. For this reason, the Argentine Society of Pediatric Neurology established the Ketogenic Diet Working Group. It is integrated by pediatric dietitians, pediatricians, pediatric neurologists and B.S. in Nutrition, who developed recommendations for the optimal management of patients receiving the classical ketogenic diet based on expert consensus and scientific publications in this field.

  11. Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation.

    PubMed

    Sirikonda, Naga S; Patten, William D; Phillips, John R; Mullett, Charles J

    2012-06-01

    Selenium-deficiency cardiomyopathy is a known secondary complication from long-term treatment with a ketogenic diet for medical refractory epilepsy. Our patient, a 5-year-old boy on a ketogenic diet for intractable seizures, had a normal selenium level before starting the diet, but he shortly thereafter developed acute reversible cardiomyopathy and ventricular tachycardia, which was unmasked during a hospitalization for an elective operative procedure. His cardiomyopathy was suspected to be secondary to a selenium-deficient state and was confirmed by way of a markedly low serum selenium level and supported by rapid improvement with the initiation of selenium supplementation and cessation of the ketogenic diet. For patients being initiated on a ketogenic diet, current screening guidelines call for baseline and follow-up selenium levels every 3 months during the first year along with RDA selenium supplementation, which is 30 mcg/day. Most of the new ketogenic diet formulas meet this requirement. Our patient underwent elective surgery before his planned 3-month selenium level check and had potentially preventable complications. Secondary to this experience, we suggest that all patients initiated on a ketogenic diet should have a preoperative electrocardiogram (EKG), an echocardiogram, and selenium level determined before any elective surgery. These steps would prevent unnecessary perioperative morbidity and mortality.

  12. Ketogenic diet - A novel treatment for early epileptic encephalopathy due to PIGA deficiency.

    PubMed

    Joshi, Charuta; Kolbe, Diana L; Mansilla, M Adela; Mason, Sara; Smith, Richard J H; Campbell, Colleen A

    2016-10-01

    We describe the presentation and workup of two brothers with early-onset epileptic encephalopathy who became seizure-free on a ketogenic diet. Extensive testing culminated in whole exome sequencing, which led to the diagnosis of phosphatidyl inositol glycan biosynthesis class A protein (PIGA) deficiency. This familial case highlights the importance of genetic testing for early-onset epileptic encephalopathies and underscores the potential value of a ketogenic diet in the treatment of this condition.

  13. Anesthetic management of a pediatric patient on a ketogenic diet.

    PubMed

    Ichikawa, Junko; Nishiyama, Keiko; Ozaki, Kyoko; Ikeda, Misako; Takii, Yoshitaka; Ozaki, Makoto

    2006-01-01

    There are several specific considerations regarding seizure control during the perioperative period in patients who have been placed on a ketogenic diet (KD). A KD is high in fat and low in protein and carbohydrates and has a long history of use for the treatment of intractable seizures in children. Maintaining therapeutic ketosis and modifying the acid-base balance are particularly important for preventing seizures in patients on a KD. We report changes in the biochemical parameters of a patient with double cortex syndrome who was on a KD and who had been scheduled for the treatment of dental caries under sevoflurane anesthesia and acetate Ringer administration. Inhalation induction with a high concentration of sevoflurane should be reconsidered in view of recent reports describing the epileptogenic potential of sevoflurane.

  14. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

    PubMed

    Schugar, Rebecca C; Huang, Xiaojing; Moll, Ashley R; Brunt, Elizabeth M; Crawford, Peter A

    2013-01-01

    Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

  15. The complete control of glucose level utilizing the composition of ketogenic diet with the gluconeogenesis inhibitor, the anti-diabetic drug metformin, as a potential anti-cancer therapy.

    PubMed

    Oleksyszyn, Józef

    2011-08-01

    In the animal models of glucose dependent cancer growth, the growth is decreased 15-30% through the use of low-carbohydrate, calorically restricted and/or ketogenic diet. The remaining growth depends on glucose formed by the liver-kidney gluconeogenesis as is the case in the cancer cachexia. It is hypothesized that a new treatment for cancer diseases should be explored which includes the ketogenic diet combined with the inhibition of gluconeogenesis by the anti-diabetic drug metformin.

  16. An overview of the ketogenic diet for pediatric epilepsy.

    PubMed

    Zupec-Kania, Beth A; Spellman, Emily

    Epilepsy is the most common serious neurological condition in the world, with an estimated prevalence of 1% of the population. The highest incidence occurs in childhood and in the elderly, with lower levels in early adulthood. Traditional epilepsy management includes pharmacological treatment, epilepsy surgery, and vagal nerve stimulation. Despite these therapies, 25% of children continue to have uncontrolled seizures. The ketogenic diet (KD), which has been in use since 1921, is a treatment option for many of these children. A meta-analysis of 19 studies with a combined sample of 1084 pediatric patients was completed in 1998 by Blue Cross Blue Shield. Estimates of the overall efficacy of the KD in controlling seizures were reported as follows: 16% became seizure free, 32% had a >90% reduction in seizures, and 56% had a >50% reduction. The KD is high in fat, moderate in protein, and low in carbohydrates. This combination of energy results in a sustained ketosis that somehow serves to abate seizures through an unknown mechanism. Strict adherence to the diet is required for it to be effective. Newer, more liberal versions of the KDs have been recently introduced and are being studied in children and adults. Administration of all of these metabolically adjusted diets must be medically managed as there can be adverse effects. The focus of this review is on the pediatric application of the KD.

  17. Ketogenic diets in patients with inherited metabolic disorders.

    PubMed

    Scholl-Bürgi, S; Höller, A; Pichler, K; Michel, M; Haberlandt, E; Karall, D

    2015-07-01

    Ketogenic diets (KDs) are diets that bring on a metabolic condition comparable to fasting, usually without catabolism. Since the mid-1990s such diets have been widely used in patients with seizures/epilepsies, mostly children. This review focuses on the use of KDs in patients with various inherited metabolic disorders (IMD). In glucose transporter type 1 deficiency syndrome (GLUT1-DS) and pyruvate dehydrogenase complex (PDHc) deficiency, KDs are deemed the therapy of choice and directly target the underlying metabolic disorder. Moreover, in other IMD, mainly of intermediary metabolism such as glycogen storage diseases and disorders of mitochondrial energy supply, KDs may ameliorate clinical symptoms and laboratory parameters. KDs have also been used successfully to treat symptoms such as seizures/epilepsy in IMD, e.g. in urea cycle disorders and non-ketotic hyperglycinemia. As a note of caution, catabolism may cause the condition of patients with IMD to deteriorate and should thus be avoided during KDs. For this reason, careful monitoring (clinical, laboratory and apparatus-supported) is warranted. In some IMDs specific macronutrient supply is critical. Therefore, in cases of PDHc deficiency the carbohydrate intake tolerated without lactate increase and in urea cycle disorders the protein tolerance should be determined. Considering this, it is particularly important in patients with IMD that the use of KDs be individualized and well documented.

  18. Ketogenic diet prevents cardiac arrest-induced cerebral ischemic neurodegeneration.

    PubMed

    Tai, K-K; Nguyen, N; Pham, L; Truong, D D

    2008-07-01

    Ketogenic diet (KD) is an effective treatment for intractable epilepsies. We recently found that KD can prevent seizure and myoclonic jerk in a rat model of post-hypoxic myoclonus. In the present study, we tested the hypothesis that KD can prevent the cerebral ischemic neurodegeneration in this animal model. Rats fed a standard diet or KD for 25 days were being subjected to mechanically induced cardiac arrest brain ischemia for 8 min 30 s. Nine days after cardiac arrest, frozen rat brains were sectioned for evaluation of ischemia-induced neurodegeneration using fluoro-jade (FJ) staining. The FJ positive degenerating neurons were counted manually. Cardiac arrest-induced cerebral ischemia in rats fed the standard diet exhibited extensive neurodegeneration in the CA1 region of the hippocampus, the number of FJ positive neurons was 822+/-80 (n=4). They also showed signs of neurodegeneration in the Purkinje cells of the cerebellum and in the thalamic reticular nucleus, the number of FJ positive neurons in the cerebellum was 55+/-27 (n=4), the number of FJ positive neurons in the thalamic reticular nucleus was 22+/-5 (n=4). In contrast, rats fed KD showed no evidence of neurodegeneration, the number of FJ positive neurons in these areas were zero. The results demonstrate that KD can prevent cardiac arrest-induced cerebral ischemic neurodegeneration in selected brain regions.

  19. Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats.

    PubMed

    Blaise, J Harry; Ruskin, David N; Koranda, Jessica L; Masino, Susan A

    2015-05-01

    Ketogenic diets are low-carbohydrate, sufficient protein, high-fat diets with anticonvulsant activity used primarily as a treatment for pediatric epilepsy. The anticonvulsant mechanism is thought to involve elevating inhibition and/or otherwise limiting excitability in the brain. Such a mechanism, however, might also significantly affect normal brain activity and limit synaptic plasticity, effects that would be important to consider in the developing brain. To assess ketogenic diet effects on synaptic transmission and plasticity, electrophysiological recordings were performed at the perforant path/dentate gyrus synapse in awake, freely-behaving juvenile male rats. Electrodes were implanted 1 week prior to recording. Animals were fed regular chow or a ketogenic diet ad libitum for 3 weeks before recording. Although the ketogenic diet did not significantly alter baseline excitability (assessed by input-output curves) or short-term plasticity (using the paired-pulse ratio), it did reduce the magnitude of long-term potentiation at all poststimulation timepoints out to the last time measured (48 h). The results suggest an effect of ketogenic diet-feeding on the induction magnitude but not the maintenance of long-term potentiation. The lack of effect of the diet on baseline transmission and the paired-pulse ratio suggests a mechanism that limits excitation preferentially in conditions of strong stimulation, consonant with clinical reports in which the ketogenic diet alleviates seizures without a major impact on normal brain activity. Limiting plasticity in a seizure-susceptible network may limit seizure-induced epileptogenesis which may subserve the ongoing benefit of the ketogenic diet in epilepsy.

  20. Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats

    PubMed Central

    Blaise, J Harry; Ruskin, David N; Koranda, Jessica L; Masino, Susan A

    2015-01-01

    Ketogenic diets are low-carbohydrate, sufficient protein, high-fat diets with anticonvulsant activity used primarily as a treatment for pediatric epilepsy. The anticonvulsant mechanism is thought to involve elevating inhibition and/or otherwise limiting excitability in the brain. Such a mechanism, however, might also significantly affect normal brain activity and limit synaptic plasticity, effects that would be important to consider in the developing brain. To assess ketogenic diet effects on synaptic transmission and plasticity, electrophysiological recordings were performed at the perforant path/dentate gyrus synapse in awake, freely-behaving juvenile male rats. Electrodes were implanted 1 week prior to recording. Animals were fed regular chow or a ketogenic diet ad libitum for 3 weeks before recording. Although the ketogenic diet did not significantly alter baseline excitability (assessed by input–output curves) or short-term plasticity (using the paired-pulse ratio), it did reduce the magnitude of long-term potentiation at all poststimulation timepoints out to the last time measured (48 h). The results suggest an effect of ketogenic diet-feeding on the induction magnitude but not the maintenance of long-term potentiation. The lack of effect of the diet on baseline transmission and the paired-pulse ratio suggests a mechanism that limits excitation preferentially in conditions of strong stimulation, consonant with clinical reports in which the ketogenic diet alleviates seizures without a major impact on normal brain activity. Limiting plasticity in a seizure-susceptible network may limit seizure-induced epileptogenesis which may subserve the ongoing benefit of the ketogenic diet in epilepsy. PMID:26009636

  1. Ketogenic diet slows down mitochondrial myopathy progression in mice.

    PubMed

    Ahola-Erkkilä, Sofia; Carroll, Christopher J; Peltola-Mjösund, Katja; Tulkki, Valtteri; Mattila, Ismo; Seppänen-Laakso, Tuulikki; Oresic, Matej; Tyynismaa, Henna; Suomalainen, Anu

    2010-05-15

    Mitochondrial dysfunction is a major cause of neurodegenerative and neuromuscular diseases of adult age and of multisystem disorders of childhood. However, no effective treatment exists for these progressive disorders. Cell culture studies suggested that ketogenic diet (KD), with low glucose and high fat content, could select against cells or mitochondria with mutant mitochondrial DNA (mtDNA), but proper patient trials are still lacking. We studied here the transgenic Deletor mouse, a disease model for progressive late-onset mitochondrial myopathy, accumulating mtDNA deletions during aging and manifesting subtle progressive respiratory chain (RC) deficiency. We found that these mice have widespread lipidomic and metabolite changes, including abnormal plasma phospholipid and free amino acid levels and ketone body production. We treated these mice with pre-symptomatic long-term and post-symptomatic shorter term KD. The effects of the diet for disease progression were followed by morphological, metabolomic and lipidomic tools. We show here that the diet decreased the amount of cytochrome c oxidase negative muscle fibers, a key feature in mitochondrial RC deficiencies, and prevented completely the formation of the mitochondrial ultrastructural abnormalities in the muscle. Furthermore, most of the metabolic and lipidomic changes were cured by the diet to wild-type levels. The diet did not, however, significantly affect the mtDNA quality or quantity, but rather induced mitochondrial biogenesis and restored liver lipid levels. Our results show that mitochondrial myopathy induces widespread metabolic changes, and that KD can slow down progression of the disease in mice. These results suggest that KD may be useful for mitochondrial late-onset myopathies.

  2. Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet.

    PubMed

    Caraballo, Roberto; Noli, Daniel; Cachia, Pedro

    2015-06-01

    We present three patients with epilepsy of infancy with migrating focal seizures treated with the ketogenic diet. Between February 1, 2012 and January 31, 2014, three patients who met the diagnostic criteria for migrating focal seizures in infancy at our department were placed on the ketogenic diet and followed for a minimum of seven months. Two of the three children responded well to the ketogenic diet. One of these patients became seizure-free and his neuropsychological performance also significantly improved. The other child had a seizure reduction of 75% to 99% with only weekly seizures and moderate psychomotor improvement. For these two patients who responded well to the ketogenic diet, hospital admission was not required. The remaining patient had a seizure reduction of less than 50%. Tolerability of the diet was good in all three patients. Early treatment with the ketogenic diet should be considered for epilepsy of infancy with migrating focal seizures to control seizures and status epilepticus, and avoid progressive cognitive impairment.

  3. Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

    PubMed

    Viggiano, Andrea; Stoddard, Madison; Pisano, Simone; Operto, Francesca Felicia; Iovane, Valentina; Monda, Marcellino; Coppola, Giangennaro

    2016-07-01

    The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons.

  4. Linear growth of children on a ketogenic diet: does the protein-to-energy ratio matter?

    PubMed

    Nation, Judy; Humphrey, Maureen; MacKay, Mark; Boneh, Avihu

    2014-11-01

    Ketogenic diet is a structured effective treatment for children with intractable epilepsy. Several reports have indicated poor linear growth in children on the diet but the mechanism of poor growth has not been elucidated. We aimed to explore whether the protein to energy ratio plays a role in linear growth of children on ketogenic diet. Data regarding growth and nutrition were, retrospectively, collected from the clinical histories of 35 children who were treated with ketogenic diet for at least 6 months between 2002 and 2010. Patients were stratified into groups according to periods of satisfactory or poor linear growth. Poor linear growth was associated with protein or caloric intake of <80% recommended daily intake, and with a protein-to-energy ratio consistently ≤1.4 g protein/100 kcal even when protein and caloric intakes were adequate. We recommend a protein-to-energy ratio of 1.5 g protein/100 kcal be prescribed to prevent growth retardation.

  5. Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

    PubMed

    Brownlow, Milene L; Benner, Leif; D'Agostino, Dominic; Gordon, Marcia N; Morgan, Dave

    2013-01-01

    Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition.

  6. Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets

    PubMed Central

    Giordano, Carmela; Marchiò, Maddalena; Timofeeva, Elena; Biagini, Giuseppe

    2014-01-01

    Various ketogenic diet (KD) therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine) and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin, and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs). In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the neurohormonal

  7. A ketogenic diet increases succinic dehydrogenase activity in aging cardiomyocytes.

    PubMed

    Balietti, Marta; Fattoretti, Patrizia; Giorgetti, Belinda; Casoli, Tiziana; Di Stefano, Giuseppina; Solazzi, Moreno; Platano, Daniela; Aicardi, Giorgio; Bertoni-Freddari, Carlo

    2009-08-01

    Impairment of energy metabolism and an increase of reactive oxygen species (ROS) production seem to play a major role in age-related apoptotic loss of cardiomyocytes. Succinic dehydrogenase (SDH) is an important marker of the mitochondrial capability to provide an adequate amount of ATP. Moreover, because of its unique redox properties, SDH activity contributes to maintain the reduced state of the ubiquinone pool. Recent reports have shown that ketone body intake improves cardiac metabolic efficiency and exerts a cardioprotective antioxidant action, we therefore performed a cytochemical investigation of SDH activity in cardiomyocytes of late-adult (19-month-old) rats fed for 8 weeks with a medium-chain triglycerides ketogenic diet (MCT-KD). Young, age-matched and old animals fed with a standard chow were used as controls. The overall area of the precipitates (PA) from SDH activity and the area of the SDH-positive mitochondria (MA) were measured. The percent ratios PA/MA and MA/total myocardial tissue area (MA/TA) were the parameters taken into account. We found that PA/MA was significantly higher in young control rats and in MCT-KD-fed rats versus late-adult and old control rats and in young control versus MCT-KD-fed rats. MA/TA of MCT-KD-fed rats was significantly higher versus age-matched and old control rats and tended to be higher versus young control rats; this parameter was significantly higher in young versus old control rats. Thus, MCT-KD intake partially recovers age-related decrease of SDH activity and increases the myocardial area occupied by metabolically active mitochondria. These effects might counteract metabolic alterations leading to apoptosis-induced myocardial atrophy and failure during aging.

  8. Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study.

    PubMed

    Tregellas, Jason R; Smucny, Jason; Legget, Kristina T; Stevens, Karen E

    2015-12-01

    Although the ketogenic diet has shown promise in a pilot study and case report in schizophrenia, its effects in animal models of hypothesized disease mechanisms are unknown. This study examined effects of treatment with the ketogenic diet on hippocampal P20/N40 gating in DBA/2 mice, a translational endophenotype that mirrors inhibitory deficits in P50 sensory gating in schizophrenia patients. As expected, the diet increased blood ketone levels. Animals with the highest ketone levels showed the lowest P20/N40 gating ratios. These preliminary results suggest that the ketogenic diet may effectively target sensory gating deficits and is a promising area for additional research in schizophrenia.

  9. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

    PubMed Central

    Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A

    2013-01-01

    Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand. PMID:23801097

  10. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets.

    PubMed

    Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A

    2013-08-01

    Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.

  11. Prospective study of the modified atkins diet in combination with a ketogenic liquid supplement during the initial month.

    PubMed

    Kossoff, Eric H; Dorward, Jennifer L; Turner, Zahava; Pyzik, Paula L

    2011-02-01

    The modified Atkins diet is a high-fat, low-carbohydrate treatment for intractable childhood epilepsy. As data suggest that a stricter diet onset can be more effective, we added a ketogenic supplement to the modified Atkins diet during its initial month. Thirty children with intractable epilepsy were prospectively started on the modified Atkins diet in combination with a daily 400-calorie KetoCal shake. At 1 month, 24 (80%) children had >50% seizure reduction, of which 11 (37%) had >90% seizure reduction. There was no significant loss of efficacy during the second month after KetoCal was discontinued. The use of this ketogenic supplement increased daily fat intake and thus the ketogenic ratio (1.8:1 versus 1.0:1 in the modified Atkins diet alone, P = .0002), but did not change urinary or serum ketosis. The addition of a ketogenic supplement to the modified Atkins diet during its initial month appears to be beneficial.

  12. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice.

    PubMed

    Dang, Mai T; Wehrli, Suzanne; Dang, Chi V; Curran, Tom

    2015-01-01

    The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice.

  13. The ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies.

    PubMed

    Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier

    2015-07-01

    Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates.

  14. Long-term use of the ketogenic diet in the treatment of epilepsy.

    PubMed

    Groesbeck, Darcy K; Bluml, Renee M; Kossoff, Eric H

    2006-12-01

    Long-term outcomes of the ketogenic diet in the treatment of epilepsy have not previously been reported. A retrospective chart review of children treated with the ketogenic diet for more than 6 years at the Johns Hopkins Hospital was performed. The response was documented at clinic visits and by telephone contacts; laboratory studies were obtained approximately every 6 to 12 months. Satisfaction and tolerability were assessed by means of a brief parental telephone questionnaire. In all, 28 patients (15 males, 13 females), currently aged 7 to 23 years, were identified. The median baseline seizure frequency per week at diet onset was 630 (range 1-1400). Diet duration ranged from 6 to 12 years; 19 remain on the diet currently. After 6 years or more, 24 children experienced a more than 90% decrease in seizures, and 22 parents reported satisfaction with the diet's efficacy. Ten children were at less than the 10th centile for height at diet initiation; this number increased to 23 at the most recent follow-up (p=0.001). Kidney stones occurred in seven children and skeletal fractures in six. After 6 years or more the mean cholesterol level was 201mg/dl, high-density lipoprotein was 54mg/dl, low-density lipoprotein was 129mg/dl, and triglycerides were 97mg/dl. Efficacy and overall tolerability for children are maintained after prolonged use of the ketogenic diet. However, side effects, such as slowed growth, kidney stones, and fractures, should be monitored closely.

  15. Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse.

    PubMed

    Ruskin, David N; Fortin, Jessica A; Bisnauth, Subrina N; Masino, Susan A

    2017-01-01

    The core symptoms of autism spectrum disorder are poorly treated with current medications. Symptoms of autism spectrum disorder are frequently comorbid with a diagnosis of epilepsy and vice versa. Medically-supervised ketogenic diets are remarkably effective nonpharmacological treatments for epilepsy, even in drug-refractory cases. There is accumulating evidence that supports the efficacy of ketogenic diets in treating the core symptoms of autism spectrum disorders in animal models as well as limited reports of benefits in patients. This study tests the behavioral effects of ketogenic diet feeding in the EL mouse, a model with behavioral characteristics of autism spectrum disorder and comorbid epilepsy. Male and female EL mice were fed control diet or one of two ketogenic diet formulas ad libitum starting at 5weeks of age. Beginning at 8weeks of age, diet protocols continued and performance of each group on tests of sociability and repetitive behavior was assessed. A ketogenic diet improved behavioral characteristics of autism spectrum disorder in a sex- and test-specific manner; ketogenic diet never worsened relevant behaviors. Ketogenic diet feeding improved multiple measures of sociability and reduced repetitive behavior in female mice, with limited effects in males. Additional experiments in female mice showed that a less strict, more clinically-relevant diet formula was equally effective in improving sociability and reducing repetitive behavior. Taken together these results add to the growing number of studies suggesting that ketogenic and related diets may provide significant relief from the core symptoms of autism spectrum disorder, and suggest that in some cases there may be increased efficacy in females.

  16. Lack of long-term histopathologic changes in brain and skeletal muscle of mice treated with a ketogenic diet.

    PubMed

    Rho, Jong M; Sarnat, Harvey B; Sullivan, Patrick G; Robbins, Carol A; Kim, Dong W

    2004-07-01

    Although there is increasing awareness of adverse effects associated with use of the high-fat ketogenic diet, very little is known regarding its long-term clinical consequences, especially in relation to cardiovascular health. Recent reports have highlighted rare but significant cardiac problems in patients treated with the ketogenic diet. Given the inherent limitations in conducting detailed pathologic assessments in patients, we asked whether histologic changes might develop in the brain and skeletal muscle of mice fed a high-fat diet for 2 to 3 months. We found no evidence of gross morphologic or histochemical alterations in muscle or brain after administration of the ketogenic diet. Further, there was no abnormal lipid storage or mitochondrial enzymatic staining. Our data suggest that patients chronically treated with a ketogenic diet are not likely to develop a lipid myopathy or neuronal inclusions.

  17. Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets.

    PubMed

    Liu, Yeou-mei Christiana; Wang, Huei-Shyong

    2013-01-01

    The ketogenic diet (KD) is one of the most effective therapies for drug-resistant epilepsy. The efficacy of the medium-chain triglyceride KD (MCTKD) is as excellent as the classic KD (CKD), which has been documented in several subsequent retrospective, prospective, and randomized studies. MCT oil is more ketogenic than long-chain triglycerides. Therefore, the MCTKD allows more carbohydrate and protein food, which makes the diet more palatable than the CKD. The MCTKD is not based on diet ratios as is the CKD, but uses a percentage of calories from MCT oil to create ketones. There has also been literature which documents the associated gastrointestinal side effects from the MCTKD, such as diarrhea, vomiting, bloating, and cramps. Therefore, the MCTKD has been an underutilized diet therapy for intractable epilepsy among children.The author has used up to >70% MCTKD diet to maximize seizure control with gastrointestinal side effects optimally controlled. As long as health care professionals carefully manage MCTKD, many more patients with epilepsy who are not appropriate for CKD or modified Atkins diet or low glycemic index treatment will benefit from this treatment. A comparison between the MCTKD and other KDs is also discussed.

  18. Refractory epilepsy and the ketogenic diet: pathophysiological aspects and possible implications in dental practice.

    PubMed

    Sharma, A; Mathur, V P

    2011-01-01

    Epilepsy denotes any disorder characterized by recurrent seizures due to abnormal paroxysmal neuronal discharge in the brain. Symptoms range from sensory absences to convulsive movements and loss of consciousness. Antiepileptic drugs are the first line of treatment. However, 20% individuals with epilepsy have drug-resistant seizures despite optimal treatment. For those with refractory epilepsy, the ketogenic diet is an effective alternative therapeutic approach. The ketogenic diet is a high-fat, low-carbohydrate, and adequate-protein diet that mimics the biochemical effects of fasting. There are many disparate mechanistic theories of how this diet protects against seizures. Key insights indicate that it has effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. This paper discusses the implicitly significant and diverse biochemical changes affected by this unique therapeutic approach that may have a bearing on oral health and the delivery of dental care to individuals with refractory epilepsy.

  19. Effects of ketogenic diet on electroconvulsive threshold and brain contents of adenosine nucleotides.

    PubMed

    Nakazawa, M; Kodama, S; Matsuo, T

    1983-01-01

    The anticonvulsive effect of a ketogenic diet was investigated using mice fed on a ketogenic milk powder which contained medium-chain triglycerides (MCT). Electroconvulsive shocking and determination of adenosine nucleotides in mice brain were performed on three mice groups, (1) a control group; free access to a commercially available diet, (2) a fasted group; fasted for two days, and (3) a ketotic group; fasted for two days and then fed on the ketogenic milk powder for two weeks. The maximal electroconvulsive threshold of the ketotic group was significantly higher than that of the fasted group (p less than 0.001). The maximal electroconvulsive threshold of the fasted group was significantly higher than that of the control group (p less than 0.05). The contents of adenosine triphosphate (ATP) in the brain of the ketotic group was significantly higher than that of the control group (p less than 0.01). These results suggest that chronic ketosis with the ketogenic diet increases the contents of ATP in the brain and this increase in ATP probably accounts for the neuronal stability.

  20. Adenosine, Ketogenic Diet and Epilepsy: The Emerging Therapeutic Relationship Between Metabolism and Brain Activity

    PubMed Central

    Masino, S.A; Kawamura, M; Wasser, C.D.; Pomeroy, L.T; Ruskin, D.N

    2009-01-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a “retaliatory metabolite.” As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor–based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  1. Diet and identity: being a good parent in the face of contradictions presented by the ketogenic diet.

    PubMed

    Webster, Michelle; Gabe, Jonathan

    2016-01-01

    The ketogenic diet is a high-fat diet used to treat drug-resistant childhood epilepsy. Given that negative meanings tend to be attached to fatty foods and children's food consumption is seen to be the responsibility of parents, the ketogenic diet may be problematic for parenting identity. This article draws upon in-depth semi-structured interviews with 12 parents from 10 families that have a child whose epilepsy is being treated with the ketogenic diet. The main focus of the article is the meanings these parents attached to foods and how they were drawn upon or altered to overcome some of the contradictions presented by the diet. It will be argued that the diet was medicalised and parents came to view food as medicine. When viewing food in this way, negative associations with fat were reversed. Furthermore, parents also used food as a symbol of inclusion and prioritised portion size or the child's enjoyment of food in order to use food as a symbol of love. In turn this enabled parents to feel they were being good parents. Overall, it seems that diet can be medicalised and the identity of the good parent maintained if dietary treatment is successful.

  2. Dietary and medication adjustments to improve seizure control in patients treated with the ketogenic diet.

    PubMed

    Selter, Jessica H; Turner, Zahava; Doerrer, Sarah C; Kossoff, Eric H

    2015-01-01

    Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007 to 2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments led to >50% further seizure reduction in 18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs 15%, P = .08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit).

  3. Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.

    PubMed

    Liśkiewicz, Arkadiusz D; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin-Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska-Szypułka, Halina

    2016-02-19

    Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

  4. Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis

    PubMed Central

    Liśkiewicz, Arkadiusz D.; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin–Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska–Szypułka, Halina

    2016-01-01

    Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/−) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth. PMID:26892894

  5. Long term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol.

    PubMed

    Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A; Lodi, Alessandra; Bosco, Gerardo

    2013-12-18

    Weight loss protocols can only be considered successful if they deliver consistent results over the long term-a goal which is often elusive, so much so that the term "yo-yo" is used to describe the perennial weight loss/weight regain battle common in obesity. We hypothesized that a ketogenic Mediterranean diet with phytoextracts (KEMEPHY) combined with the acknowledged health benefits of traditional Mediterranean nutrition may favor long term weight loss. We analysed 89 male and female obese subjects, aged between 25 and 65 years who were overall healthy apart from being overweight. The subjects followed a staged diet protocol over a period of 12 months: 20 day of KEMEPHY; 20 days low carb-non ketogenic; 4 months Mediterranean normocaloric nutrition; a second 20 day ketogenic phase followed by 6 months of Mediterranean normocaloric nutrition. For the majority of subjects (88.25%) there was significant loss of weight (from 100.7 ± 16.54 to 84.59 ± 9.71 kg; BMI from 35.42 ± 4.11 to 30.27 ± 3.58) and body fat (form 43.44% ± 6.34% to 33.63% ± 7.6%) during both ketogenic phases followed by successful maintenance, without weight regain, during the 6 month stabilization phase with only 8 subjects failing to comply. There were also significant and stable decreases in total cholesterol, LDLc, triglycerides and glucose levels over the 12 month study period. HDLc showed small increases after the ketogenic phases but over the full 12 months there was no significant change. No significant changes were observed in ALT, AST, Creatinine or BUN. The combination of a biphasic KEMEPHY diet separated by longer periods of maintenance nutrition, based on the traditional Mediterranean diet, led to successful long term weight loss and improvements in health risk factors in a majority of subjects; compliance was very high which was a key determinant of the results seen.

  6. The Efficacy of Ketogenic Diet and Associated Hypoglycemia as an Adjuvant Therapy for High-Grade Gliomas: A Review of the Literature

    PubMed Central

    Carico, Christine; Ortega, Alicia; Patil, Chirag G.

    2015-01-01

    Background: A high-fat, low-carbohydrate diet, often referred to as a ketogenic diet (KD), has been suggested to reduce frequency and severity of chronic pediatric and adult seizures. A hypoglycemic state, perpetuated by administration of a KD, has been hypothesized as a potential aid to the current standard treatments of high-grade gliomas. Methods: To understand the effectiveness of the ketogenic diet as a therapy for malignant gliomas, studies analyzing components of a KD were reviewed. Both preclinical and clinical studies were included. The keywords “ketogenic diet, GBM, malignant glioma, hyperglycemia, hypoglycemia” were utilized to search for both abstracts and full articles in English. Overall, 39 articles were found and included in this review. Results: Studies in animal models showed that a KD is able to control tumor growth and increase overall survival. Other pre-clinical studies have suggested that a KD sustains an environment in which tumors respond better to standard treatments, such as chemoradiation. In human cohorts, the KD was well tolerated. Quality of life was improved, compared to a standard, non-calorie or carbohydrate restricted diet. Hyperglycemia was independently associated with diminished survival. Conclusion: Recent clinical findings have demonstrated that induced hypoglycemia and ketogenic diet are tolerable and can potentially be an adjuvant to standard treatments, such as surgery and chemoradiation. Other findings have advocated for KD as a malignant cell growth inhibitor, and indicate that further studies analyzing larger cohorts of GBM patients treated with a KD are needed to determine the breadth of impact a KD can have on GBM treatment. PMID:26180675

  7. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain.

    PubMed

    Lauritzen, Knut H; Hasan-Olive, Md Mahdi; Regnell, Christine E; Kleppa, Liv; Scheibye-Knudsen, Morten; Gjedde, Albert; Klungland, Arne; Bohr, Vilhelm A; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-12-01

    Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABAA) receptor subunits α1. However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders.

  8. Long-term management of the ketogenic diet: seizure monitoring, nutrition, and supplementation.

    PubMed

    Zupec-Kania, Beth; Zupanc, Mary L

    2008-11-01

    The ketogenic diet (KD) is a medical nutrition therapy (MNT) for the treatment of epilepsy. As such, it can affect the outcome of an individual's health and chronic medical condition. The components of MNT which have been established by the American Dietetic Association as core guidelines for nutrition care include a diet history, assessment, diet therapy and a follow-up plan of care (American Dietetic Assoc 2002). We have utilized these guidelines in designing our approach to KD therapy in our pediatric population. Many of the practices described here have been adopted from our practical experience.

  9. Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

    PubMed

    Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

    2016-06-01

    Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI.

  10. Ketogenic diet-fed rats have increased fat mass and phosphoenolpyruvate carboxykinase activity.

    PubMed

    Ribeiro, Letícia C; Chittó, Ana L; Müller, Alexandre P; Rocha, Juliana K; Castro da Silva, Mariane; Quincozes-Santos, André; Nardin, Patrícia; Rotta, Liane N; Ziegler, Denize R; Gonçalves, Carlos-Alberto; Da Silva, Roselis S M; Perry, Marcos L S; Gottfried, Carmem

    2008-11-01

    The ketogenic diet (KD), characterized by high fat and low carbohydrate and protein contents, has been proposed to be beneficial in children with epilepsy disorders not helped by conventional anti-epileptic drug treatment. Weight loss and inadequate growth is an important drawback of this diet and metabolic causes are not well characterized. The aim of this study was to examine body weight variation during KD feeding for 6 wk of Wistar rats; fat mass and adipocyte cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity were also observed. PEPCK activity was determined based on the [H(14)CO(3) (-)]-oxaloacetate exchange reaction. KD-fed rats gained weight at a less rapid rate than normal-fed rats, but with a significant increment in fat mass. The fat mass/body weight ratio already differed between ketogenic and control rats after the first week of treatment, and was 2.4 x higher in ketogenic rats. The visceral lipogenesis was supported by an increment in adipocyte PEPCK, aiming to provide glycerol 3-phosphate to triacylglycerol synthesis and this fat accumulation was accompanied by glucose intolerance. These data contribute to our understanding of the metabolic effects of the KD in adipose tissue and liver and suggest some potential risks of this diet, particularly visceral fat accumulation.

  11. Ketogenic diet in early myoclonic encephalopathy due to non ketotic hyperglycinemia.

    PubMed

    Cusmai, Raffaella; Martinelli, Diego; Moavero, Romina; Dionisi Vici, Carlo; Vigevano, Federico; Castana, Cinzia; Elia, Mirella; Bernabei, Silvia; Bevivino, Elsa

    2012-09-01

    Non ketotic hyperglycinemia is a rare inborn error of glycine metabolism due to deficient activity of glycine cleavage system, a multienzymatic complex consisting of four protein subunits: the P-protein, the H-protein, the T-protein and the L-protein. The neonatal form of non ketotic hyperglycinemia presents in the first days of life with encephalopathy, seizures, multifocal myoclonus and characteristic "hiccups". Rapid progression may lead to intractable seizures, coma and respiratory failure requiring mechanical ventilation. Clinical trial with scavenges drugs decreasing glycine levels such as sodium benzoate, and with drugs reducing NMDA receptors excitatory properties, such as ketamine and dextromethorphan, have been tried but the outcome is usually poor; antiepileptic therapy, moreover, is unable to control epileptic seizures. Ketogenic diet has been successfully tried for refractory epilepsy in pediatric patients. We report three cases affected by neonatal non ketotic hyperglycinemia and early myoclonic encephalopathy treated with ketogenic diet. In our patients ketogenic diet, in association with standard pharmacological therapy, determined dramatic reduction of seizures and improved quality of life.

  12. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    PubMed Central

    Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

  13. Cardiovascular and hormonal aspects of very-low-carbohydrate ketogenic diets.

    PubMed

    Volek, Jeff S; Sharman, Matthew J

    2004-11-01

    In recent years, restriction of carbohydrate intake for weight loss has become widespread. Our research group began studying physiological responses to very-low-carbohydrate ketogenic diets (VLCKDs) in the late 1990s because we felt there was a significant void in the literature and limited understanding of metabolic responses to VLCKDs. This launched us into a line of research examining the physiological effects of VLCKDs. In this paper, we briefly overview nine studies we have published on isoenergetic and hypoenergetic VLCKDs in men and women. These studies have focused on blood lipid responses to VLCKDs, but we have also addressed changes in body weight, body composition, and hormones. Compared with low-fat diets, short-term VLCKDs consistently result in improvements in fat loss, fasting and postprandial triacylglycerols, high-density lipoprotein-cholesterol, the distribution of low-density lipoprotein-cholesterol subclasses, and insulin resistance. These are the key metabolic abnormalities of metabolic syndrome, a problem of epidemic proportions in the United States. There is substantial variability in total cholesterol and low-density lipoprotein-cholesterol responses to VLCKD. The factors responsible for this variability are not known, and studies designed to identify methods to predict blood lipid responses to VLCKD and other dietary approaches represent critical areas for nutrition researchers. Further research is warranted to validate the physiological effects of VLCKD over longer periods of time, including studies that modify the quality of macronutrients (i.e., the type of fat and protein) and the interaction with other interventions (e.g., exercise, dietary supplements, drugs).

  14. The use of ketogenic diet in special situations: expanding use in intractable epilepsy and other neurologic disorders

    PubMed Central

    2012-01-01

    The ketogenic diet has been widely used and proved to be effective for intractable epilepsy. Although the mechanisms underlying its anti-epileptic effects remain to be proven, there are increasing experimental evidences for its neuroprotective effects along with many researches about expanding use of the diet in other neurologic disorders. The first success was reported in glucose transporter type 1 deficiency syndrome, in which the diet served as an alternative metabolic source. Many neurologic disorders share some of the common pathologic mechanisms such as mitochondrial dysfunction, altered neurotransmitter function and synaptic transmission, or abnormal regulation of reactive oxygen species, and the role of the ketogenic diet has been postulated in these mechanisms. In this article, we introduce an overview about the expanding use and emerging trials of the ketogenic diet in various neurologic disorders excluding intractable epilepsy and provide explanations of the mechanisms in that usage. PMID:23049588

  15. The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.

    PubMed

    Zamani, Gholam Reza; Mohammadi, Mahmoud; Ashrafi, Mahmoud Reza; Karimi, Parviz; Mahmoudi, Maryam; Badv, Reza Shervin; Tavassoli, Ali Reza; Azizi Malamiri, Reza

    2016-12-01

    More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P < 0.001), median total cholesterol was significantly increased (from 180 to 285 mg/dl, P < 0.001), median serum low-density lipoprotein (LDL) was significantly increased (from 91 to 175 mg/dl, P < 0.001), and median serum high-density lipoprotein (HDL) was significantly increased (from 51 to 58 mg/dl, P < 0.001). Results of this study indicate that a classic ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.

  16. Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet.

    PubMed

    Garbow, Joel R; Doherty, Jason M; Schugar, Rebecca C; Travers, Sarah; Weber, Mary L; Wentz, Anna E; Ezenwajiaku, Nkiruka; Cotter, David G; Brunt, Elizabeth M; Crawford, Peter A

    2011-06-01

    Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.

  17. Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices.

    PubMed

    Kawamura, Masahito Jr; Ruskin, David N; Masino, Susan A

    2016-01-01

    The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet-fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy.

  18. Neurological and cardiac responses after treatment with miglustat and a ketogenic diet in a patient with Sandhoff disease.

    PubMed

    Villamizar-Schiller, Ives T; Pabón, Laudy A; Hufnagel, Sophia B; Serrano, Norma C; Karl, Gabriela; Jefferies, John L; Hopkin, Robert J; Prada, Carlos E

    2015-03-01

    Sandhoff disease is a progressive neurodegenerative disorder characterized by accumulation of GM2 gangliosides. We describe a 6-year-old male with coarse facial features, developmental delay, refractory seizures, hypertrophic cardiomyopathy, who was later found to have Sandhoff disease. Previous studies have revealed that caloric restriction in combination with miglustat increased survival and motor behavior in mouse model of Sandhoff disease. These findings suggest that combination therapy may result in improved outcomes for patients with Sandhoff. Initiation of treatment with miglustat and a ketogenic diet was followed by improvement of the patient's seizure control and cardiac function. Further clinical investigation is required to better determine the benefit of management in late-onset forms of Sandhoff disease.

  19. The biochemical changes in hippocampal formation occurring in normal and seizure experiencing rats as a result of a ketogenic diet.

    PubMed

    Chwiej, Joanna; Skoczen, Agnieszka; Janeczko, Krzysztof; Kutorasinska, Justyna; Matusiak, Katarzyna; Figiel, Henryk; Dumas, Paul; Sandt, Christophe; Setkowicz, Zuzanna

    2015-04-07

    In this study, ketogenic diet-induced biochemical changes occurring in normal and epileptic hippocampal formations were compared. Four groups of rats were analyzed, namely seizure experiencing animals and normal rats previously fed with ketogenic (KSE and K groups respectively) or standard laboratory diet (NSE and N groups respectively). Synchrotron radiation based Fourier-transform infrared microspectroscopy was used for the analysis of distributions of the main organic components (proteins, lipids, compounds containing phosphate group(s)) and their structural modifications as well as anomalies in creatine accumulation with micrometer spatial resolution. Infrared spectra recorded in the molecular layers of the dentate gyrus (DG) areas of normal rats on a ketogenic diet (K) presented increased intensity of the 1740 cm(-1) absorption band. This originates from the stretching vibrations of carbonyl groups and probably reflects increased accumulation of ketone bodies occurring in animals on a high fat diet compared to those fed with a standard laboratory diet (N). The comparison of K and N groups showed, moreover, elevated ratios of absorbance at 1634 and 1658 cm(-1) for DG internal layers and increased accumulation of creatine deposits in sector 3 of the Ammon's horn (CA3) hippocampal area of ketogenic diet fed rats. In multiform and internal layers of CA3, seizure experiencing animals on ketogenic diet (KSE) presented a lower ratio of absorbance at 1634 and 1658 cm(-1) compared to rats on standard laboratory diet (NSE). Moreover, in some of the examined cellular layers, the increased intensity of the 2924 cm(-1) lipid band as well as the massifs of 2800-3000 cm(-1) and 1360-1480 cm(-1), was found in KSE compared to NSE animals. The intensity of the 1740 cm(-1) band was diminished in DG molecular layers of KSE rats. The ketogenic diet did not modify the seizure induced anomalies in the unsaturation level of lipids or the number of creatine deposits.

  20. Ketogenic Diet for Children with Epilepsy: A Practical Meal Plan in a Hospital

    PubMed Central

    2016-01-01

    A ketogenic diet (KD) is a dietary approach to treat intractable epilepsy. The KD begins with hospitalization and the child and their parents can adapt to the KD for 1-2 weeks. Recently, various type of dietary intervention such as the modified Atkins diet (MAD) and the low glycemic index treatment (LGIT) have been performed. Since 2010, we carried out the KD, MAD, and LGIT for total of 802 patients; 489 patients (61%) for the KD, 147 patients (18.3%) with the MAD, and 166 patients (20.7%) for the LGIT. In this report, application of these dietary practices in Severance Hospital is shared. PMID:26839878

  1. [Ketogenic diets: additional benefits to the weight loss and unfounded secondary effects].

    PubMed

    Pérez-Guisado, Joaquin

    2008-12-01

    It is also necessary to emphasize that as well as the weight loss, ketogenic diets are healthier because they promote a non-atherogenic lipid profile, lower blood pressure and diminish resistance to insulin with an improvement in blood levels of glucose and insulin. Such diets also have antineoplastic benefits, do not alter renal or liver functions, do not produce metabolic acidosis by Ketosis, have many neurological benefits in central nervous system, do not produce osteoporosis and could increase the perfomance in aerobic sports.

  2. An unfortunate challenge: Ketogenic diet for the treatment of Lennox-Gastaut syndrome in tyrosinemia type 1.

    PubMed

    De Lucia, Silvana; Pichard, Samia; Ilea, Adina; Greneche, Marie-Odile; François, Laurent; Delanoë, Catherine; Schiff, Manuel; Auvin, Stéphane

    2016-07-01

    The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed.

  3. Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

    PubMed Central

    Kawamura, Masahito Jr.; Ruskin, David N.; Masino, Susan A.

    2016-01-01

    The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy. PMID:27847463

  4. Ketogenic Diet Improves Motor Performance but Not Cognition in Two Mouse Models of Alzheimer’s Pathology

    PubMed Central

    Brownlow, Milene L.; Benner, Leif; D’Agostino, Dominic; Gordon, Marcia N.; Morgan, Dave

    2013-01-01

    Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer’s disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition. PMID:24069439

  5. Ketogenic Diet Prevents Epileptogenesis and Disease Progression in Adult Mice and Rats

    PubMed Central

    Lusardi, Theresa A.; Akula, Kiran K.; Coffman, Shayla Q.; Ruskin, David; Masino, Susan A.; Boison, Detlev

    2015-01-01

    Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects. PMID:26256422

  6. Seizure control by ketogenic diet-associated medium chain fatty acids.

    PubMed

    Chang, Pishan; Terbach, Nicole; Plant, Nick; Chen, Philip E; Walker, Matthew C; Williams, Robin S B

    2013-06-01

    The medium chain triglyceride (MCT) ketogenic diet is used extensively for treating refractory childhood epilepsy. This diet increases the plasma levels of medium straight chain fatty acids. A role for these and related fatty acids in seizure control has not been established. We compared the potency of an established epilepsy treatment, Valproate (VPA), with a range of MCT diet-associated fatty acids (and related branched compounds), using in vitro seizure and in vivo epilepsy models, and assessed side effect potential in vitro for one aspect of teratogenicity, for liver toxicology and in vivo for sedation, and for a neuroprotective effect. We identify specific medium chain fatty acids (both prescribed in the MCT diet, and related compounds branched on the fourth carbon) that provide significantly enhanced in vitro seizure control compared to VPA. The activity of these compounds on seizure control is independent of histone deacetylase inhibitory activity (associated with the teratogenicity of VPA), and does not correlate with liver cell toxicity. In vivo, these compounds were more potent in epilepsy control (perforant pathway stimulation induced status epilepticus), showed less sedation and enhanced neuroprotection compared to VPA. Our data therefore implicates medium chain fatty acids in the mechanism of the MCT ketogenic diet, and highlights a related new family of compounds that are more potent than VPA in seizure control with a reduced potential for side effects. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.

  7. The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

    PubMed

    Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

    2015-02-01

    Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients.

  8. Long Term Successful Weight Loss with a Combination Biphasic Ketogenic Mediterranean Diet and Mediterranean Diet Maintenance Protocol

    PubMed Central

    Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A; Lodi, Alessandra; Bosco, Gerardo

    2013-01-01

    Weight loss protocols can only be considered successful if they deliver consistent results over the long term—a goal which is often elusive, so much so that the term “yo-yo” is used to describe the perennial weight loss/weight regain battle common in obesity. We hypothesized that a ketogenic Mediterranean diet with phytoextracts (KEMEPHY) combined with the acknowledged health benefits of traditional Mediterranean nutrition may favor long term weight loss. We analysed 89 male and female obese subjects, aged between 25 and 65 years who were overall healthy apart from being overweight. The subjects followed a staged diet protocol over a period of 12 months: 20 day of KEMEPHY; 20 days low carb-non ketogenic; 4 months Mediterranean normocaloric nutrition; a second 20 day ketogenic phase followed by 6 months of Mediterranean normocaloric nutrition. For the majority of subjects (88.25%) there was significant loss of weight (from 100.7 ± 16.54 to 84.59 ± 9.71 kg; BMI from 35.42 ± 4.11 to 30.27 ± 3.58) and body fat (form 43.44% ± 6.34% to 33.63% ± 7.6%) during both ketogenic phases followed by successful maintenance, without weight regain, during the 6 month stabilization phase with only 8 subjects failing to comply. There were also significant and stable decreases in total cholesterol, LDLc, triglycerides and glucose levels over the 12 month study period. HDLc showed small increases after the ketogenic phases but over the full 12 months there was no significant change. No significant changes were observed in ALT, AST, Creatinine or BUN. The combination of a biphasic KEMEPHY diet separated by longer periods of maintenance nutrition, based on the traditional Mediterranean diet, led to successful long term weight loss and improvements in health risk factors in a majority of subjects; compliance was very high which was a key determinant of the results seen. PMID:24352095

  9. Occurrence of GLUT1 deficiency syndrome in patients treated with ketogenic diet.

    PubMed

    Ramm-Pettersen, Anette; Nakken, Karl O; Haavardsholm, Kathrine Cammermeyer; Selmer, Kaja Kristine

    2014-03-01

    Glucose transporter 1 deficiency syndrome (GLUT1-DS) is a treatable metabolic encephalopathy caused by a mutation in the SLC2A1 gene. This mutation causes a compromised transport of glucose across the blood-brain barrier. The treatment of choice is ketogenic diet, with which most patients become seizure-free. At the National Centre for Epilepsy, we have, since 2005, offered treatment with ketogenic diet (KD) and modified Atkins diet (MAD) to children with difficult-to-treat epilepsy. As we believe many children with GLUT1-DS are unrecognized, the aim of this study was to search for patients with GLUT1-DS among those who had been responders (>50% reduction in seizure frequency) to KD or MAD. Of the 130 children included, 58 (44%) were defined as responders. Among these, 11 were already diagnosed with GLUT1-DS. No mutations in the SLC2A1 gene were detected in the remaining patients. However, the clinical features of these patients differed considerably from the patients diagnosed with GLUT1-DS. While 9 out of 10 patients with GLUT1-DS became seizure-free with dietary treatment, only 3 out of the 33 remaining patients were seizure-free with KD or MAD treatment. We therefore conclude that a seizure reduction of >50% following dietary treatment is not a suitable criterion for identifying patients with GLUT1-DS, as these patients generally achieve complete seizure freedom shortly after diet initiation.

  10. The efficacy of the ketogenic diet in infants and young children with refractory epilepsies using a formula-based powder.

    PubMed

    Ashrafi, Mahmoud Reza; Hosseini, Seyed Ahmad; Zamani, Gholam Reza; Mohammadi, Mahmoud; Tavassoli, Alireza; Badv, Reza Shervin; Heidari, Morteza; Karimi, Parviz; Malamiri, Reza Azizi

    2017-03-01

    To evaluate the efficacy, safety, and tolerability of a classic 4:1 ketogenic diet using a formula-based powder in infants and children with refractory seizures who are reluctant to eat homemade foods. We conducted an open label trial and administered a ketogenic diet using formula-based power (Ketocal(®)). Twenty-seven infants and children aged between 12 months and 5 years were enrolled who had refractory seizures and were reluctant to eat homemade foods. Of 27 children, 5 were lost to follow-up and 22 were remained at the end of the study. After 4 months, the median frequency of seizures per week was reduced >50% in 68.2% of patients, while 9/22 children (40.9%) showed a 50-90% reduction in seizure frequency per week, and 6/22 children (27.3%) showed more than 90% reduction in seizure frequency per week. Over the study course, 6/22 (27%) children who continued to receive the diet developed constipation, one child developed gastroesophageal reflux, and one child developed hypercholesterolemia. None of these children discontinued the diet because of the complications. Thirteen children and their parents (59%) reported that the diet was palatable and tolerable enough. The ketogenic diet using a formula-based powder (Ketocal(®)) is effective, safe, and tolerable in infants and children with refractory seizures who are reluctant to eat homemade foods according to the rules of the ketogenic diet.

  11. Intractable pediatric epilepsy: vagal nerve stimulation and the ketogenic diet.

    PubMed

    Sheth, Raj D; Stafstrom, Carl E

    2002-11-01

    The KD has been proven an effective alternative epilepsy treatment in children refractory to standard anticonvulsants. Children to be placed on the diet must be carefully selected, monitored, and followed. The diet is to be regarded as a strict medical regimen and requires a comprehensive medical team approach in concert with intensive parental involvement. With better understanding of the scientific principles underlying brain ketosis, we should be able to optimize the KD to achieve even better results.

  12. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway.

    PubMed

    McDaniel, Sharon S; Rensing, Nicholas R; Thio, Liu Lin; Yamada, Kelvin A; Wong, Michael

    2011-03-01

    The ketogenic diet (KD) is an effective treatment for epilepsy, but its mechanisms of action are poorly understood. We investigated the hypothesis that the KD inhibits mammalian target of rapamycin (mTOR) pathway signaling. The expression of pS6 and pAkt, markers of mTOR pathway activation, was reduced in hippocampus and liver of rats fed KD. In the kainate model of epilepsy, KD blocked the hippocampal pS6 elevation that occurs after status epilepticus. Because mTOR signaling has been implicated in epileptogenesis, these results suggest that the KD may have anticonvulsant or antiepileptogenic actions via mTOR pathway inhibition.

  13. Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet.

    PubMed

    Krebs, Philippe; Fan, Weiwei; Chen, Yen-Hui; Tobita, Kimimasa; Downes, Michael R; Wood, Malcolm R; Sun, Lei; Li, Xiaohong; Xia, Yu; Ding, Ning; Spaeth, Jason M; Moresco, Eva Marie Y; Boyer, Thomas G; Lo, Cecilia Wen Ya; Yen, Jeffrey; Evans, Ronald M; Beutler, Bruce

    2011-12-06

    Deficiencies of subunits of the transcriptional regulatory complex Mediator generally result in embryonic lethality, precluding study of its physiological function. Here we describe a missense mutation in Med30 causing progressive cardiomyopathy in homozygous mice that, although viable during lactation, show precipitous lethality 2-3 wk after weaning. Expression profiling reveals pleiotropic changes in transcription of cardiac genes required for oxidative phosphorylation and mitochondrial integrity. Weaning mice to a ketogenic diet extends viability to 8.5 wk. Thus, we establish a mechanistic connection between Mediator and induction of a metabolic program for oxidative phosphorylation and fatty acid oxidation, in which lethal cardiomyopathy is mitigated by dietary intervention.

  14. The effects of a ketogenic diet on exercise metabolism and physical performance in off-road cyclists.

    PubMed

    Zajac, Adam; Poprzecki, Stanisław; Maszczyk, Adam; Czuba, Miłosz; Michalczyk, Małgorzata; Zydek, Grzegorz

    2014-06-27

    The main objective of this research was to determine the effects of a long-term ketogenic diet, rich in polyunsaturated fatty acids, on aerobic performance and exercise metabolism in off-road cyclists. Additionally, the effects of this diet on body mass and body composition were evaluated, as well as those that occurred in the lipid and lipoprotein profiles due to the dietary intervention. The research material included eight male subjects, aged 28.3 ± 3.9 years, with at least five years of training experience that competed in off-road cycling. Each cyclist performed a continuous exercise protocol on a cycloergometer with varied intensity, after a mixed and ketogenic diet in a crossover design. The ketogenic diet stimulated favorable changes in body mass and body composition, as well as in the lipid and lipoprotein profiles. Important findings of the present study include a significant increase in the relative values of maximal oxygen uptake (VO2max) and oxygen uptake at lactate threshold (VO2 LT) after the ketogenic diet, which can be explained by reductions in body mass and fat mass and/or the greater oxygen uptake necessary to obtain the same energy yield as on a mixed diet, due to increased fat oxidation or by enhanced sympathetic activation. The max work load and the work load at lactate threshold were significantly higher after the mixed diet. The values of the respiratory exchange ratio (RER) were significantly lower at rest and during particular stages of the exercise protocol following the ketogenic diet. The heart rate (HR) and oxygen uptake were significantly higher at rest and during the first three stages of exercise after the ketogenic diet, while the reverse was true during the last stage of the exercise protocol conducted with maximal intensity. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity were significantly lower at rest and during particular stages of the 105-min exercise protocol following the low carbohydrate ketogenic diet

  15. Ketogenic diet does not affect strength performance in elite artistic gymnasts

    PubMed Central

    2012-01-01

    Background Despite the increasing use of very low carbohydrate ketogenic diets (VLCKD) in weight control and management of the metabolic syndrome there is a paucity of research about effects of VLCKD on sport performance. Ketogenic diets may be useful in sports that include weight class divisions and the aim of our study was to investigate the influence of VLCKD on explosive strength performance. Methods 8 athletes, elite artistic gymnasts (age 20.9 ± 5.5 yrs) were recruited. We analyzed body composition and various performance aspects (hanging straight leg raise, ground push up, parallel bar dips, pull up, squat jump, countermovement jump, 30 sec continuous jumps) before and after 30 days of a modified ketogenic diet. The diet was based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrates, but which mimicked their taste, with the addition of some herbal extracts. During the VLCKD the athletes performed the normal training program. After three months the same protocol, tests were performed before and after 30 days of the athletes’ usual diet (a typically western diet, WD). A one-way Anova for repeated measurements was used. Results No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg) and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p < 0.001) with a non-significant increase in muscle mass. Conclusions Despite concerns of coaches and doctors about the possible detrimental effects of low carbohydrate diets on athletic performance and the well known importance of carbohydrates there are no data about VLCKD and strength performance. The undeniable and sudden effect of VLCKD on fat loss may be useful for those athletes who compete in sports based on weight class. We have

  16. Environmental Enrichment Mitigates Detrimental Cognitive Effects of Ketogenic Diet in Weanling Rats.

    PubMed

    Scichilone, John M; Yarraguntla, Kalyan; Charalambides, Ana; Harney, Jacob P; Butler, David

    2016-09-01

    For decades, the ketogenic diet has been an effective treatment of intractable epilepsy in children. Childhood epilepsy is pharmacoresistant in 25-40 % of patients taking the current prescribed medications. Chronic seizure activity has been linked to deficits in cognitive function and behavioral problems which negatively affect the learning abilities of the child. Recent studies suggest the ketogenic diet (KD), a high fat with low carbohydrate and protein diet, has adverse effects on cognition in weanling rats. The diet reduces circulating glucose levels to where energy metabolism is converted from glycolysis to burning fat and generating ketone bodies which has been suggested as a highly efficient source of energy for the brain. In contrast, when weanling rats are placed in an enriched environment, they exhibit increased spatial learning, memory, and neurogenesis. Thus, this study was done to determine if weanling rats being administered a KD in an environmental enrichment (EE) would still exhibit the negative cognitive effects of the diet previously observed. The present study suggests that an altered environment is capable of reducing the cognitive deficits in weanling rats administered a KD. Learning was improved with an EE. The effect of diet and environment on anxiety and depression suggests a significant reduction in anxiety with enrichment rearing. Interestingly, circulating energy substrate levels were increased in the EE groups along with brain-derived neurotrophic factor despite the least changes in weight gain. In light of numerous studies using KDs that seemingly have adverse effects on cognition, KD-induced reductions in excitotoxic events would not necessarily eliminate that negative aspect of seizures.

  17. Lipoid pneumonia--a case of refractory pneumonia in a child treated with ketogenic diet.

    PubMed

    Buda, Piotr; Wieteska-Klimczak, Anna; Własienko, Anna; Mazur, Agnieszka; Ziołkowski, Jerzy; Jaworska, Joanna; Kościesza, Andrzej; Dunin-Wąsowicz, Dorota; Książyk, Janusz

    2013-01-01

    Lipoid pneumonia (LP) is a chronic inflammation of the lung parenchyma with interstitial involvement due to the accumulation of endogenous or exogenous lipids. Exogenous LP (ELP) is associated with the aspiration or inhalation of oil present in food, oil-based medications or radiographic contrast media. The clinical manifestations of LP range from asymptomatic cases to severe pulmonary involvement, with respiratory failure and death, according to the quantity and duration of the aspiration. The diagnosis of exogenous lipoid pneumonia is based on a history of exposure to oil and the presence of lipid-laden macrophages on sputum or bronchoalveolar lavage (BAL) analysis. High-resolution computed tomography (HRCT) is the imaging technique of choice for evaluation of patients with suspected LP. The best therapeutic strategy is to remove the oil as early as possible through bronchoscopy with multiple BALs and interruption in the use of mineral oil. Steroid therapy remains controversial, and should be reserved for severe cases. We describe a case of LP due to oil aspiration in 3-year-old girl with intractable epilepsy on ketogenic diet. Diagnostic problems were due to non-specific symptoms that were mimicking serious infectious pneumonia. A high index of suspicion and precise medical history is required in cases of refractory pneumonia and fever unresponsive to conventional therapy. Gastroesophageal reflux and a risk of aspiration may be regarded as relative contraindications to the ketogenic diet. Conservative treatment, based on the use of oral steroids, proved to be an efficient therapeutic approach in this case.

  18. MED23-associated refractory epilepsy successfully treated with the ketogenic diet.

    PubMed

    Lionel, Anath C; Monfared, Nasim; Scherer, Stephen W; Marshall, Christian R; Mercimek-Mahmutoglu, Saadet

    2016-09-01

    We report a new patient with refractory epilepsy associated with a novel pathogenic homozygous MED23 variant. This 7.5-year-old boy from consanguineous parents had infantile onset global developmental delay and refractory epilepsy. He was treated with the ketogenic diet at 2.5 years of age and became seizure free on the first day. He had microcephaly and truncal hypotonia. His brain MRI showed delayed myelination and thin corpus callosum. He was enrolled in a whole exome sequencing research study, which identified a novel, homozygous, likely pathogenic (c.1937A>G; p.Gln646Arg) variant in MED23. MED23 is a regulator of energy homeostasis and glucose production. Liver-specific Med23-knockout mice showed reduced liver gluconeogenesis and lower blood glucose levels compared to control mice. This is the first patient with documented refractory epilepsy caused by a novel homozygous pathogenic variant in MED23 expanding the phenotypic spectrum. Identification of the underlying genetic defect in MED23 sheds light on the possible mechanism of complete response to the ketogenic diet in this child. © 2016 Wiley Periodicals, Inc.

  19. Despite transient ketosis, the classic high-fat ketogenic diet induces marked changes in fatty acid metabolism in rats.

    PubMed

    Taha, Ameer Y; Ryan, Mary Ann A; Cunnane, Stephen C

    2005-09-01

    In contrast to humans, rats on a high-fat ketogenic diet seem incapable of maintaining plasma beta-hydroxybutyrate above 1 mmol/L for more than a week. Our goal was to determine whether fatty acid metabolism in rats changes despite the absence of sustained ketosis induced by the ketogenic diet. Fatty acid metabolism was assessed as changes in tissue fatty acid profiles and change in 13C-alpha-linolenic acid incorporation into plasma, liver, adipose tissue, and brain lipids. Despite loss of ketosis, the ketogenic diet reduced some polyunsaturated fatty acids in adipose tissue (up to 44%) and plasma (up to 90%) but raised polyunsaturates in liver triglycerides by up to 25-fold and raised arachidonic and docosahexaenoic acids in the brain by 15%. Lower tissue incorporation of 13C-alpha-linolenic acid but higher unlabeled and 13C-labeled docosahexaenoic acid in brain supports the view that the principal changes in fatty acid composition resulted from enhanced mobilization of polyunsaturates from adipose tissue to liver and brain. In the absence of sustained ketosis, changes in fatty acid metabolism resulting in an increase in brain polyunsaturates, particularly docosahexaenoic acid may, nevertheless, contribute to the seizure protection by the ketogenic diet.

  20. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects.

  1. Elemental changes in the hippocampal formation following two different formulas of ketogenic diet: an X-ray fluorescence microscopy study.

    PubMed

    Chwiej, J; Patulska, A; Skoczen, A; Janeczko, K; Ciarach, M; Simon, R; Setkowicz, Z

    2015-12-01

    The main purpose of the following study was the determination of elemental changes occurring within hippocampal formation as a result of high-fat and carbohydrate-restricted ketogenic diet (KD). To realize it, X-ray fluorescence microscopy was applied for topographic and quantitative analysis of P, S, K, Ca, Fe, Cu, Zn and Se in hippocampal formations taken from rats fed with two different KDs and naive controls. The detailed comparisons were done for sectors 1 and 3 of the Ammon's, the dentate gyrus and hilus of dentate gyrus. The results of elemental analysis showed that the KDs induced statistically significant changes in the accumulation of P, K, Ca, Zn and Se in particular areas of hippocampal formation and these alterations strongly depended on the composition of the diets. Much greater influence on the hippocampal areal densities of examined elements was found for the KD which was characterized by a lower content of carbohydrates, higher content of fats and increased proportion of unsaturated fatty acids. The levels of P, K and Zn decreased whilst those of Ca and Se increased as a result of the treatment with the KDs.

  2. Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with altering autophagy-associated molecules.

    PubMed

    Xu, Ling; Kanasaki, Megumi; He, Jianhua; Kitada, Munehiro; Nagao, Kenji; Jinzu, Hiroko; Noguchi, Yasushi; Maegawa, Hiroshi; Kanasaki, Keizo; Koya, Daisuke

    2013-10-01

    Ketogenic amino acid (KAA) replacement diet has been shown to cure hepatic steatosis, a serious liver disease associated with diverse metabolic defects. In this study, we investigated the effects of KAA replacement diet on nutrition sensing signaling pathway and analyzed whether induction of hepatic autophagy was involved. Mice are fed with high fat diet (HFD) or KAA replacement in high-fat diet (30% fat in food; HFD)-fed (HFD(KAAR)) and sacrificed at 8, 12, 16 weeks after initiation of experimental food. Hepatic autophagy was analyzed in protein expression of several autophagy-associated molecules and in light chain-3 green fluorescent protein (LC-3 GFP) transgenic mice. HFD(KAAR) showed increased AMP-activated protein kinase (AMPK) phosphorylation and enhanced liver kinase B1 (LKB1) expression compared to control HFD-fed mice. The KAA-HFD-induced activation of AMPK was associated with an increased protein expression of sirtuin 1 (Sirt1), decreased forkhead box protein O3a (Foxo3a) level, and suppression of mammalian target of rapamycin (mTOR) phosphorylation compared with the HFD-fed mice. The intervention study revealed that a KAA-replacement diet also ameliorated all the established metabolic and autophagy defects in the HFD-fed mice, suggesting that a KAA-replacement diet can be used therapeutically in established diseases. These results indicate that KAA replacement in food could be a novel strategy to combat hepatic steatosis and metabolic abnormalities likely involvement of an induction of autophagy.

  3. Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder

    PubMed Central

    Ruskin, David N.; Murphy, Michelle I.; Slade, Sierra L.; Masino, Susan A.

    2017-01-01

    Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD. PMID:28166277

  4. Effects of ketogenic diets on the occurrence of pilocarpine-induced status epilepticus of rats.

    PubMed

    Gama, Iclea Rocha; Trindade-Filho, Euclides Marinho; Oliveira, Suzana Lima; Bueno, Nassib Bezerra; Melo, Isabelle Tenório; Cabral-Junior, Cyro Rego; Barros, Elenita M; Galvão, Jaqueline A; Pereira, Wanessa S; Ferreira, Raphaela C; Domingos, Bruna R; da Rocha Ataide, Terezinha

    2015-02-01

    Two sources of medium-chain triglycerides--triheptanoin with anaplerotic properties and coconut oil with antioxidant features--have emerged as promising therapeutic options for the management of pharmacoresistant epilepsy. We investigated the effects of ketogenic diets (KDs) containing coconut oil, triheptanoin, or soybean oil on pilocarpine-induced status epilepticus (SE) in rats. Twenty-four adult male Wistar rats were divided into 4 groups and fed a control diet (7% lipids) or a KD containing soybean oil, coconut oil, or triheptanoin (69.8% lipids). The ketogenic and control diets had a lipid:carbohydrate + protein ratio of 1:11.8 and 3.5:1, respectively. SE was induced in all rats 20 days after initiation of the dietary treatment, through the administration of pilocarpine (340 mg/kg; i.p.). The latency, frequency, duration, and severity of seizures before and during SE were observed with a camcorder. SE was aborted after 3 h with the application of diazepam (5 mg/kg; i.p.). The rats in the triheptanoin-based KD group needed to undergo a higher number of seizures to develop SE, as compared to the control group (P < 0.05). Total weight gain, intake, energy intake, and feed efficiency coefficient, prior to induction of SE, differed between groups (P < 0.05), where the triheptanoin-based KD group showed less weight gain than all other groups, less energy intake than the Control group and intermediate values of feed efficiency coefficient between Control and other KDs groups. Triheptanoin-based KD may have a neuroprotective effect on the establishment of SE in Wistar rats.

  5. A light- and electron-microscope study of hepatocytes of rats fed different diets.

    PubMed

    Eagles, Douglas A; Chapman, George B

    2007-01-01

    Ketogenic diets are used in the treatment of epilepsy in children refractory to drug therapy. This study identifies changes in liver morphology in rats fed four different diets: a normal rodent chow diet, a calorie-restricted high-fat (ketogenic) diet and each diet supplemented with clofibric acid. Hepatocytes of rats fed the ketogenic diet show many lipid droplets and these are reduced to control levels when clofibrate is present in the diet. Mitochondria are enlarged in the livers of rats fed the ketogenic diet and further enlarged if clofibrate is present. Alterations in the appearance or numbers of other organelles are also found.

  6. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study.

    PubMed

    Tendler, David; Lin, Sauyu; Yancy, William S; Mavropoulos, John; Sylvestre, Pam; Rockey, Don C; Westman, Eric C

    2007-02-01

    Nonalcoholic fatty liver disease is an increasingly common condition that may progress to hepatic cirrhosis. This pilot study evaluated the effects of a low-carbohydrate, ketogenic diet on obesity-associated fatty liver disease. Five patients with a mean body mass index of 36.4 kg/m(2) and biopsy evidence of fatty liver disease were instructed to follow the diet (<20 g/d of carbohydrate) with nutritional supplementation for 6 months. Patients returned for group meetings biweekly for 3 months, then monthly for the second 3 months. The mean weight change was -12.8 kg (range 0 to -25.9 kg). Four of 5 posttreatment liver biopsies showed histologic improvements in steatosis (P=.02) inflammatory grade (P=.02), and fibrosis (P=.07). Six months of a low-carbohydrate, ketogenic diet led to significant weight loss and histologic improvement of fatty liver disease. Further research is into this approach is warranted.

  7. Ketogenic diet in the treatment of seizures associated with hypothalamic hamartomas.

    PubMed

    Chapman, Kevin E; Kim, Do-Young; Rho, Jong M; Ng, Yu-Tze; Kerrigan, John F

    2011-05-01

    Seizures associated with hypothalamic hamartoma (HH) are notoriously intractable to medical therapy, and while surgical resection affords most affected patients with complete or near seizure-freedom, there remains a need to identify alternative treatments. In this retrospective study, we identified six patients from a large cohort of 220 patients with HH who were treated with the ketogenic diet (KD). Four patients had a 50-90% reduction in multiple seizure types (including gelastic, partial-onset and atonic seizures), and two individuals failed to respond. In order to study possible mechanisms, we then performed microelectrode recordings of small neurons in surgically resected HH tissue slices. Exposure to ketone bodies decreased spontaneous firing in 5 of 7 small HH neurons. These preliminary results suggest that seizures associated with HH may respond favorably to the KD, and that ketone bodies might directly modulate the intrinsic epileptogenicity of HH tissue.

  8. The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders.

    PubMed

    Cullingford, Tim E

    2004-03-01

    This review outlines the molecular sensors that reprogram cellular metabolism in response to the ketogenic diet (KD). Special emphasis is placed on the fasting-, fatty acid- and drug-activated transcription factor, peroxisome proliferator-activated receptor alpha (PPARalpha). The KD causes a switch to ketogenesis that is coordinated with an array of changes in cellular lipid, amino acid, carbohydrate and inflammatory pathways. The role of both liver and brain PPARalpha in mediating such changes will be examined, with special reference to the anti-epileptic effects not only of the KD but a range of synthetic anti-epileptic drugs such as valproate. Finally, the implications of the KD and activated brain PPARalpha will be discussed in the context of their potential involvement in a range of disorders of neuro-degeneration and neuro-inflammation.

  9. To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question.

    PubMed

    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Bogucka-Kocka, Anna; Czuczwar, Stanisław J

    2016-12-23

    Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory. This is why other treatment options may be recommended, and ketogenic diet seems a last-chance method, especially in children and adolescents with epilepsy. The diet contains high amounts of fat and low carbohydrates with vitamin supplementation. The elevated concentrations of ketones induced by the diet may result in inhibition of the synaptic activity of glutamate, the mammalian target of the rapamycin pathway, and activation of adenosine triphosphate-sensitive potassium channels. One of the main ketones is acetone, shown to increase the seizure threshold and potentiate the anticonvulsant activity of some antiepileptic drugs. The clinical effectiveness of the ketogenic diet has been confirmed in a number of clinical trials carried out mainly on children. A wider use of the ketogenic diet may be limited by the number of early adverse effects (gastrointestinal distress, acidosis, hypoglycaemia, dehydration and lethargy), and late adverse effects (hyperuricaemia, hyperlipidaemia, kidney stones, easy bruising, and decreases in height and weight). Recently, data are available on the negative impact of the ketogenic diet on the qualitative characteristics of lipoprotein subfractions which points to the atherogenic fenotype as a new side-effect. In conclusion, future research directed to the proper identification of patients (in terms of age, epilepsy type and duration, recommended antiepileptic

  10. Changes in cerebral metabolism during ketogenic diet in patients with primary brain tumors: (1)H-MRS study.

    PubMed

    Artzi, Moran; Liberman, Gilad; Vaisman, Nachum; Bokstein, Felix; Vitinshtein, Faina; Aizenstein, Orna; Ben Bashat, Dafna

    2017-04-01

    Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy ((1)H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD. MR scans included conventional imaging and (1)H-MRS acquired from normal appearing-white-matter (NAWM) and lesion. High adherence to KD was obtained only in two patients, based on high urine ketones; in these two patients ketone bodies, Acetone and Acetoacetate were detected in four MR spectra-three within the NAWM and one in the lesion area -4 and 25 months following initiation of the diet. No ketone-bodies were detected in the control group. In one patient with gliomatosis-cerebri, who adhered to the diet for 3 years and showed stable disease, an increase in glutamin + glutamate and reduction in N-Acetyl-Aspartate and myo-inositol were detected during KD. (1)H-MRS was able to detect ketone-bodies in patients with brain tumors who adhered to KD. Yet it remains unclear whether accumulation of ketone bodies is due to increased brain uptake or decreased utilization of ketone bodies within the brain.

  11. Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis.

    PubMed

    Castaldo, Giuseppe; Galdo, Giovanna; Rotondi Aufiero, Felice; Cereda, Emanuele

    2016-01-01

    Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis.

  12. Brain ketones detected by proton magnetic resonance spectroscopy in an infant with Ohtahara syndrome treated with ketogenic diet.

    PubMed

    Cecil, Kim M; Mulkey, Sarah B; Ou, Xiawei; Glasier, Charles M

    2015-01-01

    Atypical resonances on proton magnetic resonance spectroscopy (MRS) examinations are occasionally found in children undergoing a metabolic evaluation for neurological conditions. While a radiologist's first instinct is to suspect a pathological metabolite, usually the origin of the resonance arises from an exogenous source. We report the appearance of distinct resonances associated with a ketogenic diet in a male infant presenting with Ohtahara syndrome. These resonances can be confused in interpretation with lactate and glutamate. To confirm assignments, the basis set for quantification was supplemented with simulations of β-hydroxybutyrate, acetone and acetoacetate in LCModel spectroscopy processing software. We were able to quantitate the levels of end products of a ketogenic diet and illustrate how to distinguish these resonances.

  13. The impact of a ketogenic diet and liver dysfunction on serum very long-chain fatty acids levels.

    PubMed

    Stradomska, T J; Bachański, M; Pawłowska, J; Syczewska, M; Stolarczyk, A; Tylki-Szymańska, A

    2013-04-01

    Peroxisomes play an essential role in mammalian cellular metabolism, particularly in oxidation fatty acid pathways. Serum very long-chain fatty acids (VLCFA), the main biochemical diagnostic parameters for peroxisomal disorders, were examined in 25 neurological patients with epilepsy on a ketogenic diet and 27 patients with liver dysfunction. The data show that patients on a ketogenic diet have increased levels of C22:0 and C24:0, but not C26:0, and normal C24:0/C22:0 and C26:0/C22:0. Patients with liver insufficiency showed a slightly elevated level of C26:0, a normal level of C24:0 and a decreased level of C22:0; thus in 21/27 the ratio of C24:0/C22:0 was increased and 15/27 the ratio of C26:0/C22:0 was increased.

  14. An observational study of sequential protein-sparing, very low-calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean-like diet for the treatment of obesity.

    PubMed

    Castaldo, Giuseppe; Monaco, Luigi; Castaldo, Laura; Galdo, Giovanna; Cereda, Emanuele

    2016-09-01

    The impact of a rehabilitative multi-step dietary program consisting in different diets has been scantily investigated. In an open-label study, 73 obese patients underwent a two-phase weight loss (WL) program: a 3-week protein-sparing, very low-calorie, ketogenic diet (<500 kcal/day; Oloproteic(®) Diet) and a 6-week hypocaloric (25-30 kcal/kg of ideal body weight/day), low glycemic index, Mediterranean-like diet (hypo-MD). Both phases improved visceral adiposity, liver enzymes, GH levels, blood pressure and glucose and lipid metabolism. However, the hypo-MD was responsible for a re-increase in blood lipids and glucose tolerance parameters. Changes in visceral adiposity and glucose control-related variables were more consistent in patients with metabolic syndrome. However, in these patients the hypo-MD did not result in a consistent re-increase in glucose control-related variables. A dietary program consisting in a ketogenic regimen followed by a balanced MD appeared to be feasible and efficacious in reducing cardiovascular risk, particularly in patients with metabolic syndrome.

  15. Effects of n-3 Polyunsaturated Fatty Acids (ω-3) Supplementation on Some Cardiovascular Risk Factors with a Ketogenic Mediterranean Diet

    PubMed Central

    Paoli, Antonio; Moro, Tatiana; Bosco, Gerardo; Bianco, Antonino; Grimaldi, Keith A.; Camporesi, Enrico; Mangar, Devanand

    2015-01-01

    Background: the ketogenic diet (KD) has become a widely used nutritional approach for weight loss. Some of the KD’s positive effects on metabolism and cardiovascular risk factors are similar to those seen after n-3 polyunsaturated fatty acids (ω-3) supplementation. We hypothesized that a ketogenic Mediterranean diet with phytoextracts combined with ω-3 supplementation may have increased positive effects on cardiovascular risk factors and inflammation. Methods: We analyzed 34 male overweight subjects; aged between 25 and 65 years who were overall healthy apart from overweight. The subjects followed a ketogenic diet protocol for four weeks; with (KDO3) or without (KD) ω-3 supplementation. Results: All subjects experienced a significant loss of body weight and body fat and there was no significant differences between treatment (body weight: KD—4.7 kg, KDO3—4.03 kg, body fat KD—5.41 kg, KDO3—5.86 kg). There were also significant decreases in total cholesterol, LDL-c, and glucose levels. Triglycerides and insulin levels decreased more in KDO3 vs. KD subjects, with a significant difference. All the investigated inflammatory cytokines (IL-1β, IL-6, TNF-α) decreased significantly in KDO3 subjects whilst only TNF-α showed a significant decrease in KD subjects over the 12 month study period. No significant changes were observed in anti-inflammatory cytokines (IL-10 and IL-1Ra), creatinine, urea and uric acid. Adiponectin increased significantly only in the KDO3 group. Conclusions: ω-3 supplementation improved the positive effects of a ketogenic Mediterranean diet with phytoextracts on some cardiovascular/metabolic risk factors and inflammatory state. PMID:25689563

  16. Triheptanoin supplementation to ketogenic diet curbs cognitive impairment in APP/PS1 mice used as a model of familial Alzheimer's disease.

    PubMed

    Aso, Ester; Semakova, Jana; Joda, Laura; Semak, Vladislav; Halbaut, Lyda; Calpena, Ana; Escolano, Carmen; Perales, Jose C; Ferrer, Isidro

    2013-03-01

    Diets containing a high proportion of fat with respect to protein plus carbohydrates are capable of inducing ketone body production in the liver, which provides an energetic alternative to glucose. Some ketogenic diets have been tested as therapeutic strategies for treating metabolic disorders related to a deficiency in glucose-driven ATP generation. However, ketone bodies are not capable of providing extra tricarboxylic acid cycle intermediates, limiting the anabolic capacity of the cell. Therefore, it is reasonable to hypothesize that supplementing a ketogenic diet with anaplerotic compounds such as triheptanoin may improve ketogenic diet effectiveness. The present study tests this hypothesis in APP/PS1 (APPswe/PS1dE9) transgenic mice, used as a model of familial Alzheimer's disease because impaired energy supply to neurons has been linked to this neurodegenerative process. Triheptanoin supplementation to a ketogenic diet for three months and starting at the age of three months reduces the memory impairment of APP/PS1 mice at the age of 6 months. The Aβ production and deposition were not significantly altered by the ketogenic diet, supplemented or not by triheptanoin. However, mice fed with triheptanoin-rich ketogenic diet have shown decreased astroglial response in the vicinity of Aβ plaques and decreased expression of the pro-inflammatory cytokine interferon-γ in astrocytes. These findings correlate with transcriptional up-regulation of the ROS detoxifying mechanisms Sirt1 and Pparg, thus linking triheptanoin with improved mitochondrial status. Present findings support the concept that ketogenic diets supplemented with anaplerotic compounds can be considered potential therapeutic strategies at early stages of Alzheimer's disease.

  17. The Nervous System and Metabolic Dysregulation: Emerging Evidence Converges on Ketogenic Diet Therapy

    PubMed Central

    Ruskin, David N.; Masino, Susan A.

    2012-01-01

    A link between metabolism and brain function is clear. Since ancient times, epileptic seizures were noted as treatable with fasting, and historical observations of the therapeutic benefits of fasting on epilepsy were confirmed nearly 100 years ago. Shortly thereafter a high fat, low-carbohydrate ketogenic diet (KD) debuted as a therapy to reduce seizures. This strict regimen could mimic the metabolic effects of fasting while allowing adequate caloric intake for ongoing energy demands. Today, KD therapy, which forces predominantly ketone-based rather than glucose-based metabolism, is now well-established as highly successful in reducing seizures. Cellular metabolic dysfunction in the nervous system has been recognized as existing side-by-side with nervous system disorders – although often with much less obvious cause-and-effect as the relationship between fasting and seizures. Rekindled interest in metabolic and dietary therapies for brain disorders complements new insight into their mechanisms and broader implications. Here we describe the emerging relationship between a KD and adenosine as a way to reset brain metabolism and neuronal activity and disrupt a cycle of dysfunction. We also provide an overview of the effects of a KD on cognition and recent data on the effects of a KD on pain, and explore the relative time course quantified among hallmark metabolic changes, altered neuron function and altered animal behavior assessed after diet administration. We predict continued applications of metabolic therapies in treating dysfunction including and beyond the nervous system. PMID:22470316

  18. Modulation of oxidative stress and mitochondrial function by the ketogenic diet

    PubMed Central

    Milder, Julie B.; Patel, Manisha

    2011-01-01

    The ketogenic diet (KD) is a high-fat, low carbohydrate diet that is used as a therapy for intractable epilepsy. However, the mechanism(s) by which the KD achieves neuroprotection and/or seizure control are not yet known. The broad efficacy of the KD in diverse epilepsies coupled with its profound influence on metabolism suggests that mitochondrial functions may be critical in its mechanism(s) of seizure control. Mitochondria subserve important cellular functions that include the production of cellular ATP, control of apoptosis, maintenance of calcium homeostasis and the production and elimination of reactive oxygen species (ROS). This review will focus on recent literature reporting the regulation of mitochondrial functions and redox signaling by the KD. The review highlights a potential mechanism of the KD involving the production of low levels of redox signaling molecules such as H2O2 and electrophiles e.g. 4-hydroxynonenal (4-HNE), which in turn activate adaptive pathways such as the protective transcription factor, NF E2-related factor 2 (Nrf2). This can ultimately result in increased production of antioxidants (e.g. GSH) and detoxification enzymes which may be critical in mediating the protective effects of the KD. PMID:22078747

  19. Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome.

    PubMed

    Klepper, Jörg; Diefenbach, Sonja; Kohlschütter, Alfried; Voit, Thomas

    2004-03-01

    The ketogenic diet (KD), established to treat intractable childhood epilepsy, has emerged as the principal treatment of GLUT1 deficiency syndrome (OMIM 606777). This defect of glucose transport into the brain results in hypoglycorrhachia causing epilepsy, developmental delay, and a complex motor disorder in early childhood. Ketones provided by a high-fat, low-carbohydrate diet serve as an alternative fuel to the brain. Glucose, lactate, lipids, and ketones in blood and cerebrospinal fluid were investigated in five GLUT1-deficient patients before and on the KD. Hypoglycorrhachia was detected in the non-ketotic and ketotic state. In ketosis, lactate concentrations in the cerebrospinal fluid increased moderately. The CSF/blood ratio for acetoacetate was higher compared to beta-hydroxybutyrate. Free fatty acids did not enter the brain in significant amounts. Blood concentrations of essential fatty acids determined in 18 GLUT1-deficient patients on the KD were sufficient in all age groups. The effects of the KD in GLUT1 deficiency syndrome, particularly the course of blood lipids, are discussed in an illustrative case. In this syndrome, the KD effectively restores brain energy metabolism. Ketosis does not influence impaired GLUT1-mediated glucose transport into brain: hypoglycorrhachia, the biochemical hallmark of the disease, can be identified in GLUT1-deficient patients on a KD. The effects of ketosis on the concentrations of glucose, lactate, ketones, and fatty acids in blood and cerebrospinal fluid in this entity are discussed in view of previous data on ketosis in man.

  20. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial

    PubMed Central

    2011-01-01

    Background Tumor patients exhibit an increased peripheral demand of fatty acids and protein. Contrarily, tumors utilize glucose as their main source of energy supply. Thus, a diet supplying the cancer patient with sufficient fat and protein for his demands while restricting the carbohydrates (CHO) tumors thrive on, could be a helpful strategy in improving the patients' situation. A ketogenic diet (KD) fulfills these requirements. Therefore, we performed a pilot study to investigate the feasibility of a KD and its influence on the quality of life of patients with advanced metastatic tumors. Methods Sixteen patients with advanced metastatic tumors and no conventional therapeutic options participated in the study. The patients were instructed to follow a KD (less than 70 g CHO per day) with normal groceries and were provided with a supply of food additives to mix a protein/fat shake to simplify the 3-month intervention period. Quality of life [assessed by EORTC QLQ-C30 (version 2)], serum and general health parameters were determined at baseline, after every two weeks of follow-up, or after drop out. The effect of dietary change on metabolism was monitored daily by measuring urinary ketone bodies. Results One patient did not tolerate the diet and dropped out within 3 days. Among those who tolerated the diet, two patients died early, one stopped after 2 weeks due to personal reasons, one felt unable to stick to the diet after 4 weeks, one stopped after 6 and two stopped after 7 and 8 weeks due to progress of the disease, one had to discontinue after 6 weeks to resume chemotherapy and five completed the 3 month intervention period. These five and the one who resumed chemotherapy after 6 weeks report an improved emotional functioning and less insomnia, while several other parameters of quality of life remained stable or worsened, reflecting their very advanced disease. Except for temporary constipation and fatigue, we found no severe adverse side effects, especially no

  1. Capacity for Moderate Exercise in Obese Subjects after Adaptation to a Hypocaloric, Ketogenic Diet

    PubMed Central

    Phinney, Stephen D.; Horton, Edward S.; Sims, Ethan A. H.; Hanson, John S.; Danforth, Elliot; Lagrange, Betty M.

    1980-01-01

    To study the capacity for moderate endurance exercise and change in metabolic fuel utilization during adaptation to a ketogenic diet, six moderately obese, untrained subjects were fed a eucaloric, balanced diet (base line) for 2 wk, followed by 6 wk of a protein-supplemented fast (PSF), which provided 1.2 g of protein/kg ideal body wt, supplemented with minerals and vitamins. The mean weight loss was 10.6 kg. The duration of treadmill exercise to subjective exhaustion was 80% of base line after 1 wk of the PSF, but increased to 155% after 6 wk. Despite adjusting up to base line, with a backpack, the subjects' exercise weight after 6 wk of dieting, the final exercise test was performed at a mean of 60% of maximum aerobic capacity, whereas the base-line level was 76%. Resting vastus lateralis glycogen content fell to 57% of base line after 1 wk of the PSF, but rose to 69% after 6 wk, at which time no decrement in muscle glycogen was measured after >4 h of uphill walking. The respiratory quotient (RQ) during steady-state exercise was 0.76 during base line, and fell progressively to 0.66 after 6 wk of the PSF. Blood glucose was well maintained during exercise in ketosis. The sum of acetoacetate and beta hydroxybutyrate rose from 3.28 to 5.03 mM during exercise after 6 wk of the PSF, explaining in part the low exercise RQ. The low RQ and the fact that blood glucose and muscle glycogen were maintained during exhausting exercise after 6 wk of a PSF suggest that prolonged ketosis results in an adaptation, after which lipid becomes the major metabolic fuel, and net carbohydrate utilization is markedly reduced during moderate but ultimately exhausting exercise. PMID:7000826

  2. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis

    PubMed Central

    Zhao, Zhong; Lange, Dale J; Voustianiouk, Andrei; MacGrogan, Donal; Ho, Lap; Suh, Jason; Humala, Nelson; Thiyagarajan, Meenakshisundaram; Wang, Jun; Pasinetti, Giulio M

    2006-01-01

    Background The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization. Results SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD) based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-β-3 hydroxybutyrate (DBH), has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047). In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030). DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH. Conclusion This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain. PMID:16584562

  3. Ketogenic Diet Improves Forelimb Motor Function after Spinal Cord Injury in Rodents

    PubMed Central

    Streijger, Femke; Plunet, Ward T.; Lee, Jae H. T.; Liu, Jie; Lam, Clarrie K.; Park, Soeyun; Hilton, Brett J.; Fransen, Bas L.; Matheson, Keely A. J.; Assinck, Peggy; Kwon, Brian K.; Tetzlaff, Wolfram

    2013-01-01

    High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (α-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited. PMID:24223849

  4. A Nutritional Perspective of Ketogenic Diet in Cancer: A Narrative Review.

    PubMed

    Oliveira, Camila L P; Mattingly, Stephanie; Schirrmacher, Ralf; Sawyer, Michael B; Fine, Eugene J; Prado, Carla M

    2017-03-30

    The predominant use of glucose anaerobically by cancer cells (Warburg effect) may be the most important characteristic the majority of these cells have in common and, therefore, a potential metabolic pathway to be targeted during cancer treatment. Because this effect relates to fuel oxidation, dietary manipulation has been hypothesized as an important strategy during cancer treatment. As such, the concept of a ketogenic diet (KD) in cancer emerged as a metabolic therapy (ie, targeting cancer cell metabolism) rather than a dietary approach. The therapeutic mechanisms of action of this high-fat, moderate-to-low protein, and very-low-carbohydrate diet may potentially influence cancer treatment and prognosis. Considering the lack of a dietetics-focused narrative review on this topic, we compiled the evidence related to the use of this diet in humans with diverse cancer types and stages, also focusing on the nutrition and health perspective. The use of KD in cancer shows potentially promising, but inconsistent, results. The limited number of studies and differences in study design and characteristics contribute to overall poor quality evidence, limiting the ability to draw evidence-based conclusions. However, the potential positive influences a KD may have on cancer treatment justify the need for well-designed clinical trials to better elucidate the mechanisms by which this dietary approach affects nutritional status, cancer prognosis, and overall health. The role of registered dietitian nutritionists is demonstrated to be crucial in planning and implementing KD protocols in oncology research settings, while also ensuring patients' adherence and optimal nutritional status.

  5. A ketogenic diet improves motor performance but does not affect β-amyloid levels in a mouse model of Alzheimer's disease.

    PubMed

    Beckett, Tina L; Studzinski, Christa M; Keller, Jeffrey N; Paul Murphy, M; Niedowicz, Dana M

    2013-04-10

    β-Amyloid (Aβ), a small, fibrillogenic peptide, is known to play an important role in the pathogenesis of Alzheimer's disease (AD) in the brain. In addition, Aβ accumulates in skeletal muscle cells in individuals with sporadic inclusion body myositis (sIBM), an age-related muscle disease. Because of the socioeconomic burden associated with age-related diseases, particularly AD, there has been considerable emphasis on studying potential therapeutic strategies. The high-fat, low carbohydrate ketogenic diet has been used extensively to treat refractory childhood epilepsy and has been studied as a potential treatment for other neurological diseases, including Parkinson's disease and AD. In this study, we fed young APP/PS1 knock-in mice, which have a whole body knock-in of AD-related genes, a ketogenic diet and determined the effect on Aβ levels in the brain and skeletal muscle, as well motor performance and oxidative stress. Aβ and its precursor, the β-C-terminal fragment of amyloid precursor protein (CTFβ), were unchanged overall in both the brain and quadriceps after 1 month on the ketogenic diet, and there was no effect on nitrotyrosine, a product of oxidative stress. The ketogenic diet improved performance on the Rota-rod apparatus (p=0.007), however. These data indicate that the ketogenic diet may have some efficacy in the treatment of both neurologic and muscle diseases though the underlying mechanisms do not involve amelioration of Aβ pathology.

  6. A ketogenic diet improves motor performance but does not affect β-amyloid levels in a mouse model of Alzheimer’s Disease

    PubMed Central

    Beckett, Tina L.; Studzinski, Christa M.; Keller, Jeffrey N.; Murphy, M. Paul; Niedowicz, Dana M.

    2013-01-01

    β-Amyloid (Aβ), a small, fibrillogenic peptide, is known to play an important role in the pathogenesis of Alzheimer’s disease (AD) in the brain. In addition, Aβ accumulates in skeletal muscle cells in individuals with sporadic inclusion body myositis (sIBM), an age-related muscle disease. Because of the socioeconomic burden associated with age-related diseases, particularly AD, there has been considerable emphasis on studying potential therapeutic strategies. The high fat, low carbohydrate ketogenic diet has been used extensively to treat refractory childhood epilepsy and has been studied as a potential treatment for other neurological diseases, including Parkinson’s disease and AD. In this study, we fed young APP/PS1 knock-in mice, which have a whole body knock-in of AD-related genes, a ketogenic diet and determined the effect on Aβ levels in the brain and skeletal muscle, as well motor performance and oxidative stress. Aβ and its precursor, the β-C-terminal fragment of amyloid precursor protein (CTFβ), were unchanged overall in both the brain and quadriceps after 1 month on the ketogenic diet, and there was no effect on nitrotyrosine, a product of oxidative stress. The ketogenic diet improved performance on the Rota-rod apparatus (p=0.007), however. These data indicate that the ketogenic diet may have some efficacy in the treatment of both neurologic and muscle diseases though the underlying mechanisms do not involve amelioration of Aβ pathology. PMID:23415649

  7. Is the interaction between fatty acids and tryptophan responsible for the efficacy of a ketogenic diet in epilepsy? The new hypothesis of action.

    PubMed

    Maciejak, P; Szyndler, J; Turzyńska, D; Sobolewska, A; Kołosowska, K; Krząścik, P; Płaźnik, A

    2016-01-28

    The effects of a ketogenic diet in controlling seizure activity have been proven in many studies, although its mechanism of action remains elusive in many regards. We hypothesize that the ketogenic diet may exert its antiepileptic effects by influencing tryptophan (TRP) metabolism. The aim of this study was to investigate the influence of octanoic and decanoic fatty acids (FAs), the main components in the MCT diet (medium-chain triglyceride diet, a subtype of the ketogenic diet), on the metabolism of TRP, the activity of the kynurenic pathway and the concentrations of monoamines and amino acids, including branched-chain amino acids (BCAA) and aromatic amino acids (AAA) in rats. The acute effects of FA on the sedation index and hippocampal electrical after-discharge threshold were also assessed. We observed that intragastric administration of FA increased the brain levels of TRP and the central and peripheral concentrations of kynurenic acid (KYNA), as well as caused significant changes in the brain and plasma concentrations of BCAA and AAA. We found that the administration of FA clearly increased the seizure threshold and induced sedation. Furthermore, we have demonstrated that blocking TRP passage into the brain abolished these effects of FA but had no similar effect on the formation of ketone bodies. Given that FAs are major components of a ketogenic diet, it is suggested that the anticonvulsant effects of a ketogenic diet may be at least partly dependent on changes in TRP metabolism. We also propose a more general hypothesis concerning the intracellular mechanism of the ketogenic diet.

  8. Counting calories in Drosophila diet restriction.

    PubMed

    Min, Kyung-Jin; Flatt, Thomas; Kulaots, Indrek; Tatar, Marc

    2007-03-01

    The extension of life span by diet restriction in Drosophila has been argued to occur without limiting calories. Here we directly measure the calories assimilated by flies when maintained on full- and restricted-diets. We find that caloric intake is reduced on all diets that extend life span. Flies on low-yeast diet are long-lived and consume about half the calories of flies on high-yeast diets, regardless of the energetic content of the diet itself. Since caloric intake correlates with yeast concentration and thus with the intake of every metabolite in this dietary component, it is premature to conclude for Drosophila that calories do not explain extension of life span.

  9. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet

    PubMed Central

    Krznar, Petra; Hörl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

    2016-01-01

    Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic profiles, and both defects could be restored by reexpression of MPC1. Labeling experiments using 13C-labeled glucose and glutamine demonstrated that MPC deficiency causes increased glutaminolysis and reduced contribution of glucose-derived pyruvate to the TCA cycle. Morphological defects were observed in mutant embryonic brains, together with major alterations of their metabolome including lactic acidosis, diminished TCA cycle intermediates, energy deficit and a perturbed balance of neurotransmitters. Strikingly, these changes were reversed when the pregnant dams were fed a ketogenic diet, which provides acetyl-CoA directly to the TCA cycle and bypasses the need for a functional MPC. This allowed the normal gestation and development of MPC deficient pups, even though they all died within a few minutes post-delivery. This study establishes the MPC as a key player in regulating the metabolic state necessary for embryonic development, neurotransmitter balance and post-natal survival. PMID:27176894

  10. The role of ketogenic diet in the treatment of refractory status epilepticus.

    PubMed

    Nam, Sook Hyun; Lee, Bo Lyun; Lee, Cha Gon; Yu, Hee Joon; Joo, Eun Yeon; Lee, Jeehun; Lee, Munhyang

    2011-11-01

    Ketogenic diet (KD) is known to be effective in intractable epilepsy. However, the role of KD in refractory status epilepticus (RSE) has not been well described. The aim of this study is to explore the role of KD in patients with RSE. We retrospectively reviewed the medical records of four children and one adult with RSE between October 2006 and August 2010. All presented with status epilepticus (SE) that was presumed to be associated with viral encephalitis. After we failed to control the seizures with standard measures for SE, we tried KD. The overall seizure frequency decreased to <50% of baseline in median eight (1-19) days. At one month of KD, two patients were seizure-free, one patient showed >90% seizure reduction, and the others had >75% decrease without generalized seizures. With improvement in the RSE, we were able to taper the antiepileptic drugs (AEDs) and wean patients from prolonged mechanical ventilation. The adverse events of KD in RSE included aspiration pneumonia, gastroesophageal reflux, constipation, and hypertriglyceridemia. Those results demonstrate that KD can be a valuable therapeutic option for patients with RSE.

  11. Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet.

    PubMed

    Milder, Julie B; Liang, Li-Ping; Patel, Manisha

    2010-10-01

    The mechanisms underlying the efficacy of the ketogenic diet (KD) remain unknown. Recently, we showed that the KD increased glutathione (GSH) biosynthesis. Since the NF E2-related factor 2 (Nrf2) transcription factor is a primary responder to cellular stress and can upregulate GSH biosynthesis, we asked whether the KD activates the Nrf2 pathway. Here we report that rats consuming a KD show acute production of H(2)O(2) from hippocampal mitochondria, which decreases below control levels by 3 weeks, suggestive of an adaptive response. 4-Hydroxy-2-nonenal (4-HNE), an electrophilic lipid peroxidation end product known to activate the Nrf2 detoxification pathway, was also acutely increased by the KD. Nrf2 nuclear accumulation was evident in both the hippocampus and liver, and the Nrf2 target, NAD(P)H:quinone oxidoreductase (NQO1), exhibited increased activity in both the hippocampus and liver after 3 weeks. We also found chronic depletion of liver tissue GSH, while liver mitochondrial antioxidant capacity was preserved. These data suggest that the KD initially produces mild oxidative and electrophilic stress, which may systemically activate the Nrf2 pathway via redox signaling, leading to chronic cellular adaptation, induction of protective proteins, and improvement of the mitochondrial redox state.

  12. A Ketogenic Diet Increases Brown Adipose Tissue Mitochondrial Proteins and UCP1 Levels in Mice

    PubMed Central

    Srivastava, Shireesh; Baxa, Ulrich; Niu, Gang; Chen, Xiaoyuan; Veech, Richard L.

    2013-01-01

    We evaluated the effects of feeding a ketogenic diet (KD) for a month on general physiology with emphasis on brown adipose tissue (BAT) in mice. KD did not reduce the caloric intake, or weight or lipid content of BAT. Relative epididymal fat pads were 40% greater in the mice fed the KD (P = 0.06) while leptin was lower (P < 0.05). Blood glucose levels were 30% lower while D-β-hydroxybutyrate levels were about 3.5-fold higher in the KD group. Plasma insulin and leptin levels in the KD group were about half of that of the mice fed NIH-31 pellets (chow group). Median mitochondrial size in the inter-scapular BAT (IBAT) of the KD group was about 60% greater, whereas the median lipid droplet size was about half of that in the chow group. Mitochondrial oxidative phosphorylation proteins were increased (1.5–3-fold) and the uncoupling protein 1 levels were increased by threefold in mice fed the KD. The levels of PPARγ, PGC-1α, and Sirt1 in KD group were 1.5–3-fold while level of Sirt3 was about half of that in the chow-fed group. IBAT cyclic AMP levels were 60% higher in the KD group and cAMP response element binding protein was 2.5-fold higher, suggesting increased sympathetic system activity. These results demonstrate that a KD can also increase BAT mitochondrial size and protein levels. PMID:23233333

  13. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester

    PubMed Central

    Hashim, Sami A.; VanItallie, Theodore B.

    2014-01-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer’s disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson’s disease. PMID:24598140

  14. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.

    PubMed

    Hashim, Sami A; VanItallie, Theodore B

    2014-09-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease.

  15. A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain.

    PubMed

    Jornayvaz, François R; Jurczak, Michael J; Lee, Hui-Young; Birkenfeld, Andreas L; Frederick, David W; Zhang, Dongyang; Zhang, Xian-Man; Samuel, Varman T; Shulman, Gerald I

    2010-11-01

    Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more effective in promoting weight loss than conventional caloric restriction, whereas their effect on hepatic glucose and lipid metabolism and the mechanisms by which they may promote weight loss remain controversial. The aim of this study was to explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid metabolism, energy expenditure, and food intake. Using hyperinsulinemic-euglycemic clamps, we studied insulin action in mice fed a KD or regular chow (RC). Body composition was assessed by ¹H magnetic resonance spectroscopy. Despite being 15% lighter (P < 0.001) than RC-fed mice because of a 17% increase in energy expenditure (P < 0.001), KD-fed mice manifested severe hepatic insulin resistance, as reflected by decreased suppression (0% vs. 100% in RC-fed mice, P < 0.01) of endogenous glucose production during the clamp. Hepatic insulin resistance could be attributed to a 350% increase in hepatic diacylglycerol content (P < 0.001), resulting in increased activation of PKCε (P < 0.05) and decreased insulin receptor substrate-2 tyrosine phosphorylation (P < 0.01). Food intake was 56% (P < 0.001) lower in KD-fed mice, despite similar caloric intake, and could partly be attributed to a more than threefold increase (P < 0.05) in plasma N-acylphosphatidylethanolamine concentrations. In conclusion, despite preventing weight gain in mice, KD induces hepatic insulin resistance secondary to increased hepatic diacylglycerol content. Given the key role of nonalcoholic fatty liver disease in the development of type 2 diabetes and the widespread use of KD for the treatment of obesity, these results may have potentially important clinical implications.

  16. The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice.

    PubMed

    Jansen, Natalie; Walach, Harald

    2016-01-01

    Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, P<0.0001), indicating that more progressed and aggressive tumours may require a higher level of aerobic glycolysis. In palliative patients, a clear trend was observed in patients who adhered strictly to a ketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials.

  17. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials.

    PubMed

    Bueno, Nassib Bezerra; de Melo, Ingrid Sofia Vieira; de Oliveira, Suzana Lima; da Rocha Ataide, Terezinha

    2013-10-01

    The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.

  18. The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders

    PubMed Central

    Stafstrom, Carl E.; Rho, Jong M.

    2012-01-01

    Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component. PMID:22509165

  19. Fibrogenic response of hepatic stellate cells in ovariectomised rats exposed to ketogenic diet.

    PubMed

    Bobowiec, R; Wojcik, M; Jaworska-Adamu, J; Tusinska, E

    2013-02-01

    The discrepancy about the role of estrogens in hepatic fibrogenesis and lack of studies addressed of ketogenic diet (KD) on hepatic stellate cells (HSC), prompted us to investigate the activity of HSC in control, KD- and thioacetamide (TAA)-administrated rats with different plasma concentration of estradiol (E2). HSC were isolated by the collagenase perfusion methods and separated by the Percoll gradient centrifugation. After the 4(th) and 8(th) day of incubation, lysates of HSC and the media were collected for further analysis. The HSC derived from KD-rats released remarkably more transforming growth factor (TGF)-β1 than cells obtained from animals fed with a standard diet. The ovariectomy of KD-rats markedly intensified the secretion of this fibrogenic cytokine on the 8(th) day of incubation (201.33 ±1 7.15 pg/ml). In HSC of rats exposed to E2, the TGF-β1 concentration did not exceed 157 ± 34.39 pg/ml. In respect to the collagen type I, the HSC obtained from ovariectomised KD-rats released an augmented amount of this ECM protein after the 8(th) day of culture (1.83 ± 0.14 U/ml). In the same time, higher quantities of ASMA appeared in the KD rats (1.41 ± 0.3 pg/mg protein). Exposition of rats to E2 did not markedly decrease the amount of ASMA. In summary, KD was able to induce morphological and functional changes in HSC, especially derived from rats deprived of ovarian estrogens. However, the preservation of E2 in ovariectomised rats didn't substantially alter the activation of HSC.

  20. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy

    PubMed Central

    Woolf, Eric C.; Syed, Nelofer; Scheck, Adrienne C.

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma. PMID:27899882

  1. Electrophysiological observations in hippocampal slices from rats treated with the ketogenic diet.

    PubMed

    Stafstrom, C E; Wang, C; Jensen, F E

    1999-11-01

    The electrophysiological effects of the high-fat, low-carbohydrate ketogenic diet (KD) were assessed in normal and epileptic [kainic-acid(KA)-treated] adult rats using hippocampal slices. In the first set of experiments, normal rats were fed the KD or a standard control diet for 6-8 weeks (beginning on postnatal day 56, P56), after which they were sacrificed for hippocampal slices. All rats on the KD became ketotic. The baseline effects of the KD were determined by comparing extracellular measures of synaptic transmission and responses to evoked stimulation, and hippocampal excitability was tested in Mg(2+)-free medium. There were no differences in EPSP slope, input/output relationship, responses to evoked stimulation or Mg(2+)-free burst frequency between slices from control and KD-fed rats. In another set of experiments, rats were made epileptic by intraperitoneal injection of kainic acid (KA) on P54, which caused status epilepticus followed by the development of spontaneous recurrent seizures (SRS) over the next few weeks. Two days after KA-induced status, rats were divided into a control-fed group and a KD-fed group. Animals on the KD had significantly fewer SRS over the ensuing 8 weeks. In hippocampal slices from KA-treated, KD-fed rats, there were fewer evoked CA1 population spikes than from slices of control-fed rats. These results suggest that the KD does not alter baseline electrophysiological parameters in normal rats. In rats made chronically epileptic by administration of KA, KD treatment was associated with fewer spontaneous seizures and reduced CA1 excitability in vitro. Therefore, at least part of the KD mechanism of action may involve long-term changes in network excitability.

  2. The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children.

    PubMed

    Güzel, Orkide; Yılmaz, Unsal; Uysal, Utku; Arslan, Nur

    2016-03-01

    Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

  3. The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer

    PubMed Central

    Poff, Angela M.; Ari, Csilla; Seyfried, Thomas N.; D’Agostino, Dominic P.

    2013-01-01

    Introduction Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO2T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. Methods We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO2T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging. Results KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO2T alone did not influence cancer progression, combining the KD with HBO2T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. Conclusions KD and HBO2T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease. PMID:23755243

  4. What are the minimum requirements for ketogenic diet services in resource-limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy.

    PubMed

    Kossoff, Eric H; Al-Macki, Nabil; Cervenka, Mackenzie C; Kim, Heung D; Liao, Jianxiang; Megaw, Katherine; Nathan, Janak K; Raimann, Ximena; Rivera, Rocio; Wiemer-Kruel, Adelheid; Williams, Emma; Zupec-Kania, Beth A

    2015-09-01

    Despite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow-up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost-effective recommendations for new ketogenic diet centers in resource-limited regions of the world.

  5. Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease.

    PubMed

    Moreno, Basilio; Crujeiras, Ana B; Bellido, Diego; Sajoux, Ignacio; Casanueva, Felipe F

    2016-12-01

    The long-term effect of therapeutic diets in obesity treatment is a challenge at present. The current study aimed to evaluate the long-term effect of a very low-calorie-ketogenic (VLCK) diet on excess adiposity. Especial focus was set on visceral fat mass, and the impact on the individual burden of disease. A group of obese patients (n = 45) were randomly allocated in two groups: either the very low-calorie-ketogenic diet group (n = 22), or a standard low-calorie diet group; (n = 23). Both groups received external support. Adiposity parameters and the cumulative number of months of successful weight loss (5 or 10 %) over a 24-month period were quantified. The very low-calorie-ketogenic diet induced less than 2 months of mild ketosis and significant effects on body weight at 6, 12, and 24 months. At 24 months, a trend to regress to baseline levels was observed; however, the very low-calorie-ketogenic diet induced a greater reduction in body weight (-12.5 kg), waist circumference (-11.6 cm), and body fat mass (-8.8 kg) than the low-calorie diet (-4.4 kg, -4.1 cm, and -3.8 kg, respectively; p < 0.001). Interestingly, a selective reduction in visceral fat measured by a specific software of dual-energy x-ray absorptiometry (DEXA)-scan (-600 g vs. -202 g; p < 0.001) was observed. Moreover, the very low-calorie-ketogenic diet group experienced a reduction in the individual burden of obesity because reduction in disease duration. Very low-calorie-ketogenic diet patients were 500 months with 5 % weight lost vs. the low-calorie diet group (350 months; p < 0.001). In conclusion, a very low-calorie-ketogenic diet was effective 24 months later, with a decrease in visceral adipose tissue and a reduction in the individual burden of disease.

  6. Ketogenic Diets Enhance Oxidative Stress and Radio-Chemo-Therapy Responses in Lung Cancer Xenografts

    PubMed Central

    Allen, Bryan G.; Bhatia, Sudershan K.; Buatti, John M.; Brandt, Kristin E.; Lindholm, Kaleigh E.; Button, Anna M.; Szweda, Luke I.; Smith, Brian J.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Purpose Ketogenic diets (KDs) are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that KDs enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress. Experimental Design Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a KD (KetoCal® 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8-2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immuno-reactive 4-hydroxy-2-nonenal-(4HNE) modified proteins as a marker of oxidative stress as well as PCNA and γH2AX as indices of proliferation and DNA damage, respectively. Results The KD combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (p<0.05), relative to radiation alone. The KD also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a KD in combination with radiation demonstrated increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA. Conclusions These results show that a KD enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress. PMID:23743570

  7. Ketogenic diet prevents seizure and reduces myoclonic jerks in rats with cardiac arrest-induced cerebral hypoxia.

    PubMed

    Tai, Kwok-Keung; Truong, Daniel D

    2007-09-20

    Although the mechanism underlying the anti-epileptic effects of a ketogenic diet (KD) is not known, KD is reported to be an effective treatment for intractable epilepsy, in particular among children. Here, we evaluated whether a KD can reduce posthypoxic seizure and myoclonic jerks in a rat model of cardiac arrest-induced cerebral hypoxia. In this study, rats were divided into two groups: one group received a normal diet while the other group was fed a KD for 25 days before being subjected to cardiac arrest-induced cerebral hypoxia. We found that rats fed a normal diet developed seizures and severe myoclonic jerks in response to auditory stimuli after the hypoxic insults, whereas the rats on the KD did not develop seizure and showed much less severe myoclonic jerks in response to auditory stimuli. The results suggested that the KD has beneficial effects against posthypoxic seizure and myoclonus.

  8. The effect of weight loss by ketogenic diet on the body composition, performance-related physical fitness factors and cytokines of Taekwondo athletes

    PubMed Central

    Rhyu, Hyun-seung; Cho, Su-Youn

    2014-01-01

    The purpose of this study was to investigate the effects of the weight loss through 3 weeks of ketogenic diet on performance-related physical fitness and inflammatory cytokines in Taekwondo athletes. The subjects selected for this research were 20 Taekwondo athletes of the high schools who participated in a summer camp training program. The subjects were randomly assigned to 2 groups, 10 subjects to each group: the ketogenic diet (KD) group and the non-ketogenic diet (NKD) group. Body composition, performance-related physical fitness factors (2,000 m sprint, Wingate test, grip force, back muscle strength, sit-up, 100 m sprint, standing broad jump, single leg standing) and cytokines (Iinterleukin-6, Interferon-γ, tumor necrosis factor-α) were analyzed before and after 3weeks of ketogenic diet. No difference between the KD and NKD groups in weight, %body fat, BMI and fat free mass. However, the KD group, compared to the NKD group, finished 2,000 m sprint in less time after weight loss, and also felt less fatigue as measured by the Wingate test and showed less increase in tumor necrosis factor-α. This result suggests that KD diet can be helpful for weight category athletes, such as Taekwondo athletes, by improving aerobic capacity and fatigue resistance capacity, and also by exerting positive effect on inflammatory response. PMID:25426472

  9. The effect of weight loss by ketogenic diet on the body composition, performance-related physical fitness factors and cytokines of Taekwondo athletes.

    PubMed

    Rhyu, Hyun-Seung; Cho, Su-Youn

    2014-10-01

    The purpose of this study was to investigate the effects of the weight loss through 3 weeks of ketogenic diet on performance-related physical fitness and inflammatory cytokines in Taekwondo athletes. The subjects selected for this research were 20 Taekwondo athletes of the high schools who participated in a summer camp training program. The subjects were randomly assigned to 2 groups, 10 subjects to each group: the ketogenic diet (KD) group and the non-ketogenic diet (NKD) group. Body composition, performance-related physical fitness factors (2,000 m sprint, Wingate test, grip force, back muscle strength, sit-up, 100 m sprint, standing broad jump, single leg standing) and cytokines (Iinterleukin-6, Interferon-γ, tumor necrosis factor-α) were analyzed before and after 3weeks of ketogenic diet. No difference between the KD and NKD groups in weight, %body fat, BMI and fat free mass. However, the KD group, compared to the NKD group, finished 2,000 m sprint in less time after weight loss, and also felt less fatigue as measured by the Wingate test and showed less increase in tumor necrosis factor-α. This result suggests that KD diet can be helpful for weight category athletes, such as Taekwondo athletes, by improving aerobic capacity and fatigue resistance capacity, and also by exerting positive effect on inflammatory response.

  10. Blood-brain barrier, ion homeostatis and epilepsy: possible implications towards the understanding of ketogenic diet mechanisms.

    PubMed

    Janigro, D

    1999-12-01

    The finding that epileptic seizures alter blood-brain barrier (BBB) properties has stimulated interest into the possibility that phenotypic changes in brain endothelium may constitute a pathological initiator leading to seizures. Recent evidence obtained from epileptic patients undergoing cortical resection, demonstrated abnormal expression of glucose transporter molecules (GLUT1), while [18F]deoxyglucose PET studies demonstrated regions of decreased glucose uptake and hypometabolism in seizure foci. The properties of other 'nonexcitable CNS cells' are also altered in epileptic tissue, and glial cells from epileptic brain displayed diminished capacity for ionic homeostasis; voltage-dependent mechanisms were primarily affected, increasing reliance on energy-dependent mechanisms. Diminished ion homeostasis together with increased metabolic demand of hyperactive neurons may further aggravate the neuropathological consequences of BBB loss of glucose uptake mechanisms. Since ketone bodies can provide an alternative to glucose to support brain energy requirements, it is hypothesized that one of the mechanisms of the ketogenic diet in epilepsy may relate to increased availability of beta-hydroxybutyrate, a ketone body readily transported at the BBB. This hypothesis is supported by the fact that the ketogenic diet is the treatment of choice for the glucose transporter protein syndrome and pyruvate dehydrogenase deficiency, both associated with cerebral energy failure and seizures.

  11. The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells.

    PubMed

    Hughes, Sean David; Kanabus, Marta; Anderson, Glenn; Hargreaves, Iain P; Rutherford, Tricia; O'Donnell, Maura; Cross, J Helen; Rahman, Shamima; Eaton, Simon; Heales, Simon J R

    2014-05-01

    The Ketogenic diet (KD) is an effective treatment with regards to treating pharmaco-resistant epilepsy. However, there are difficulties around compliance and tolerability. Consequently, there is a need for refined/simpler formulations that could replicate the efficacy of the KD. One of the proposed hypotheses is that the KD increases cellular mitochondrial content which results in elevation of the seizure threshold. Here, we have focussed on the medium-chain triglyceride form of the diet and the observation that plasma octanoic acid (C8) and decanoic acid (C10) levels are elevated in patients on the medium-chain triglyceride KD. Using a neuronal cell line (SH-SY5Y), we demonstrated that 250-μM C10, but not C8, caused, over a 6-day period, a marked increase in the mitochondrial enzyme, citrate synthase along with complex I activity and catalase activity. Increased mitochondrial number was also indicated by electron microscopy. C10 is a reported peroxisome proliferator activator receptor γ agonist, and the use of a peroxisome proliferator activator receptor γ antagonist was shown to prevent the C10-mediated increase in mitochondrial content and catalase. C10 may mimic the mitochondrial proliferation associated with the KD and raises the possibility that formulations based on this fatty acid could replace a more complex diet. We propose that decanoic acid (C10) results in increased mitochondrial number. Our data suggest that this may occur via the activation of the PPARγ receptor and its target genes involved in mitochondrial biogenesis. This finding could be of significant benefit to epilepsy patients who are currently on a strict ketogenic diet. Evidence that C10 on its own can modulate mitochondrial number raises the possibility that a simplified and less stringent C10-based diet could be developed.

  12. The Short-Term Effect of Ketogenic Diet on Carotid Intima-Media Thickness and Elastic Properties of the Carotid Artery and the Aorta in Epileptic Children.

    PubMed

    Doksöz, Önder; Güzel, Orkide; Yılmaz, Ünsal; İşgüder, Rana; Çeleğen, Kübra; Meşe, Timur; Uysal, Utku

    2015-10-01

    The aim of this prospective study is to investigate the effect of a 6-month-long ketogenic diet on carotid intima-media thickness, carotid artery, and aortic vascular functions. Thirty-eight drug-resistant epileptic patients who were being treated with ketogenic diet were enrolled. Fasting total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and glucose concentrations were measured and echocardiography was performed in all patients before the beginning of ketogenic diet and at the sixth month of treatment. The body weight, height, body mass index, serum levels of triglyceride, total cholesterol, and low-density lipoprotein increased significantly at month 6 when compared to baseline values (P < .05). Carotid intima-media thickness, elastic properties of the aorta, and carotid artery did not change at the sixth month of therapy compared to baseline values. A 6-month-long ketogenic diet has no effect on carotid intima-media thickness and elastic properties of the carotid artery and the aorta.

  13. A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study.

    PubMed

    Calderón, Naima; Betancourt, Luis; Hernández, Luis; Rada, Pedro

    2017-03-06

    The ketogenic diet (KD) is acknowledged as an unconventional option in the treatment of epilepsy. Several lines of investigation point to a possible role of glutamate and gamma-aminobutyric acid (GABA) as main contributors in this protective effect. Other biomolecules could also be involved in the beneficial consequence of the KD, for example, the diamine agmatine has been suggested to block imidazole and glutamate NMDA receptor and serves as an endogenous anticonvulsant in different animal models of epilepsy. In the present report, we have used microdialysis coupled to capillary electrophoresis to monitor microdialysate levels of GABA, glutamate and agmatine in the hippocampus of rats submitted to a KD for 15days compared to rats on a normal rat chow diet. A significant increase in GABA and agmatine levels while no change in glutamate levels was observed. These results support the notion that the KD modifies different transmitters favoring inhibitory over excitatory neurotransmitters.

  14. Transcript profiling of the ruminant liver indicates a unique program of transcriptional regulation of ketogenic enzymes during food restriction.

    PubMed

    Doelman, John; Cao, Honghe; Purdie, Norman G; Kim, Julie J M; Swanson, Kendall C; Osborne, Vernon R; Tey, Jasper; Ali, Ayesha; Feng, Zeny; Karrow, Niel A; Cant, John P

    2012-09-01

    Ruminants absorb little glucose and rely on hepatic gluconeogenesis and ketogenesis in the fed state to convert short-chain fatty acids produced during digestion into glucose and ketone bodies, respectively. In contrast to the non-ruminant response, fluxes through gluconeogenic and ketogenic pathways decrease during food restriction. Transcriptional regulation responsible for these unique food restriction responses has not been established. To determine the hepatic transcriptional response of ruminants to an acute drop in dietary nutrient supply, 102 yearling heifers were assigned to either ad libitum feeding or 24 h of food withdrawal in a randomized block design. Liver biopsies were obtained for microarray and quantitative real-time PCR analyses of gene expression. Plasma concentrations of non-esterified fatty acids were higher in food restricted heifers, while levels of β-hydroxybutyrate, triacylglycerol, and glucose were decreased. Despite a decline in substrate supply and a lower hepatic production of glucose, expression of the key gluconeogenic enzymes pyruvate carboxylase, phosphoenolpyruvate carboxykinase and fructose-1,6-bisphosphatase was upregulated as in non-ruminants. Downregulation of cholesterolgenic genes and upregulation of fatty acid oxidative genes were consistent with SREBP-2 and PPARα control, respectively. Ketogenesis from short-chain fatty acids was downregulated, contrary to the non-ruminant response to food restriction. Short-chain fatty acids may exert transcriptional control in the ruminant liver similar to that demonstrated in the large intestine of non-ruminants.

  15. Ketogenic diet and fasting induce the expression of cold-inducible RNA-binding protein with time-dependent hypothermia in the mouse liver.

    PubMed

    Oishi, Katsutaka; Yamamoto, Saori; Uchida, Daisuke; Doi, Ryosuke

    2013-01-01

    Cold-inducible RNA-binding protein (CIRBP) induced by cold stress modulates the molecular circadian clock in vitro. The present study examines the effect of a ketogenic diet (KD) and fasting on Cirbp expression in the mouse liver. Chronic KD administration induced time-dependent Cirbp expression with hypothermia in mice. The circadian expression of clock genes such as Bmal1 and Clock was phase-advanced and augmented in the liver of mice fed with a KD. Transient food deprivation also induced time-dependent Cirbp expression with hypothermia in mice. These findings suggest that hypothermia is involved in the increased expression of Cirbp under ketogenic or fasting conditions.

  16. Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures.

    PubMed

    Ni, Hong; Zhao, Dong-Jing; Tian, Tian

    2016-02-01

    Because the ketogenic diet (KD) was affecting expression of energy metabolism- related genes in hippocampus and because lipid membrane peroxidation and its associated autophagy stress were also found to be involved in energy depletion, we hypothesized that KD might exert its neuroprotective action via lipid membrane peroxidation and autophagic signaling. Here, we tested this hypothesis by examining the long-term expression of lipid membrane peroxidation-related cPLA2 and clusterin, its downstream autophagy marker Beclin-1, LC3 and p62, as well as its execution molecule Cathepsin-E following neonatal seizures and chronic KD treatment. On postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizures group and control group. On P28, they were further randomly divided into the seizure group without ketogenic diet (RS+ND), seizure plus ketogenic diet (RS+KD), the control group without ketogenic diet (NS+ND), and the control plus ketogenic diet (NS+KD). Morris water maze test was performed during P37-P43. Then mossy fiber sprouting and the protein levels were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced RS+ND rats show a long-term lower amount of cPLA2 and LC3II/I, and higher amount of clusterin, Beclin-1, p62 and Cathepsin-E which are in parallel with hippocampal mossy fiber sprouting and cognitive deficits. Furthermore, chronic KD treatment (RS+KD) is effective in restoring these molecular, neuropathological and cognitive changes. The results imply that a lipid membrane peroxidation and autophagy-associated pathway is involved in the aberrant hippocampal mossy fiber sprouting and cognitive deficits following neonatal seizures, which might be a potential target of KD for the treatment of neonatal seizure-induced brain damage.

  17. Revealing the molecular relationship between type 2 diabetes and the metabolic changes induced by a very-low-carbohydrate low-fat ketogenic diet

    PubMed Central

    2010-01-01

    Background The prevalence of type 2 diabetes is increasing worldwide, accounting for 85-95% of all diagnosed cases of diabetes. Clinical trials provide evidence of benefits of low-carbohydrate ketogenic diets in terms of clinical outcomes on type 2 diabetes patients. However, the molecular events responsible for these improvements still remain unclear in spite of the high amount of knowledge on the primary mechanisms of both the diabetes and the metabolic state of ketosis. Molecular network analysis of conditions, diseases and treatments might provide new insights and help build a better understanding of clinical, metabolic and molecular relationships among physiological conditions. Accordingly, our aim is to reveal such a relationship between a ketogenic diet and type 2 diabetes through systems biology approaches. Methods Our systemic approach is based on the creation and analyses of the cell networks representing the metabolic state in a very-low-carbohydrate low-fat ketogenic diet. This global view might help identify unnoticed relationships often overlooked in molecule or process-centered studies. Results A strong relationship between the insulin resistance pathway and the ketosis main pathway was identified, providing a possible explanation for the improvement observed in clinical trials. Moreover, the map analyses permit the formulation of some hypothesis on functional relationships between the molecules involved in type 2 diabetes and induced ketosis, suggesting, for instance, a direct implication of glucose transporters or inflammatory processes. The molecular network analysis performed in the ketogenic-diet map, from the diabetes perspective, has provided insights on the potential mechanism of action, but also has opened new possibilities to study the applications of the ketogenic diet in other situations such as CNS or other metabolic dysfunctions. PMID:21143928

  18. The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study.

    PubMed

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés

    2011-01-01

    The "Spanish Ketogenic Mediterranean Diet" (SKMD) has been shown to be an effective and safe way to cure patients suffering from metabolic syndrome (MS). Keeping in mind that nonalcoholic fatty liver disease (NAFLD) is closely associated with MS, the purpose of this study was to evaluate the potential therapeutic properties under free living conditions of the SKMD in patients with MS (following the International Diabetes Federation [IDF] consensus guidelines) and NAFLD (suspected by using a cutoff value of alanine aminotransferase [ALT] levels of >40 U/L and confirmed by abdominal ultrasonography) over a 12-week period. A prospective study was carried out in 14 obese men meeting the inclusion criteria and whose body mass index (BMI) and age were 36.58±0.54 kg/m² and 41.18±2.28 years, respectively. Statistical differences between the parameters studied before and after administration of the SKMD (week 0 and 12) were analyzed by paired Student's t test (continuous variables) and the χ² test (discontinuous variables). P<.05 was considered statistically significant. There was an extremely significant (P<.001) improvement in body weight (from 109.79 kg to 95.86 kg), low-density lipoprotein-cholesterol (from 123.43 mg/dL to 100.35 mg/dL), ALT (from 71.92 U/L to 37.07 U/L), aspartate aminotransferase (from 47.71 U/L to 29.57 U/L), steatosis degree (complete fatty liver regression was observed in 21.4% of the patients, and an overall reduction was found in 92.86% of the patients), and all the parameters studied associated with the MS: BMI (from 36.99 kg/m² to 32.42 kg/m²), waist circumference (from 114.01 cm to 98.59 cm), fasting plasma glucose (from 118.57 mg/dL to 90.14 mg/dL), triacylglycerols (from 232.64 mg/dL to 111.21 mg/dL), high-density lipoprotein-cholesterol (HDLc) (from 42.81 mg/dL to 58.71 mg/dL), systolic blood pressure (from 142.86 mm Hg to 125.36 mm Hg), and diastolic blood pressure (from 89.64 mm Hg to 77

  19. Research into the (Cost-) effectiveness of the ketogenic diet among children and adolescents with intractable epilepsy: design of a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Epilepsy is a neurological disorder, characterized by recurrent unprovoked seizures which have a high impact on the individual as well as on society as a whole. In addition to the economic burden, epilepsy imposes a substantial burden on the patients and their surroundings. Patients with uncontrolled epilepsy depend heavily on informal care and on health care professionals. About 30% of patients suffer from drug-resistant epilepsy. The ketogenic diet can be a treatment of last resort, especially for children. The beneficial effect of the ketogenic diet has been proven, but information is lacking about its cost-effectiveness. In the current study we will evaluate the (cost-) effectiveness of the ketogenic diet in children and adolescents with intractable epilepsy. Methods/Design In a RCT we will compare the ketogenic diet with usual care. Embedded in this RCT will be a trial-based and model-based economic evaluation, looking from a societal perspective at the cost-effectiveness and cost-utility of the ketogenic diet versus usual care. Fifty children and adolescents (aged 1-18) with intractable epilepsy will be screened for eligibility before randomization into the intervention or the usual care group. The primary outcome measure is the proportion of children with a 50% or more reduction in seizure frequency. Secondary outcomes include seizure severity, side effects/complaints, neurocognitive, socio-emotional functioning, and quality of life. Costs and productivity losses will be assessed continuously by a prospective diary and a retrospective questionnaire. Measurements will take place during consults at baseline, at 6 weeks and at 4 months after the baseline period, and 3, 6, 9 and 12 months follow-up after the 4 months consult. Discussion The proposed research project will be the first study to provide data about the cost-effectiveness of the ketogenic diet for children and adolescents with intractable epilepsy, in comparison with usual care. It is

  20. Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder.

    PubMed

    Smith, Jacklyn; Rho, Jong M; Teskey, G Campbell

    2016-05-01

    Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder characterized by deficits in sociability and communication, and restricted and/or repetitive motor behaviors. Amongst the diverse hypotheses regarding the pathophysiology of ASD, one possibility is that there is increased neuronal excitation, leading to alterations in sensory processing, functional integration and behavior. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD), traditionally used in the treatment of medically intractable epilepsy, has already been shown to reduce autistic behaviors in both humans and in rodent models of ASD. While the mechanisms underlying these effects remain unclear, we hypothesized that this dietary approach might shift the balance of excitation and inhibition towards more normal levels of inhibition. Using high-resolution intracortical microstimulation, we investigated basal sensorimotor excitation/inhibition in the BTBR T+Itpr(tf)/J (BTBR) mouse model of ASD and tested whether the KD restores the balance of excitation/inhibition. We found that BTBR mice had lower movement thresholds and larger motor maps indicative of higher excitation/inhibition compared to C57BL/6J (B6) controls, and that the KD reversed both these abnormalities. Collectively, our results afford a greater understanding of cortical excitation/inhibition balance in ASD and may help expedite the development of therapeutic approaches aimed at improving functional outcomes in this disorder.

  1. Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.

    PubMed

    Sanya, E O; Soladoye, A O; Desalu, O O; Kolo, P M; Olatunji, L A; Olarinoye, J K

    2017-03-06

    The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures

  2. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet.

    PubMed

    Douris, Nicholas; Melman, Tamar; Pecherer, Jordan M; Pissios, Pavlos; Flier, Jeffrey S; Cantley, Lewis C; Locasale, Jason W; Maratos-Flier, Eleftheria

    2015-10-01

    Ingestion of very low-carbohydrate ketogenic diets (KD) is associated with weight loss, lowering of glucose and insulin levels and improved systemic insulin sensitivity. However, the beneficial effects of long-term feeding have been the subject of debate. We therefore studied the effects of lifelong consumption of this diet in mice. Complete metabolic analyses were performed after 8 and 80weeks on the diet. In addition we performed a serum metabolomic analysis and examined hepatic gene expression. Lifelong consumption of KD had no effect on morbidity or mortality (KD vs. Chow, 676 vs. 630days) despite hepatic steatosis and inflammation in KD mice. The KD fed mice lost weight initially as previously reported (Kennnedy et al., 2007) and remained lighter and had less fat mass; KD consuming mice had higher levels of energy expenditure, improved glucose homeostasis and higher circulating levels of β-hydroxybutyrate and triglycerides than chow-fed controls. Hepatic expression of the critical metabolic regulators including fibroblast growth factor 21 were also higher in KD-fed mice while expression levels of lipogenic enzymes such as stearoyl-CoA desaturase-1 was reduced. Metabolomic analysis revealed compensatory changes in amino acid metabolism, primarily involving down-regulation of catabolic processes, demonstrating that mice eating KD can shift amino acid metabolism to conserve amino acid levels. Long-term KD feeding caused profound and persistent metabolic changes, the majority of which are seen as health promoting, and had no adverse effects on survival in mice.

  3. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet

    PubMed Central

    Douris, Nicholas; Melman, Tamar; Pecherer, Jordan M.; Pissios, Pavlos; Flier, Jeffrey S.; Cantley, Lewis C.; Locasale, Jason W.; Maratos-Flier, Eleftheria

    2016-01-01

    Ingestion of very low-carbohydrate ketogenic diets (KD) is associated with weight loss, lowering of glucose and insulin levels and improved systemic insulin sensitivity. However, the beneficial effects of long-term feeding have been the subject of debate. We therefore studied the effects of lifelong consumption of this diet in mice. Complete metabolic analyses were performed after 8 and 80 weeks on the diet. In addition we performed a serum metabolomic analysis and examined hepatic gene expression. Lifelong consumption of KD had no effect on morbidity or mortality (KD vs. Chow, 676 vs. 630 days) despite hepatic steatosis and inflammation in KD mice. The KD fed mice lost weight initially as previously reported (Kennnedy et al., 2007) and remained lighter and had less fat mass; KD consuming mice had higher levels of energy expenditure, improved glucose homeostasis and higher circulating levels of β-hydroxybutyrate and triglycerides than chow-fed controls. Hepatic expression of the critical metabolic regulators including fibroblast growth factor 21 were also higher in KD-fed mice while expression levels of lipogenic enzymes such as stearoyl-CoA desaturase-1 was reduced. Metabolomic analysis revealed compensatory changes in amino acid metabolism, primarily involving down-regulation of catabolic processes, demonstrating that mice eating KD can shift amino acid metabolism to conserve amino acid levels. Long-term KD feeding caused profound and persistent metabolic changes, the majority of which are seen as health promoting, and had no adverse effects on survival in mice. PMID:26170063

  4. Plasma phospholipid fatty acids are influenced by a ketogenic diet enriched with n-3 fatty acids in children with epilepsy.

    PubMed

    Dahlin, Maria; Hjelte, Lena; Nilsson, Susanne; Amark, Per

    2007-02-01

    The ketogenic diet (KD) is used to treat medically refractory epilepsy in children. Alterations of fatty acid (FA) levels may reflect one mechanism of action. We examined the influence of the KD on FA levels and seizure control. The levels of 17 FAs in plasma phospholipids were determined before and 1, 3, 6, and 12 months after initiation of the KD in 25 children (mean age 6.3 years) with intractable epilepsy. Fluid omega-3 FA was supplemented in the diet after one month. Highly significant changes of the levels of several FAs were found. Linoleic acid (LA) and eicosapentaenoic acid (EPA) increased, whereas arachidonic acid (AA) and Mead acid (20:3 n-9) decreased. Docosahexaenoic acid (DHA) increased insignificantly. However, no correlation of changes in FA levels with seizure response was found. The ratio of omega-6 to omega-3 gradually decreased from 7.0 before to 4.9 at 12 months after starting the diet, presumably a cardiovascular benefit. The composition of the KD differs as to FA content and type between different treating centers but, still, the efficacy reports are very similar. This study demonstrates the possibility of composing the KD in such a way that the FA profile is kept within a normal range, which may reduce cardiovascular risks.

  5. Proliferative and oxidative response of hepatocytes (Hep) and hepatic stellate cells (HSC) isolated from rats exposed to ketogenic diet.

    PubMed

    Wójcik, M; Wessely-Szponder, J; Kosior-Korzecka, U

    2014-01-01

    Ketogenic diet (KD) is considered in the context of its anti-epileptic effects, but its influence on liver dysfunction has not been elucidated yet. The study was aimed to investigate the activity of hepatocytes (Hep) and hepatic stellate cells (HSC) isolated from rats fed with KD, in respect of NO and superoxide generation by these cells as well as their proliferative activity in vitro. We also sought to characterize the plasma FFA profiles in control and ketogenic rats. Hep and HSC were isolated by the collagenase perfusion method and separated by the Percoll gradient centrifugation. After the 4th, 8th and 12th day of incubation, the media were collected for further analysis. NO generation increased within the time of incubation both in Hep and HSC isolated from KD-rats. In HSC group NO production raised significantly from 2.65 ± 0.07 μM/10(6) cells on 4th day of incubation to 5.49 ± 1.2 μM/10(6) cells on 12th day of incubation. In respect to O2⁻· generation experimental Hep and HSC provide considerably higher quantities of this free radical until 12th day of incubation (2.5 ± 0.07 and 3.2 ± 0.3 nM/10(6) cells, respectively). Although KD exerts anti-proliferative effect on hepatocytes, in respect to HSC it intensifies their proliferative activity. Furthermore, as we estimated on the basis of NO and O2⁻. generation both Hep and HSC exposed to KD are the source of free radicals.

  6. Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats

    PubMed Central

    Zhao, Ming; Huang, Xin; Cheng, Xiang; Lin, Xiao; Zhao, Tong; Wu, Liying; Yu, Xiaodan; Wu, Kuiwu; Fan, Ming

    2017-01-01

    Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h). In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role. PMID:28355243

  7. A Ketogenic Diet in Rodents Elicits Improved Mitochondrial Adaptations in Response to Resistance Exercise Training Compared to an Isocaloric Western Diet

    PubMed Central

    Hyatt, Hayden W.; Kephart, Wesley C.; Holland, A. Maleah; Mumford, Petey; Mobley, C. Brooks; Lowery, Ryan P.; Roberts, Michael D.; Wilson, Jacob M.; Kavazis, Andreas N.

    2016-01-01

    Purpose: Ketogenic diets (KD) can facilitate weight loss, but their effects on skeletal muscle remain equivocal. In this experiment we investigated the effects of two diets on skeletal muscle mitochondrial coupling, mitochondrial complex activity, markers of oxidative stress, and gene expression in sedentary and resistance exercised rats. Methods: Male Sprague-Dawley rats (9–10 weeks of age, 300–325 g) were fed isocaloric amounts of either a KD (17 g/day, 5.2 kcal/g, 20.2% protein, 10.3% CHO, 69.5% fat, n = 16) or a Western diet (WD) (20 g/day, 4.5 kcal/g, 15.2% protein, 42.7% CHO, 42.0% fat, n = 16) for 6 weeks. During these 6 weeks animals were either sedentary (SED, n = 8 per diet group) or voluntarily exercised using resistance-loaded running wheels (EXE, n = 8 per diet group). Gastrocnemius was excised and used for mitochondrial isolation and biochemical analyses. Results: In the presence of a complex II substrate, the respiratory control ratio (RCR) of isolated gastrocnemius mitochondria was higher (p < 0.05) in animals fed the KD compared to animals fed the WD. Complex I and IV enzyme activity was higher (p < 0.05) in EXE animals regardless of diet. SOD2 protein levels and GLUT4 and PGC1α mRNA expression were higher (p < 0.05) in EXE animals regardless of diet. Conclusion: Our data indicate that skeletal muscle mitochondrial coupling of complex II substrates is more efficient in chronically resistance trained rodents fed a KD. These findings may provide merit for further investigation, perhaps on humans. PMID:27877138

  8. Neurobehavioral Deficits in a Rat Model of Recurrent Neonatal Seizures Are Prevented by a Ketogenic Diet and Correlate with Hippocampal Zinc/Lipid Transporter Signals.

    PubMed

    Tian, Tian; Ni, Hong; Sun, Bao-liang

    2015-10-01

    The ketogenic diet (KD) has been shown to be effective as an antiepileptic therapy in adults, but it has not been extensively tested for its efficacy in neonatal seizure-induced brain damage. We have previously shown altered expression of zinc/lipid metabolism-related genes in hippocampus following penicillin-induced developmental model of epilepsy. In this study, we further investigated the effect of KD on the neurobehavioral and cognitive deficits, as well as if KD has any influence in the activity of zinc/lipid transporters such as zinc transporter 3 (ZnT-3), MT-3, ApoE, ApoJ (clusterin), and ACAT-1 activities in neonatal rats submitted to flurothyl-induced recurrent seizures. Postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizure group (EXP) and control group (CONT). On P28, they were further randomly divided into the seizure group without ketogenic diet (EXP1), seizure plus ketogenic diet (EXP2), the control group without ketogenic diet (CONT1), and the control plus ketogenic diet (CONT2). Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed from P35 to P49. Morris water maze test was performed during P51-P57. Then hippocampal mossy fiber sprouting and the protein levels of ZnT3, MT3, ApoE, CLU, and ACAT-1 were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced neurobehavioral toxicology and aberrant mossy fiber sprouting were blocked by KD. In parallel with these behavioral changes, rats treated with KD (EXP2) showed a significant down-regulated expression of ZnT-3, MT-3, ApoE, clusterin, and ACAT-1 in hippocampus when compared with the non-KD-treated EXP1 group. Our findings provide support for zinc/lipid transporter signals being potential targets for the treatment of neonatal seizure-induced brain damage by KD.

  9. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    SciTech Connect

    Oishi, Katsutaka; Uchida, Daisuke; Ohkura, Naoki; Horie, Shuichi

    2010-10-15

    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR

  10. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    PubMed Central

    Otto, Christoph; Kaemmerer, Ulrike; Illert, Bertram; Muehling, Bettina; Pfetzer, Nadja; Wittig, Rainer; Voelker, Hans Ullrich; Thiede, Arnulf; Coy, Johannes F

    2008-01-01

    Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in

  11. Seizure control by derivatives of medium chain fatty acids associated with the ketogenic diet show novel branching-point structure for enhanced potency.

    PubMed

    Chang, Pishan; Zuckermann, Alexandra M E; Williams, Sophie; Close, Adam J; Cano-Jaimez, Marife; McEvoy, James P; Spencer, John; Walker, Matthew C; Williams, Robin S B

    2015-01-01

    The medium chain triglyceride (MCT) ketogenic diet is a major treatment of drug-resistant epilepsy but is problematic, particularly in adults, because of poor tolerability. Branched derivatives of octanoic acid (OA), a medium chain fat provided in the diet have been suggested as potential new treatments for drug-resistant epilepsy, but the structural basis of this functionality has not been determined. Here we investigate structural variants of branched medium chain fatty acids as new seizure-control treatments. We initially employ a series of methyl-branched OA derivatives, and using the GABAA receptor antagonist pentylenetetrazol to induce seizure-like activity in rat hippocampal slices, we show a strong, branch-point-specific activity that improves upon the related epilepsy treatment valproic acid. Using low magnesium conditions to induce glutamate excitotoxicity in rat primary hippocampal neuronal cultures for the assessment of neuroprotection, we also show a structural dependence identical to that for seizure control, suggesting a related mechanism of action for these compounds in both seizure control and neuroprotection. In contrast, the effect of these compounds on histone deacetylase (HDAC) inhibition, associated with teratogenicity, shows no correlation with therapeutic efficacy. Furthermore, small structural modifications of the starting compounds provide active compounds without HDAC inhibitory effects. Finally, using multiple in vivo seizure models, we identify potent lead candidates for the treatment of epilepsy. This study therefore identifies a novel family of fatty acids, related to the MCT ketogenic diet, that show promise as new treatments for epilepsy control and possibly other MCT ketogenic diet-responding conditions, such as Alzheimer disease.

  12. A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss.

    PubMed

    Badman, Michael K; Kennedy, Adam R; Adams, Andrew C; Pissios, Pavlos; Maratos-Flier, Eleftheria

    2009-11-01

    In mice of normal weight and with diet-induced obesity, a high-fat, low-carbohydrate ketogenic diet (KD) causes weight loss, reduced circulating glucose and lipids, and dramatic changes in hepatic gene expression. Many of the effects of KD are mediated by fibroblast growth factor 21 (FGF21). We tested the effects of KD feeding on ob/ob mice to determine if metabolic effects would occur in obesity secondarily to leptin deficiency. We evaluated the effect of prolonged KD feeding on weight, energy homeostasis, circulating metabolites, glucose homeostasis, and gene expression. Subsequently, we evaluated the effects of leptin and fasting on FGF21 expression in ob/ob mice. KD feeding of ob/ob mice normalized fasting glycemia and substantially reduced insulin and lipid levels in the absence of weight loss. KD feeding was associated with significant increases in lipid oxidative genes and reduced expression of lipid synthetic genes, including stearoyl-coenzyme A desaturase 1, but no change in expression of inflammatory markers. In chow-fed ob/ob mice, FGF21 mRNA was elevated 10-fold compared with wild-type animals, and no increase from this elevated baseline was seen with KD feeding. Administration of leptin to chow-fed ob/ob mice led to a 24-fold induction of FGF21. Fasting also induced hepatic FGF21 in ob/ob mice. Thus, KD feeding improved ob/ob mouse glucose homeostasis without weight loss or altered caloric intake. These data demonstrate that manipulation of dietary macronutrient composition can lead to marked improvements in metabolic profile of leptin-deficient obese mice in the absence of weight loss.

  13. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model.

    PubMed

    Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d'Amati, Giulia; Tiranti, Valeria

    2014-01-01

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2(-/-)) mouse model did not recapitulate the human disease but showed azoospermia and mitochondrial dysfunctions. We challenged this mouse model with a low glucose and high lipid content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta-oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a general impairment of bioenergetic metabolism. Only Pank2(-/-) mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. These mice also showed structural alteration of muscle morphology, which was comparable with that observed in a patient with pantothenate kinase-associated neurodegeneration. We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration.

  14. Tissue Specific Impacts of a Ketogenic Diet on Mitochondrial Dynamics in the BTBRT+tf/j Mouse

    PubMed Central

    Newell, Christopher; Shutt, Timothy E.; Ahn, Younghee; Hittel, Dustin. S.; Khan, Aneal; Rho, Jong M.; Shearer, Jane

    2016-01-01

    The ketogenic diet (KD) has been utilized as a dietary therapeutic for nearly a century. One experimental model particularly responsive to the KD is the BTBRT+tf/j (BTBR) mouse, which displays phenotypic characteristics of autism spectrum disorder (ASD) and insulin resistance. Recently, the study of impaired mitochondrial function has become a focal point of research investigating the pathophysiology of ASD. As highly dynamic organelles, mitochondria undergo constant fluctuations in morphology, biogenesis, and quality control in order to maintain cellular homeostasis. An important modifier of mitochondrial dynamics is energy availability. Therefore, the aim of this study was to examine the impact of a KD on mitochondrial dynamics in the liver and brain (prefrontal cortex) of the BTBR mouse model of ASD. Juvenile male C57Bl/6 (B6) and BTBR mice were age-matched to 5 weeks of age before being fed standard chow (CD, 13% kcal fat) or a KD (75% kcal fat) for 10–14 days. Analysis of brain tissue identified differences in mitochondrial gene expression but no correlation with protein levels. Unlike in the brain, KD led to decreased levels of mitochondrial proteins in the liver, despite increased gene expression. Consistent with decreased mitochondrial proteins, we also observed decreased mtDNA for all mice on the KD, demonstrating that the KD reduces the total amount of mitochondria in the liver. In order to explain the discrepancy between protein levels and gene expression, we investigated whether mitochondrial turnover via mitophagy was increased. To this end, we examined expression levels of the mitophagy regulator BNIP3 (BCL2/adenovirus E1B 19 kd-interacting protein 3). BNIP3 gene and protein expression were significantly elevated in liver of KD animals (p < 0.05), indicating the potential activation of mitophagy. Therefore, consumption of a KD exerts highly tissue-specific effects, ultimately increasing mitochondrial turnover in the liver, while gene and protein

  15. Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats.

    PubMed

    Balietti, Marta; Giorgetti, Belinda; Fattoretti, Patrizia; Grossi, Yessica; Di Stefano, Giuseppina; Casoli, Tiziana; Platano, Daniela; Solazzi, Moreno; Orlando, Fiorenza; Aicardi, Giorgio; Bertoni-Freddari, Carlo

    2008-06-01

    Ketogenic diets (KDs) have beneficial effects on several diseases, such as epilepsy, mitochondriopathies, cancer, and neurodegeneration. However, little is known about their effects on aging individuals. In the present study, late-adult (19-month-old) rats were fed for 8 weeks with two medium chain triglycerides (MCT)-KDs, and the following morphologic parameters reflecting synaptic plasticity were evaluated in stratum moleculare of hippocampal CA1 region (SM CA1) and outer molecular layer of hippocampal dentate gyrus (OML DG): average area (S), numeric density (Nv(s)), and surface density (Sv) of synapses, and average volume (V), numeric density (Nv(m)), and volume density (Vv) of synaptic mitochondria. In SM CA1, MCT-KDs induced the early appearance of the morphologic patterns typical of old animals (higher S and V, and lower Nv(s) and Nv(m)). On the contrary, in OML DG, Sv and Vv of MCT-KDs-fed rats were higher (as a result of higher Nv(s) and Nv(m)) versus controls; these modifications are known to improve synaptic function and metabolic supply. The opposite effects of MCT-KDs might reflect the different susceptibility to aging processes: OML DG is less vulnerable than SM CA1, and the reactivation of ketone bodies uptake and catabolism might occur more efficiently in this region, allowing the exploitation of their peculiar metabolic properties. Present findings provide the first evidence that MCT-KDs may cause opposite morphologic modifications, being potentially harmful for SM CA1 and potentially advantageous for OML DG. This implies risks but also promising potentialities for their therapeutic use during aging.

  16. PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPARγ activation in the liver.

    PubMed

    Oishi, Katsutaka; Uchida, Daisuke; Ohkura, Naoki; Horie, Shuichi

    2010-10-15

    An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor α (PPARα) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPARα-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPARα-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPARα target genes such as Cyp4A10 and FGF21 was damped in PPARα-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPARα-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPARα activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPARγ and its coactivator PCG-1α were more effectively induced in PPARα-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPARγ antagonist, in both WT and PPARα-null mice. PPARγ activation seems to be involved in KD-induced hypofibrinolysis by augmenting PAI-1 gene expression in the fatty liver.

  17. Tissue Specific Impacts of a Ketogenic Diet on Mitochondrial Dynamics in the BTBR(T+tf/j) Mouse.

    PubMed

    Newell, Christopher; Shutt, Timothy E; Ahn, Younghee; Hittel, Dustin S; Khan, Aneal; Rho, Jong M; Shearer, Jane

    2016-01-01

    The ketogenic diet (KD) has been utilized as a dietary therapeutic for nearly a century. One experimental model particularly responsive to the KD is the BTBR(T+tf/j) (BTBR) mouse, which displays phenotypic characteristics of autism spectrum disorder (ASD) and insulin resistance. Recently, the study of impaired mitochondrial function has become a focal point of research investigating the pathophysiology of ASD. As highly dynamic organelles, mitochondria undergo constant fluctuations in morphology, biogenesis, and quality control in order to maintain cellular homeostasis. An important modifier of mitochondrial dynamics is energy availability. Therefore, the aim of this study was to examine the impact of a KD on mitochondrial dynamics in the liver and brain (prefrontal cortex) of the BTBR mouse model of ASD. Juvenile male C57Bl/6 (B6) and BTBR mice were age-matched to 5 weeks of age before being fed standard chow (CD, 13% kcal fat) or a KD (75% kcal fat) for 10-14 days. Analysis of brain tissue identified differences in mitochondrial gene expression but no correlation with protein levels. Unlike in the brain, KD led to decreased levels of mitochondrial proteins in the liver, despite increased gene expression. Consistent with decreased mitochondrial proteins, we also observed decreased mtDNA for all mice on the KD, demonstrating that the KD reduces the total amount of mitochondria in the liver. In order to explain the discrepancy between protein levels and gene expression, we investigated whether mitochondrial turnover via mitophagy was increased. To this end, we examined expression levels of the mitophagy regulator BNIP3 (BCL2/adenovirus E1B 19 kd-interacting protein 3). BNIP3 gene and protein expression were significantly elevated in liver of KD animals (p < 0.05), indicating the potential activation of mitophagy. Therefore, consumption of a KD exerts highly tissue-specific effects, ultimately increasing mitochondrial turnover in the liver, while gene and protein

  18. Anticonvulsant profile of caprylic acid, a main constituent of the medium-chain triglyceride (MCT) ketogenic diet, in mice.

    PubMed

    Wlaź, Piotr; Socała, Katarzyna; Nieoczym, Dorota; Łuszczki, Jarogniew J; Zarnowska, Iwona; Zarnowski, Tomasz; Czuczwar, Stanisław J; Gasior, Maciej

    2012-03-01

    The purpose of the present study was to evaluate the acute anticonvulsant effects of caprylic acid (CA), the main constituent of the medium-chain triglyceride ketogenic diet (MCT KD), in seizure tests typically used in screening for potential antiepileptic drugs in mice. Pharmacodynamic and pharmacokinetic interactions between CA and valproate (VPA) were also investigated. CA (p.o.) and VPA (i.p.) were administered 30 min before testing. Acute effects on motor coordination were assessed in the chimney test. Total plasma and brain concentrations of CA and VPA, when administered alone or in combination, were determined by high performance liquid chromatography. CA (10-30 mmol/kg) increased the threshold for i.v. pentylenetetrazole-induced myoclonic and clonic convulsions, but not tonic convulsions. CA (5-30 mmol/kg) increased the threshold for 6-Hz psychomotor seizures but was ineffective in the maximal electroshock seizure threshold test. CA (10-60 mmol/kg p.o.) impaired motor performance in the chimney test (TD(50) value, 58.4 mmol/kg). Increasing doses of CA (5-30 mmol/kg) produced proportional increases in plasma and brain exposure with constant brain/plasma partitioning. CA increased anticonvulsant potency of VPA in the maximal electroshock seizure and 6-Hz seizure tests. Co-administration of CA and VPA had no effect on brain and plasma concentrations of either compound. In summary, CA exerts acute anticonvulsant effects and potentiates the anticonvulsant effect of VPA at doses that result in plasma exposures comparable to those reported in epileptic patients on the MCT KD. Thus, this acute anticonvulsant property of CA may benefit and add to the overall clinical efficacy of the MCT KD.

  19. Comments on dietary restriction, Okinawa diet and longevity.

    PubMed

    Gavrilova, Natalia S; Gavrilov, Leonid A

    2012-01-01

    Longevity in Okinawa is considered to be a result of traditional low calorie diet. Le Bourg suggests that Okinawa is an example of severe malnutrition, which is harmful for later generations. We believe that current loss of longevity advantage in Okinawa is a result of diet westernization and that the dietary restriction is a valid way of life extension in humans.

  20. Changes in quality of life as a result of ketogenic diet therapy: A new approach to assessment with the potential for positive therapeutic effects.

    PubMed

    Bruce, Susan; Devlin, Anita; Air, Linda; Cook, Lucy

    2017-01-01

    There are difficulties inherent in measuring Quality of life (QoL) in patients with chronic illness, including agreement on definitions of quality of life and the type of measure used, disease specific or generic. Well validated QoL instruments for epilepsy exist but focus on capturing common themes pertinent to children and families as a group instead of focusing on themes important to individual patients and their families/carers. In addition, it is common for numerous items on these inventories to be left incomplete or responded to with "not applicable" since many of the items are not suitable for children with disabilities and their families. This led us to devise a way to capture individual quality-of-life measures that are linked to parental/carer expectations in families of children undergoing ketogenic diet therapy for epilepsy. As part of our routine clinical assessment, parents/carers were asked to describe what they would like to see happen or change as a result of their child being on ketogenic diet therapy. A simple unstructured form was designed to facilitate the assessment process. Parents were then asked to rate their own QoL against these criteria on a Likert scale of 0-10 prior to commencement of the diet. This assessment was repeated at subsequent visits with parents/carers initially blinded to their original responses. Our assessments indicated that ketogenic diet therapy improves quality of life over a twelve-month period when measured against parental expectations. This ideographic approach has demonstrated changes in parental Qol and parental perceptions of their child's quality of life that would not have been captured by other validated measures. A lengthy questionnaire is avoided and is replaced by a skilled supportive conversation that identifies goals for treatment that are important to parents. This helps parents to reflect on the progress their child makes on the diet by revisiting their previously stated aspirations, and assessing

  1. Very low calorie ketogenic weight reduction diet in patients with cirrhosis: a case series.

    PubMed

    Temmerman, J C; Friedman, A N

    2013-11-18

    Weight reduction may be necessary in patients with end-stage liver disease (ESLD) before liver transplantation. Although very low calorie diets (VLCDs) are a highly effective weight loss strategy, they risk inducing protein-calorie malnutrition, sarcopenia and hepatic encephalopathy in ESLD patients. We report for the first time on the use of VCLDs in ESLD. Two severely obese individuals with ESLD underwent a modified VLCD to become eligible for liver transplantation. Patients consumed four protein supplements and one lean meal daily, equivalent to 800 kilocalories (kcal) and were closely monitored during the diet period. Subject 1, a 46-year-old male with alcoholic cirrhosis, lost 44.1 kg after 28 weeks on a modified VLCD. Liver function and MELD (model for end-stage liver disease) scores improved and he currently does not require listing for transplantation. Subject 2, a 64-year-old female with non-alcoholic steatohepatitis, lost 39.7 kg after a 30-week modified VLCD. She is awaiting liver transplantation listing with a stable MELD score. VLCDs were well tolerated by both patients without adverse effects. In conclusion, under close medical supervision VLCDs in patients with ESLD can be safe and effective in reducing weight, facilitating liver transplantation listing, and possibly improving liver damage.

  2. Catabolism of (2E)-4-hydroxy-2-nonenal via ω- and ω-1-oxidation stimulated by ketogenic diet.

    PubMed

    Jin, Zhicheng; Berthiaume, Jessica M; Li, Qingling; Henry, Fabrice; Huang, Zhong; Sadhukhan, Sushabhan; Gao, Peng; Tochtrop, Gregory P; Puchowicz, Michelle A; Zhang, Guo-Fang

    2014-11-14

    Oxidative stress triggers the peroxidation of ω-6-polyunsaturated fatty acids to reactive lipid fragments, including (2E)-4-hydroxy-2-nonenal (HNE). We previously reported two parallel catabolic pathways of HNE. In this study, we report a novel metabolite that accumulates in rat liver perfused with HNE or 4-hydroxynonanoic acid (HNA), identified as 3-(5-oxotetrahydro-2-furanyl)propanoyl-CoA. In experiments using a combination of isotopic analysis and metabolomics studies, three catabolic pathways of HNE were delineated following HNE conversion to HNA. (i) HNA is ω-hydroxylated to 4,9-dihydroxynonanoic acid, which is subsequently oxidized to 4-hydroxynonanedioic acid. This is followed by the degradation of 4-hydroxynonanedioic acid via β-oxidation originating from C-9 of HNA breaking down to 4-hydroxynonanedioyl-CoA, 4-hydroxyheptanedioyl-CoA, or its lactone, 2-hydroxyglutaryl-CoA, and 2-ketoglutaric acid entering the citric acid cycle. (ii) ω-1-hydroxylation of HNA leads to 4,8-dihydroxynonanoic acid (4,8-DHNA), which is subsequently catabolized via two parallel pathways we previously reported. In catabolic pathway A, 4,8-DHNA is catabolized to 4-phospho-8-hydroxynonanoyl-CoA, 3,8-dihydroxynonanoyl-CoA, 6-hydroxyheptanoyl-CoA, 4-hydroxypentanoyl-CoA, propionyl-CoA, and acetyl-CoA. (iii) The catabolic pathway B of 4,8-DHNA leads to 2,6-dihydroxyheptanoyl-CoA, 5-hydroxyhexanoyl-CoA, 3-hydroxybutyryl-CoA, and acetyl-CoA. Both in vivo and in vitro experiments showed that HNE can be catabolically disposed via ω- and ω-1-oxidation in rat liver and kidney, with little activity in brain and heart. Dietary experiments showed that ω- and ω-1-hydroxylation of HNA in rat liver were dramatically up-regulated by a ketogenic diet, which lowered HNE basal level. HET0016 inhibition and mRNA expression level suggested that the cytochrome P450 4A are main enzymes responsible for the NADPH-dependent ω- and ω-1-hydroxylation of HNA/HNE.

  3. Catabolism of (2E)-4-Hydroxy-2-nonenal via ω- and ω-1-Oxidation Stimulated by Ketogenic Diet*

    PubMed Central

    Jin, Zhicheng; Berthiaume, Jessica M.; Li, Qingling; Henry, Fabrice; Huang, Zhong; Sadhukhan, Sushabhan; Gao, Peng; Tochtrop, Gregory P.; Puchowicz, Michelle A.; Zhang, Guo-Fang

    2014-01-01

    Oxidative stress triggers the peroxidation of ω-6-polyunsaturated fatty acids to reactive lipid fragments, including (2E)-4-hydroxy-2-nonenal (HNE). We previously reported two parallel catabolic pathways of HNE. In this study, we report a novel metabolite that accumulates in rat liver perfused with HNE or 4-hydroxynonanoic acid (HNA), identified as 3-(5-oxotetrahydro-2-furanyl)propanoyl-CoA. In experiments using a combination of isotopic analysis and metabolomics studies, three catabolic pathways of HNE were delineated following HNE conversion to HNA. (i) HNA is ω-hydroxylated to 4,9-dihydroxynonanoic acid, which is subsequently oxidized to 4-hydroxynonanedioic acid. This is followed by the degradation of 4-hydroxynonanedioic acid via β-oxidation originating from C-9 of HNA breaking down to 4-hydroxynonanedioyl-CoA, 4-hydroxyheptanedioyl-CoA, or its lactone, 2-hydroxyglutaryl-CoA, and 2-ketoglutaric acid entering the citric acid cycle. (ii) ω-1-hydroxylation of HNA leads to 4,8-dihydroxynonanoic acid (4,8-DHNA), which is subsequently catabolized via two parallel pathways we previously reported. In catabolic pathway A, 4,8-DHNA is catabolized to 4-phospho-8-hydroxynonanoyl-CoA, 3,8-dihydroxynonanoyl-CoA, 6-hydroxyheptanoyl-CoA, 4-hydroxypentanoyl-CoA, propionyl-CoA, and acetyl-CoA. (iii) The catabolic pathway B of 4,8-DHNA leads to 2,6-dihydroxyheptanoyl-CoA, 5-hydroxyhexanoyl-CoA, 3-hydroxybutyryl-CoA, and acetyl-CoA. Both in vivo and in vitro experiments showed that HNE can be catabolically disposed via ω- and ω-1-oxidation in rat liver and kidney, with little activity in brain and heart. Dietary experiments showed that ω- and ω-1-hydroxylation of HNA in rat liver were dramatically up-regulated by a ketogenic diet, which lowered HNE basal level. HET0016 inhibition and mRNA expression level suggested that the cytochrome P450 4A are main enzymes responsible for the NADPH-dependent ω- and ω-1-hydroxylation of HNA/HNE. PMID:25274632

  4. Medium-chain triglyceride (MCT) ketogenic therapy.

    PubMed

    Liu, Yeou-mei Christiana

    2008-11-01

    The medium-chain triglyceride diet (MCTD) is a variant of the classic 4:1 ketogenic diet (KD) introduced in 1971 by Huttenlocher as an attempt to improve the palatability of the KD by allowing more carbohydrates yet preserving ketosis. Although initially found to be equally effective as the classic KD, use of the MCTD declined because of frequent gastrointestinal side effects such as cramps, diarrhea, and vomiting. Recently, we have used the MCTD in more than 50 patients. We have found excellent seizure control, similar to the classic KD, and with careful monitoring, we have encountered minimal side effects. The MCTD should remain a viable dietary option for children with refractory epilepsy who have large appetites, can tolerate more calories, or cannot accept the restrictions of the classic KD.

  5. Rapid adaptation of rat brain and liver metabolism to a ketogenic diet: an integrated study using (1)H- and (13)C-NMR spectroscopy.

    PubMed

    Roy, Maggie; Beauvieux, Marie-Christine; Naulin, Jérôme; El Hamrani, Dounia; Gallis, Jean-Louis; Cunnane, Stephen C; Bouzier-Sore, Anne-Karine

    2015-07-01

    The ketogenic diet (KD) is an effective alternative treatment for refractory epilepsy in children, but the mechanisms by which it reduces seizures are poorly understood. To investigate how the KD modifies brain metabolism, we infused control (CT) and 7-day KD rats with either [1-(13)C]glucose (Glc) or [2,4-(13)C2]β-hydroxybutyrate (β-HB). Specific enrichments of amino acids (AAs) measured by (1)H- and (13)C-NMR in total brain perchloric acid extracts were similar between CT and KD rats after [1-(13)C]Glc infusion whereas they were higher in KD rats after [2,4-(13)C2]β-HB infusion. This suggests better metabolic efficiency of ketone body utilization on the KD. The relative rapid metabolic adaptation to the KD included (1) 11%-higher brain γ-amino butyric acid (GABA)/glutamate (Glu) ratio versus CT, (2) liver accumulation of the ketogenic branched-chain AAs (BCAAs) leucine (Leu) and isoleucine (ILeu), which were never detected in CT, and (3) higher brain Leu and ILeu contents. Since Glu and GABA are excitatory and inhibitory neurotransmitters, respectively, higher brain GABA/Glu ratio could contribute to the mechanism by which the KD reduces seizures in epilepsy. Increased BCAA on the KD may also contribute to better seizure control.

  6. Rapid adaptation of rat brain and liver metabolism to a ketogenic diet: an integrated study using 1H- and 13C-NMR spectroscopy

    PubMed Central

    Roy, Maggie; Beauvieux, Marie-Christine; Naulin, Jérôme; El Hamrani, Dounia; Gallis, Jean-Louis; Cunnane, Stephen C; Bouzier-Sore, Anne-Karine

    2015-01-01

    The ketogenic diet (KD) is an effective alternative treatment for refractory epilepsy in children, but the mechanisms by which it reduces seizures are poorly understood. To investigate how the KD modifies brain metabolism, we infused control (CT) and 7-day KD rats with either [1-13C]glucose (Glc) or [2,4-13C2]β-hydroxybutyrate (β-HB). Specific enrichments of amino acids (AAs) measured by 1H- and 13C-NMR in total brain perchloric acid extracts were similar between CT and KD rats after [1-13C]Glc infusion whereas they were higher in KD rats after [2,4-13C2]β-HB infusion. This suggests better metabolic efficiency of ketone body utilization on the KD. The relative rapid metabolic adaptation to the KD included (1) 11%-higher brain γ-amino butyric acid (GABA)/glutamate (Glu) ratio versus CT, (2) liver accumulation of the ketogenic branched-chain AAs (BCAAs) leucine (Leu) and isoleucine (ILeu), which were never detected in CT, and (3) higher brain Leu and ILeu contents. Since Glu and GABA are excitatory and inhibitory neurotransmitters, respectively, higher brain GABA/Glu ratio could contribute to the mechanism by which the KD reduces seizures in epilepsy. Increased BCAA on the KD may also contribute to better seizure control. PMID:25785828

  7. Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice.

    PubMed

    Zhang, Xiaoyu; Qin, Juliang; Zhao, Yihan; Shi, Jueping; Lan, Rong; Gan, Yunqiu; Ren, Hua; Zhu, Bing; Qian, Min; Du, Bing

    2016-04-01

    The ketogenic diet (KD) has been widely used in weight and glycemic control, although potential side effects of long-term KD treatment have caused persistent concern. In this study, we hypothesized that the KD would ameliorate the progression of diabetes but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered streptozotocin treatment before given the test diets for 8 weeks. Subsequently, ameliorated glucose and insulin tolerance in KD-fed diabetic mice was found, although the body weight of high-fat diet- and KD-fed mice was similar. Interestingly, the weight of adipose tissue in KD mice was greater than in the other groups. The KD diet resulted in higher serum triacylglycerol and cholesterol levels in diabetic mice. Moreover, the KD-fed mice showed greater hepatic lipid accumulation. Mice fed the KD showed significant changes in several key genes such as sterol regulatory element-binding protein, fibroblast growth factor 21, and peroxisome proliferator-activated receptor α, which are all important in metabolism. In summary, KD ameliorates glucose and insulin tolerance in a mouse model of diabetes, but severe hepatic lipid accumulation and hepatic steatosis were observed, which should be considered carefully in the long-term application of KD.

  8. The Impact of 3:1 Ketogenic Diet on Cardiac Repolarization Changes in Children with Refractory Seizures: A Prospective Follow-Up Study.

    PubMed

    Özdemir, Rahmi; Güzel, Orkide; Küçük, Mehmet; Karadeniz, Cem; Yılmaz, Ünsal; Calik, Tansel; Meşe, Timur

    2016-06-01

    Background The association between ketogenic diet (KD) and prolonged QT interval, life-threatening ventricular arrhythmias, and sudden death is controversial. Aim We aimed to prospectively evaluate the effect of KD on electrocardiography (ECG) measures in children with refractory epilepsy. Method A total of 70 children with drug-resistant epilepsy who received a KD for at least 12 months were included in the study. The standard 12-lead electrocardiography was performed in all patients before the beginning and in the 12th month of KD. Heart rate, P-wave duration and dispersion, corrected QT interval and QT dispersion, and Tp-e interval were measured. Results All ECG-derived parameters, but P-wave dispersion increased after 12 months of KD compared with the baseline values. However, these changes were not statistically significant. Conclusion A 12-month long 3:1 KD treatment exerts no deleterious effect on cardiac repolarization measures.

  9. Long-Term Effects of Ketogenic Diet on Subsequent Seizure-Induced Brain Injury During Early Adulthood: Relationship of Seizure Thresholds to Zinc Transporter-Related Gene Expressions.

    PubMed

    Tian, Tian; Li, Li-Li; Zhang, Shu-Qi; Ni, Hong

    2016-12-01

    The divalent cation zinc is associated with cortical plasticity. However, the mechanism of zinc in the pathophysiology of cortical injury-associated neurobehavioral damage following neonatal seizures is uncertain. We have previously shown upregulated expression of ZnT-3; MT-3 in hippocampus of neonatal rats submitted to flurothyl-induced recurrent seizures, which was restored by pretreatment with ketogenic diet (KD). In this study, utilizing a novel "twist" seizure model by coupling early-life flurothyl-induced seizures with later exposure to penicillin, we further investigated the long-term effects of KD on cortical expression of zinc homeostasis-related genes in a systemic scale. Ten Sprague-Dawley rats were assigned each averagely into the non-seizure plus normal diet (NS + ND), non-seizure plus KD (NS + KD), recurrent seizures plus normal diet (RS + ND) and recurrent seizures plus KD (RS + KD) group. Recurrent seizures were induced by volatile flurothyl during P9-P21. During P23-P53, rats in NS + KD and RS + KD groups were dieted with KD. Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed at P43. At P63, we examined seizure threshold using penicillin, then the cerebral cortex were evaluated for real-time RT-PCR and western blot study. The RS + ND group showed worse performances in neurological reflex tests and reduced latencies to myoclonic seizures induced by penicillin compared with the control, which was concomitant with altered expressions of ZnT-7, MT-1, MT-2, and ZIP7. Specifically, there was long-term elevated expression of ZIP7 in RS + ND group compared with that in NS + ND that was restored by chronic ketogenic diet (KD) treatment in RS + KD group, which was quite in parallel with the above neurobehavioral changes. Taken together, these findings indicate that the long-term altered expression of the metal transporter ZIP7 in adult cerebral cortex might

  10. An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial

    PubMed Central

    Mason, Ashley E; Kim, Sarah; Goldman, Veronica; Ploutz-Snyder, Robert; Bayandorian, Hovig; Daubenmier, Jennifer

    2017-01-01

    Background Type 2 diabetes is a prevalent, chronic disease for which diet is an integral aspect of treatment. In our previous trial, we found that recommendations to follow a very low-carbohydrate ketogenic diet and to change lifestyle factors (physical activity, sleep, positive affect, mindfulness) helped overweight people with type 2 diabetes or prediabetes improve glycemic control and lose weight. This was an in-person intervention, which could be a barrier for people without the time, flexibility, transportation, social support, and/or financial resources to attend. Objective The aim was to determine whether an online intervention based on our previous recommendations (an ad libitum very low-carbohydrate ketogenic diet with lifestyle factors; “intervention”) or an online diet program based on the American Diabetes Associations’ “Create Your Plate” diet (“control”) would improve glycemic control and other health outcomes among overweight individuals with type 2 diabetes. Methods In this pilot feasibility study, we randomized overweight adults (body mass index ≥25) with type 2 diabetes (glycated hemoglobin [HbA1c] 6.5%-9.0%) to a 32-week online intervention based on our previous recommendations (n=12) or an online diet program based around a plate method diet (n=13) to assess the impact of each intervention on glycemic control and other health outcomes. Primary and secondary outcomes were analyzed by mixed-effects linear regression to compare outcomes by group. Results At 32 weeks, participants in the intervention group reduced their HbA1c levels more (estimated marginal mean [EMM] –0.8%, 95% CI –1.1% to –0.6%) than participants in the control group (EMM –0.3%, 95% CI –0.6% to 0.0%; P=.002). More than half of the participants in the intervention group (6/11, 55%) lowered their HbA1c to less than 6.5% versus 0% (0/8) in the control group (P=.02). Participants in the intervention group lost more weight (EMM –12.7 kg, 95% CI –16.1 to

  11. Successful treatment of severe cardiomyopathy in glycogen storage disease type III With D,L-3-hydroxybutyrate, ketogenic and high-protein diet.

    PubMed

    Valayannopoulos, Vassili; Bajolle, Fanny; Arnoux, Jean-Baptiste; Dubois, Sandrine; Sannier, Nathalie; Baussan, Christiane; Petit, François; Labrune, Philippe; Rabier, Daniel; Ottolenghi, Chris; Vassault, Anne; Broissand, Christine; Bonnet, Damien; de Lonlay, Pascale

    2011-12-01

    Glycogen storage disease type III (GSD III) due to debranching enzyme deficiency presenting usually with hepatomegaly and hypoglycemia may be responsible for severe cardiomyopathy which is often fatal. Current treatment of GSD III is based on frequent high-carbohydrate meals that have no effect on the cardiomyopathy. We describe a 2-mo-old infant presenting with a familial form of GSD III complicated with cardiomyopathy. As conventional treatment was unable to improve his sister's cardiomyopathy who was deceased at age 11 mo, we proposed an experimental treatment combining the use of synthetic ketone bodies (D,L-3-OH butyrate) as an alternative energy source, 2:1 ketogenic diet to reduce glucose intake and high-protein diet to enhance gluconeogenesis. Twenty-four months after the onset of this treatment, echocardiography showed an improvement of cardiomyopathy. Growth and liver size remained normal, and no side effects were observed. Blood glucose levels remained within the normal range and insulin levels decreased. These findings show that synthetic ketone bodies as well as low-carbohydrate, high-lipid, and high-protein diet may be a more beneficial therapeutic choice therapeutic choice for GSD III patients with cardiomyopathy. These encouraging data need to be confirmed in more GSD III patients presenting with cardiac or muscular symptoms.

  12. Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

    PubMed

    Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

    2016-08-01

    We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss.

  13. Effect of DHA supplementation in a very low-calorie ketogenic diet in the treatment of obesity: a randomized clinical trial.

    PubMed

    de Luis, Daniel; Domingo, Joan Carles; Izaola, Olatz; Casanueva, Felipe F; Bellido, Diego; Sajoux, Ignacio

    2016-10-01

    A VLCK diet supplemented with DHA, commercially available, was tested against an isocaloric VLCK diet without DHA. The main purpose of this study was to compare the effect of DHA supplementation in classic cardiovascular risk factors, adipokine levels, and inflammation-resolving eicosanoids. A total of obese patients were randomized into two groups: a group supplemented with DHA (n = 14) (PnK-DHA group) versus a group with an isocaloric diet free of supplementation (n = 15) (control group). The follow-up period was 6 months. The average weight loss after 6 months of treatment was 20.36 ± 5.02 kg in control group and 19.74 ± 5.10 kg in PnK-DHA group, without statistical differences between both groups. The VLCK diets induced a significant change in some of the biological parameters, such as insulin, HOMA-IR, triglycerides, LDL cholesterol, C-reactive protein, resistin, TNF alpha, and leptin. Following DHA supplementation, the DHA-derived oxylipins were significantly increased in the intervention group. The ratio of proresolution/proinflammatory lipid markers was increased in plasma of the intervention group over the entire study. Similarly, the mean ratios of AA/EPA and AA/DHA in erythrocyte membranes were dramatically reduced in the PnK-DHA group and the anti-inflammatory fatty acid index (AIFAI) was consistently increased after the DHA treatment (p < 0.05). The present study demonstrated that a very low-calorie ketogenic diet supplemented with DHA was significantly superior in the anti-inflammatory effect, without statistical differences in weight loss and metabolic improvement.

  14. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus

    PubMed Central

    Goday, A; Bellido, D; Sajoux, I; Crujeiras, A B; Burguera, B; García-Luna, P P; Oleaga, A; Moreno, B; Casanueva, F F

    2016-01-01

    Brackground: The safety and tolerability of very low-calorie-ketogenic (VLCK) diets are a current concern in the treatment of obese type 2 diabetes mellitus (T2DM) patients. Objective: Evaluating the short-term safety and tolerability of a VLCK diet (<50 g of carbohydrate daily) in an interventional weight loss program including lifestyle and behavioral modification support (Diaprokal Method) in subjects with T2DM. Methods: Eighty-nine men and women, aged between 30 and 65 years, with T2DM and body mass index between 30 and 35 kg m−2 participated in this prospective, open-label, multi-centric randomized clinical trial with a duration of 4 months. Forty-five subjects were randomly assigned to the interventional weight loss (VLCK diet), and 44 to the standard low-calorie diet. Results: No significant differences in the laboratory safety parameters were found between the two study groups. Changes in the urine albumin-to-creatinine ratio in VLCK diet were not significant and were comparable to control group. Creatinine and blood urea nitrogen did not change significantly relative to baseline nor between groups. Weight loss and reduction in waist circumference in the VLCK diet group were significantly larger than in control subjects (both P<0.001). The decline in HbA1c and glycemic control was larger in the VLCK diet group (P<0.05). No serious adverse events were reported and mild AE in the VLCK diet group declined at last follow-up. Conclusions: The interventional weight loss program based on a VLCK diet is most effective in reducing body weight and improvement of glycemic control than a standard hypocaloric diet with safety and good tolerance for T2DM patients. PMID:27643725

  15. Effect of ketogenic diet on nucleotide hydrolysis and hepatic enzymes in blood serum of rats in a lithium-pilocarpine-induced status epilepticus.

    PubMed

    da Silveira, Vanessa Gass; de Paula Cognato, Giana; Müller, Alexandre Pastoris; Figueiró, Fabrício; Bonan, Carla Denise; Perry, Marcos L Santos; Battastini, Ana Maria Oliveira

    2010-06-01

    The ketogenic diet (KD) is a high-fat and low-carbohydrate diet, used for treating refractory epilepsy in children. We have previously shown alterations in nucleotidase activities from the central nervous system and blood serum of rats submitted to different models of epilepsy. In this study we investigated the effect of KD on nucleotidase activities in the blood serum, as well if KD has any influence in the activity of liver enzymes such as alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities in Wistar rats submitted to the lithium-pilocarpine model of epilepsy. At 21 days of age, rats received an injection of lithium chloride and, 18-19 h later, they received an injection of pilocarpine hydrochloride for status epilepticus induction. The results reported herein show that seizures induced by lithium-pilocarpine elicit a significant increase in ATP hydrolysis and alkaline phosphatase activity, as well as a decrease in ADP hydrolysis and aspartate aminotransferase activity. The KD is a rigorous regimen that can be associated with hepatic damage, as shown herein by the elevated activities of liver enzymes and 5'-nucleotidase in blood serum. Further studies are necessary to investigate the mechanism of inhibition of lithium on nucleotidases in blood serum.

  16. Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver.

    PubMed

    Genzer, Yoni; Dadon, Maayan; Burg, Chen; Chapnik, Nava; Froy, Oren

    2015-12-05

    Ketogenic diet (KD) is used for weight loss or to treat epilepsy. KD leads to liver AMP-activated protein kinase (AMPK) activation, which would be expected to inhibit gluconeogenesis. However, KD leads to increased hepatic glucose output. As AMPK and its active phosphorylated form (pAMPK) show circadian oscillation, this discrepancy could stem from wrong-time-of-day sampling. The effect of KD was tested on mouse clock gene expression, AMPK, mTOR, SIRT1 and locomotor activity for 2 months and compared to low-fat diet (LFD). KD led to 1.5-fold increased levels of blood glucose and insulin. Brain pAMPK/AMPK ratio was 40% higher under KD, whereas that in liver was not affected. KD led to 40% and 20% down-regulation of the ratio of pP70S6K/P70S6K, the downstream target of mTOR, in the brain and liver, respectively. SIRT1 levels were 40% higher in the brain, but 40% lower in the liver of KD-fed mice. Clock genes showed delayed rhythms under KD. In the brain of KD-fed mice, amplitudes of clock genes were down-regulated, whereas 6-fold up-regulation was found in the liver. The metabolic state under KD indicates reduced satiety in the brain and reduced anabolism alongside increased gluconeogenesis in the liver.

  17. The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up.

    PubMed

    Lambrechts, Danielle A J E; de Kinderen, Reina J A; Vles, Hans S H; de Louw, Anton J; Aldenkamp, Albert P; Majoie, Marian J M

    2015-10-01

    The present study assessed the long-term (i.e., 24months) efficacy of the ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy, with focus on seizure frequency, seizure severity, and tolerability. Most patients were treated with the MCT-diet. At one and two years, 33% and 23%, respectively, of the 48 included patients were still on the KD. After three months, one year, and two years of treatment, 16.7% of the patients were responders. The highest responder rate (i.e., 22.9%) was seen at six and nine months of treatment. Of the fifteen patients with seizure clusters during baseline, 60% were responders after three months when looking at cluster reduction and most of them were not responders for the total seizure frequency. From three months of treatment onwards, most of the patients had a relevant decrease in seizure severity which was mainly related to the most severe seizure type. Gastrointestinal dysfunction was often reported, especially in the first six weeks of treatment. Growth deceleration was present in 30% of the patients, and weight reduction in 15%. Improved arousal was mentioned in 30% of patients. No patients developed ECG abnormalities or kidney stones. Increase in lipid profile was rare. The KD is an effective therapy for children with therapy-resistant epilepsy. Effectiveness is reflected in the reduction of seizure frequency as well as in the reduction of seizure severity. After 6months of treatment, it is obvious which patients are responders and tolerate the treatment well. Most of these patients will continue to benefit from the KD for a longer time. Long-term use of the diet was well tolerated.

  18. Altered expression of O-GlcNAc-modified proteins in a mouse model whose glycemic status is controlled by a low carbohydrate ketogenic diet.

    PubMed

    Okuda, Tetsuya; Fukui, Asami; Morita, Naoki

    2013-11-01

    Abnormal modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) is known to be associated with the pathology induced by hyperglycemia. However, the dynamic mechanism of O-GlcNAc modification under hyperglycemic conditions in vivo has not been fully characterized. To understand the mechanism, we established an animal model in which the glycemic status is controlled by the diet. A mutant mouse (ob/ob) which exhibits diet-induced hyperglycemia when fed a regular chow (chow) was used to establish this model; the mice were fed a very low carbohydrate ketogenic diet (KD) to improve hyperglycemia. Using this model, we evaluated the levels of O-GlcNAc-modified proteins in tissues under a hyperglycemic or its improved condition. ELISA and Western blot analyses revealed that altered expression of certain proteins modified by O-GlcNAc were found in the mice tissues, although global O-GlcNAc levels in the tissues remained unaltered by improvement of hyperglycemia. We also found the Akt protein kinase was modified by O-GlcNAc in the liver of ob/ob mice, and the modification levels were decreased by improvement of hyperglycemia. Furthermore, aberrant phosphorylation of Akt was found in the liver of ob/ob mice under hyperglycemic condition. In conclusion, our established mouse model is useful for evaluating the dynamics of O-GlcNAc-modified proteins in tissues associated with glycemic status. This study revealed that the expression level of certain proteins modified by O-GlcNAc is altered when KD improves the hyperglycemia. These proteins could be prospective indexes for nutritional therapy for hyperglycemia-associated diseases, such as diabetes mellitus.

  19. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model

    PubMed Central

    Woolf, Eric C.; Curley, Kara L.; Liu, Qingwei; Turner, Gregory H.; Charlton, Julie A.; Preul, Mark C.; Scheck, Adrienne C.

    2015-01-01

    Background The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood. Methods To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma. Results Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4. Conclusions The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas. PMID:26083629

  20. The ketogenic diet has no effect on the expression of spike-and-wave discharges and nutrient transporters in genetic absence epilepsy rats from Strasbourg.

    PubMed

    Nehlig, Astrid; Dufour, Franck; Klinger, Marianne; Willing, Lisa B; Simpson, Ian A; Vannucci, Susan J

    2009-05-01

    The genetic absence epilepsy rat from Strasbourg is considered an isomorphic, predictive, and homologous model of typical childhood absence epilepsy. It is characterized by the expression of spike-and-wave discharges (SWDs) in the thalamus and cortex. The ketogenic diet (KD) is successfully used in humans and animals with various types of seizures, but was not effective in children with intractable atypical absence epilepsy. Here, we studied its potential impact on the occurrence of SWDs in genetic absence epilepsy rat from Strasbourg. Rats were fed the KD for 3 weeks during which they were regularly subjected to the electroencephalographic recording of SWDs. The KD did not influence the number and duration of SWDs despite a 15-22% decrease in plasma glucose levels and a large increase in beta-hydroxybutyrate levels. Likewise, the KD did not affect the level of expression of the blood-brain barrier glucose transporter GLUT1 or of the monocarboxylate transporters, MCT1 and MCT2. This report extends the observation in humans that the KD does not appear to show effectiveness in intractable atypical absence epilepsy to this model of typical childhood absence epilepsy which responds to specific antiepileptic drugs.

  1. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy

    PubMed Central

    Poff, A. M.; Ward, N.; Seyfried, T. N.; Arnold, P.; D’Agostino, D. P.

    2015-01-01

    The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies – the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation – could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control), low glucose (LG), ketone supplementation (βHB), hyperbaric oxygen (HBOT), or combination therapy (LG+βHB+HBOT) on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers. PMID:26061868

  2. Medicinal Chemistry of the Epigenetic Diet and Caloric Restriction

    PubMed Central

    Martin, S.L.; Hardy, T.M.; Tollefsbol, T.O.

    2013-01-01

    The pronounced effects of the epigenetic diet (ED) and caloric restriction (CR) have on epigenetic gene regulation have been documented in many pre-clinical and clinical studies. Understanding epigenetics is of high importance because of the concept that external factors such as nutrition and diet may possess the ability to alter gene expression without modifying the DNA sequence. The ED introduces bioactive medicinal chemistry compounds such as sulforaphane (SFN), curcumin (CCM), epigallocatechin gallate (EGCG) and resveratrol (RSV) that are thought to aid in extending the human lifespan. CR, although similar to ED in the target of longevity, mildly reduces the total daily calorie intake while concurrently providing all beneficial nutrients. Both CR and ED may act as epigenetic modifiers to slow the aging process through histone modification, DNA methylation, and by modulating microRNA expression. CR and ED have been proposed as two important mechanisms that modulate and potentially slow the progression of age-related diseases such as cardiovascular disease (CVD), cancer, obesity, Alzheimer’s and osteoporosis to name a few. While many investigators have examined CR and ED as separate entities, this review will primarily focus on both as they relate to age-related diseases, their epigenetic effects and their medicinal chemistry. PMID:23895687

  3. Muscle PGC-1α is required for long term systemic and local adaptations to a ketogenic diet in mice.

    PubMed

    Schnyder, Svenia; Svensson, Kristoffer; Cardel, Bettina; Handschin, Christoph

    2017-02-21

    Low carbohydrate/high-fat (LCHF) diets are increasingly popular dietary interventions for body weight control and as treatment for different pathological conditions. However, the mechanisms of action are still poorly understood, in particular in long-term administration. Besides liver, brain and heart, skeletal muscle is one of the major organs involved in the regulation of physiological and pathophysiological ketosis. We now assessed the role of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle of male wild type control (CTRL) and PGC-1α muscle-specific knockout (PGC-1α mKO) mice upon 12 weeks of LCHF diet feeding. Interestingly, LCHF diet administration increased oxygen consumption in a muscle PGC-1α-dependent manner concomitant with a blunted transcriptional induction of genes involved in fatty acid oxidation and impairment in exercise performance. These data reveal a new role for muscle PGC-1α in regulating the physiological adaptation to long-term LCHF diet administration.

  4. Dairy-Rich Diets Augment Fat Loss on an Energy-Restricted Diet: A Multicenter Trial

    PubMed Central

    Zemel, Michael B.; Teegarden, Dorothy; Loan, Marta Van; Schoeller, Dale A.; Matkovic, Velimir; Lyle, Roseann M.; Craig, Bruce A.

    2009-01-01

    A 12-week randomized controlled multi-center clinical trial was conducted in 106 overweight and obese adults. Diets were designed to produce a 2,093 kJ/day energy deficit with either low calcium (LC; ~600 mg/day), high calcium (HC; ~1,400 mg/day), or high dairy (HD; three dairy servings, diet totaling ~1,400 mg/day). Ninety-three subjects completed the trial, and 68 met all a priori weekly compliance criteria. Both HC and HD contained comparable levels of calcium, but HC was only ~30% as effective as HD in suppressing 1,25-(OH)2D and exerted no significant effects on weight loss or body composition compared to LC. In the group that met compliance criteria, HD resulted in ~two-fold augmentation of fat loss compared to LC and HC (HD: -4.43 ± 0.53 kg; LC: -2.69 ± 0.0.53 kg; HC: -2.23 ± 0.73kg, p < 0.025); assessment of all completers and an intent-to-treat analysis produced similar trends. HD augmentated central (trunk) fat loss (HD: -2.38 ± 0.30 kg; HC: -1.42 ± 0.30 kg; LC: -1.36 ± 0.42 kg, p < 0.05) and waist circumference (HD: -7.65 ± 0.75 cm; LC: -4.92 ± 0.74 cm; LC: -4.95 ± 1.05 cm, p < 0.025). Similar effects were noted among all subjects completing the study and in an intent-to-treat analysis. These data indicate that dairy-rich diets augment weight loss by targeting the fat compartment during energy restriction. PMID:22253969

  5. Mechanism of protection of moderately diet restricted rats against doxorubicin-induced acute cardiotoxicity

    SciTech Connect

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Latendresse, John R.; Mehendale, Harihara M.

    2007-11-15

    Clinical use of doxorubicin (Adriamycin (registered) ), an antitumor agent, is limited by its oxyradical-mediated cardiotoxicity. We tested the hypothesis that moderate diet restriction protects against doxorubicin-induced cardiotoxicity by decreasing oxidative stress and inducing cardioprotective mechanisms. Male Sprague-Dawley rats (250-275 g) were maintained on diet restriction [35% less food than ad libitum]. Cardiotoxicity was estimated by measuring biomarkers of cardiotoxicity, cardiac function, lipid peroxidation, and histopathology. A LD{sub 100} dose of doxorubicin (12 mg/kg, ip) administered on day 43 led to 100% mortality in ad libitum rats between 7 and 13 days due to higher cardiotoxicity and cardiac dysfunction, whereas all the diet restricted rats exhibited normal cardiac function and survived. Toxicokinetic analysis revealed equal accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the ad libitum and diet restricted hearts. Mechanistic studies revealed that diet restricted rats were protected due to (1) lower oxyradical stress from increased cardiac antioxidants leading to downregulation of uncoupling proteins 2 and 3, (2) induction of cardiac peroxisome proliferators activated receptor-{alpha} and plasma adiponectin increased cardiac fatty acid oxidation (666.9 {+-}14.0 nmol/min/g heart in ad libitum versus 1035.6 {+-} 32.3 nmol/min/g heart in diet restriction) and mitochondrial AMP{alpha}2 protein kinase. The changes led to 51% higher cardiac ATP levels (17.7 {+-} 2.1 {mu}mol/g heart in ad libitum versus 26.7 {+-} 1.9 {mu}mol/g heart in diet restriction), higher ATP/ADP ratio, and (3) increased cardiac erythropoietin and decreased suppressor of cytokine signaling 3, which upregulates cardioprotective JAK/STAT3 pathway. These findings collectively show that moderate diet restriction renders resiliency against doxorubicin cardiotoxicity by lowering oxidative stress, enhancing ATP synthesis, and inducing the JAK/STAT3 pathway.

  6. Time-restricted feeding reduces adiposity in mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disruption of the circadian rhythm contributes to obesity. The present study investigated the effects of time-restricted feeding (TRF) of a high-fat diet on adiposity in male C57BL/6 mice. Three-week-old mice were fed a low-fat or high-fat diet (16% or 45% of energy from corn oil) ad libitum (ad l...

  7. A decade of the modified Atkins diet (2003–2013): Results, insights, and future directions.

    PubMed

    Kossoff, Eric H; Cervenka, Mackenzie C; Henry, Bobbie J; Haney, Courtney A; Turner, Zahava

    2013-12-01

    The modified Atkins diet has been used since 2003 for the treatment of children and adults with refractory epilepsy.This “alternative” ketogenic diet is started in clinic, without fasting, hospitalization, and restriction of protein,calories, or fluid intake. Now after 10 years of continued use, approximately 400 patients have been reported in over 30 studies of the modified Atkins diet as treatment for intractable seizures, with results demonstrating similar efficacy to the ketogenic diet and improved tolerability. The modified Atkins diet is being increasingly used in the adult population. Clinical trials have provided insight into the mechanisms of action of dietary therapies overall. This review will discuss the past decade of experience with the modified Atkins diet as well as predictions for its role in the treatment of epilepsy a decade from now.

  8. [Effect of dosed diet restriction on physiological remodeling and bioelectric properties of bone].

    PubMed

    Levashov, M I; Ianko, R V; Chaka, E G; Safonov, S L

    2014-07-01

    The effect of dosed diet restriction on the physiological remodeling and bioelectric properties of bone tissue was studied in 48 male Wistar rats 3- and 18-months of age. The rate of bone tissue apposition was studied by the dynamic histomorphometry method (intravital tetracycline labeling). Electric potentials on the periosteal surface of the freshly isolated femurs were recorded. The magnitude of dielectric loss factor was determined to assess the quality of bone tissue. The control rats received a standard diet. The experimental rats received a limited diet (60 % of the standard mass) for 28 days. The magnitude and rate of the bone tissue apposition on the endosteal and periosteal surface of the tibia were less by 38.4% and 122.7% respectively in experimental rats after dosed diet restriction. Electric potential in the metaphyseal-epiphyseal growth zones of the femur was 29.7% lower, and the dielectric loss factor increased by 15.8%. The bone tissue apposition rate and the electric potential magnitude were increased 10 days after completion of the dosed diet restriction. The magnitude of the dielectric loss factor decreased after returning to the standard diet. Key words: dosed diet restriction, bone, remodelling, bioelectric properties.

  9. Restricted diets in children with reactions to milk and egg perceived by their parents.

    PubMed

    Eggesbø, M; Botten, G; Stigum, H

    2001-10-01

    The aim of this study was to investigate the degree to which parents alter the diets of their children on the basis of perceived reactions. From a population-based sample of 2979 2-year old children with reactions to egg or milk perceived by their parents, one third had strict limitations on the intakes of these foods, representing 2.5% of the children in the cohort. In approximately 1 of 6 families the strict diets were initiated without consulting a doctor, and in a substantial proportion the restrictions were unwarranted. High maternal education level and irritability attributed to food were among the risk factors for unwarranted diets. On the other hand, many children, in whom an adverse reaction was verified, lacked appropriate diet restrictions. We conclude that the handling of adverse reactions to food frequently occurs outside the medical care system at the cost of correct diagnosis and appropriate diets.

  10. Vitamin E Restriction in the Diet Enhances Phagocytic Activation by Dichloroacetate and Trichloroacetate in Mice

    PubMed Central

    Hassoun, Ezdihar A.; Al-Dieri, Ali

    2011-01-01

    The effects of a Vitamin E-restricted diet on the induction of phagocytic activation by dichloro-acetate (DCA) and trichloroacetate (TCA) was investigated. Groups of B6C3F1 male mice were either kept on standard diet (Std diet group) or diet that had the vitamin provided only by its natural ingredients (Low-E diet group). The animals in each diet group were administered 77 mg of DCA or TCA/ kg/day, or 5 ml/kg water (controls), by gavage, for 13 weeks. Thereafter, peritoneal lavage cells (PLC) were assayed for superoxide anion (SA), tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO), as well as for the activities of the anti-oxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). SA and TNFα production, as well as MPO, SOD, CAT and GSH-Px activities were significantly increased in the cells from the Low-E diet group treated with the compounds as compared with cells from hosts in the Std-diet group that received the corresponding treatments. The results indicate that consumption of a Vitamin E-restricted diet enhances the induction of phagocytic activation by DCA and TCA, a mechanism that was previously suggested to be an initial adaptive/protective response against the compounds long-term effects. PMID:22178223

  11. Efficacy of the Atkins diet as therapy for intractable epilepsy.

    PubMed

    Kossoff, Eric H; Krauss, Gregory L; McGrogan, Jane R; Freeman, John M

    2003-12-23

    The ketogenic diet is effective for treating seizures in children with epilepsy. The Atkins diet can also induce a ketotic state, but has fewer protein and caloric restrictions, and has been used safely by millions of people worldwide for weight reduction. Six patients, aged 7 to 52 years, were started on the Atkins diet for the treatment of intractable focal and multifocal epilepsy. Five patients maintained moderate to large ketosis for periods of 6 weeks to 24 months; three patients had seizure reduction and were able to reduce antiepileptic medications. This provides preliminary evidence that the Atkins diet may have a role as therapy for patients with medically resistant epilepsy.

  12. Dieting in bulimia nervosa is associated with increased food restriction and psychopathology but decreased binge eating.

    PubMed

    Lowe, Michael R; Witt, Ashley A; Grossman, Stephanie L

    2013-08-01

    The cognitive behavioral model of bulimia nervosa (BN) suggests that dieting is central to the maintenance of binge eating. However, correlational and experimental studies suggest that additional clarification is needed about the nature of this relationship. Dieting, weight, eating disorder psychopathology, and depression were assessed at admission among 166 patients with BN presenting for residential treatment. As in past research, a significant fraction (43%) of patients with BN reported not currently dieting. A comparison of weight loss dieters and non-dieters found greater food restriction and eating disorder psychopathology among weight loss dieters. However, dieters reported less frequent binge eating. There were no significant group differences in depression. Results suggest that 1) while many individuals with BN are attempting to restrict their food intake, the goal of losing weight fundamentally alters the effect of such restriction on binge eating, and 2) treatment may benefit from helping patients to establish a healthier approach to achieving long-term weight stability.

  13. Safety and role of ketogenic parenteral nutrition for intractable childhood epilepsy.

    PubMed

    Jung, Da Eun; Kang, Hoon-Chul; Lee, Joon Soo; Lee, Eun Joo; Kim, Heung Dong

    2012-09-01

    To retrospectively evaluate the safety and role of ketogenic parenteral nutrition in patients with intractable childhood epilepsy. The ketogenic parenteral nutrition was given to 10 patients who were unable to absorb nutrients through the intestinal tract because of various gastrointestinal disorders and required complete bowel rest. This nutrition consisted of conventional intravenous fat emulsion (20% Lipision) plus dextrose and amino acid (6% Trophamine) hyperalimentation in a 4:1 (or 3:1) lipid to non-lipid ratio, infused during the bowel rest. If the ketogenic parenteral nutrition allowed normal daily functioning or resolved the underlying problems, we soon changed it to the enteral ketogenic diet (KD). The mean (±SD) duration of the ketogenic parenteral nutrition was 4.1 (±1.5) days. Although a brief span of several days, all patients could maintain ketosis and the efficacy of the previous enteral KD during the ketogenic parenteral nutrition. Complications included elevated aspartate aminotransferase and/or alanine aminotransferase in one patient. Amylase and lipase increased in one patient. Serum triglyceride level increased to the level of 1885 mg/dl in one patient, but normalized in one week after discontinuation of the ketogenic parenteral nutrition and resuming of the enteral KD. Nine patients (90%) remained on the enteral KD after the ketogenic parenteral nutrition (the mean follow-up period was 9 months), including 2 patients who successfully completed the diet with seizure free state. Only one patient discontinued the ketogenic parenteral nutrition because of persistent increase of the amylase and lipase levels. The ketogenic parenteral nutrition proved to be a relatively safe short-term method of continuing KD to maintain ketosis for seizure control, while patients were unable to absorb nutrients through their intestinal tract.

  14. Xerophthalmia and vitamin A deficiency in an autistic child with a restricted diet.

    PubMed

    Chiu, Mimi; Watson, Stephanie

    2015-10-05

    We report the ocular and systemic manifestations of vitamin A deficiency in a child with a complicated medical history including autism and a restricted diet, living in a developed country. This child had significant vitamin A deficiency despite being under long-term medical care, yet the diagnosis was not considered until he had an ophthalmology review for visual deterioration.

  15. Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat

    PubMed Central

    Seip, Richard L; Volek, Jeff S; Windemuth, Andreas; Kocherla, Mohan; Fernandez, Maria Luz; Kraemer, William J; Ruaño, Gualberto

    2008-01-01

    Background Genetic factors that predict responses to diet may ultimately be used to individualize dietary recommendations. We used physiogenomics to explore associations among polymorphisms in candidate genes and changes in relative body fat (Δ%BF) to low fat and low carbohydrate diets. Methods We assessed Δ%BF using dual energy X-ray absorptiometry (DXA) in 93 healthy adults who consumed a low carbohydrate diet (carbohydrate ~12% total energy) (LC diet) and in 70, a low fat diet (fat ~25% total energy) (LF diet). Fifty-three single nucleotide polymorphisms (SNPs) selected from 28 candidate genes involved in food intake, energy homeostasis, and adipocyte regulation were ranked according to probability of association with the change in %BF using multiple linear regression. Results Dieting reduced %BF by 3.0 ± 2.6% (absolute units) for LC and 1.9 ± 1.6% for LF (p < 0.01). SNPs in nine genes were significantly associated with Δ%BF, with four significant after correction for multiple statistical testing: rs322695 near the retinoic acid receptor beta (RARB) (p < 0.005), rs2838549 in the hepatic phosphofructokinase (PFKL), and rs3100722 in the histamine N-methyl transferase (HNMT) genes (both p < 0.041) due to LF; and the rs5950584 SNP in the angiotensin receptor Type II (AGTR2) gene due to LC (p < 0.021). Conclusion Fat loss under LC and LF diet regimes appears to have distinct mechanisms, with PFKL and HNMT and RARB involved in fat restriction; and AGTR2 involved in carbohydrate restriction. These discoveries could provide clues to important physiologic mechanisms underlying the Δ%BF to low carbohydrate and low fat diets. PMID:18254975

  16. Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy.

    PubMed

    Yuen, Alan W C; Sander, Josemir W

    2014-04-01

    There has been resurgence in the use of dietary treatment, principally the classical ketogenic diet and its variants, for people with epilepsy. These diets generally require significant medical and dietician support. An effective but less restrictive dietary regimen is likely to be more acceptable and more widely used. Calorie-restricted diets appear to produce a range of biochemical and metabolic changes including reduced glucose levels, reduced inflammatory markers, increased sirtuins, increased AMPK signaling, inhibition of mTOR signaling, and increase in autophagy. There are studies in animal seizure models that suggest that these biochemical and metabolic changes may decrease ictogenesis and epileptogenesis. A calorie-restricted diet might be effective in reducing seizures in people with epilepsy. Hence, there is a sufficient rationale to undertake clinical trials to assess the efficacy and safety of calorie-restricted diets in people with epilepsy.

  17. Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment.

    PubMed

    Wentz, Anna E; d'Avignon, D André; Weber, Mary L; Cotter, David G; Doherty, Jason M; Kerns, Robnet; Nagarajan, Rakesh; Reddy, Naveen; Sambandam, Nandakumar; Crawford, Peter A

    2010-08-06

    Heart muscle is metabolically versatile, converting energy stored in fatty acids, glucose, lactate, amino acids, and ketone bodies. Here, we use mouse models in ketotic nutritional states (24 h of fasting and a very low carbohydrate ketogenic diet) to demonstrate that heart muscle engages a metabolic response that limits ketone body utilization. Pathway reconstruction from microarray data sets, gene expression analysis, protein immunoblotting, and immunohistochemical analysis of myocardial tissue from nutritionally modified mouse models reveal that ketotic states promote transcriptional suppression of the key ketolytic enzyme, succinyl-CoA:3-oxoacid CoA transferase (SCOT; encoded by Oxct1), as well as peroxisome proliferator-activated receptor alpha-dependent induction of the key ketogenic enzyme HMGCS2. Consistent with reduction of SCOT, NMR profiling demonstrates that maintenance on a ketogenic diet causes a 25% reduction of myocardial (13)C enrichment of glutamate when (13)C-labeled ketone bodies are delivered in vivo or ex vivo, indicating reduced procession of ketones through oxidative metabolism. Accordingly, unmetabolized substrate concentrations are higher within the hearts of ketogenic diet-fed mice challenged with ketones compared with those of chow-fed controls. Furthermore, reduced ketone body oxidation correlates with failure of ketone bodies to inhibit fatty acid oxidation. These results indicate that ketotic nutrient environments engage mechanisms that curtail ketolytic capacity, controlling the utilization of ketone bodies in ketotic states.

  18. Parental restriction and children's diets. The chocolate coin and Easter egg experiments.

    PubMed

    Ogden, Jane; Cordey, Phillipa; Cutler, Laura; Thomas, Hayley

    2013-02-01

    Two naturalistic experiments are reported exploring the impact of parental restriction on children's diets. For study 1, 53 parents gave 75 g of chocolate coins to their child over a weekend. For study 2, 86 parents were recruited prior to the 2 week Easter break when their children would be receiving chocolate Easter eggs. For both studies, parents were randomly allocated to either the non-restriction or restriction conditions and rated their child's preoccupation with the target food and other sweet foods (demanding and eating) at the start and end of the interventions. Perceived and actual food intake was assessed. Children in the restriction conditions consumed fewer chocolate coins and Easter eggs. All children showed decreased preoccupation with chocolate coins or Easter eggs over the course of the studies yet by the end the restriction group were more preoccupied with the target food. In contrast, all children showed an increased preoccupation with other sweet foods as the studies progressed which was greater in the non-restriction group for the chocolate coins study. Overall, restriction resulted in reduced intake but relative increased preoccupation with the food being restricted. Non-restriction resulted in a greater preoccupation with other sweet foods once the target foods had been consumed.

  19. A practical guide to fad diets.

    PubMed

    Porcello, L A

    1984-07-01

    This discussion of fad diets may be concluded by comparing the 14 selected diets with the standards previously outlined for desirable weight reducing plans. Many of the popular diets supply large quantities of saturated fat and cholesterol, which are dietary components that have been associated with cardiovascular disease. Ketogenic diets are not appropriate for athletes because of problems with secondary dehydration and hyponatremia. Almost all of the diets are nutritionally inadequate. The rate of anticipated weight loss will vary according to the age, sex, weight, basal energy requirement, and activity level of an individual. However, it is expected that weight loss will be excessively rapid if a competitive athlete consumes a diet of less than 1000 calories per day. These hypocaloric diets cannot meet the training demands of athletes and will promote loss of lean body mass and carbohydrate stores. Many of the ketogenic diets do not restrict calories; therefore, weight loss will depend upon individual daily caloric consumption. The Cambridge Diet and starvation diets produce weight loss far in excess of that desired for an athlete in training. Long-term eating patterns to maintain weight loss are not encouraged in any of the 14 selected fad diets. In fact, most of these diets promote patterns of poor nutrition. Not one of the diets provides options or choices for dieters to use in accommodating food preference and lifestyle patterns. Some of the diets are fairly easy to comply with and others require special foods and supplements. None of the 14 diets reviewed fulfull all of the standards for a sound weight reduction diet plan.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Time-restricted feeding reduces adiposity in mice fed a high-fat diet.

    PubMed

    Sundaram, Sneha; Yan, Lin

    2016-06-01

    Disruption of the circadian rhythm contributes to obesity. This study tested the hypothesis that time-restricted feeding (TRF) reduces high-fat diet-induced increase in adiposity. Male C57BL/6 mice were fed the AIN93G or the high-fat diet ad libitum (ad lib); TRF of the high-fat diet for 12 or 8hours during the dark cycle was initiated when high-fat diet-fed mice exhibited significant increases in body weight. Energy intake of the TRF 12-hour group was not different from that of the high-fat ad lib group, although that of the TRF 8-hour group was slightly but significantly lower. Restricted feeding of the high-fat diet reduced body fat mass and body weight compared with mice fed the high-fat diet ad lib. There were no differences in respiratory exchange ratio (RER) among TRF and high-fat ad lib groups, but the RER of these groups was lower than that of the AIN93G group. Energy expenditure of the TRF groups was slightly but significantly lower than that of the high-fat ad lib group. Plasma concentrations of ghrelin were increased in TRF groups compared with both AIN93G and high-fat ad lib groups. Elevations of plasma concentrations of insulin, leptin, monocyte chemoattractant protein-1, and tissue inhibitor metalloproteinase-1 by high-fat ad lib feeding were reduced by TRF to the levels of mice fed the AIN93G diet. In conclusion, TRF during the dark cycle reduces high-fat diet-induced increases in adiposity and proinflammatory cytokines. These results indicate that circadian timing of food intake may prevent obesity and abate obesity-related metabolic disturbance.

  1. Dietary energy restriction reduces high-fat diet-enhanced metastasis of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a risk factor for cancer. The objective of this study was to determine the effects of dietary energy restriction on high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma (LLC) in mice. Male C57BL/6 mice were fed an AIN93G diet or a high-fat diet (16% or 45% of energy fro...

  2. Nutrition and Healthy Ageing: Calorie Restriction or Polyphenol-Rich “MediterrAsian” Diet?

    PubMed Central

    Rimbach, Gerald

    2013-01-01

    Diet plays an important role in mammalian health and the prevention of chronic diseases such as cardiovascular disease (CVD). Incidence of CVD is low in many parts of Asia (e.g., Japan) and the Mediterranean area (e.g., Italy, Spain, Greece, and Turkey). The Asian and the Mediterranean diets are rich in fruit and vegetables, thereby providing high amounts of plant bioactives including polyphenols, glucosinolates, and antioxidant vitamins. Furthermore, oily fish which is rich in omega-3 fatty acids is an important part of the Asian (e.g., Japanese) and also of the Mediterranean diets. There are specific plant bioactives which predominantly occur in the Mediterranean (e.g., resveratrol from red wine, hydroxytyrosol, and oleuropein from olive oil) and in the Asian diets (e.g., isoflavones from soybean and epigallocatechin gallate from green tea). Interestingly, when compared to calorie restriction which has been repeatedly shown to increase healthspan, these polyphenols activate similar molecular targets such as Sirt1. We suggest that a so-called “MediterrAsian” diet combining sirtuin-activating foods (= sirtfoods) of the Asian as well as Mediterranean diet may be a promising dietary strategy in preventing chronic diseases, thereby ensuring health and healthy ageing. Future (human) studies are needed which take the concept suggested here of the MediterrAsian diet into account. PMID:24069505

  3. Time-restricted feeding of a high-fat diet reduces diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reducing obesity may alleviate many medical complications including diabetes, cardiovascular disease and cancer. It has been suggested that obesity is contributed by the disruption of the circadian rhythms in addition to increased caloric intake. Restricting feeding to particular times of the day ma...

  4. Clinical, echocardiographic, and neurohormonal effects of a sodium-restricted diet in dogs with heart failure.

    PubMed

    Rush, J E; Freeman, L M; Brown, D J; Brewer, B P; Ross, J N; Markwell, P J

    2000-01-01

    The use of low-sodium diets in dogs with heart failure is common practice, but randomized, double-blind studies have not been conducted to examine the benefits or problems with this approach. The purpose of this study was to determine the effects of a low-sodium diet on clinical, echocardiographic, and neurohormonal parameters in dogs with heart failure. Dogs with stable chronic heart failure were fed exclusively a low-sodium (LS) and a moderate-sodium (MS) diet for 4 weeks each in a randomized, double-blind, crossover design. At days 0, 28, and 56, echocardiography and thoracic radiography were performed, and blood was analyzed for electrolytes and neurohormones. Fourteen dogs completed the study (9 with chronic valvular disease and 5 with dilated cardiomyopathy). Electrolyte abnormalities were common during the study, and serum sodium and chloride concentrations decreased significantly on the LS diet. Neurohormones did not change significantly between diet groups. Maximum left atrial (P = .05) and standard left atrial (P = .09) size decreased on the LS diet. For dogs with chronic valvular disease, vertebral heart score (P = .05), left ventricular internal dimension in diastole (P = .006) and systole (P = .02), standard left atrial dimension (P = .03), maximum left atrial dimension (P = .02), end-diastolic volume index (P = .02), and end-systolic volume index (P = .04) decreased significantly on the LS diet compared to the MS diet. Although analysis of these data suggests some benefits of a low-sodium diet, future studies with improved study design are needed to further evaluate the advantages and disadvantages of sodium restriction in dogs with heart failure.

  5. Dietary energy restriction reduces high-fat diet-enhanced metastasis of Lewis lung carcinoma in mice

    PubMed Central

    Sundaram, Sneha; Yan, Lin

    2016-01-01

    The objective of this study was to determine whether a reduction in energy intake ameliorated the high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma in mice. Male C57BL/6 mice were fed the AIN93G diet, a high-fat diet or a high-fat diet with a 5% restriction of the intake. Energy restriction reduced body adiposity and body weight, but maintained growth similar to mice fed the AIN93G diet. The high-fat diet significantly increased the number and size (cross-sectional area and volume) of metastases formed in lungs. Restricted feeding reduced the number of metastases by 23%, metastatic cross-sectional area by 32% and volume by 45% compared to the high-fat diet. The high-fat diet elevated plasma concentrations of proinflammatory cytokines (monocyte chemotactic protein-1, plasminogen activator inhibitor-1, leptin), angiogenic factors (vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1) and insulin. Restricted feeding significantly reduced the high-fat diet-induced elevations in plasma concentrations of proinflammatory cytokines, angiogenic factors and insulin. These results demonstrated that a reduction in diet intake by 5% reduced high-fat diet-enhanced metastasis, which may be associated with the mitigation of adiposity and down-regulation of cancer-promoting proinflammatory cytokines and angiogenic factors. PMID:27582541

  6. Body-mass, survival, and pairing consequences of winter-diet restriction in wood ducks

    USGS Publications Warehouse

    Demarest, D.W.; Kaminski, R.M.; Brennan, L.A.; Boyle, C.R.

    1997-01-01

    We conducted feeding experiments with captive, wild-strain wood ducks (Aix sponsa) during winters 1990-91 and 1991-92 to test effects of increasing levels of food restriction on body mass dynamics, mortality, and pair formation. Male and female wood ducks fed restricted diets (i.e., 5, 10, 15, or 20% less food [g] than consumed on the previous day by a control group fed ad libitum) weighed less (P ??? 0.037) than birds fed ad libitum; those on 15 and 20% restricted diets weighed least. Increased mortality and decreased pair formation occurred only within the 20% restricted group (P ??? 0.049). We concluded that food restriction ranging between 15 and 20% of ad libitum intake may signify a threshold above which survival and reproduction of captive wood ducks may be impaired. Because energy costs of free living are greater than in captivity, a lower threshold may exist for wild wood ducks. Research is needed to validate the threshold theory for free-ranging wood ducks and other waterfowl, and to evaluate its potential application for conservation of winter foraging habitat. Conservation of bottomland hardwood ecosystems, which provide important foraging habitat for migrating and wintering wood ducks, should be encouraged to prevent potential negative effects on wood duck life-cycle events.

  7. Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss?

    PubMed

    Varady, K A

    2011-07-01

    Dietary restriction is an effective strategy for weight loss in obese individuals. The most common form of dietary restriction implemented is daily calorie restriction (CR), which involves reducing energy by 15-60% of usual caloric intake every day. Another form of dietary restriction employed is intermittent CR, which involves 24 h of ad libitum food consumption alternated with 24 h of complete or partial food restriction. Although both diets are effective for weight loss, it remains unknown whether one of these interventions produces superior changes in body weight and body composition when compared to the other. Accordingly, this review examines the effects of daily CR versus intermittent CR on weight loss, fat mass loss and lean mass retention in overweight and obese adults. Results reveal similar weight loss and fat mass loss with 3 to 12 weeks' intermittent CR (4-8%, 11-16%, respectively) and daily CR (5-8%, 10-20%, respectively). In contrast, less fat free mass was lost in response to intermittent CR versus daily CR. These findings suggest that these diets are equally as effective in decreasing body weight and fat mass, although intermittent CR may be more effective for the retention of lean mass.

  8. Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss

    PubMed Central

    Nedeltcheva, A. V.; Imperial, J. G.; Penev, P. D.

    2012-01-01

    Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-hour blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean [SD] age 41 [5] y; BMI 27.4 [2.0] kg/m2) completed two 14-day treatments with hypocaloric diet and 8.5 or 5.5-h nighttime sleep opportunity in random order 7 [3] months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free-fatty acids (FFA), and 24-hour blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 [0.3] BMI units) during each treatment. Bedtime restriction reduced sleep by 131 [30] min/day. Recurrent sleep curtailment decreased 24-hour serum insulin concentrations (i.e. enhanced 24-hour insulin economy) without changes in oral glucose tolerance and 24-hour glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA which suppressed normally following glucose ingestion, and lower total and LDL cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-hour insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability. PMID:22513492

  9. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction

    PubMed Central

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2015-01-01

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent. PMID:25895126

  10. Physical and Cognitive Performance of the Least Shrew (Cryptotis parva) on a Calcium-Restricted Diet

    PubMed Central

    Czajka, Jessica L.; McCay, Timothy S.; Garneau, Danielle E.

    2012-01-01

    Geological substrates and air pollution affect the availability of calcium to mammals in many habitats, including the Adirondack Mountain Region (Adirondacks) of the United States. Mammalian insectivores, such as shrews, may be particularly restricted in environments with low calcium. We examined the consequences of calcium restriction on the least shrew (Cryptotis parva) in the laboratory. We maintained one group of shrews (5 F, 5 M) on a mealworm diet with a calcium concentration comparable to beetle larvae collected in the Adirondacks (1.1 ± 0.3 mg/g) and another group (5 F, 3 M) on a mealworm diet with a calcium concentration almost 20 times higher (19.5 ± 5.1 mg/g). Animals were given no access to mineral sources of calcium, such as snail shell or bone. We measured running speed and performance in a complex maze over 10 weeks. Shrews on the high-calcium diet made fewer errors in the maze than shrews on the low-calcium diet (F1,14 = 12.8, p < 0.01). Females made fewer errors than males (F1,14 = 10.6, p < 0.01). Running speeds did not markedly vary between diet groups or sexes, though there was a trend toward faster running by shrews on the high calcium diet (p = 0.087). Shrews in calcium-poor habitats with low availability of mineral sources of calcium may have greater difficulty with cognitive tasks such as navigation and recovery of food hoards. PMID:25379219

  11. Is it wise to restrict fat in the diets of children?

    PubMed

    Olson, R E

    2000-01-01

    The proponents of fat-restricted diets for children argue that low-fat diets given in childhood will prevent the development of atherosclerosis in adulthood, low-fat diets given a childhood will condition children to prefer low-fat diets in adulthood, and low-fat diets for children are safe. There is no evidence that low-fat diets in childhood will prevent atherosclerosis in adulthood. In fact, studies of migrating populations indicate that immigrants to the United States from Third World countries who consumed low-fat diets in childhood take on the character of their new environments, including higher serum cholesterol levels and more coronary disease. The prevalence of fatty streaks in childhood bears little relationship to the prevalence of atheromatous plaques in adulthood. In fact, girls have more aortic fatty streaks and higher serum cholesterol values in childhood than boys, but fewer plaques in adulthood and less coronary disease. From the PDAY study, it has also been learned that hypercholesterolemia in childhood enhances fatty streak formation, but not that of plaques. It now seems established from autopsy studies that the progression of atherosclerosis from fatty streaks to plaque is arrested in childhood and does not begin to a significant extent until after puberty in males and after menopause in females. So the oft-repeated statement that atherosclerosis begins in childhood is semantically true but very misleading. The particularly harmful form of atherosclerosis (the plaque) does not become significant until much beyond puberty. The effects of low-fat, low-cholesterol diets on serum lipids and lipoproteins are of a lesser magnitude in children than in adults. The 0.78 mmol/L decrease in LDL cholesterol in the intervention group from controls (change 1.5%) in the DISC study was biologically insignificant and reflects the tighter control of lipoprotein and cholesterol synthesis in children compared with adults. It must be remembered that the human body

  12. Feed restriction and a diet's caloric value: The influence on the aerobic and anaerobic capacity of rats

    PubMed Central

    2012-01-01

    Background The influence of feed restriction and different diet's caloric value on the aerobic and anaerobic capacity is unclear in the literature. Thus, the objectives of this study were to determine the possible influences of two diets with different caloric values and the influence of feed restriction on the aerobic (anaerobic threshold: AT) and anaerobic (time to exhaustion: Tlim) variables measured by a lactate minimum test (LM) in rats. Methods We used 40 adult Wistar rats. The animals were divided into four groups: ad libitum commercial Purina® diet (3028.0 Kcal/kg) (ALP), restricted commercial Purina® diet (RAP), ad libitum semi-purified AIN-93 diet (3802.7 Kcal/kg) (ALD) and restricted semi-purified AIN-93 diet (RAD). The animals performed LM at the end of the experiment, 48 h before euthanasia. Comparisons between groups were performed by analysis of variance (p < 0,05). Results At the end of the experiment, the weights of the rats in the groups with the restricted diets were significantly lower than those in the groups with ad libitum diet intakes. In addition, the ALD group had higher amounts of adipose tissue. With respect to energetic substrates, the groups subjected to diet restriction had significantly higher levels of liver and muscle glycogen. There were no differences between the groups with respect to AT; however, the ALD group had lower lactatemia at the AT intensity and higher Tlim than the other groups. Conclusions We conclude that dietary restriction induces changes in energetic substrates and that ad libitum intake of a semi-purified AIN-93 diet results in an increase in adipose tissue, likely reducing the density of the animals in water and favouring their performance during the swimming exercises. PMID:22448911

  13. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

    PubMed Central

    Seimon, Radhika V.; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A.; Nguyen, Amy D.; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F.; Lau, Jackie

    2016-01-01

    Background Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. Methods Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5–6 consecutive days, and ad libitum intake for 1–3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)–(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. Results Mice on the ID showed transient hyperphagia relative to controls during each 1–3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01). Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC) relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups. Conclusion Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces

  14. [Influence of protein-restricted diet on motor response fluctuations in Parkinson's disease].

    PubMed

    Hirata, H; Asanuma, M; Kondo, Y; Ogawa, N

    1992-09-01

    The clinical management of Parkinson's disease has been revolutionized by the introduction of levodopa therapy. It has significantly reduced disability and has extended life expectancies of patients with Parkinson's disease. However, motor response fluctuations frequently appear in patients after long-term treatment with levodopa. In this study, we investigated the effect of protein-restricted diet on fluctuations in eight patients with Parkinson's disease who had been receiving long-term levodopa treatment (mean 12.5 years). Two weeks of protein-restricted daytime diet (7.5 g total at breakfast and lunch) was followed by 12.5 g total at breakfast and lunch. At night, high-protein diet (40-50 g at dinner) was offered to the patients in order to maintain total daily protein intake at Japanese standard level. The medication schedule of levodopa and other antiparkinsonian drugs was not changed within 2 weeks after the study was began. Fluctuations were reduced in 7 of the 8 patients. But in only one patient (case 6), dyskinesia and general condition got worse and stopped this therapy. Body weight, serum protein and albumin levels did not change significantly for at least three month after the study was begun in every 6 patients who were examined. Homovanillic acid level of cerebrospinal fluid reduced in every 4 patients who were examined. We concluded that protein-restricted diet during the daytime offers a fascinating technique for the control of motor response fluctuations in patients with Parkinson's disease undergoing long-term levodopa treatment. But this therapy must be indicated carefully. Mechanism of this therapy may has something to do with improvement of dopamine metabolism in the brain.

  15. Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We studied the effects of weight loss induced by either a low-fat normal diet or restriction of high-fat diet on hepatic steatosis, inflammation in the liver and adipose tissue, and blood monocytes of obese mice. In mice with high-fat diet-induced obesity, weight loss was achieved by switching from ...

  16. What are the roles of calorie restriction and diet quality in promoting healthy longevity?

    PubMed

    Rizza, Wanda; Veronese, Nicola; Fontana, Luigi

    2014-01-01

    Epidemiological and experimental data indicate that diet plays a central role in the pathogenesis of many age-associated chronic diseases, and in the biology of aging itself. Data from several animal studies suggest that the degree and time of calorie restriction (CR) onset, the timing of food intake as well as diet composition, play major roles in promoting health and longevity, breaking the old dogma that only calorie intake is important in extending healthy lifespan. Data from human studies indicate that long-term CR with adequate intake of nutrients results in several metabolic adaptations that reduce the risk of developing type 2 diabetes, hypertension, cardiovascular disease and cancer. Moreover, CR opposes the expected age-associated alterations in myocardial stiffness, autonomic function, and gene expression in the human skeletal muscle. However, it is possible that some of the beneficial effects on metabolic health are not entirely due to CR, but to the high quality diets consumed by the CR practitioners, as suggested by data collected in individuals consuming strict vegan diets. More studies are needed to understand the interactions among single nutrient modifications (e.g. protein/aminoacid, fatty acids, vitamins, phytochemicals, and minerals), the degree of CR and the frequency of food consumption in modulating anti-aging metabolic and molecular pathways, and in the prevention of age-associated diseases.

  17. Acute effects of different diet compositions on skeletal muscle insulin signalling in obese individuals during caloric restriction

    PubMed Central

    Wang, Cecilia C.L.; Adochio, Rebecca L.; Leitner, J. Wayne; Abeyta, Ian M.; Draznin, Boris; Cornier, Marc-Andre

    2012-01-01

    Objective The cellular effects of restricting fat versus carbohydrate during a low-calorie diet are unclear. The aim of this study was to examine acute effects of energy and macronutrient restriction on skeletal muscle insulin signalling in obesity. Materials/Methods Eighteen obese individuals without diabetes underwent euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after: (a) 5 days of eucaloric diet (30% fat, 50% carbohydrate), and (b) 5 days of a 30% calorie-restricted diet, either low fat/high carbohydrate (LF/HC: 20% fat, 60% carbohydrate) or high-fat/low carbohydrate (HF/LC: 50% fat, 30% carbohydrate). Results Weight, body composition, and insulin sensitivity were similar between groups after eucaloric diet. Weight loss was similar between groups after hypocaloric diet, 1.3 ± 1.3 kg (p<0.0001 compared with eucaloric). Whole-body insulin sensitivity was unchanged after calorie restriction and similar between groups. However, ex vivo skeletal muscle insulin signalling differed depending on macronutrient composition of calorie-restricted diet. Skeletal muscle of the LF/HC group had increased insulin-stimulated tyrosine phosphorylation of IRS-1, decreased insulin-stimulated Ser 307 phosphorylation of IRS-1, and increased IRS-1-associated phosphatidylinositol (PI)3-kinase activity. Conversely, insulin stimulation of tyrosine phosphorylated IRS-1 was absent and serine 307 phosphorylation of IRS-1 was increased on HF/LC, with blunting of IRS-1-associated PI3-kinase activity. Conclusion Acute caloric restriction with a LF/HC diet alters skeletal muscle insulin signalling in a way that improves insulin sensitivity, while acute caloric restriction with a HF/LC diet induces changes compatible with insulin resistance. In both cases, ex vivo changes in skeletal muscle insulin signalling appear prior to changes in whole body insulin sensitivity. PMID:23174405

  18. Time-restricted feeding of a high-fat diet reduces adiposity and inflammatory cytokine production in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disruption of the circadian rhythms contributes to obesity. Restricting feeding to particular times of the day may reset the circadian rhythms and reduce obesity and resulting complications. The present study investigated the effects of time-restricted feeding (TRF) of a high-fat diet on adiposity...

  19. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy.

    PubMed

    McCarty, Mark F; Barroso-Aranda, Jorge; Contreras, Francisco

    2009-02-01

    Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.

  20. Endocrine pancreas development: effects of metabolic and intergenerational programming caused by a protein-restricted diet.

    PubMed

    Frantz, Eliete Dalla Corte; Peixoto-Silva, Nayara; Pinheiro-Mulder, Alessandra

    2012-01-01

    Experimental studies have demonstrated an association between low birth weight and the later development of type 2 diabetes. This association could be a result of the programming process that affects pancreatic beta-cell development due to poor fetal nutrition. This mechanism may not be limited to the first generation. In rodents, endocrine cells of the pancreas are derived from cells of the endodermal dorsal and ventral anlage that migrate and gather in clusters in a process termed isletogenesis. Islet development occurs relatively late in gestation, and islets undergo substantial remodeling immediately after birth under the regulation of a transcription factor network. Furthermore, the offspring of mice fed a protein-restricted diet exhibit a reduced pancreatic beta-cell mass at birth, lower vascularization, increased apoptosis rate, and changes in glucose metabolism in later life. Although the mechanisms underlying these relationships are unclear, it has been hypothesized that in utero nutritional conditions affect epigenetic patterns of gene transcription that persist throughout life and subsequent generations. We aimed to review the process of the formation of the endocrine pancreas in rodents, the consequences of a protein-restricted diet on offspring, and the transgenerational effects of this insult on the incidence of type 2 diabetes.

  1. DNA Methylation Pattern in Overweight Women under an Energy-Restricted Diet Supplemented with Fish Oil

    PubMed Central

    do Amaral, Cátia Lira; Milagro, Fermín I.; Curi, Rui; Martínez, J. Alfredo

    2014-01-01

    Dietary factors modulate gene expression and are able to alter epigenetic signatures in peripheral blood mononuclear cells (PBMC). However, there are limited studies about the effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) on the epigenetic mechanisms that regulate gene expression. This research investigates the effects of n-3-rich fish oil supplementation on DNA methylation profile of several genes whose expression has been reported to be downregulated by n-3 PUFA in PBMC: CD36, FFAR3, CD14, PDK4, and FADS1. Young overweight women were supplemented with fish oil or control in a randomized 8-week intervention trial following a balanced diet with 30% energy restriction. Fatty acid receptor CD36 decreased DNA methylation at CpG +477 due to energy restriction. Hypocaloric diet-induced weight loss also reduced the methylation percentages of CpG sites located in CD14, PDK4, and FADS1. The methylation patterns of these genes were only slightly affected by the fish oil supplementation, being the most relevant to the attenuation of the weight loss-induced decrease in CD36 methylation after adjusting by baseline body weight. These results suggest that the n-3 PUFA-induced changes in the expression of these genes in PBMC are not mediated by DNA methylation, although other epigenetic mechanisms cannot be discarded. PMID:24579084

  2. DNA methylation pattern in overweight women under an energy-restricted diet supplemented with fish oil.

    PubMed

    do Amaral, Cátia Lira; Milagro, Fermín I; Curi, Rui; Martínez, J Alfredo

    2014-01-01

    Dietary factors modulate gene expression and are able to alter epigenetic signatures in peripheral blood mononuclear cells (PBMC). However, there are limited studies about the effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) on the epigenetic mechanisms that regulate gene expression. This research investigates the effects of n-3-rich fish oil supplementation on DNA methylation profile of several genes whose expression has been reported to be downregulated by n-3 PUFA in PBMC: CD36, FFAR3, CD14, PDK4, and FADS1. Young overweight women were supplemented with fish oil or control in a randomized 8-week intervention trial following a balanced diet with 30% energy restriction. Fatty acid receptor CD36 decreased DNA methylation at CpG +477 due to energy restriction. Hypocaloric diet-induced weight loss also reduced the methylation percentages of CpG sites located in CD14, PDK4, and FADS1. The methylation patterns of these genes were only slightly affected by the fish oil supplementation, being the most relevant to the attenuation of the weight loss-induced decrease in CD36 methylation after adjusting by baseline body weight. These results suggest that the n-3 PUFA-induced changes in the expression of these genes in PBMC are not mediated by DNA methylation, although other epigenetic mechanisms cannot be discarded.

  3. Protein- and tryptophan-restricted diets induce changes in rat gonadal hormone levels.

    PubMed

    Del Angel-Meza, A R.; Feria-Velasco, A; Ontiveros-Martínez, L; Gallardo, L; Gonzalez-Burgos, I; Beas-Zárate, C

    2001-04-01

    The release of gonadotrophic hormones starts at puberty and, along with the subsequent estral cyclicity, is subject to hormonal feedback systems and to the action of diverse neuroactive substances such as gamma amino butyric acid and catecholamines. This study shows the effect of the administration during 40 days of protein-restricted and corn-based (tryptophan- and lysine-deficient) diets on the serotonin concentration in medial hypothalamic fragments as well as in follicle-stimulating luteinizing hormones, 17-beta-estradiol and progesterone serum levels, and estral cyclicity in 60- and 100-day-old rats (young, mature, and in gestation). In young rats, a delay in vaginal aperture development, and a lengthening of the estral cycle to a continuous anestral state was observed, mainly in the group fed corn. This group showed a 25% decrease in the serotonin concentration compared with the protein-restricted group, which exhibited an increase of 9% over the control group. Luteinizing hormone levels decreased in 16% and 13%, whereas follicle-stimulating hormone increased in 13% and 5% in the young animals of restricted groups, respectively, compared with the control group. Serum progesterone levels decreased only in young restricted versus control animals, and no differences were seen among adult and gestational rats. Serum levels of 17-beta-estradiol in restricted animals showed different concentration patterns, mainly in the corn group, which was higher at the 20th gestational day, falling drastically postpartum. The results obtained in this study show serotonin to be a very important factor in the release of gonadotrophic hormones and the start of puberty.

  4. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats

    PubMed Central

    Margolis, Lee M.; Rivas, Donato A.; Ezzyat, Yassine; Gaffney-Stomberg, Erin; Young, Andrew J.; McClung, James P.; Fielding, Roger A.; Pasiakos, Stefan M.

    2016-01-01

    The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g−1 lower (p < 0.05) in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN), stearoyl-CoA destaurase-1 (SCD1) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05), respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05) in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR—specifically reduction in intrahepatic triglyceride content—may be enhanced by consuming a higher-protein/lower-carbohydrate diet. PMID:27649241

  5. Components of an Anticancer Diet: Dietary Recommendations, Restrictions and Supplements of the Bill Henderson Protocol

    PubMed Central

    Mannion, Cynthia; Page, Stacey; Bell, Laurie Heilman; Verhoef, Marja

    2010-01-01

    The use of complementary and alternative medicines including dietary supplements, herbals and special diets to prevent or treat disease continues to be popular. The following paper provides a description of an alternative dietary approach to the self-management and treatment of cancer, the Bill Henderson Protocol (BHP). This diet encourages daily intake of raw foods, a combination of cottage cheese and flaxseed oil and a number of supplements. Some foods and food groups are restricted (e.g., gluten, meat, dairy). Early background theory that contributed to the protocol’s development is presented as is a summary of relevant evidence concerning the anti-cancer fighting properties of the individual components. Supplement intake is considered in relation to daily recommended intakes. Challenges and risks to protocol adherence are discussed. As with many complementary and alternative interventions, clear evidence of this dietary protocol’s safety and efficacy is lacking. Consumers of this protocol may require guidance on the ability of this protocol to meet their individual nutritional needs. PMID:22254073

  6. Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment.

    PubMed

    Slocum, Nikki; Durrant, Jessica R; Bailey, David; Yoon, Lawrence; Jordan, Holly; Barton, Joanna; Brown, Roger H; Clifton, Lisa; Milliken, Tula; Harrington, Wallace; Kimbrough, Carie; Faber, Catherine A; Cariello, Neal; Elangbam, Chandikumar S

    2013-07-01

    Drug-induced weight loss in humans has been associated with undesirable side effects not present in weight loss from lifestyle interventions (caloric restriction or exercise). To investigate the mechanistic differences of weight loss by drug-induced and lifestyle interventions, we examined the gene expression (mRNA) in brown adipose tissue (BAT) and conducted histopathologic assessments in diet-induced obese (DIO) mice given ephedrine (18 mg/kg/day orally), treadmill exercise (10 m/min, 1-h/day), and dietary restriction (DR: 26% dietary restriction) for 7 days. Exercise and DR mice lost more body weight than controls and both ephedrine and exercise reduced percent body fat. All treatments reduced BAT and liver lipid accumulation (i.e., cytoplasmic lipids in brown adipocytes and hepatocytes) and increased oxygen consumption (VO2 ml/kg/h) compared with controls. Mitochondrial biogenesis/function-related genes (TFAM, NRF1 and GABPA) were up-regulated in the BAT of all groups. UCP-1 was up-regulated in exercise and ephedrine groups, whereas MFSD2A was up-regulated in ephedrine and DR groups. PGC-1α up-regulation was observed in exercise and DR groups but not in ephedrine group. In all experimental groups, except for ephedrine, fatty acid transport and metabolism genes were up-regulated, but the magnitude of change was higher in the DR group. PRKAA1 was up-regulated in all groups but not significantly in the ephedrine group. ADRß3 was slightly up-regulated in the DR group only, whereas ESRRA remained unchanged in all groups. Although our data suggest a common pathway of BAT activation elicited by ephedrine treatment, exercise or DR, mRNA changes were indicative of additional nutrient-sensing pathways in exercise and DR.

  7. Anti-apoptotic and Pro-survival Effects of Food Restriction on High-Fat Diet-Induced Obese Hearts.

    PubMed

    Lin, Yi-Yuan; Hsieh, Po-Shiuan; Cheng, Yu-Jung; Cheng, Shiu-Min; Chen, Chiao-Nan Joyce; Huang, Chih-Yang; Kuo, Chia-Hua; Kao, Chung-Lan; Shyu, Woei-Cherng; Lee, Shin-Da

    2017-04-01

    Food restriction and weight loss are known to prevent obesity-related heart diseases. This study investigates whether food restriction elicits anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats which were fed with regular chow diet (CON, 13.5 % fat), a high-fat ad libitum diet (HFa, 45 % fat), or a high-fat food-restricted diet (HFr, 45 % fat, maintaining the same weight as CON) for 12 weeks. Body weight, blood pressure, heart weight, triglycerides, insulin, HOMAIR, interstitial spaces, cardiac fibrosis, and cardiac TUNEL-positive apoptotic cells were increased in HFa relative to CON, whereas these parameters were decreased in HFr relative to HFa. The protein levels of cardiac Fas ligand, Fas receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid/Bid, Bax/Bcl-2, Bad/p-Bad, Cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) in HFr were lower than those in HFa. Moreover, the Bcl-xL and IGF-1-related components of IGF-1, p-PI3 K/PI3 K, p-Akt/Akt in HFr were higher than those in HFa. Our findings suggest that a restricted high-fat diet for maintaining weight control could diminish cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways as well as might enhance IGF-1-related pro-survival pathways. In sum, food restriction for maintaining normal weight could elicit anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts.

  8. Improvement in metabolic parameters in obese subjects after 16 weeks on a Brazilian-staple calorie-restricted diet

    PubMed Central

    Reis, Caio E. G.; da Silva, Fábio V. P.; Casulari, Luiz A.

    2014-01-01

    BACKGROUND/OBJECTIVES The standard pattern of Brazilian food consumption is based on the combination of rice and beans served together in the main meals. This study assessed the effects of Brazilian-staple calorie-restricted (BS-diet) dietary advice, with brown rice and beans, on metabolic parameters, body composition, and food intake in overweight/obese subjects. SUBJECTS/METHODS Twentyseven subjects were randomly assigned to a conventional-type calorie-restricted diet (CT-diet) (n = 13) or a BS-diet (n = 14). Glucose metabolism, lipid profile, anthropometric and body composition parameters, and food intake were measured before and after 16 weeks. Paired t-tests/Wilcoxon tests were used for comparison of differences from baseline and unpaired t-tests/Mann-Whitney tests were used for comparison of differences between the groups. RESULTS After 16 weeks, both groups showed reductions in weight and waist circumference (P < 0.02), and the BS-diet group showed a decrease in body fat (P = 0.0001), and significant improvement in glucose metabolism (fasting plasma glucose, glucose and insulin areas under the curve, Cederholm index, and HOMA2-%β) (P ≤ 0.04) and lipid profile (cholesterol, triacylglycerol, LDL-c, VLDL-c, and cholesterol/HDL-c ratio) (P ≤ 0.05). In addition, the BS-diet group showed significant improvement in HOMA2-%β, compared to the CT-diet group (P = 0.03). The BS-diet group also showed a significant reduction in energy, lipids, carbohydrate, and cholesterol intake (P ≤ 0.04) and an increase in fiber intake (P ≤ 0.001), while the CT-diet group showed a significant reduction in intake of energy, macronutrients, PUFA, and cholesterol (P ≤ 0.002). CONCLUSIONS These results demonstrate the benefits of the BS-diet on metabolic parameters in obese subjects. PMID:25110561

  9. Long–Term Effects of Energy-Restricted Diets Differing in Glycemic Load on Metabolic Adaptation and Body Composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A randomized controlled trial of high glycemic load (HG) and low glycemic load (LG) diets with food provided for 6 months and self-administered for 6 additional months at 30% caloric restriction (CR) was performed in 29 overweight adults (mean+/-SD, age 35+/-5y; BMI 27.5+/-1.5 kg/m2). Total energy e...

  10. The Ketogenic Diet and Potassium Channel Function

    DTIC Science & Technology

    2015-11-01

    experimental differences between the excitability results obtained when ketones are administered acutely in vitro and when they are generated in vivo under...would like to determine to what extent this experimental approach emulates the conditions in vivo. 6. Publications, Abstracts and Presentations

  11. [National consensus on the ketogenic diet].

    PubMed

    Armeno, Marisa; Caraballo, Roberto; Vaccarezza, María; Alberti, M Julia; Ríos, Viviana; Galicchio, Santiago; de Grandis, Elizabeth S; Mestre, Graciela; Escobal, Nidia; Matarrese, Pablo; Viollaz, Rocío; Agostinho, Ariela; Díez, Cecilia; Cresta, Araceli; Cabrera, Analía; Blanco, Virginia; Ferrero, Hilario; Gambarini, Victoria; Sosa, Patricia; Bouquet, Cecilia; Caramuta, Luciana; Guisande, Silvina; Gamboni, Beatriz; Hassan, Amal; Pesce, Laura; Argumedo, Laura; Dlugoszewski, Corina; DeMartini, Martha G; Panico, Luis

    2014-09-01

    Introduccion. La epilepsia es una enfermedad cronica que afecta al 0,5-1% de la poblacion, mayormente de inicio durante la infancia. Un tercio de los pacientes evoluciona hacia una forma refractaria al tratamiento con farmacos antiepilepticos, lo que plantea al equipo de salud un desafio terapeutico. La dieta cetogenica (DC) es un tratamiento no farmacologico efectivo utilizado como un metodo alternativo para el tratamiento de la epilepsia refractaria. Objetivos. Es necesario establecer directrices para utilizar la DC adecuadamente y asi expandir su conocimiento y utilizacion en paises hispanoparlantes. El Comite Nacional de Dieta Cetogenica, dependiente de la Sociedad Argentina de Neurologia Infantil, elaboro este consenso para estandarizar el uso de la DC basandose en la bibliografia publicada y la experiencia clinica. El grupo esta formado por neuropediatras, medicos nutricionistas y licenciadas en nutricion de cinco provincias de Argentina pertenecientes a 10 centros que aplican la DC como tratamiento de la epilepsia refractaria. Desarrollo. Se exponen temas tales como la seleccion del paciente, el asesoramiento a la familia antes del tratamiento, las interacciones de la DC con la medicacion anticonvulsionante, los suplementos, el control de efectos adversos y la retirada de dicha dieta. Conclusiones. La DC es un tratamiento util para los pacientes pediatricos con epilepsia intratable. Es fundamental la educacion y colaboracion del paciente y la familia. El tratamiento debe llevarlo a cabo un equipo interdisciplinar experimentado, siguiendo un protocolo. La formacion de un grupo nacional interdisciplinar, y la publicacion de este consenso, ofrece la posibilidad de orientar a nuevos centros en su implantacion.

  12. Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves metabolic health.

    PubMed

    Duivenvoorde, Loes P M; van Schothorst, Evert M; Bunschoten, Annelies; Keijer, Jaap

    2011-08-01

    High energy intake and, specifically, high dietary fat intake challenge the mammalian metabolism and correlate with many metabolic disorders such as obesity and diabetes. However, dietary restriction (DR) is known to prevent the development of metabolic disorders. The current western diets are highly enriched in fat, and it is as yet unclear whether DR on a certain high-fat (HF) diet elicits similar beneficial effects on health. In this research, we report that HF-DR improves metabolic health of mice compared with mice receiving the same diet on an ad libitum basis (HF-AL). Already after five weeks of restriction, the serum levels of cholesterol and leptin were significantly decreased in HF-DR mice, whereas their glucose sensitivity and serum adiponectin levels were increased. The body weight and measured serum parameters remained stable in the following 7 weeks of restriction, implying metabolic adaptation. To understand the molecular events associated with this adaptation, we analyzed gene expression in white adipose tissue (WAT) with whole genome microarrays. HF-DR strongly influenced gene expression in WAT; in total, 8643 genes were differentially expressed between both groups of mice, with a major role for genes involved in lipid metabolism and mitochondrial functioning. This was confirmed by quantitative real-time reverse transcription-PCR and substantiated by increase in mitochondrial density in WAT of HF-DR mice. These results provide new insights in the metabolic flexibility of dietary restricted animals and suggest the development of substrate efficiency.

  13. FGF21 is an endocrine signal of protein restriction.

    PubMed

    Laeger, Thomas; Henagan, Tara M; Albarado, Diana C; Redman, Leanne M; Bray, George A; Noland, Robert C; Münzberg, Heike; Hutson, Susan M; Gettys, Thomas W; Schwartz, Michael W; Morrison, Christopher D

    2014-09-01

    Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the liver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lacking the eIF2α kinase general control nonderepressible 2 (GCN2). Finally, while protein restriction altered food intake, energy expenditure, and body weight gain in WT mice, FGF21-deficient animals did not exhibit these changes in response to a LP diet. These and other data demonstrate that reduced protein intake underlies the increase in circulating FGF21 in response to starvation and a ketogenic diet and that FGF21 is required for behavioral and metabolic responses to protein restriction. FGF21 therefore represents an endocrine signal of protein restriction, which acts to coordinate metabolism and growth during periods of reduced protein intake.

  14. Failure of lactose-restricted diets to prevent radiation-induced diarrhea in patients undergoing whole pelvis irradiation

    SciTech Connect

    Stryker, J.A.; Bartholomew, M.

    1986-05-01

    Sixty-four patients were randomized prior to pelvic radiotherapy into one of three dietary groups: the control group maintained a regular diet except that they drank at least 480 cc of milk daily; the lactose-restricted group was placed on a lactose-restricted diet; and the lactase group drank at least 480 cc of milk with lactase enzyme added to hydrolyze 90% of the lactose. The patients kept records of their stool frequency and the number of diphenoxylate tablets required to control their diarrhea during a 5 week course of standard whole pelvis irradiation. The data does not support the concept that one of the mechanisms of radiation-induced diarrhea associated with pelvic irradiation is a reduction the ability of the intestine to hydrolyze ingested lactose due to the effect of the radiation on the small intestine. There was not a significant difference in stool frequency or diphenoxylate usage among the dietary groups.

  15. High fat diet and food restriction differentially modify the behavioral effects of quinpirole and raclopride in rats.

    PubMed

    Baladi, Michelle G; France, Charles P

    2009-05-21

    Nutritional status can impact dopamine systems in a manner that might be important to understanding possible common neurobiological mechanisms that mediate abnormal compulsive food (e.g., obesity) and drug taking. Limiting food intake, for example, can increase sensitivity to the behavioral effects of indirect-acting dopamine receptor agonists. Much less is known regarding possible diet-induced changes in sensitivity to direct-acting dopamine receptor drugs. The present study investigated the effects of a high fat diet and of food restriction on sensitivity of rats to the behavioral effects of a direct-acting dopamine receptor agonist and a dopamine receptor antagonist. Free access to high fat chow increased sensitivity to quinpirole-induced yawning without changing sensitivity to raclopride-induced catalepsy or quinpirole-induced hypothermia. Food restriction (10 g/day) decreased sensitivity to quinpirole-induced yawning and raclopride-induced catalepsy without affecting sensitivity to quinpirole-induced hypothermia. Free access to a standard chow restored sensitivity to the behavioral effects of both drugs in rats that were previously food-restricted but not in rats that previously ate a high fat diet. These data confirm that food restriction can decrease sensitivity to behavioral effects of direct-acting dopamine receptor drugs, they provide evidence (i.e., no change in hypothermic effects) indicating that these changes are not due to pharmacokinetic mechanisms, and they provide initial evidence showing enhanced sensitivity to behavioral effects of dopamine receptor drugs in rats eating a high fat diet. These changes in sensitivity of dopamine systems could be relevant to understanding the impact of nutrition on therapeutic and recreational drug use.

  16. Effect of exercise and caloric restriction on DMBA induced mammary tumorigenesis and plasma lipids in rats fed high fat diets

    SciTech Connect

    Magrane, D. )

    1991-03-15

    Female Sprague-Dawley rats were given a single 10 mg dose of 7, 12-Dimethylbenz(a)anthracene (DMBA) and grouped as follows: (1) low fat-sedentary (LF-SED), (2) low fat-exercised (LF-EX), (3) high fat-sedentary (HF-SED), (4) high fat-exercised (HF-EX), (5) high fat-caloric restricted (HF-RES). Diets were isocaloric and contained 3.9% (LF) and 19.4% (HF) of corn oil. Group 5 was fed a 25% caloric restricted diet but with 24.6% fat content to equalize fat intake to HF-SED. After 12 weeks of diet or treadmill exercise, tumor data and plasma lipid profiles were determined. Results show that rats on HF-EX had more total tumors, % of tumors and tumors per tumor bearing rat than rats on HF-SED. The effect of exercise was also evident in LF-EX rats, when compared to LF-SED. Average tumor size and tumor volumes were not affected. The HF-RES group showed reduced tumor profiles compared to HF-SED. HDL, LDL, triglycerides and total cholesterol were unaffected by HF or LF diets or exercise. These data suggest that tumorigenesis is increased by moderate and constant exercise.

  17. Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

    PubMed

    Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

    2014-01-01

    Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

  18. Calcium homeostasis and bone metabolic responses to protein diets and energy restriction: a randomized control trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite some beneficial effects on bone, high protein diets are conventionally considered a primary dietary risk factor for osteoporosis and bone fracture due to the acid load associated with protein catabolism. To test the hypothesis that high dietary protein diets do not negatively affect calcium ...

  19. Effects of dry matter intake restriction on diet digestion, energy partitioning, phosphorus retention, and ruminal fermentation by beef steers.

    PubMed

    Clark, J H; Olson, K C; Schmidt, T B; Linville, M L; Alkire, D O; Meyer, D L; Rentfrow, G K; Carr, C C; Berg, E P

    2007-12-01

    Two experiments were conducted to determine the effects of DMI restriction on diet digestion, ruminal fermentation, ME intake, and P retention by beef steers. In Exp. 1, twelve Angus x steers (average initial BW = 450 +/- 18 kg) were assigned randomly to 1 of 3 diets that were formulated to promote a 1.6-kg ADG at intake levels corresponding approximately to 100% (ad libitum, AL), 90% (IR90), or 80% (IR80) of ad libitum DMI. In Exp. 2, twelve crossbred steers (average initial BW = 445 +/- 56 kg) fitted with ruminal cannulae were randomly assigned to 1 of 2 diets that were formulated to promote a 1.6-kg ADG at AL or IR80. All diets delivered similar total NE, MP, Ca, and P per day. During both experiments, fecal DM output by IR80 was less (P /= 0.20) among treatments during both experiments, whereas P retention was similar (P >/= 0.46) among treatments during Exp. 1. Total VFA and the molar proportion of acetate of AL were greater (P restricting DMI while holding NE, ruminally degradable protein, and MP intakes constant decreased fecal DM output and changed ruminal fermentation patterns in finishing steers. Improvements in performance associated with programmed-feeding regimens of the type studied here do not appear to be related to changes in diet digestion or ME intake.

  20. Energy-restricted diet benefits body composition but degrades bone integrity in middle-aged obese female rats.

    PubMed

    Shen, Chwan-Li; Zhu, Wenbin; Gao, Weimin; Wang, Shu; Chen, Lixia; Chyu, Ming-Chien

    2013-08-01

    This study investigates the effects of a restricted diet (RD) on body composition and musculoskeletal health along with endocrines and molecular mechanism in established mature obese rats. Twenty female rats were fed with a high-fat diet (HFD) ad libitum for 4 months and then assigned to either HFD or RD group for another 4 months. Another 10 rats were on a low-fat diet for 8 months. Outcome measures included body composition, bone mineral density, microarchitecrure, and strength; serum leptin, adiponectin, insulin-like growth factor I, and liver glutathione peroxidase activity; and protein expression and spleen tumor necrosis factor α messenger RNA expression. We hypothesized that mature obese rats on a 35% energy restriction diet for 4 months would improve body composition but degrade microstructural and mechanical properties of long bones, and such changes in musculoskeletal integrity are related to the modulation of obesity-related endocrines and proinflammation. Relative to HFD, RD benefited body composition (decreased body weight and %fat mass and increased %fat-free mass); decreased insulin-like growth factor I and leptin; elevated adiponectin, glutathione peroxidase activity and protein expression and tumor necrosis factor α messenger RNA expression; and suppressed bone formation and increased bone resorption, resulting in decreased trabecular and cortical bone volume, bone mineral density, and bone strength. Relative to low-fat diet, RD had a similar effect on body composition and serum markers but increased bone turnover rate and decreased bone mineral density and strength. Our data suggest that long-term RD has a negative impact on bone remodeling in obese female rats, probably through modification of endocrines and elevation of proinflammation.

  1. Long–Term Effects of High-and Low-Glycemic Load Energy-Restricted Diets on Metabolic Adaptation and the Composition of Weight Loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of high glycemic load (HG) and low glycemic load (LG) diets on resting metabolic rate (RMR) and body composition changes in response to caloric restriction (CR) remains controversial. Objective To examine the effects of two CR diets differing primarily in glycemic load on RMR and the % o...

  2. Restricted feeding of a high-fat diet reduces spontaneous metastases of Lewis lung carcinoma in C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a risk factor for cancer. We previously reported that consumption of a high-fat diet enhances metastasis in mice (Yan, Clin Exp Metastasis 2010). The present study investigated the effects of restricted feeding of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma (LLC) i...

  3. Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.

    PubMed

    Vermeij, W P; Dollé, M E T; Reiling, E; Jaarsma, D; Payan-Gomez, C; Bombardieri, C R; Wu, H; Roks, A J M; Botter, S M; van der Eerden, B C; Youssef, S A; Kuiper, R V; Nagarajah, B; van Oostrom, C T; Brandt, R M C; Barnhoorn, S; Imholz, S; Pennings, J L A; de Bruin, A; Gyenis, Á; Pothof, J; Vijg, J; van Steeg, H; Hoeijmakers, J H J

    2016-09-15

    Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1(∆/-)) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg(-/-) (also known as Ercc5(-/-)) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1(∆/-) mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1(∆/-) mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of γH2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1(∆/-) mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general.

  4. Patient Survival and Costs on Moderately Restricted Low-Protein Diets in Advanced CKD: Equivalent Survival at Lower Costs?

    PubMed Central

    Piccoli, Giorgina Barbara; Nazha, Marta; Capizzi, Irene; Vigotti, Federica Neve; Mongilardi, Elena; Bilocati, Marilisa; Avagnina, Paolo; Versino, Elisabetta

    2016-01-01

    The indications for delaying the start of dialysis have revived interest in low-protein diets (LPDs). In this observational prospective study, we enrolled all patients with chronic kidney disease (CKD) who followed a moderately restricted LPD in 2007–2015 in a nephrology unit in Italy: 449 patients, 847 years of observation. At the start of the diet, the median glomerular filtration rate (GFR) was 20 mL/min, the median age was 70, the median Charlson Index was 7. Standardized mortality rates for the “on-diet” population were significantly lower than for patients on dialysis (United States Renal Data System (USRDS): 0.44 (0.36–0.54); Italian Dialysis Registry: 0.73 (0.59–0.88); French Dialysis Registry 0.70 (0.57–0.85)). Considering only the follow-up at low GFR (≤15 mL/min), survival remained significantly higher than in the USRDS, and was equivalent to the Italian and French registries, with an advantage in younger patients. Below the e-GFR of 15 mL/min, 50% of the patients reached a dialysis-free follow-up of ≥2 years; 25% have been dialysis-free for five years. Considering an average yearly cost of about 50,000 Euros for dialysis and 1200 Euros for the diet, and different hypotheses of “spared” dialysis years, treating 100 patients on a moderately restricted LPD would allow saving one to four million Euros. Therefore, our study suggests that in patients with advanced CKD, moderately restricted LPDs may allow prolonging dialysis-free follow-up with comparable survival to dialysis at a lower cost. PMID:27898000

  5. Age-related changes in meat tenderness and tissue pentosidine: effect of diet restriction and aminoguanidine in broiler breeder hens.

    PubMed

    Iqbal, M; Kenney, P B; Klandorf, H

    1999-09-01

    The nonenzymatic glycosylation of tissue protein contributes to the formation of crosslinks that leads to structural and functional deterioration in the long-lived tissue protein, collagen. The accumulation of these crosslinks thus contributes to the objectionable toughness of meat from aged animals, decreases its economic value, and limits its use in whole muscle foods. The objectives of this study were to determine the effectiveness of diet restriction and the crosslinking inhibitor, aminoguanidine (AG), on reducing the accumulation of crosslinks, thereby improving meat tenderness in broiler breeder hens. The glycoxidation product, pentosidine, was also measured in skin (Ps) to determine whether changes in its concentrations correlated with the changes in shear value (SV). Chicks (n = 450) were randomly assigned to four treatment groups from 8 to 125 wk after hatch: ad libitum (AL), diet restricted (DR), AL and DR groups supplemented with 400 ppm AG each (AL+AG and DR+AG, respectively). Shear value was measured with an Instron Universal Mechanical Machine. Skin pentosidine was isolated by reverse phase HPLC. There was an age-related, linear increase in SV (P<0.0001, r = 0.96), which correlated (r = 0.86) with the age-related increase in Ps in AL hens. Diet restriction retarded SV (P<0.0001) over the sampling period. In general, SV values for AL+AG were similar to those measured in DR, whereas no additive effect was observed for AG in DR birds. It was concluded that there was a linear increase in meat toughness (SV) with age that correlates with the accumulation of Ps, and that the decline in meat tenderness can be retarded by DR or AG. Secondly, the effect of DR on accumulation of Ps was so pronounced that AG supplementation did not further enhance this effect.

  6. Relationship between mechanical properties and pentosidine in tendon: effects of age, diet restriction, and aminoguanidine in broiler breeder hens.

    PubMed

    Iqbal, M; Kenney, P B; Al-Humadi, N H; Klandorf, H

    2000-09-01

    Nonenzymatic glycosylation contributes to the formation of crosslinks, which leads to the structural and functional deterioration of tissue protein. The accumulation of these crosslinks in tissue proteins has been implicated in the alteration of biomechanical properties of connective tissues. The objective of this study was to determine whether tendon breaking time (TBT) and tendon breaking strength (TBS) of the flexor perforans et perforatus digiti iii tendon were related to concentrations of pentosidine in tendons (Pt) of broiler breeder hens from 8 to 125 wk of age. In addition, effects of diet restriction (DR) and a crosslinking inhibitor, aminoguanidine (AG) on Pt, TBS, and TBT were determined. Female chicks (n = 450) were randomly assigned to four treatment groups immediately after hatch: ad libitum-fed (AL); diet-restricted (DR; 60% of AL); and AL and DR groups supplemented with 1.35 mg/kg BW per day AG in the feed (AL+AG and DR+AG, respectively). In AL hens, Pt increased with increasing age (P < or = 0.0001). Concurrently, an age-related parallel increase was found for TBS (P < or = 0.0001) and TBT (P < or = 0.0001). Rate of Pt accumulation was lower in DR (P < or = 0.001), TBS (P < or = 0.01), and TBT (P < or = 0.02) hens compared with AL hens. Concentration of Pt in the AL + AG group was lower (P < or = 0.0002) than in the AL group; TBS and TBT (P < or = 0.01) followed a similar pattern. Supplementation of DR with AG did not affect Pt, TBS, or TBT. The age-related increase in Pt and loss of elasticity in the tendon was retarded by diet restriction and AG.

  7. Green tea supplementation benefits body composition and improves bone properties in obese female rats fed with high-fat diet and caloric restricted diet.

    PubMed

    Shen, Chwan-Li; Han, Jia; Wang, Shu; Chung, Eunhee; Chyu, Ming-Chien; Cao, Jay J

    2015-12-01

    This study investigated the effects of green tea polyphenols (GTP) supplementation on body composition, bone properties, and serum markers in obese rats fed a high-fat diet (HFD) or a caloric restricted diet (CRD). Forty-eight female rats were fed an HFD ad libitum for 4 months, and then either continued on the HFD or the CRD with or without 0.5% GTP in water. Body composition, bone efficacy, and serum markers were measured. We hypothesized that GTP supplementation would improve body composition, mitigate bone loss, and restore bone microstructure in obese animals fed either HFD or CRD. CRD lowered percent fat mass; bone mass and trabecular number of tibia, femur and lumbar vertebrae; femoral strength; trabecular and cortical thickness of tibia; insulin-like growth factor-I and leptin. CRD also increased percent fat-free mass; trabecular separation of tibia and femur; eroded surface of tibia; bone formation rate and erosion rate at tibia shaft; and adiponectin. GTP supplementation increased femoral mass and strength (P = .026), trabecular thickness (P = .012) and number (P = .019), and cortical thickness of tibia (P < .001), and decreased trabecular separation (P = .021), formation rate (P < .001), and eroded surface (P < .001) at proximal tibia, and insulin-like growth factor-I and leptin. There were significant interactions (diet type × GTP) on osteoblast surface/bone surface, mineral apposition rate at periosteal and endocortical bones, periosteal bone formation rate, and trabecular thickness at femur and lumbar vertebrate (P < .05). This study demonstrates that GTP supplementation for 4 months benefited body composition and improved bone microstructure and strength in obese rats fed with HFD or HFD followed by CRD diet.

  8. Effects of the dietary approaches to stop hypertension diet alone and in combination with exercise and caloric restriction on insulin sensitivity and lipids.

    PubMed

    Blumenthal, James A; Babyak, Michael A; Sherwood, Andrew; Craighead, Linda; Lin, Pao-Hwa; Johnson, Julie; Watkins, Lana L; Wang, Jenny T; Kuhn, Cynthia; Feinglos, Mark; Hinderliter, Alan

    2010-05-01

    This study examined the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on insulin sensitivity and lipids. In a randomized control trial, 144 overweight (body mass index: 25 to 40) men (n=47) and women (n=97) with high blood pressure (130 to 159/85 to 99 mm Hg) were randomly assigned to one of the following groups: (1) DASH diet alone; (2) DASH diet with aerobic exercise and caloric restriction; or (3) usual diet controls (UC). Body composition, fitness, insulin sensitivity, and fasting lipids were measured before and after 4 months of treatment. Insulin sensitivity was estimated on the basis of glucose and insulin levels in the fasting state and after an oral glucose load. Participants in the DASH diet with aerobic exercise and caloric restriction condition lost weight (-8.7 kg [95% CI: -2.0 to -9.7 kg]) and exhibited a significant increase in aerobic capacity, whereas the DASH diet alone and UC participants maintained their weight (-0.3 kg [95% CI: -1.2 to 0.5 kg] and +0.9 kg [95% CI: 0.0 to 1.7 kg], respectively) and had no improvement in exercise capacity. DASH diet with aerobic exercise and caloric restriction demonstrated lower glucose levels after the oral glucose load, improved insulin sensitivity, and lower total cholesterol and triglycerides compared with both DASH diet alone and UC, as well as lower fasting glucose and low-density lipoprotein cholesterol compared with UC. DASH diet alone participants generally did not differ from UC in these measures. Combining the DASH diet with exercise and weight loss resulted in significant improvements in insulin sensitivity and lipids. Despite clinically significant reductions in blood pressure, the DASH diet alone, without caloric restriction or exercise, resulted in minimal improvements in insulin sensitivity or lipids.

  9. Systemic Glucose Level Changes with a Carbohydrate-Restricted and Higher Protein Diet Combined with Exercise

    ERIC Educational Resources Information Center

    Bowden, Rodney G.; Lanning, Beth A.; Doyle, Eva I.; Slonaker, Becky; Johnston, Holly M.; Scanes, Georgene

    2007-01-01

    Objective: The authors' purpose in this study was to compare the effects of macronutrient intake on systemic glucose levels in previously sedentary participants who followed 1 of 4 diets that were either higher protein or high carbohydrate, while initiating an exercise program. Participants and Methods: The authors randomly assigned 94 sedentary…

  10. The influence of food restriction versus ad libitum feeding of chow and purified diets on variation in body weight, growth and physiology of female Wistar rats.

    PubMed

    Moraal, M; Leenaars, P P A M; Arnts, H; Smeets, K; Savenije, B S; Curfs, J H A J; Ritskes-Hoitinga, M

    2012-04-01

    Ad libitum (AL) supply of standard chow is the feeding method most often used for rodents in animal experiments. However, AL feeding is known to result in a shorter lifespan and decreased health as compared with restricted feeding. Restricted feeding and thus limiting calorie intake prevents many health problems, increases lifespan and can also increase group uniformity. All this leads to a reduced number of animals needed. So-called standard chows are known to be prone to variation in composition. Synthetic foods have a more standard composition, contributing to group uniformity which, like diet reduction, may decrease the number of animals necessary to obtain statistical significance. In this study, we compared the effects of AL versus restricted feeding (25% reduction in food intake) on standard chow versus synthetic food of three different suppliers on body weight (BW), growth, several blood parameters and organ weights in growing female Wistar rats over a period of 61 days. Diet restriction led to a decreased growth and significantly reduced variation in BW and growth as compared with AL feeding. AL feeding on synthetic diets caused a significantly higher BW gain than on chow diets. Due to experimental design, this same effect occurred on food restriction. Blood parameters and organ weights were affected neither by diet type nor by amount. Incidentally, variations were significantly reduced on food restriction versus AL, and on synthetic diets versus chow diets. This study demonstrates that food restriction versus AL feeding leads to a significantly reduced variation in BW and growth, thereby indicating the potential for reduction when applying this feeding schedule.

  11. Calorie restricted diet induces alternative pathways of lipid metabolism for support of proliferative processes in regenerating liver.

    PubMed

    Bozhkov, A I; Menzianova, N C

    2009-01-01

    This study deals with quality and quantity lipid composition of blood serum and liver, DNA synthesis activity (incorporation of H3-thymidine) in liver in 24 h after partial hepatectomy (PH) in 22-month-old Wistar rats, maintained for 21 months on calorie restricted diet (CRD) and on standard diet ad libitum (SD). The contain of lipids in blood serum and activity of RA-label incorporation (14C-Na-acetate) in serum lipids in 24 h after PH were the same in CRD-fed and SD-fed animals. Quantitative and qualitative composition of lipids in microsomes of regenerating liver also was the same for both groups of rats. In regenerating liver of CRD-fed animals lipid contain in cytosol was 1,8-fold more, but pool of lipid droplets (LD) was 1.5-fold less than in regenerating liver of SD-fed animals. Activity of RA-label incorporation in lipids of microsomes, cytosol and LD pool of regenerating liver of CRD-fed animals was significantly higher, than in SD-fed ones. Activity of RA-label incorporation in lipid fractions and its distribution among cytosol lipids and LD pool lipids differed significantly between SD- and CRD-fed animals. Activity of DNA synthesis in regenerating liver of 22-month-old animals on CRD and SD was the same. It is supposed that calorie restriction induces alternative pathways of lipid metabolism to support proliferation processes in liver after PH.

  12. A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys

    PubMed Central

    Kastman, EK; Willette, AA; Coe, CL; Bendlin, BB; Kosmatka, KJ; McLaren, DG; Xu, G; Canu, E; Field, AS; Alexander, AL; Voytko, ML; Beasley, TM; Colman, RJ; Weindruch, R; Johnson, SC

    2010-01-01

    Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24, 13 males, 11 females) and standard diets (n= 17, 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus and temporal cortex. A Diet x Age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species. PMID:20534842

  13. Feed restriction reduces short-chain fatty acid absorption across the reticulorumen of beef cattle independent of diet.

    PubMed

    Albornoz, R I; Aschenbach, J R; Barreda, D R; Penner, G B

    2013-10-01

    The objective of this study was to evaluate the effects of the forage-to-concentrate ratio (F:C) of diets fed before and during short-term feed restriction (FR) on rumen fermentation, absorptive capacity of the reticulorumen, and apparent total tract digestibility. Twenty ovariectomized and ruminally cannulated Angus × Hereford heifers were blocked by BW and individually penned in box stalls (9 m(2)), having free access to water throughout the study. Heifers were randomly assigned to 1 of 2 dietary treatments, receiving either a high forage diet (HF; F:C of 92:8) or a moderate forage diet (MF; F:C of 60:40). Diets were fed ad libitum for 14 d before 5 d of baseline measurements (BASE) followed by 5 d of FR where heifers were restricted to 25% of ad libitum DMI relative to BASE. Dry matter intake was measured daily and ruminal pH was recorded every 2 min throughout the study. Ruminal fluid and blood samples were collected on d 3 of BASE and FR whereas short-chain fatty acid (SCFA) absorption was assessed in vivo using the isolated washed reticulorumen technique on d 5 of BASE and FR. Indigestible NDF was used as a marker to estimate apparent total tract digestibility. Diet × period interactions (P = 0.030 and 0.025) were detected for DMI and ruminal SCFA concentration, respectively. The interaction was the result of greater DMI and numerically greater SCFA concentration for MF than HF during BASE, with a reduction observed for both during FR, although treatment effects were no longer present. Period effects (BASE vs. FR) but not treatment effects (P > 0.05) were detected for mean ruminal pH (P < 0.001) and the total SCFA absorption rate (mmol/h; P = 0.038). During BASE, mean pH was reduced (6.4 vs. 6.9) and the SCFA absorption rate was greater relative to FR (674.5 vs. 554.8 mmol/h). Diet (P < 0.001) and period (P < 0.001) effects were detected for DM and OM digestibility with greater digestibility occurring for heifers fed MF than HF (70.5 vs. 63.3% for DM and 73

  14. Effects of Short-Term Carbohydrate Restrictive and Conventional Hypoenergetic Diets and Resistance Training on Strength Gains and Muscle Thickness

    PubMed Central

    Meirelles, Claudia M.; Gomes, Paulo S.C.

    2016-01-01

    Hypoenergetic diets and resistance training (RT) have been suggested to be important components of weight loss strategy programs; however, there is little evidence as to the chronic effects of different macronutrient compositions on strength performance and muscle mass with RT. The purpose of this study was to compare the effects of carbohydrate restrictive (CRD) and conventional (CONV) diets combined with RT on strength performance and muscle thicknesses in overweight and obese participants already involved in RT programs. Twenty-one volunteers engaged in an eight-week progressive RT program three times per week were assigned to a CRD (< 30 g carbohydrate; n = 12; 30.7 ± 3.9 km·m-2) or a CONV (30% energy deficit; 55%, 15% and 30% energy from carbohydrate, protein and fat, respectively; n=9; 27.7±2.5 km·m-2). Method: At baseline and week 8, the participants underwent body composition assessment by anthropometry, measurement of muscle thickness by ultrasound, and three strength tests using isotonic equipment. Both groups had similar reductions in body mass and fat mass as well as maintenance of fat-free mass. Muscle strength increased 14 ± 6% in the CRD group (p = 0.005) and 19 ± 9% in the CONV group (p = 0.028), with no significant differences between the groups. No significant differences were detected in muscle thicknesses within or between the groups. In conclusion, hypoenergetic diets combined with RT led to significant increases in muscle strength and were capable of maintaining muscle thicknesses in the upper and lower limbs of overweight and obese participants, regardless of the carbohydrate content of the diets. Key points The study deals with the effects of carbohydrate restrictive diet associated to a typical resistance training program, in obese and overweight individuals. The study presents greater external validity, since it was devised in an actual fitness center setting with physically active participants enrolled in exercise programs in three

  15. A weekly alternating diet between caloric restriction and medium fat protects the liver from fatty liver development in middle-aged C57BL/6J mice

    PubMed Central

    Rusli, Fenni; Boekschoten, Mark V; Zubia, Arantza Aguirre; Lute, Carolien; Müller, Michael; Steegenga, Wilma T

    2015-01-01

    Scope We investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet. Methods and results Nine-week-old male C57BL/6J mice received either a (i) control (C), (ii) 30E% calorie restricted (CR), (iii) MF (25E% fat), or (iv) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight. Conclusions Our study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevents the development of NAFLD in 12-month-old male C57BL/6J mice. PMID:25504628

  16. Ketogenic dietary therapies for adults with epilepsy: feasibility and classification of response.

    PubMed

    Schoeler, Natasha E; Wood, Susan; Aldridge, Valerie; Sander, Josemir W; Cross, J Helen; Sisodiya, Sanjay M

    2014-08-01

    Ketogenic dietary therapies are an effective treatment for children with drug-resistant epilepsy. There is currently no high-quality evidence regarding ketogenic dietary therapies in adults, and further research has been recommended. This audit aimed to provide further evidence for the feasibility of dietary treatment for adults and to consider factors that may aid response classification in this population. We evaluated the effectiveness and tolerability of ketogenic dietary therapies in 23 adults with epilepsy attending specialist clinics. Medical notes were used to obtain seizure frequency information and other effects associated with dietary treatment. Individuals who achieved ≥50% seizure reduction at all follow-up points were classified as responders. Response rates, in terms of seizure frequency, were similar to those commonly reported in pediatric cohorts: 9/23 (39%) adults were classified as responders. These responders remained on the diet for at least one year (follow-up: 1-10 years). Other benefits reported by patients, but not quantified, included a reduction in seizure severity and increased alertness and concentration. Such factors often favor continuation of ketogenic dietary therapies despite a <50% seizure reduction. One individual experienced psychosis while following dietary treatment; most commonly reported adverse events were gastrointestinal. Adverse events did not lead to discontinuation of treatment in any cases. Our findings suggest that adults with epilepsy are able to follow ketogenic dietary therapies long-term, and such treatment can lead to seizure reduction. Other aspects besides seizure frequency may be relevant when classifying response in adults, and appropriate ways to quantify these factors should be considered for use in future studies.

  17. Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial.

    PubMed

    Imayama, Ikuyo; Ulrich, Cornelia M; Alfano, Catherine M; Wang, Chiachi; Xiao, Liren; Wener, Mark H; Campbell, Kristin L; Duggan, Catherine; Foster-Schubert, Karen E; Kong, Angela; Mason, Caitlin E; Wang, Ching-Yun; Blackburn, George L; Bain, Carolyn E; Thompson, Henry J; McTiernan, Anne

    2012-05-01

    Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N = 118), aerobic exercise (225 min/wk of moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte, and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity, and age. Four hundred and thirty-eight (N = 1 in diet + exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, P value): 0.92 mg/L (0.53-1.31, P < 0.001) in the diet and 0.87 mg/L (0.51-1.23, P < 0.0001) in the diet + exercise groups. IL-6 decreased by 0.34 pg/mL (0.13-0.55, P = 0.001) in the diet and 0.32 pg/mL (0.15-0.49, P < 0.001) in the diet + exercise groups. Neutrophil counts decreased by 0.31 × 10(9)/L (0.09-0.54, P = 0.006) in the diet and 0.30 × 10(9)/L (0.09-0.50, P = 0.005) in the diet + exercise groups. Diet and diet + exercise participants with 5% or more weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared with controls. The diet and diet + exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction.

  18. Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

    PubMed

    Arai, Takeshi; Kim, Hyoun-ju; Hirako, Satoshi; Nakasatomi, Maki; Chiba, Hiroshige; Matsumoto, Akiyo

    2013-01-01

    We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice.

  19. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet.

    PubMed

    Hatori, Megumi; Vollmers, Christopher; Zarrinpar, Amir; DiTacchio, Luciano; Bushong, Eric A; Gill, Shubhroz; Leblanc, Mathias; Chaix, Amandine; Joens, Matthew; Fitzpatrick, James A J; Ellisman, Mark H; Panda, Satchidananda

    2012-06-06

    While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

  20. Adiposity and serum parameters in hamsters fed energy restricted diets supplemented or not with trans-10,cis-12 conjugated linoleic acid.

    PubMed

    Lasa, A; Simón, E; Churruca, I; Fernández-Quintela, A; Rodríguez, V M; Portillo, M P

    2007-12-01

    Numerous studies have demonstrated that conjugated linoleic acid (CLA) modulates body composition, reducing body fat accumulation in various mammalian species. However, very few studies have been carried out to assess the effect of CLA on previously stored body fat. The aim of the present work was to analyse the effectiveness of trans-10,cis-12 CLA in improving alterations produced by high-fat feeding in body fat and serum parameters when it was included in an energy-restricted diet. For this purpose male Syrian Golden hamsters were fed on high-fat diet for 7 weeks in order to increase their body fat content, and a further 25% energy-restricted diet supplemented or not with 0.5% trans-10,cis-12 CLA for 3 weeks. Adipose tissues, liver and gastrocnemious muscles were dissected and weighed. Adipocyte diameter and number were assessed in epididymal adipose tissue. Total cholesterol, triacylglycerols, non-esterified fatty acids and glucose were measured in serum. Three weeks of energy restriction resulted in a reduction in body weight and white adipose tissue size in all anatomical locations, without changes in liver and gastrocnemious muscle weights. Epididymal adipocyte size was reduced, but total adipocyte number remained unchanged. Serum cholesterol, triacylglycerols and glucose were significantly reduced. No differences were observed between the restricted groups (control and CLA supplemented). In conclusion, under our experimental conditions, the addition of trans-10,cis-12 CLA to the diet does not increase the benefits produced by energy restriction.

  1. Diet restriction in migraine, based on IgG against foods: A clinical double-blind, randomised, cross-over trial

    PubMed Central

    Alpay, Kadriye; Ertaş, Mustafa; Orhan, Elif Kocasoy; Üstay, Didem Kanca; Lieners, Camille; Baykan, Betül

    2010-01-01

    Introduction: It is well-known that specific foods trigger migraine attacks in some patients. We aimed to investigate the effect of diet restriction, based on IgG antibodies against food antigens on the course of migraine attacks in this randomised, double blind, cross-over, headache-diary based trial on 30 patients diagnosed with migraine without aura. Methods: Following a 6-week baseline, IgG antibodies against 266 food antigens were detected by ELISA. Then, the patients were randomised to a 6-week diet either excluding or including specific foods with raised IgG antibodies, individually. Following a 2-week diet-free interval after the first diet period, the same patients were given the opposite 6-week diet (provocation diet following elimination diet or vice versa). Patients and their physicians were blinded to IgG test results and the type of diet (provocation or elimination). Primary parameters were number of headache days and migraine attack count. Of 30 patients, 28 were female and 2 were male, aged 19–52 years (mean, 35 ± 10 years). Results: The average count of reactions with abnormally high titre was 24 ± 11 against 266 foods. Compared to baseline, there was a statistically significant reduction in the number of headache days (from 10.5 ± 4.4 to 7.5 ± 3.7; P < 0.001) and number of migraine attacks (from 9.0 ± 4.4 to 6.2 ± 3.8; P < 0.001) in the elimination diet period. Conclusion: This is the first randomised, cross-over study in migraineurs, showing that diet restriction based on IgG antibodies is an effective strategy in reducing the frequency of migraine attacks. PMID:20647174

  2. Caloric restriction and intermittent fasting: two potential diets for successful brain aging.

    PubMed

    Martin, Bronwen; Mattson, Mark P; Maudsley, Stuart

    2006-08-01

    The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders.

  3. Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

    PubMed Central

    Martin, Bronwen; Mattson, Mark P.; Maudsley, Stuart

    2008-01-01

    The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders. PMID:16899414

  4. Developmental changes in ketogenic enzyme gene expression during sheep rumen development.

    PubMed

    Lane, M A; Baldwin, R L; Jesse, B W

    2002-06-01

    Ketogenesis is the conversion of acetyl-CoA to the ketone bodies acetoacetate and beta-hydroxybutyrate (BHBA). In hepatic ketogenesis, which occurs during fasting in both nonruminant and ruminant animals, the source of acetyl-CoA is the mitochondrial oxidation of predominantly long-chain fatty acids. In the mature, fed ruminant animal, the ruminal epithelium is also capable of producing ketone bodies. In this case, the source of acetyl-CoA is the mitochondrial oxidation of butyrate produced by the microbial fermentation of feed. The purposes of this study were to determine ontogenic and dietary effects on ketogenic enzyme gene expression in developing lamb ruminal epithelium. Twenty-seven conventionally reared lambs and twenty-seven milk-fed lambs were slaughtered between 1 and 84 d of age. Six additional milk-fed lambs were weaned (the fed group) or maintained on milk replacer with a volatile fatty acid gavage (the VFA group) until 84 d of age. At slaughter, total RNA was extracted from samples of ruminal epithelium. The expression of the genes encoding acetoacetyl-CoA thiolase, the first enzyme in the ketogenic pathway, and 3-hydroxy-3-methylglutaryl-CoA synthase, the rate-limiting enzyme in the ketogenic pathway in nonruminant liver, were examined. Acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase mRNA concentrations increased with age independent of diet. 3-Hydroxy-3-methylglutaryl-CoA synthase mRNA levels in ruminal epithelium obtained from milk-fed lambs were low before 42 d of age, but a marked increase occurred by 42 d of age. At 84 d of age, there were no differences in acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase expression due to diet. The pattern of the expression of these genes, in particular, 3-hydroxy-3-methylglutaryl-CoA synthase, parallels the rate of production of BHBA by rumen epithelial cells isolated from the same lambs, which increased to conventionally reared adult levels at 42 d of age and did not

  5. Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet

    ERIC Educational Resources Information Center

    Guest, J. F.; Bai, J. J.; Taylor, R. R.; Sladkevicius, E.; Lee, P. J.; Lachmann, R. H.

    2013-01-01

    Background: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. Methods: A computer-based model was constructed depicting the management of PKU patients over the first…

  6. Diet restriction delays accelerated aging and genomic stress in DNA repair deficient mice

    PubMed Central

    Vermeij, W.P.; Dollé, M.E.T.; Reiling, E.; Jaarsma, D.; Payan-Gomez, C.; Bombardieri, C.R.; Wu, H.; Roks, A.J.M.; Botter, S.M.; van der Eerden, B.C.; Youssef, S.A.; Kuiper, R.V.; Nagarajah, B.; van Oostrom, C.T.; Brandt, R.M.C.; Barnhoorn, S.; Imholz, S.; Pennings, J.L.A.; de Bruin, A.; Gyenis, Á.; Pothof, J.; Vijg, J.; van Steeg, H.; Hoeijmakers, J.H.J.

    2016-01-01

    DNA repair-deficient Ercc1Δ/− mice show numerous accelerated aging features limiting lifespan to 4–6 month1–4. Simultaneously they exhibit a ‘survival response’, which suppresses growth and enhances maintenance, resembling the anti-aging response induced by dietary restriction (DR)1,5. Here we report that subjecting these progeroid, dwarf mutants to 30% DR tripled median and maximal remaining lifespan, and drastically retarded numerous aspects of accelerated aging, e.g. DR animals retained 50% more neurons and maintained full motoric function, even far beyond the lifespan of ad libitum (AL) animals. Repair-deficient, progeroid Xpg−/− mice, a Cockayne syndrome model6, responded similarly, extending this observation to other repair mutants. The DR response in Ercc1Δ/− mice closely resembled DR in wild type animals. Interestingly, AL Ercc1Δ/− liver showed preferential extinction of expression of long genes, a phenomenon we also observe in several normal aging tissues. This is consistent with accumulation of stochastic, transcription-blocking lesions, affecting long genes more than short ones. DR largely prevented declining transcriptional output and reduced γH2AX DNA damage foci, indicating that DR preserves genome function by alleviating DNA damage. Our findings establish Ercc1Δ/− mice as powerful model for interventions sustaining health, reveal untapped potential for reducing endogenous damage, provide new venues for understanding the molecular mechanism of DR, and suggest a counterintuitive DR-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general. PMID:27556946

  7. Temporal changes in tissue repair permit survival of diet-restricted rats from an acute lethal dose of thioacetamide.

    PubMed

    Ramaiah, S K; Bucci, T J; Warbritton, A; Soni, M G; Mehendale, H M

    1998-10-01

    Although, diet restriction (DR) has been shown to substantially increase longevity while reducing or delaying the onset of age-related diseases, little is known about the mechanisms underlying the beneficial effects of DR on acute toxic outcomes. An earlier study (S. K. Ramaiah et al., 1998, Toxicol. Appl. Pharmacol. 150, 12-21) revealed that a 35% DR compared to ad libitum (AL) feeding leads to a substantial increase in liver injury of thioacetamide (TA) at a low dose (50 mg/kg, i.p.). Higher liver injury was accompanied by enhanced survival. A prompt and enhanced tissue repair response in DR rats at the low dose (sixfold higher liver injury) occurred, whereas at equitoxic doses (50 mg/kg in DR and 600 mg/kg in AL rats) tissue repair in AL rats was substantially diminished and delayed. The extent of liver injury did not appear to be closely related to the extent of stimulated tissue repair response. The purpose of the present study was to investigate the time course (0-120 h) of liver injury and liver tissue repair at the high dose (600 mg TA/kg, i.p., lethal in AL rats) in AL and DR rats. Male Sprague-Dawley rats (225-275 g) were 35% diet restricted compared to their AL cohorts for 21 days and on day 22 they received a single dose of TA (600 mg/kg, i.p.). Liver injury was assessed by plasma ALT and by histopathological examination of liver sections. Tissue repair was assessed by [3H]thymidine incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry during 0-120 h after TA injection. In AL-fed rats hepatic necrosis was evident at 12 h, peaked at 60 h, and persisted thereafter until mortality (3 to 6 days). Peak liver injury was approximately twofold higher in DR rats compared to that seen in AL rats. Hepatic necrosis was evident at 36 h, peaked at 48 h, persisted until 96 h, and returned to normal by 120 h. Light microscopy of liver sections revealed progression of hepatic injury in AL rats whereas injury regressed

  8. Dietary restriction in moderately obese rats improves body size and glucose handling without the renal and hepatic alterations observed with a high-protein diet.

    PubMed

    Devassy, Jessay G; Caligiuri, Stephanie P B; Mayengbam, Shyamchand; Ibrahim, Naser H M; Zahradka, Peter; Taylor, Carla G; House, James D; Aukema, Harold M

    2015-04-01

    Obesity is increasing worldwide, and high-protein (HP) diets are widely used for weight loss. However, the overall safety of HP diets is not well established in obese individuals, who make up a significant proportion of the population. To evaluate the health effects of an HP diet in obesity, obesity-prone (OP) Sprague-Dawley rats were given high-fat diets for 12 weeks to induce obesity. Following this, for 8 more weeks, these rats were given either a normal-protein (NP) (15% of energy) or an HP (35% of energy) diet ad libitum, or the NP diet at a restricted level to achieve body weights similar to those of the HP group (pair-weighted (PW) group). Obesity-resistant (OR) control rats were also given the NP diet throughout the feeding period. The HP-OP group had higher food intake but lower body weight, improved glucose handling, and lowered serum haptoglobin compared with the NP-OP group. These benefits were also observed in PW-OP rats. In addition, PW-OP rats had less fat accumulation when compared with NP-OP rats, and an improved Lee index, lower liver size, and lower serum alanine aminotransferase when compared with HP-OP rats. On the other hand, kidney size, proteinuria, and serum homocysteine were increased in HP-OP rats compared with NP-OP rats, whereas PW-OP rats did not experience these effects. These results indicate that in obese rats, more benefits are obtained via dietary restriction with an NP diet and without some of the potentially detrimental effects of an HP diet.

  9. Restricting feeding to the active phase in middle-aged mice attenuates adverse metabolic effects of a high-fat diet.

    PubMed

    Duncan, M J; Smith, J T; Narbaiza, J; Mueez, F; Bustle, L B; Qureshi, S; Fieseler, C; Legan, S J

    2016-12-01

    Time-restricted feeding ameliorates the deleterious effects of a high-fat diet on body weight and metabolism in young adult mice. Because obesity is highly prevalent in the middle-aged population, this study tested the hypothesis that time-restricted feeding alleviates the adverse effects of a high-fat diet in male middle-aged (12months) mice. C57BL6/J mice were fed one of three diets for 21-25weeks: 1) high-fat diet (60% total calories from fat) ad-libitum (HFD-AL), 2) HFD, time-restricted feeding (HFD-TRF), and 3) low-fat diet (10% total calories from fat) ad-libitum (LFD-AL) (n=15 each). HFD-TRF mice only had food access for 8h/day during their active period. HFD-TRF mice gained significantly less weight than HFD-AL mice (~20% vs 55% of initial weight, respectively). Caloric intake differed between these groups only during the first 8weeks and accounted for most but not all of their body weight difference during this time. TRF of a HFD lowered glucose tolerance in terms of incremental area under the curve (iAUC) (p<0.02) to that of LFD-AL mice. TRF of a HFD lowered liver weight (p<0.0001), but not retroperitoneal or epididymal fat pad weight, to that of LFD-AL mice. Neither HFD-AL nor HFD-TRF had any effect on performance in the novel object recognition or object location memory tests. Circulating corticosterone levels either before or after restraint stress were not affected by diet. In conclusion, TRF without caloric restriction is an effective strategy in middle-aged mice for alleviating the negative effects of a HFD on body weight, liver weight, and glucose tolerance.

  10. Sugared water consumption by adult offspring of mothers fed a protein-restricted diet during pregnancy results in increased offspring adiposity: the second hit effect.

    PubMed

    Cervantes-Rodríguez, M; Martínez-Gómez, M; Cuevas, E; Nicolás, L; Castelán, F; Nathanielsz, P W; Zambrano, E; Rodríguez-Antolín, J

    2014-02-01

    Poor maternal nutrition predisposes offspring to metabolic disease. This predisposition is modified by various postnatal factors. We hypothesised that coupled to the initial effects of developmental programming due to a maternal low-protein diet, a second hit resulting from increased offspring postnatal sugar consumption would lead to additional changes in metabolism and adipose tissue function. The objective of the present study was to determine the effects of sugared water consumption (5% sucrose in the drinking-water) on adult offspring adiposity as a 'second hit' following exposure to maternal protein restriction during pregnancy. We studied four offspring groups: (1) offspring of mothers fed the control diet (C); (2) offspring of mothers fed the restricted protein diet (R); (3) offspring of control mothers that drank sugared water (C-S); (4) offspring of restricted mothers that drank sugared water (R-S). Maternal diet in pregnancy was considered the first factor and sugared water consumption as the second factor - the second hit. Body weight and total energy consumption, before and after sugared water consumption, were similar in all the groups. Sugared water consumption increased TAG, insulin and cholesterol concentrations in both the sexes of the C-S and R-S offspring. Sugared water consumption increased leptin concentrations in the R-S females and males but not in the R offspring. There was also an interaction between sugared water and maternal diet in males. Sugared water consumption increased adipocyte size and adiposity index in both females and males, but the interaction with maternal diet was observed only in females. Adiposity index and plasma leptin concentrations were positively correlated in both the sexes. The present study shows that a second hit during adulthood can amplify the effects of higher adiposity arising due to poor maternal pregnancy diet in an offspring sex dependent fashion.

  11. Cardiolipin profiles as a potential biomarker of mitochondrial health in diet-induced obese mice subjected to exercise, diet-restriction and ephedrine treatment.

    PubMed

    Faber, Catherine; Zhu, Zhaohai J; Castellino, Stephen; Wagner, David S; Brown, Roger H; Peterson, Richard A; Gates, Lisa; Barton, Joanna; Bickett, Mark; Hagerty, Laura; Kimbrough, Carie; Sola, Mario; Bailey, David; Jordan, Holly; Elangbam, Chandikumar S

    2014-11-01

    Cardiolipin (CL) is crucial for mitochondrial energy metabolism and structural integrity. Alterations in CL quantity or CL species have been associated with mitochondrial dysfunction in several pathological conditions and diseases, including mitochondrial dysfunction-related compound attrition and post-market withdrawal of promising drugs. Here we report alterations in the CL profiles in conjunction with morphology of soleus muscle (SM) and brown adipose tissue (BAT) in diet-induced obese (DIO) mice, subjected to ephedrine treatment (EPH: 200 mg kg(-1)  day(-1) orally), treadmill exercise (EX: 10 meters per min, 1 h per day), or dietary restriction (DR: 25% less of mean food consumed by the EX group) for 7 days. Mice from the DR and EPH groups had a significant decrease in percent body weight and reduced fat mass compared with DIO controls. Morphologic alterations in the BAT included brown adipocytes with reduced cytoplasmic lipid droplets and increased cytoplasmic eosinophilia in the EX, DR and EPH groups. Increased cytoplasmic eosinophilia in the BAT was ultrastructurally manifested by increased mitochondrial cristae, fenestration of mitochondrial cristae, increased electron density of mitochondrial matrix, and increased complexity of shape and elongation of mitochondria. Mitochondrial ultrastructural alterations in the SM of the EX and DR groups included increased mitochondrial cristae, cup-shaped mitochondria and mitochondrial degeneration. All four CL species (tri-linoleoyl-mono-docosahexaenoyl, tetralinoleoyl, tri-linoleoyl-mono-oleoyl, and di-linoleoyl-di-oleoyl) were increased in the BAT of the DR and EPH groups and in the SM of the EPH and EX groups. In conclusion, cardiolipin profiling supported standard methods for assessing mitochondrial biogenesis and health, and may serve as a potential marker of mitochondrial dysfunction in preclinical toxicity studies.

  12. [COLD and HOT nature of Coptis & Evodia and their prescriptions investigated with diet restriction/cold-water swimming mice models].

    PubMed

    Ren, Yong-shen; Wang, Jia-bo; Zhao, Yan-ling; Zhang, Ping; Zhao, Hai-ping; Zhang, Xue-ru; Zhou, Can-ping; Xiao, Xiao-he; Jin, Cheng

    2009-11-01

    To establish a new method to evaluate the COLD and HOT nature of Coptis & Evodia and their prescriptions Zuojinwan and Fanzuojinwan. Physical models of mice were established by diet restriction with cold-water swimming (weak model, WM) and fed with high protein animal feeds (strong model, SM). An instrument with cold and hot pads was used to investigate the variation of temperature tropism among SM and WM groups of mice affected by drugs. Meanwhile, the oxygen consumption and activity of adenosine triphosphatase (ATPase) were detected, in order to investigate the mechanism of energy metabolism which might be affected by these drugs. The results showed that the drug effects gradually changed in an order of "Coptis-->Zuojinwan--> Fanzuojinwan-->Evodia". In detail, Coptis increased the remaining rate (RR) of mice on hot pad, decreased oxygen consumption and ATPase activity (n=6, P < 0.01 or P < 0.05), while Evodia performed inversely; which indicated the COLD nature of Coptis and HOT nature of Evodia, and confirmed with their traditional definition in medicinal works. In conclusion, the methods applied in this work, can objectively and directly express the nature disparity between the two herbs and predict the tendency of changes of the nature of their combination, which brings a new approach in investigation of the nature theory of traditional Chinese medicine.

  13. Diet Therapy Career Ladder, AFSC 926XO.

    DTIC Science & Technology

    1985-12-01

    diet . On the other hand, first-termers in AFSC tend to have experience with more types of thera- peutic diets , such as gluten restricted, high...DENTAL SOFT DIET 96 95 95 DIABETIC DIET 96 95 96 k FAT CONTROLLED, CHOLESTEROL RESTRICTED DIET 91 92 92 FAT FREE TEST DIET 60 71 70 FAT RESTRICTED DIET ...ELIMINATION DIET 36 45 46 CARBOHYDRATE TEST DIET , 150GM AND 300GM 40 62 69 - GLUTEN RESTRICTED DIET 30 40 55 . HIGH POTASSIUM DIET

  14. [Is the Atkins diet safe in respect to health?].

    PubMed

    Förster, H

    1978-09-14

    The "Atkins dietary revolution" is a ketogenic diet consisting almost exclusively of food from animal origin. A similar diet was introduced as the "Banting diet" more than a century ago by the English physician Harvey. This carbohydrate-free diet is high in fat, cholesterol and purines. The measurable ketosis is a precondition for the effect of this kind of diet. However, the predictable hyperlipacidemia and ketosis are recognized health risks. Additionally, hypercholesterolemia is to be expected in a greater part of the adherents to such a diet. Even children under ketogenic diet develop hypercholesterolemia within a short time. A similar high-fat diet, known as the Sippy diet for ulcer therapy, was found earlier to cause an increased incidence in coronary heart disease. On the basis of the known facts the Atkins diet seems to be potentially hazardous to health, unless a controlled study is performed. However, considering the risks it seems very problematic to perform such a study.

  15. Soy compared to casein meal replacement shakes with energy-restricted diets for obese women: randomized controlled trial.

    PubMed

    Anderson, James W; Fuller, Jennifer; Patterson, Katy; Blair, Robert; Tabor, Aaron

    2007-02-01

    Recent studies suggest that obese individuals lose weight more rapidly and lose more total weight with soy protein than with animal protein as a major diet component. The purpose of the present study was to evaluate the weight-loss efficacy and changes in body composition, waist circumference, blood pressure, and levels of plasma glucose, insulin, serum lipids, C-reactive protein, and homocysteine from consumption of either 3 soy shakes or 3 casein shakes daily as part of a 16-week, energy-restricted diet for obese women. Forty-three women with body mass index values of 30 to 40 kg/m(2) were randomized to intensive dietary interventions using either casein (n = 21) or soy (n = 22) shakes. Subjects were instructed to consume 3 shakes, 1 prepackaged entrée, and 5 servings of fruits or vegetables daily to achieve an energy intake of 4.5 to 5.0 MJ/d. Subjects attended classes weekly or biweekly. Weight, body fat, lipid, and glucose measurements were obtained at baseline and at 8 and 16 weeks. For both groups combined, subjects lost 8.1% of initial body weight (7.7 kg) at 8 weeks and 13.4% (12.7 kg) at 16 weeks. Weight loss from baseline did not differ significantly by group and, for completing subjects, was 14.0% +/- 1.2% (mean +/- SE) for casein and 12.8% +/- 1.4% for soy. With the intention-to-treat analysis, weight losses at 16 weeks were 12.5% +/- 1.4% for casein and 11.3% +/- 1.2% for soy. Body fat losses were 23.7% +/- 2.0% for casein and 21.8% +/- 2.4% for soy and did not differ significantly. Both study groups lost significant amounts of weight with a highly structured behavioral program incorporating 4 meal replacements and vegetables and fruits. Differences in weight loss and body composition changes between casein and soy treatments were not significant.

  16. Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure.

    PubMed

    Smith, Patrick J; Blumenthal, James A; Babyak, Michael A; Craighead, Linda; Welsh-Bohmer, Kathleen A; Browndyke, Jeffrey N; Strauman, Timothy A; Sherwood, Andrew

    2010-06-01

    High blood pressure increases the risks of stroke, dementia, and neurocognitive dysfunction. Although aerobic exercise and dietary modifications have been shown to reduce blood pressure, no randomized trials have examined the effects of aerobic exercise combined with dietary modification on neurocognitive functioning in individuals with high blood pressure (ie, prehypertension and stage 1 hypertension). As part of a larger investigation, 124 participants with elevated blood pressure (systolic blood pressure 130 to 159 mm Hg or diastolic blood pressure 85 to 99 mm Hg) who were sedentary and overweight or obese (body mass index: 25 to 40 kg/m(2)) were randomized to the Dietary Approaches to Stop Hypertension (DASH) diet alone, DASH combined with a behavioral weight management program including exercise and caloric restriction, or a usual diet control group. Participants completed a battery of neurocognitive tests of executive function-memory-learning and psychomotor speed at baseline and again after the 4-month intervention. Participants on the DASH diet combined with a behavioral weight management program exhibited greater improvements in executive function-memory-learning (Cohen's D=0.562; P=0.008) and psychomotor speed (Cohen's D=0.480; P=0.023), and DASH diet alone participants exhibited better psychomotor speed (Cohen's D=0.440; P=0.036) compared with the usual diet control. Neurocognitive improvements appeared to be mediated by increased aerobic fitness and weight loss. Also, participants with greater intima-medial thickness and higher systolic blood pressure showed greater improvements in executive function-memory-learning in the group on the DASH diet combined with a behavioral weight management program. In conclusion, combining aerobic exercise with the DASH diet and caloric restriction improves neurocognitive function among sedentary and overweight/obese individuals with prehypertension and hypertension.

  17. Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats.

    PubMed

    Gopalan, Venkatesh; Michael, Navin; Ishino, Seigo; Lee, Swee Shean; Yang, Adonsia Yating; Bhanu Prakash, K N; Yaligar, Jadegoud; Sadananthan, Suresh Anand; Kaneko, Manami; Zhou, Zhihong; Satomi, Yoshinori; Hirayama, Megumi; Kamiguchi, Hidenori; Zhu, Bin; Horiguchi, Takashi; Nishimoto, Tomoyuki; Velan, S Sendhil

    2016-05-20

    Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity.

  18. Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats

    PubMed Central

    Gopalan, Venkatesh; Michael, Navin; Ishino, Seigo; Lee, Swee Shean; Yang, Adonsia Yating; Bhanu Prakash, K. N.; Yaligar, Jadegoud; Sadananthan, Suresh Anand; Kaneko, Manami; Zhou, Zhihong; Satomi, Yoshinori; Hirayama, Megumi; Kamiguchi, Hidenori; Zhu, Bin; Horiguchi, Takashi; Nishimoto, Tomoyuki; Velan, S. Sendhil

    2016-01-01

    Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity. PMID:27197769

  19. Retention and utilization of amino acids in piglets fed ad libitum or restrictively diets supplemented with organic acids.

    PubMed

    Walz, O P; Pallauf, J

    1997-01-01

    In a metabolic trial 4 groups of 8 piglets of 5 kg weight each were kept individually for 45 days (final weight 23 kg) and fed a practical diet. At the beginning of the experiment the body amino acid contents of an additional group of 8 piglets were determined by carcass analysis, and at the end of the experiment the body amino acid contents of the 4 test group piglets (A = control fed ad libitum, B and C = supplement of 1.5% fumaric acid fed ad libitum or restrictively, D = supplement of 1.5% citric acid fed ad libitum) were also analysed. The amino acid retention during the experimental period was determined by difference. The supplements of fumaric or citric acid did not influence the amount of the amino acid retention. The quotient of amino acid retention to amino acid consumed or the "productive amino acid value" was calculated and the maintenance requirements of essential amino acids for piglets were used to estimate the productive amino acid value for both retention and maintenance. The mean amino acid retention amounted to about 56 g/d, i.e. 3.49 g/kg W0.75.d of essential amino acids. The essential amino acid requirements for maintenance was 2.0 g, i.e. 0.29 g/kg W0.75.d, showing a variation of 4% (Leu) to 20% (Met+Cys) when related to the amount of the corresponding amino acid retention. With regard to the amino acid pattern for retention of the nutritionally most important amino acids, the following ratios were found: Lys, 100 (6.27 g/16 g N): Met+Cys, 48 (3.03 g): Thr, 56 (3.49 g): Trp, 13 (0.80 g). The productive amino acid values ranged from 40% (Trp), 55% (Thr), 66% (Met) to 80% (Lys). Under the conditions investigated, neither the supplements of organic acids nor the feed restriction influenced the amino acid utilization.

  20. Role of CYP2E1 and saturation kinetics in the bioactivation of thioacetamide: Effects of diet restriction and phenobarbital

    SciTech Connect

    Chilakapati, Jaya; Korrapati, Midhun C.; Shankar, Kartik; Hill, Ronald A.; Warbritton, Alan; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2007-02-15

    Thioacetamide (TA) undergoes saturation toxicokinetics in ad libitum (AL) fed rats. Diet restriction (DR) protects rats from lethal dose of TA despite increased bioactivation-mediated liver injury via CYP2E1 induction. While a low dose (50 mg TA/kg) produces 6-fold higher initial injury, a 12-fold higher dose produces delayed and mere 2.5-fold higher injury. The primary objective was to determine if this less-than-expected increase in injury is due to saturation toxicokinetics. Rats on AL and DR for 21 days received either 50 or 600 mg TA/kg i.p. T {sub 1/2} and AUCs for TA and TA-S-oxide were consistent with saturable kinetics. Covalent binding of {sup 14}C-TA-derived-radiolabel to liver macromolecules after low dose was 2-fold higher in DR than AL rats. However, following lethal dose, no differences were found between AL and DR. This lack of dose-dependent response appears to be due to saturation of bioactivation at the higher dose. The second objective was to investigate the effect of phenobarbital pretreatment (PB) on TA-initiated injury following a sub-lethal dose (500 mg/kg). PB induced CYP2B1/2 {approx} 350-fold, but did not increase covalent binding of {sup 14}C-TA, TA-induced liver injury and mortality, suggesting that CYP2B1/2 has no major role in TA bioactivation. The third objective was to investigate the role of CYP2E1 using cyp2e1 knockout mice (KO). Injury was assessed over time (0-48 h) in wild type (WT) and KO mice after LD{sub 100} dose (500 mg/kg) in WT. While WT mice exhibited robust injury which progressed to death, KO mice exhibited neither initiation nor progression of injury. These findings confirm that CYP2E1 is responsible for TA bioactivation.

  1. Protein Restriction with Amino Acid-Balanced Diets Shrinks Circulating Pool Size of Amino Acid by Decreasing Expression of Specific Transporters in the Small Intestine

    PubMed Central

    Luo, Min; Zhang, Xin; Sun, Wen Juan; Jiao, Ning; Li, De Fa; Yin, Jing Dong

    2016-01-01

    Dietary protein restriction is not only beneficial to health and longevity in humans, but also protects against air pollution and minimizes feeding cost in livestock production. However, its impact on amino acid (AA) absorption and metabolism is not quite understood. Therefore, the study aimed to explore the effect of protein restriction on nitrogen balance, circulating AA pool size, and AA absorption using a pig model. In Exp.1, 72 gilts weighting 29.9 ± 1.5 kg were allocated to 1 of the 3 diets containing 14, 16, or 18% CP for a 28-d trial. Growth (n = 24), nitrogen balance (n = 6), and the expression of small intestinal AA and peptide transporters (n = 6) were evaluated. In Exp.2, 12 barrows weighting 22.7 ± 1.3 kg were surgically fitted with catheters in the portal and jejunal veins as well as the carotid artery and assigned to a diet containing 14 or 18% CP. A series of blood samples were collected before and after feeding for determining the pool size of circulating AA and AA absorption in the portal vein, respectively. Protein restriction did not sacrifice body weight gain and protein retention, since nitrogen digestibility was increased as dietary protein content reduced. However, the pool size of circulating AA except for lysine and threonine, and most AA flux through the portal vein were reduced in pigs fed the low protein diet. Meanwhile, the expression of peptide transporter 1 (PepT-1) was stimulated, but the expression of the neutral and cationic AA transporter systems was depressed. These results evidenced that protein restriction with essential AA-balanced diets, decreased AA absorption and reduced circulating AA pool size. Increased expression of small intestinal peptide transporter PepT-1 could not compensate for the depressed expression of jejunal AA transporters for AA absorption. PMID:27611307

  2. Effects of feed consumption rate of beef cattle offered a diet supplemented with nitrate ad libitum or restrictively on potential toxicity of nitrate.

    PubMed

    Lee, C; Araujo, R C; Koenig, K M; Beauchemin, K A

    2015-10-01

    The objective of the study was to investigate the effects of feed consumption rate on potential toxicity, rumen fermentation, and eating behavior when beef heifers were fed a diet supplemented with nitrate (NI). Twelve ruminally cannulated heifers (827 ± 65.5 kg BW) were used in a randomized complete block design. The experiment consisted of 10-d adaptation, 8-d urea-feeding, and 3-d nitrate-feeding periods. All heifers were fed a diet supplemented with urea (UR) during the adaptation and urea-feeding periods, whereas the NI diet (1.09% NO in dietary DM) was fed during the nitrate-feeding period. After adaptation, heifers were randomly assigned to ad libitum or restrictive feeding (about 80% of ad libitum intake) for the urea- and nitrate-feeding periods. Ad libitum DMI decreased (14.1 vs. 15.1 kg/d; < 0.01) when heifers were fed the NI diet compared with the UR diet. The amount of feed consumed increased ( < 0.01) at 0 to 3 h and decreased ( ≤ 0.03) at 3 to 24 h for restrictive vs. ad libitum feeding of both the UR and NI diets. Compared to the UR diet, the NI diet decreased ( < 0.01) feed consumption at 0 to 3 h and increased ( < 0.02) feed consumption at 3 to 24 h (except feed consumption at 9 to 12 h; = 0.90), indicating nitrate feeding changed the consumption pattern (a more even distribution of feed intake over the day). The increased feed consumption from 0 to 3 h after feeding the NI diet restrictively vs. ad libitum numerically decreased ( = 0.11) rumen pH and numerically or significantly increased ( = 0.01 to 0.28) rumen ammonia, NO, and NO; blood methemoglobin; and plasma NO and NO at 3 h. Regression analysis indicated that increased feed consumption (0 to 3 h) exponentially elevated ( < 0.01; = 0.75) blood methemoglobin, and plasma NO + NO among other rumen and blood variables had the greatest correlation (sigmoid response; < 0.01, = 0.47) with feed consumption (0 to 3 h). Particle size distribution of orts was partially altered ( = 0.02 to 0

  3. Effects of dumb-bell exercise with and without energy restriction on resting metabolic rate, diet-induced thermogenesis and body composition in mildly obese women.

    PubMed

    Matsuo, T; Suzuki, M

    1999-06-01

    The effects of dumb-bell exercise (aerobic-resistance exercise) with and without low calorie diet (LCD) therapy on resting metabolic rate (RMR), diet-induced thermogenesis (DIT) and body composition were studied in 12 mildly obese women aged 19-20 years. The subjects were randomly assigned to one of the following two groups: dumb-bell exercise with LCD (DEx + LCD group), and dumb-bell exercise only (DEx group). The subjects performed dumb-bell exercises with pairs of 2 kg dumb-bells every day after dinner for approximately 20 min. In the DEx + LCD group, subjects also received a liquid-formula diet based on a commercially available diet supplement, Micro Diet, for two of their three daily meals. Thus, they were restricted to approximately 4.18 MJ of energy intake per day for 12 weeks. Subjects underwent several measurements (body composition, RMR and DIT tests) before commencing the experiment and again after 12 weeks while still dieting. During the 12 week experimental period, body weight and body fat decreased significantly in both the DEx + LCD and the DEx groups without reducing fat free mass (FFM). The decreases in body weight and body fat were significantly larger in the LCD + DEx group than in the DEx group. These results suggest that dumb-bell exercise decreases body weight and body fat without reducing FFM in relation to increasing RMR and DIT. Micro Diet LCD may strengthen the effect of dumb-bell exercise on body weight and body fat, but weaken the effects on RMR and DIT.

  4. The contrasting effects of ad libitum and restricted feeding of a diet very high in saturated fats on sex ratio and metabolic hormones in mice.

    PubMed

    Alexenko, Andrei P; Mao, Jiude; Ellersieck, Mark R; Davis, Angela M; Whyte, Jeffrey J; Rosenfeld, Cheryl S; Roberts, R Michael

    2007-10-01

    Skewing of the sex ratio towards males occurs among pups born to mice fed a very high saturated fat (VHF) diet. In the present study, we tested whether the fat content of the VHF diet rather than the number of calories consumed is responsible for this effect. Eight-week-old NIH Swiss mice were placed on the VHF diet either ad libitum (VHF) or in a restricted manner (VHF-R). The VHF-R mice gained weight at a similar rate to controls fed a standard chow diet. Mice were bred at 15 wk and subsequently at 26 wk and 35 wk of age. Overall, the VHF, VHF-R, and control groups delivered 244, 242, and 274 pups, respectively, with male proportions of 0.60, 0.43, and 0.48, respectively. The pup sex ratios of the VHF group (favoring males) and VHF-R group (favoring females) each differed from 0.5 (P < 0.01). The sex ratios also differed (P < 0.0001) between the VHF and control groups, and between the VHF and VHF-R groups. Within the diet groups, maternal body weight had no effect on sex ratio. Serum leptin concentrations among the dams were similar in the VHF and VHF-R groups but higher than in the control group, while the IGF1 and corticosterone levels were comparable in all three groups. Therefore, the atypical sex ratios of offspring born to dams on the VHF diet seem to be influenced by the amount of fat consumed. Since males fed the VHF diet had neither more Y-sperm nor sired more sons than daughters, the dietary effects are manifested exclusively through the female.

  5. The effect of an iodine restricted including no sea foods diet, on technetium-99m thyroid scintigraphy: a neglected issue in nuclear medicine practice.

    PubMed

    Javadi, Hamid; Neshandarasli, Isa; Mogharrabi, Mehdi; Jalallat, Sara; Nabipour, Iraj; Assadi, Majid

    2012-01-01

    Although it is recommended to patients to avoid sea food and iodine-containing medications prior to iodine-131 (¹³¹I) scanning, the efficacy of this diet as for technetium-99m pertechnetate ((99m)Tc-P) thyroid scintigraphy is not well addressed in the literature. We evaluated a self-managed, outpatients, iodine restricted diet (IRD) designed to reduce total body iodine in preparation for such a scan. We have studied 39 patients who referred to our Department for multinodular goiter, 30 females and 9 males, aged:14-54 years and their (99m)Tc-P thyroid scintigraphy showed poor visualization of the thyroid gland. These patiens were living in regions with high consumption of sea foods went underwent a two-weeks iodine restriction including restriction of sea food diet for the reduction of iodine body content. These patients were called for a repeated scan after going on a IRD for at least two weeks. The two scans were compared visually, and by semiquantitative analysis. Semiquantitative analysis was applied in 8 regions of interest (ROI) by using Wilcoxon signed rank test. Thirty-six subjects had better quality scintigraphy images in the post IRD thyroid scan, as was visually assessed by two nuclear medicine physicians. Semiquantitatetively, there was a significant difference in the mean counts of ROI of the right and the left thyroid lobes in favor of the post IRD scans (P<0.05). In conclusion, this study suggests that in patients with multinodular goiter, living in regions with high consumption of sea foods a two-weeks diet for the reduction of iodine body content induces in most of the cases a slightly better diagnostic thyroid (99m)Tc-P scan.

  6. Validating growth and development of a seabird as an indicator of food availability: captive-reared Caspian Tern chicks fed ad libitum and restricted diets

    USGS Publications Warehouse

    Lyons, Donald E.; Roby, Daniel D.

    2011-01-01

    For seabirds raising young under conditions of limited food availability, reducing chick provisioning and chick growth rates are the primary means available to avoid abandonment of a breeding effort. For most seabirds, however, baseline data characterizing chick growth and development under known feeding conditions are unavailable, so it is difficult to evaluate chick nutritional status as it relates to foraging conditions near breeding colonies. To address this need, we examined the growth and development of young Caspian Terns (Hydroprogne caspia), a cosmopolitan, generalist piscivore, reared in captivity and fed ad libitum and restricted (ca. one-third lower caloric intake) diets. Ad libitum-fed chicks grew at similar rates and achieved a similar size at fledging as previously documented for chicks in the wild and had energetic demands that closely matched allometric predictions. We identified three general characteristics of food-restricted Caspian Tern chicks compared to ad libitum chicks: (1) lower age-specific body mass, (2) lower age-specific skeletal and feather size, such as wing chord length, and (3) heightened levels of corticosterone in blood, both for baseline levels and in response to acute stress. Effects of diet restriction on feather growth (10-11% slower growth in diet-restricted chicks) were less pronounced than effects on structural growth (37-52% slower growth) and body mass (24% lower at fledging age), apparently due to preferential allocation of food resources to maintain plumage growth. Our results suggest that measurements of chick body mass and feather development (e.g., wing chord or primary length) or measurement of corticosterone levels in the blood would allow useful evaluation of the nutritional status of chicks reared in the wild and of food availability in the foraging range of adults. Such evaluations could also inform demography studies (e.g., predict future recruitment) and assist in evaluating designated piscivorous waterbird

  7. Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice.

    PubMed

    Maia-Ceciliano, Thais C; Barreto-Vianna, Andre R C; Barbosa-da-Silva, Sandra; Aguila, Marcia B; Faria, Tatiane S; Mandarim-de-Lacerda, Carlos A

    2016-10-01

    The maternal deficiency of vitamin D can act on organogenesis in mice offspring, being a risk factor for chronic diseases in adulthood. This study investigates the effects of maternal deficiency of vitamin D on structural islet remodeling and insulin-signaling pathway in the offspring. We studied male C57Bl/6 offspring at 3-month old (n = 10/group) from mother fed one of the two diets: control diet (C) or vitamin D-restricted diet (VitD(-)). After weaning, offspring only fed the control diet ad libitum. In the offspring, we studied insulin production, islet remodeling, and islet protein expression of the insulin-signaling pathway (Western blotting, isolated islet, n = 5/group). VitD(-) offspring showed greater glycemia (P = 0.012), smaller beta-cell mass (P = 0.014), and hypoinsulinemia (P = 0.024) than C offspring. Comparing VitD(-) offspring with C offspring, we observed lower protein levels in islet of insulin (P = 0.003), insulin receptor substrate-1 (P = 0.025), phosphatidylinositol-3-kinases (P = 0.045), 3-phosphoinositide-dependent protein kinase 1 (P = 0.017), protein kinase B (P = 0.028), with reduced expression of pancreas/duodenum homeobox-1 (PDX-1) (P = 0.016), glucose transporter-2 (P = 0.003), and glucokinase (P = 0.045). The maternal vitamin D-restricted diet modifies the development of the pancreas of the offspring, leading to islet remodeling and altered insulin-signaling pathway. The decrease of PDX-1 is probably significant to the changes in the beta-cell mass and insulin secretion in adulthood.

  8. The protective effect of intermittent calorie restriction on mammary tumorigenesis is not compromised by consumption of a high fat diet during refeeding.

    PubMed

    Rogozina, Olga P; Nkhata, Katai J; Nagle, Emily J; Grande, Joseph P; Cleary, Margot P

    2013-04-01

    Previously we reported that intermittent calorie restriction (ICR) provided greater prevention of mammary tumors (MTs) than chronic calorie restriction (CCR). Here the impact of increased fat intake during refeeding in an ICR protocol was evaluated. MMTV-TGF-α female mice were assigned to one of three groups: ad libitum (AL) fed (n = 45) with free access to a moderately high fat diet (22 % fat calories); ICR (n = 45) 50 % calorie restricted for 3-week intervals followed by 3 weeks of 100 % of AL intake; and CCR (n = 45) fed 75 % of AL mice, matching each 6-week cycle of ICR mice. ICR mice were further designated as ICR-Restricted or ICR-Refed for data obtained during these intervals. All mice consumed the same absolute amount of dietary fat. Mice were followed to assess MT incidence, body weight and serum IGF-1, IGFBP3, leptin and adiponectin levels until 79 (end of final 3-week restriction) or 82 (end of final 3-weeks refeeding) weeks of age. Age of MT detection was significantly extended for CCR (74 weeks) and ICR (82 weeks) mice, compared to 57.5 weeks for AL mice. MT incidence for AL, ICR and CCR mice was 66.7, 4.4, and 52.3 %, respectively. Mammary and fat pad weights were reduced significantly following 50 % calorie restriction in ICR-Restricted mice compared to AL, CCR and ICR-Refed mice. IGF-1 and leptin levels also tended to be reduced in ICR-Restricted mice over the course of the study while adiponectin was not compared to AL, CCR, and ICR-Refed mice. The adiponectin:leptin ratio was consistently higher following 50 % restriction in ICR-Restricted mice. There was no relationship of IGF-1, leptin, or adiponectin with the presence of MTs in any groups. Thus the manner in which calories are restricted impacts the protective effect of calorie restriction independently of high fat intake.

  9. A high calcium, skim milk powder diet results in a lower fat mass in male, energy-restricted, obese rats more than a low calcium, casein, or soy protein diet.

    PubMed

    Eller, Lindsay K; Reimer, Raylene A

    2010-07-01

    The combination of dairy protein and dietary calcium (Ca) may enhance weight loss more effectively than either compound alone. Our purpose in this study was to determine the effect of various protein sources [skim milk powder (SMP), whey, casein, and soy protein isolate (SPI)] and 2 levels of Ca [low, 0.67% Ca (LC) or high, 2.4% Ca (HC)] on weight loss. Sixty-four 12-wk-old Sprague-Dawley, diet-induced obese rats were assigned to 1 of 8 energy-restricted (ER) diets for 4 wk with 1 of the 4 protein sources and either LC or HC concentrations. Rats were ER to 70% of the ad libitum food and energy intake of a reference group (n = 8) fed the AIN-93M diet. The interaction between dietary protein and Ca affected final body weight and fat mass (FM) (P < 0.05). FM was less in rats fed SMP-HC than in those fed casein-LC or SPI-LC. Lean body mass was greater in rats fed SMP than in those fed whey. Rats fed HC diets had a lower plasma glucagon area under the curve (AUC) than those fed LC diets. The blood glucose AUC, homeostatic model of insulin resistance, and the expression of certain hepatic genes involved in energy metabolism were affected by protein and Ca. These data suggest that consuming a diet containing SMP and HC is associated with a lower FM in obese, male, ER rats than in diets containing casein or SPI and LC; however, the role of SMP and Ca in glucose homeostasis remains to be determined.

  10. Branched-chain Amino Acids are Beneficial to Maintain Growth Performance and Intestinal Immune-related Function in Weaned Piglets Fed Protein Restricted Diet

    PubMed Central

    Ren, M.; Zhang, S. H.; Zeng, X. F.; Liu, H.; Qiao, S. Y.

    2015-01-01

    As a novel approach for disease control and prevention, nutritional modulation of the intestinal health has been proved. However, It is still unknown whether branched-chain amino acid (BCAA) is needed to maintain intestinal immune-related function. The objective of this study was to determine whether BCAA supplementation in protein restricted diet affects growth performance, intestinal barrier function and modulates post-weaning gut disorders. One hundred and eight weaned piglets (7.96±0.26 kg) were randomly fed one of the three diets including a control diet (21% crude protein [CP], CON), a protein restricted diet (17% CP, PR) and a BCAA diet (BCAA supplementation in the PR diet) for 14 d. The growth performance, plasma amino acid concentrations, small intestinal morphology and intestinal immunoglobulins were tested. First, average daily gain (ADG) (p<0.05) and average daily feed intake (ADFI) (p<0.05) of weaned pigs in PR group were lower, while gain:feed ratio was lower than the CON group (p<0.05). Compared with PR group, BCAA group improved ADG (p<0.05), ADFI (p<0.05) and feed:gain ratio (p<0.05) of piglets. The growth performance data between CON and BCAA groups was not different (p>0.05). The PR and BCAA treatments had a higher (p<0.05) plasma concentration of methionine and threonine than the CON treatment. The level of some essential and functional amino acids (such as arginine, phenylalanine, histidine, glutamine etc.) in plasma of the PR group was lower (p<0.05) than that of the CON group. Compared with CON group, BCAA supplementation significantly increased BCAA concentrations (p<0.01) and decreased urea concentration (p<0.01) in pig plasma indicating that the efficiency of dietary nitrogen utilization was increased. Compared with CON group, the small intestine of piglets fed PR diet showed villous atrophy, increasing of intra-epithelial lymphocytes (IELs) number (p<0.05) and declining of the immunoglobulin concentration, including jejunal

  11. Branched-chain Amino Acids are Beneficial to Maintain Growth Performance and Intestinal Immune-related Function in Weaned Piglets Fed Protein Restricted Diet.

    PubMed

    Ren, M; Zhang, S H; Zeng, X F; Liu, H; Qiao, S Y

    2015-12-01

    As a novel approach for disease control and prevention, nutritional modulation of the intestinal health has been proved. However, It is still unknown whether branched-chain amino acid (BCAA) is needed to maintain intestinal immune-related function. The objective of this study was to determine whether BCAA supplementation in protein restricted diet affects growth performance, intestinal barrier function and modulates post-weaning gut disorders. One hundred and eight weaned piglets (7.96±0.26 kg) were randomly fed one of the three diets including a control diet (21% crude protein [CP], CON), a protein restricted diet (17% CP, PR) and a BCAA diet (BCAA supplementation in the PR diet) for 14 d. The growth performance, plasma amino acid concentrations, small intestinal morphology and intestinal immunoglobulins were tested. First, average daily gain (ADG) (p<0.05) and average daily feed intake (ADFI) (p<0.05) of weaned pigs in PR group were lower, while gain:feed ratio was lower than the CON group (p<0.05). Compared with PR group, BCAA group improved ADG (p<0.05), ADFI (p<0.05) and feed:gain ratio (p<0.05) of piglets. The growth performance data between CON and BCAA groups was not different (p>0.05). The PR and BCAA treatments had a higher (p<0.05) plasma concentration of methionine and threonine than the CON treatment. The level of some essential and functional amino acids (such as arginine, phenylalanine, histidine, glutamine etc.) in plasma of the PR group was lower (p<0.05) than that of the CON group. Compared with CON group, BCAA supplementation significantly increased BCAA concentrations (p<0.01) and decreased urea concentration (p<0.01) in pig plasma indicating that the efficiency of dietary nitrogen utilization was increased. Compared with CON group, the small intestine of piglets fed PR diet showed villous atrophy, increasing of intra-epithelial lymphocytes (IELs) number (p<0.05) and declining of the immunoglobulin concentration, including jejunal

  12. Assessing parents' attitudes towards ketogenic dietary therapies.

    PubMed

    Schoeler, Natasha E; MacDonald, Lindsay; Champion, Helena; Cross, J Helen; Sander, Josemir W; Sisodiya, Sanjay M; Horne, Rob

    2014-10-01

    We aimed to assess and quantify parental beliefs regarding ketogenic dietary therapies (KDTs). We also aimed to determine whether beliefs were related to response to KDTs. Adapted versions of the Beliefs about Medicine Questionnaire were completed by parents of children following KDTs for epilepsy. Demographic and clinical data were collected from hospital records. Ketogenic dietary therapy response was defined as ≥50% seizure reduction compared to baseline. Many parents had a positive perception of KDTs and were convinced of the necessity of KDTs for their children, although beliefs were wide-ranging. Over half of parents reported concerns about the potential long-term effects of KDTs. Parental beliefs about KDTs were significantly correlated with patient response. This was an attempt to quantify parents' beliefs regarding the use of KDTs for their child's epilepsy. The questionnaire may be used to identify individuals with a less positive attitude towards KDTs and who may be less likely to report a favorable response to KDTs. It is unknown whether people who have positive beliefs about KDTs engage in less nonadherent behavior or whether beliefs regarding KDTs simply reflect outcomes. The evidence behind the long-term side effects of KDTs should be emphasized when counseling patients and their families.

  13. Adipose tissue metabolism and inflammation are differently affected by weight loss in obese mice due to either a high-fat diet restriction or change to a low-fat diet.

    PubMed

    Hoevenaars, Femke P M; Keijer, Jaap; Herreman, Laure; Palm, Inge; Hegeman, Maria A; Swarts, Hans J M; van Schothorst, Evert M

    2014-05-01

    Restriction of a high-fat diet (HFD) and a change to a low-fat diet (LFD) are two interventions that were shown to promote weight loss and improve parameters of metabolic health in obesity. Examination of the biochemical and molecular responses of white adipose tissue (WAT) to these interventions has not been performed so far. Here, male C57BL/6JOlaHsd mice, harboring an intact nicotinamide nucleotide transhydrogenase gene, were fed a purified 40 energy% HFD for 14 weeks to induce obesity. Afterward, mice were divided into three dietary groups: HFD (maintained on HFD), LFD (changed to LFD with identical ingredients), and HFD-CR (restricted to 70 % of the HFD). The effects of the interventions were examined after 5 weeks. Beneficial effects were seen for both HFD-CR and LFD (compared to HFD) regarding physiological parameters (body weight and fat mass) and metabolic parameters, including circulating insulin and leptin levels. Macrophage infiltration in WAT was reduced by both interventions, although more effectively by HFD-CR. Strikingly, molecular parameters in WAT differed between HFD-CR and LFD, with increased activation of mitochondrial carbohydrate and fat metabolism in HFD-CR mice. Our results confirm that restriction of the amount of dietary intake and reduction in the dietary energy content are both effective in inducing weight loss. The larger decrease in WAT inflammation and increase in mitochondrial carbohydrate metabolism may be due to a larger degree of energy restriction in HFD-CR, but could also be due to superior effectiveness of dietary restriction in weight loss strategies.

  14. Intrauterine growth restriction combined with a maternal high-fat diet increases hepatic cholesterol and low-density lipoprotein receptor activity in rats.

    PubMed

    Zinkhan, Erin K; Zalla, Jennifer M; Carpenter, Jeanette R; Yu, Baifeng; Yu, Xing; Chan, Gary; Joss-Moore, Lisa; Lane, Robert H

    2016-07-01

    Intrauterine growth restriction (IUGR) and maternal consumption of a high-saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation.

  15. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

    PubMed Central

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation. PMID:25892856

  16. Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet.

    PubMed

    Kimani, S; Moterroso, V; Morales, P; Wagner, J; Kipruto, S; Bukachi, F; Maitai, C; Tshala-Katumbay, D

    2014-04-01

    We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC.

  17. Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure response of obese subjects, even after following an energy-restricted diet

    PubMed Central

    Ibero-Baraibar, Idoia; Suárez, Manuel; Arola-Arnal, Anna; Zulet, M. Angeles; Martinez, J. Alfredo

    2016-01-01

    Background Cardiometabolic profile is usually altered in obesity. Interestingly, the consumption of flavanol-rich foods might be protective against those metabolic alterations. Objective To evaluate the postprandial cardiometabolic effects after the acute consumption of cocoa extract before and after 4 weeks of its daily intake. Furthermore, the bioavailability of cocoa extract was investigated. Design Twenty-four overweight/obese middle-aged subjects participated in a 4-week intervention study. Half of the volunteers consumed a test meal enriched with 1.4 g of cocoa extract (415 mg flavanols), while the rest of the volunteers consumed the same meal without the cocoa extract (control group). Glucose and lipid profile, as well as blood pressure and cocoa metabolites in plasma, were assessed before and at 60, 120, and 180 min post-consumption, at the beginning of the study (Postprandial 1) and after following a 4-week 15% energy-restricted diet including meals containing or not containing the cocoa extract (Postprandial 2). Results In the Postprandial 1 test, the area under the curve (AUC) of systolic blood pressure (SBP) was significantly higher in the cocoa group compared with the control group (p=0.007), showing significant differences after 120 min of intake. However, no differences between groups were observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of SBP (AUC_Postprandial 2-AUC_Postprandial 1) was higher in the cocoa group (p=0.016). Furthermore, cocoa-derived metabolites were detected in plasma of the cocoa group, while the absence or significantly lower amounts of metabolites were found in the control group. Conclusions The daily consumption of cocoa extract within an energy-restricted diet for 4 weeks resulted in a greater reduction of postprandial AUC of SBP compared with the effect of energy-restricted diet alone and independently of body weight loss. These results suggest the role of cocoa flavanols on postprandial blood

  18. Use of a long-chain triglyceride-restricted/medium-chain triglyceride-supplemented diet in a case of malonyl-CoA decarboxylase deficiency with cardiomyopathy.

    PubMed

    Footitt, E J; Stafford, J; Dixon, M; Burch, M; Jakobs, C; Salomons, G S; Cleary, M A

    2010-12-01

    Malonyl coenzyme A (CoA) decarboxylase (EC 4.1.1.9, MCD) deficiency, or malonic aciduria, is a rare inborn error of metabolism characterised by a variable phenotype of developmental delay, seizures, cardiomyopathy and acidosis. There is no consensus for dietary treatment in this condition. This case describes the effect of a long-chain triglyceride (LCT)-restricted/medium-chain triglyceride (MCT)-supplemented diet upon the progress of an affected child. A full-term Asian girl of birth weight 3590 g was screened for malonic aciduria after birth due to a positive family history. She had elevated urine malonic and methylmalonic acids and was presumably homozygous for a deleterious mutation in the MLYCD gene. Her echocardiography showed mild cardiomyopathy at 0.5 months of age, but heart function was good. She was treated with carnitine 100 mg/kg per day and continued a high-energy formula feed, as her growth was slow. At 3 months of age, echocardiography showed deteriorating cardiac function with a fractional shortening of 18%. She started an angiotensin-converting enzyme (ACE) inhibitor (Captopril). Over the next few months, her diet was altered to comprise 1.9% energy from LCT, 25% from MCT and the remainder carbohydrate. Cardiac function improved and was optimal at 23 months of age, with a fractional shortening of 28% and good systolic function. During a period of low MCT intake, her cardiac function was noted to deteriorate. This reversed and stabilised following reinstatement of the diet. This case of malonic aciduria with cardiomyopathy demonstrates improvement in cardiac function attributable to LCT-restricted/MCT-supplemented diet.

  19. Meta-Analysis of Attention-Deficit/Hyperactivity Disorder or Attention-Deficit/Hyperactivity Disorder Symptoms, Restriction Diet, and Synthetic Food Color Additives

    PubMed Central

    Nigg, Joel T.; Lewis, Kara; Edinger, Tracy; Falk, Michael

    2015-01-01

    Objective The role of diet and of food colors in attention-deficit/hyperactivity disorder (ADHD) or its symptoms warrants updated quantitative meta-analysis, in light of recent divergent policy in Europe and the United States. Method Studies were identified through a literature search using the PubMed, Cochrane Library, and PsycNET databases through February 2011. Twenty-four publications met inclusion criteria for synthetic food colors; 10 additional studies informed analysis of dietary restriction. A random-effects meta-analytic model generated summary effect sizes. Results Restriction diets reduced ADHD symptoms at an effect of g = 0.29 (95% CI, 0.07–0.53). For food colors, parent reports yielded an effect size of g = 0.18 (95% CI, 0.08–0.24; p = .0007), which decreased to 0.12 (95% CI, 0.01–0.23; p < .05) after adjustment for possible publication bias. The effect was reliable in studies restricted to food color additives (g = 0.21, 95% CI = 0.06–0.36) but did not survive correction for possible publication bias and was not reliable in studies confined to Food and Drug Administration–approved food colors. Teacher/observer reports yielded a nonsignificant effect of 0.07 (95% CI = −0.03 to 0.18; p = .14). However, high-quality studies confined to color additives yielded a reliable effect (g = 0.22, 95% CI = 0.10–0.41, p = .030) that survived correction. In psychometric tests of attention, the summary effect size was 0.27 (95% CI = 0.07–0.47; p = .007) and survived correction. An estimated 8% of children with ADHD may have symptoms related to synthetic food colors. Conclusions A restriction diet benefits some children with ADHD. Effects of food colors were notable were but susceptible to publication bias or were derived from small, nongeneralizable samples. Renewed investigation of diet and ADHD is warranted. PMID:22176942

  20. [Autism spectrum disorder and epilepsy: the role of ketogenic diet].

    PubMed

    Garcia-Penas, J J

    2016-01-01

    Introduccion. Un 5-40% de los pacientes autistas desarrolla epilepsia. Aunque generalmente se controlan bien con medicacion, hasta un 20-30% de estas epilepsias son refractarias al tratamiento farmacologico. En esta poblacion, la dieta cetogenica (DC) puede ser una terapia alternativa altamente eficaz y debe considerarse seriamente. Objetivo. Revisar el papel de la DC en el tratamiento de la epilepsia infantil refractaria y en los pacientes que asocian autismo y epilepsia. Desarrollo. La DC es un tratamiento eficaz y bien tolerado para las epilepsias infantiles refractarias, incluyendo los pacientes que asocian autismo y epilepsia. Es fundamental caracterizar de forma precisa el sindrome epileptico para conocer cuales son los mejores candidatos para tratar con DC. Por otra parte, el efecto positivo de la DC sobre las alteraciones del metabolismo oxidativo mitocondrial y la evidencia experimental obtenida con DC en animales autistas sugieren que pueda ser una alternativa eficaz en los pacientes con autismo. Conclusiones. Basandose en la utilidad demostrada de la DC en el tratamiento de pacientes con epilepsia y autismo, esta terapia se ha usado en los ultimos años como una terapia alternativa para los pacientes autistas, aunque se desconoce cual es su eficacia real. Es necesario realizar un estudio aleatorizado y controlado para definir el perfil de eficacia y seguridad en esta poblacion.

  1. Calorie restriction in overweight seniors: response of older adults to a dieting study: the CROSSROADS randomized controlled clinical trial.

    PubMed

    Haas, Marilyn C; Bodner, Eric V; Brown, Cynthia J; Bryan, David; Buys, David R; Keita, Akilah Dulin; Flagg, Lee Anne; Goss, Amy; Gower, Barbara; Hovater, Martha; Hunter, Gary; Ritchie, Christine S; Roth, David L; Wingo, Brooks C; Ard, Jamy; Locher, Julie L

    2014-01-01

    We conducted a study designed to evaluate whether the benefits of intentional weight loss exceed the potential risks in a group of community-dwelling obese older adults who were at increased risk for cardiometabolic disease. The CROSSROADS trial used a prospective randomized controlled design to compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition and adipose tissue deposition (Specific Aim #1: To compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition, namely visceral adipose tissue), cardiometabolic disease risk (Specific Aim #2: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on cardiometabolic disease risk), and functional status and quality of life (Specific Aim #3: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on functional status and quality of life). Participants were randomly assigned to one of three groups: Exercise Only (Control) Intervention, Exercise + Diet Quality + Weight Maintenance Intervention, or Exercise + Diet Quality + Weight Loss Intervention. CROSSROADS utilized a lifestyle intervention approach consisting of exercise, dietary, and behavioral components. The development and implementation of the CROSSROADS protocol, including a description of the methodology, detailing specific elements of the lifestyle intervention, assurances of treatment fidelity, and participant retention; outcome measures and adverse event monitoring; as well as unique data management features of the trial results, are presented in this article.

  2. Diet-induced ketosis does not cause cerebral acidosis.

    PubMed

    Al-Mudallal, A S; LaManna, J C; Lust, W D; Harik, S I

    1996-03-01

    Ketosis is beneficial for seizure control, possibly through induction of cerebral acidosis. However, cerebral intracellular pH has not previously been measured in ketotic humans and the animal data are sparse. We describe a high-fat diet, avidly consumed by rats, that induced consistent and moderate ketosis. Adult male rats were fed either the high-fat ketogenic diet, a high-carbohydrate diet with the same protein content as the ketogenic diet, or regular laboratory chow. Five to 6 weeks later, the rats were anesthetized, paralyzed, and injected with neutral red; their brains were frozen in situ. Intracellular pH of the cerebral cortex and cerebral glucose, lactate, ATP, phosphocreatine, and gama-aminobutyric acid (GABA) levels were measured. Rats fed the ketogenic diet had > 10-fold increase in their plasma ketones, but we noted no significant differences in cerebral pH or in cerebral metabolites and GABA levels among the three groups. Therefore, the antiepileptic effect of the ketogenic diet probably is not mediated by cerebral acidosis or changes in total cerebral GABA levels.

  3. 21 CFR 862.1385 - 17-Hydroxycorticosteroids (17-ketogenic steroids) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false 17-Hydroxycorticosteroids (17-ketogenic steroids... Clinical Chemistry Test Systems § 862.1385 17-Hydroxycorticosteroids (17-ketogenic steroids) test system. (a) Identification. A 17-hydroxycorticosteroids (17-ketogenic steroids) test system is a...

  4. 21 CFR 862.1385 - 17-Hydroxycorticosteroids (17-ketogenic steroids) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false 17-Hydroxycorticosteroids (17-ketogenic steroids... Clinical Chemistry Test Systems § 862.1385 17-Hydroxycorticosteroids (17-ketogenic steroids) test system. (a) Identification. A 17-hydroxycorticosteroids (17-ketogenic steroids) test system is a...

  5. 21 CFR 862.1385 - 17-Hydroxycorticosteroids (17-ketogenic steroids) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false 17-Hydroxycorticosteroids (17-ketogenic steroids... Clinical Chemistry Test Systems § 862.1385 17-Hydroxycorticosteroids (17-ketogenic steroids) test system. (a) Identification. A 17-hydroxycorticosteroids (17-ketogenic steroids) test system is a...

  6. 21 CFR 862.1385 - 17-Hydroxycorticosteroids (17-ketogenic steroids) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 17-Hydroxycorticosteroids (17-ketogenic steroids... Clinical Chemistry Test Systems § 862.1385 17-Hydroxycorticosteroids (17-ketogenic steroids) test system. (a) Identification. A 17-hydroxycorticosteroids (17-ketogenic steroids) test system is a...

  7. Effect of a dairy and calcium rich diet on weight loss and appetite during energy restriction in overweight and obese adults: a randomized trial

    PubMed Central

    Jones, Kim Wagner; Eller, Lindsay K.; Parnell, Jill A.; Doyle-Baker, Patricia K.; Edwards, Alun L.; Reimer, Raylene A.

    2014-01-01

    Background/Objectives A diet rich in dairy and calcium (Ca) has been variably associated with improvements in body composition and decreased risk of type 2 diabetes. Our objective was to determine if a dietary pattern high in dairy and Ca improves weight loss and subjective appetite to a greater extent than a low dairy/Ca diet during energy restriction in overweight and obese adults with metabolic syndrome. Subjects/Methods 49 participants were randomized to one of two treatment groups: CONTROL [low dairy, ~700 mg/day Ca, −500 kcal/d] or DAIRY/CA [high dairy, ~1400 mg/day Ca, −500 kcal/d] for 12wk. Body composition, subjective ratings of appetite, food intake, plasma satiety hormones, glycemic response and inflammatory cytokines were measured. Results CONTROL (−2.2±0.5 kg) and DAIRY/CA (−3.3±0.6 kg) had similar weight loss. Based on self-reported energy intake, the percent of expected weight loss achieved was higher with DAIRY/CA (82.1±19.4%) than CONTROL (32.2±7.7%)(P=0.03). Subjects in the DAIRY/CA group reported feeling more satisfied (P=0.01) and had lower dietary fat intake (P=0.02) over 12wk compared to CONTROL. Compared to CONTROL, DAIRY/CA had higher plasma levels of peptide tyrosine tyrosine (PYY, P=0.01) during the meal tolerance test at wk12. Monocyte chemoattractant protein-1 was reduced at 30 min with DAIRY/CA compared to CONTROL (P=0.04). Conclusions In conclusion, a dairy and Ca rich diet was not associated with greater weight loss than control. Modest increases in plasma PYY concentrations with increased dairy/Ca intake, however, may contribute to enhanced sensations of satisfaction and reduced dietary fat intake during energy restriction. Registered Trial: ClinicalTrials.gov (NCT00564551). PMID:23462943

  8. Effectiveness of Annealing Blocking Primers versus Restriction Enzymes for Characterization of Generalist Diets: Unexpected Prey Revealed in the Gut Contents of Two Coral Reef Fish Species

    PubMed Central

    Leray, Matthieu; Agudelo, Natalia; Mills, Suzanne C.; Meyer, Christopher P.

    2013-01-01

    Characterization of predator-prey interactions is challenging as researchers have to rely on indirect methods that can be costly, biased and too imprecise to elucidate the complexity of food webs. DNA amplification and sequencing techniques of gut and fecal contents are promising approaches, but their success largely depends on the ability to amplify the taxonomic array of prey consumed and then match prey amplicons with reference sequences. When little a priori information on diet is available or a generalist predator is targeted, versatile primer sets (also referred to as universal or general primers) as opposed to group- or species-specific primer sets are the most powerful to unveil the full range of prey consumed. However, versatile primers are likely to preferentially amplify the predominant, less degraded predator DNA if no manipulation is performed to exclude this confounding DNA template. In this study we compare two approaches that eliminate the confounding predator template: restriction digestion and the use of annealing blocking primers. First, we use a preliminary DNA barcode library provided by the Moorea BIOCODE project to 1) evaluate the cutting frequency of commercially available restriction enzymes and 2) design predator specific annealing blocking primers. We then compare the performance of the two predator removal strategies for the detection of prey templates using two versatile primer sets from the gut contents of two generalist coral reef fish species sampled in Moorea. Our study demonstrates that blocking primers should be preferentially used over restriction digestion for predator DNA removal as they recover greater prey diversity. We also emphasize that a combination of versatile primers may be required to best represent the breadth of a generalist's diet. PMID:23579925

  9. Diet-related restrictive parenting practices. Impact on dietary intake of 2-year-old children and interactions with child characteristics.

    PubMed

    Gubbels, Jessica S; Kremers, Stef P J; Stafleu, Annette; Dagnelie, Pieter C; Goldbohm, R Alexandra; de Vries, Nanne K; Thijs, Carel

    2009-04-01

    This study examined the relationship between diet-related parenting practices, parental characteristics, child characteristics, and 2-year-old child's dietary intake. Cross-sectional data (N=2578) originated from the KOALA Birth Cohort Study. Principal component analyses revealed two restrictive parenting practice clusters: a cluster characterized by prohibition of the intake of various snacks and soft drinks, and a separate cluster characterized by prohibition of cookies and cake. Regression analyses showed that these clusters were related to the children's behavioural style (i.e. oppositional, depressive and/or aggressive behaviour) and to educational level, age and alternative lifestyle of the mother. The clusters also had a favourable influence on dietary intake (i.e. restrictive parenting practices were related to less consumption of the restricted (unhealthy) items and higher consumption of items considered to be healthy), which was moderated by child characteristics. The parenting practices showed a stronger association with dietary intake in children with a favourable behavioural style (i.e. non-depressed, low anxious, low overactive), a favourable eating style or a lower BMI. The findings suggest opportunities for preventive interventions focussing on parents of young children, and indicate that different approaches to parenting practice interventions are needed for different types of children.

  10. Long-term health consequences of epilepsy diet treatments.

    PubMed

    Vining, Eileen P G

    2008-11-01

    The ketogenic diet (KD) typically provides a marginally healthy diet and in recent years has been used for more protracted courses of therapy. This results in concern about the impact of the diet on the general health of the child. Studies have demonstrated poor growth, dyslipidemia, kidney stones, and numerous other problems seen less frequently. Major areas of concern are reviewed as well as some emerging evidence of more beneficial long-term health consequences beyond the expected control of seizures.

  11. Effects of Calorie Restriction and Diet-Induced Obesity on Murine Colon Carcinogenesis, Growth and Inflammatory Factors, and MicroRNA Expression

    PubMed Central

    Olivo-Marston, Susan E.; Hursting, Stephen D.; Perkins, Susan N.; Schetter, Aaron; Khan, Mohammed; Croce, Carlo; Harris, Curtis C.; Lavigne, Jackie

    2014-01-01

    Obesity is an established colon cancer risk factor, while preventing or reversing obesity via a calorie restriction (CR) diet regimen decreases colon cancer risk. Unfortunately, the biological mechanisms underlying these associations are poorly understood, hampering development of mechanism-based approaches for preventing obesity-related colon cancer. We tested the hypotheses that diet-induced obesity (DIO) would increase (and CR would decrease) colon tumorigenesis in the mouse azoxymethane (AOM) model. In addition, we established that changes in inflammatory cytokines, growth factors, and microRNAs are associated with these energy balance-colon cancer links, and thus represent mechanism-based targets for colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and randomized to: 1) control diet; 2) 30% CR diet; or 3) DIO diet. Mice were euthanized at week 5 (n = 12/group), 10 (n = 12/group), and 20 (n = 20/group) after the last AOM injection. Colon tumors were counted, and cytokines, insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), adipokines, proliferation, apoptosis, and expression of microRNAs (miRs) were measured. The DIO diet regimen induced an obese phenotype (∼36% body fat), while CR induced a lean phenotype (∼14% body fat); controls were intermediate (∼26% body fat). Relative to controls, DIO increased (and CR decreased) the number of colon tumors (p = 0.01), cytokines (p<0.001), IGF-1 (p = 0.01), and proliferation (p<0.001). DIO decreased (and CR increased) IGFBP-3 and apoptosis (p<0.001). miRs including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138 were differentially expressed between the dietary groups. We conclude that the enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis are associated with alterations in several biological pathways, including inflammation, IGF-1, and microRNAs. PMID:24732966

  12. Restricting carbohydrates to fight head and neck cancer—is this realistic?

    PubMed Central

    Klement, Rainer J.

    2014-01-01

    Head and neck cancers (HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates (CHOs) and their replacement with fat, mostly in form of a ketogenic diet (KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are (1) targeting the origin and specific aspects of tumor glycolysis; (2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill; (3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself. PMID:25364576

  13. A 3-week feed restriction after weaning as an alternative to a medicated diet: effects on growth, health, carcass and meat traits of rabbits of two genotypes.

    PubMed

    Alabiso, M; Di Grigoli, A; Mazza, F; Maniaci, G; Vitale, F; Bonanno, A

    2016-12-21

    Feed restriction after weaning is widely used in meat rabbit farms to promote health and reduce mortality, but this practice impacts negatively on rabbit growth and slaughter performance. This study compared a 3-week post-weaning feed restriction with ad libitum medicated feeding, evaluating effects on feed intake, growth, health, carcass and meat quality of rabbits of two genotypes: Italian White pure breed and Hycole hybrid×Italian White crossbred. A total of 512 rabbits at 36 days of age, of both sexes and two genotypes, were divided into four homogeneous groups assigned, from 36 to 57 days of age, to different feeding programmes (FP): restricted non-medicated (R-N), ad libitum non-medicated (L-N), restricted medicated (R-M) and ad libitum medicated (L-M). The diets were medicated with oxytetracycline (1540 mg/kg) and colistin sulphate (240 mg/kg). The restriction, performed by giving 70, 80 and 90 g/day of feed for the 1st, 2nd and 3rd week, was followed by ad libitum feeding in the successive 5 weeks, up to slaughter at 92 days of age. Restricted feeds were ingested at a level of 64% of the feed intake recorded in the ad libitum fed rabbits; it was significantly associated, regardless of medication and rabbit genotype, with a lower feed intake (-22 to -24 g dry matter/day) during the entire experiment, compensatory growth and a lower feed conversion ratio in the ad libitum period, and a lower final live weight (-150 g) than ad libitum feeding (P<0.001). During restriction, mortality was lower in the restricted rabbits (6.25%, 5.47% v. 12.5%, 14.8% for R-N, R-M, L-N and L-M; P<0.05), whereas in the ad libitum period mortality did not differ among the groups (9.23%, 9.90%, 11.0% and 4.59% for R-N, R-M, L-N and L-M). Dressing out percentage was not affected by FP or genotype; heavier carcasses were produced by rabbits fed ad libitum (+100 g; P<0.001) and crossbred rabbits (+122 g; P<0.001). Restriction did not alter meat quality, except for a tendency towards a

  14. Influences of dietary vitamin D restriction on bone strength, body composition and muscle in rats fed a high-fat diet: involvement of mRNA expression of MyoD in skeletal muscle.

    PubMed

    Oku, Yuno; Tanabe, Rieko; Nakaoka, Kanae; Yamada, Asako; Noda, Seiko; Hoshino, Ayumi; Haraikawa, Mayu; Goseki-Sone, Masae

    2016-06-01

    Vitamin D insufficiency is associated with a greater risk of osteoporosis and also influences skeletal muscle functions, differentiation and development. The present study investigated the influences of vitamin D restriction on the body composition, bone and skeletal muscle in rats fed a high-fat diet. Sprague-Dawley strain male rats (11weeks old) were divided into four groups and fed experimental diets: a basic control diet (Cont.), a basic control diet with vitamin D restriction (DR), a high-fat diet (F) and a high-fat diet with vitamin D restriction (FDR). At 28days after starting the experimental diets, the visceral fat mass was significantly increased in the F group compared with Cont. group, and the muscle mass tended to decrease in the DR group compared with Cont. group. The total volume of the femur was significantly lower in the DR group compared with Cont. group, and the bone mineral density (BMD) of the femur was significantly lower in the FDR group compared with F group. MyoD is one of the muscle-specific transcription factors. The levels of mRNA expression of MyoD of the gastrocnemius and soleus muscles from the DR group were reduced markedly compared with those from the Cont. group. In conclusion, our findings revealed the influences of a vitamin D-restricted high-fat diet on the bone strength, body composition and muscle. Further studies on vitamin D insufficiency in the regulation of muscle as well as fat and bone metabolism would provide valuable data for the prevention of lifestyle-related disorders, including osteoporosis and sarcopenia.

  15. Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

    PubMed

    Cunha, Fábio da Silva; Dalle Molle, Roberta; Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms.

  16. Short-term moderate diet restriction in adulthood can reverse oxidative, cardiovascular and metabolic alterations induced by postnatal overfeeding in mice

    PubMed Central

    Li, Na; Guenancia, Charles; Rigal, Eve; Hachet, Olivier; Chollet, Pauline; Desmoulins, Lucie; Leloup, Corinne; Rochette, Luc; Vergely, Catherine

    2016-01-01

    We aimed to determine whether moderate diet restriction could restore cardiac, oxidative and metabolic alterations induced by postnatal overfeeding (PNOF). Litters of C57BL/6 male mice were either maintained at 9 (normal litter, NL), or reduced to 3 (small litter, SL) in order to induce PNOF. At 6 months, half of the NL and SL mice were subjected to 20% calorie-restriction (CR: NLCR, SLCR) for one month, while the other half continued to eat ad libitum (AL: NLAL, SLAL). Six-month old SL mice presented overweight, fat accumulation, hyperleptinemia, glucose intolerance, insulin resistance, increased cardiac ROS production and decreased left ventricular ejection fraction (LVEF). After CR, SL mice body weight was normalized; however, their fat mass and leptinemia were not decreased, glucose metabolism was improved and LVEF was increased. In SL mice, CR increased the cardiac mitochondrial respiratory rate and decreased cardiac ROS production. Hearts from SLCR mice showed better recovery and smaller postischemic infarct size. Intriguingly, no difference was observed between NLAL and NLCR mice for most of the parameters investigated. Short-term moderate CR not only normalized body weight in SL mice but also improved metabolic programming and reversed oxidative and cardiac dysfunction induced by PNOF. PMID:27465434

  17. Higher-protein diets improve indexes of sleep in energy-restricted overweight and obese adults: results from 2 randomized controlled trials123

    PubMed Central

    Zhou, Jing; Kim, Jung Eun; Armstrong, Cheryl LH; Chen, Ningning; Campbell, Wayne W

    2016-01-01

    Background: Limited and inconsistent research findings exist about the effect of dietary protein intake on indexes of sleep. Objective: We assessed the effect of protein intake during dietary energy restriction on indexes of sleep in overweight and obese adults in 2 randomized, controlled feeding studies. Design: For study 1, 14 participants [3 men and 11 women; mean ± SE age: 56 ± 3 y; body mass index (BMI; in kg/m2): 30.9 ± 0.6] consumed energy-restricted diets (a 750-kcal/d deficit) with either beef and pork (BP; n = 5) or soy and legume (SL; n = 9) as the main protein sources for 3 consecutive 4-wk periods with 10% (control), 20%, or 30% of total energy from protein (random order). At baseline and the end of each period, the global sleep score (GSS) was assessed with the use of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. For study 2, 44 participants (12 men and 32 women; age: 52 ± 1 y; BMI: 31.4 ± 0.5) consumed a 3-wk baseline energy-balance diet with 0.8 g protein · kg baseline body mass−1 · d−1. Then, study 2 subjects consumed either a normal-protein [NP (control); n = 23] or a high-protein (HP; n = 21) (0.8 compared with 1.5 g · kg−1 · d−1, respectively) energy-restricted diet (a 750-kcal/d deficit) for 16 wk. The PSQI was administered during baseline week 3 and intervention weeks 4, 8, 12, and 16. GSSs ranged from 0 to 21 arbitrary units (au), with a higher value representing a worse GSS during the preceding month. Results: In study 1, we showed that a higher protein quantity improved GSSs independent of the protein source. The GSS was higher (P < 0.05) when 10% (6.0 ± 0.4 au) compared with 20% (5.0 ± 0.4 au) protein was consumed, with 30% protein (5.4 ± 0.6 au) intermediate. In study 2, at baseline, the GSS was not different between NP (5.2 ± 0.5 au) and HP (5.4 ± 0.5 au) groups. Over time, the GSS was unchanged for the NP group and improved for the HP group (P-group-by-time interaction < 0.05). After intervention (week

  18. The modified Atkins diet for intractable epilepsy may be associated with late-onset egg-induced anaphylactic reaction: a case report.

    PubMed

    Levy, Yael; Peleg-Weiss, Lilach; Goldberg-Stern, Hadassa

    2011-03-01

    The modified Atkins diet is a therapeutic option for children with intractable epilepsy. It is less restrictive than the traditional ketogenic diet, with ≈60% of calories from fat sources. We describe a 6-y-old boy with intractable epilepsy treated with the modified Atkins diet who presented to the emergency department with first-time anaphylactic reaction to egg. Symptoms of urticaria and angioedema, shortness of breath, wheezing, and cyanosis developed several minutes after he ate a hard-boiled egg. His history was remarkable for asthma, but no food allergies were documented. The anaphylactic reaction appeared after 6 mo of treatment with the modified Atkins diet (including 10-15 eggs daily), which ameliorated his seizures, and was preceded by streptococcal pharyngitis. Laboratory workup revealed specific immunoglobulin E antibodies to egg. This is the first report of new-onset egg allergy in a child, probably triggered by the high egg content of the modified Atkins diet. The risk of egg allergy should be kept in mind when treating epileptic children with the modified Atkins diet, especially those with comorbid asthma.

  19. Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs.

    PubMed

    Manjarín, Rodrigo; Columbus, Daniel A; Suryawan, Agus; Nguyen, Hanh V; Hernandez-García, Adriana D; Hoang, Nguyet-Minh; Fiorotto, Marta L; Davis, Teresa

    2016-01-01

    Suboptimal nutrient intake represents a limiting factor for growth and long-term survival of low-birth weight infants. The objective of this study was to determine if in neonates who can consume only 70 % of their protein and energy requirements for 8 days, enteral leucine supplementation will upregulate the mammalian target of rapamycin (mTOR) pathway in skeletal muscle, leading to an increase in protein synthesis and muscle anabolism. Nineteen 4-day-old piglets were fed by gastric tube 1 of 3 diets, containing (kg body weight(-1) · day(-1)) 16 g protein and 190 kcal (CON), 10.9 g protein and 132 kcal (R), or 10.8 g protein + 0.2 % leucine and 136 kcal (RL) at 4-h intervals for 8 days. On day 8, plasma AA and insulin levels were measured during 6 post-feeding intervals, and muscle protein synthesis rate and mTOR signaling proteins were determined at 120 min post-feeding. At 120 min, leucine was highest in RL (P < 0.001), whereas insulin, isoleucine and valine were lower in RL and R compared to CON (P < 0.001). Compared to RL and R, the CON diet increased (P < 0.01) body weight, protein synthesis, phosphorylation of S6 kinase (p-S6K1) and 4E-binding protein (p-4EBP1), and activation of eukaryotic initiation factor 4 complex (eIF4E · eIF4G). RL increased (P ≤ 0.01) p-S6K1, p-4EBP1 and eIF4E · eIF4G compared to R. In conclusion, when protein and energy intakes are restricted for 8 days, leucine supplementation increases muscle mTOR activation, but does not improve body weight gain or enhance skeletal muscle protein synthesis in neonatal pigs.

  20. In Vitro Cellular Adaptations of Indicators of Longevity in Response to Treatment with Serum Collected from Humans on Calorie Restricted Diets

    PubMed Central

    Allard, Joanne S.; Heilbronn, Leonie K.; Smith, Carolina; Hunt, Nicole D.; Ingram, Donald K.; Ravussin, Eric; de Cabo, Rafael

    2008-01-01

    Calorie restriction (CR) produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF) and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL) animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals. Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period). Cells cultured in serum from ADF participants, showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1α mRNA levels. This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity. The use of this in vitro technique may be helpful for predicting the potential of CR, ADF and other dietary manipulations to affect markers of longevity in humans. PMID:18791640

  1. Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs

    PubMed Central

    Suryawan, Agus; Nguyen, Hanh V.; Hernandez-García, Adriana D.; Hoang, Nguyet-Minh; Fiorotto, Marta L.; Davis, Teresa

    2016-01-01

    Suboptimal nutrient intake represents a limiting factor for growth and long-term survival of low-birth weight infants. The objective of this study was to determine if in neonates who can consume only 70 % of their protein and energy requirements for 8 days, enteral leucine supplementation will upregulate the mammalian target of rapamycin (mTOR) pathway in skeletal muscle, leading to an increase in protein synthesis and muscle anabolism. Nineteen 4-day-old piglets were fed by gastric tube 1 of 3 diets, containing (kg body weight−1·day−1) 16 g protein and 190 kcal (CON), 10.9 g protein and 132 kcal (R), or 10.8 g protein + 0.2 % leucine and 136 kcal (RL) at 4-h intervals for 8 days. On day 8, plasma AA and insulin levels were measured during 6 post-feeding intervals, and muscle protein synthesis rate and mTOR signaling proteins were determined at 120 min post-feeding. At 120 min, leucine was highest in RL (P < 0.001), whereas insulin, isoleucine and valine were lower in RL and R compared to CON (P < 0.001). Compared to RL and R, the CON diet increased (P < 0.01) body weight, protein synthesis, phosphorylation of S6 kinase (p-S6K1) and 4E-binding protein (p-4EBP1), and activation of eukaryotic initiation factor 4 complex (eIF4E·eIF4G). RL increased (P ≤ 0.01) p-S6K1, p-4EBP1 and eIF4E · eIF4G compared to R. In conclusion, when protein and energy intakes are restricted for 8 days, leucine supplementation increases muscle mTOR activation, but does not improve body weight gain or enhance skeletal muscle protein synthesis in neonatal pigs. PMID:26334346

  2. Effects of a carbohydrate-restricted diet with and without supplemental soluble fiber on plasma low-density lipoprotein cholesterol and other clinical markers of cardiovascular risk.

    PubMed

    Wood, Richard J; Fernandez, Maria Luz; Sharman, Matthew J; Silvestre, Ricardo; Greene, Christine M; Zern, Tosca L; Shrestha, Sudeep; Judelson, Daniel A; Gomez, Ana L; Kraemer, William J; Volek, Jeff S

    2007-01-01

    Carbohydrate-restricted diets (CRDs) promote weight loss, reductions in plasma triacylglycerol (TAG) levels, and increases in high-density lipoprotein cholesterol (HDL-C) levels but may cause undesirable low-density lipoprotein cholesterol (LDL-C) responses in some people. The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease. Using a parallel-arm, double-blind, placebo-controlled design, 30 overweight and obese men (body mass index, 25-35 kg/m(2)) were randomly assigned to supplement a CRD with soluble fiber (Konjac-mannan, 3g/d) (n = 15) or placebo (n = 15). Plasma lipids, anthropometrics, body composition, blood pressure, and nutrient intake were evaluated at baseline and at 6 and 12 weeks. Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria. Both groups experienced decreases in (P < .01) body weight, percent body fat, systolic blood pressure, waist circumference, and plasma glucose levels. After 12 weeks, HDL-C and TAG improved significantly in the fiber (10% and -34%) and placebo (14%, -43%) groups. LDL-C decreased by 17.6% (P < .01) at week 6 and 14.1% (P < .01) at week 12 in the fiber group. Conversely, LDL-C reductions were significant in the placebo group only after 12 weeks (-6.0%, P < .05). We conclude that although clearly effective at lowering LDL-C, adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone. Furthermore, a CRD led to clinically important positive alterations in cardiovascular disease risk factors.

  3. Regional, but not total, body composition changes in overweight and obese adults consuming a higher protein, energy-restricted diet are sex specific.

    PubMed

    Tang, Minghua; Leidy, Heather J; Campbell, Wayne W

    2013-08-01

    Secondary analyses of data from 2 studies were used to assess the effects of protein intake and sex on diet-induced changes in body composition. The primary hypothesis was that the changes of body composition via energy restriction (ie, lean body mass [LBM], fat mass [FM], and bone) would be sex and diet specific. For 12 weeks, 43 male (study 1) and 45 female (study 2) overweight and obese adults consumed an energy-deficit diet (750 kcal/d less than energy needs) containing either 0.8 (normal protein [NP], 21 men and 23 women) or 1.4 g protein∙kg(-1)∙d(-1) (high protein [HP], 22 men and 22 women). Body composition measurements were performed at preintervention and postintervention. Over time, all research participants lost weight, LBM, and FM. Independent of protein intake, the men lost more LBM in the trunk (-0.9 vs -0.5 kg) and less in the legs (-1.5 vs -1.1 kg) compared with the women (P < .05). Independent of sex, the HP group lost less LBM in the trunk and legs than the NP group. These sex and protein intake responses resulted in the NP men losing the most LBM in the legs and the NP women losing the most LBM in the trunk. Over time, men lost more FM (-5.0 vs -3.9 kg) from the trunk and less from legs (-1.7 vs -2.1 kg) than women (P < .05), which resulted in a greater decrease of the android-to-gynoid fat ratio for the men. Protein intake did not influence these sex-specific responses or have any independent effects on changes in FM. In addition, protein intake did not influence bone mineral density responses over time; bone mineral density was reduced in women, but not in men. These findings indicate that higher protein intake during weight loss promotes the retention of LBM in both the trunk and legs despite the sex-specific changes in these body regions.

  4. 21 CFR 862.1385 - 17-Hydroxycorticosteroids (17-ketogenic steroids) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1385 17-Hydroxycorticosteroids (17-ketogenic steroids) test...

  5. Liquid chromatography-mass spectrometry based metabolomics study of cloned versus normal pigs fed either restricted or ad libitum high-energy diets.

    PubMed

    Christensen, Kirstine L; Hedemann, Mette S; Jørgensen, Henry; Stagsted, Jan; Knudsen, Knud Erik B

    2012-07-06

    Genetically identical cloned pigs should in principle eliminate biological variation and provide more pronounced effects when subjected to, e.g., dietary interventions, but little is known about how phenotype and phenotypic variation is affected by cloning. Therefore, an investigation of the metabolome of cloned pigs compared to normal control pigs was performed to elucidate the variation and possible differences in the metabolic phenotypes during a dietary intervention. A total of 19 control pigs and 17 cloned pigs were given the same high-energy dense diet either ad libitum or in a restricted manner (60% of ad libitum) for ∼6 months, and plasma was subjected to liquid chromatography-mass spectrometry nontargeted metabolomics and biochemical analyses. Low systemic levels of IGF-1 could indicate altered growth conditions and energy metabolism in cloned pigs. In response to ad libitum feeding, clones had a decreased energy intake and lower weight gain compared to controls, and plasma lipid profiles were changed accordingly. Elevated lactate and decreased creatine levels implied an increased anaerobic metabolism in ad libitum fed clones. Less interindividual variation between cloned pigs was however not established, suggesting a strong role for epigenetics and/or the gut microbiota to develop variation.

  6. A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner.

    PubMed

    Ramírez-López, María Teresa; Vázquez, Mariam; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemi; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Bindila, Laura; Rodríguez de Fonseca, Fernando

    2017-01-01

    Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid

  7. A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner

    PubMed Central

    Ramírez-López, María Teresa; Vázquez, Mariam; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemi; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Bindila, Laura

    2017-01-01

    Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid

  8. Egg consumption as part of an energy-restricted high-protein diet improves blood lipid and blood glucose profiles in individuals with type 2 diabetes.

    PubMed

    Pearce, Karma L; Clifton, Peter M; Noakes, Manny

    2011-02-01

    The role of dietary cholesterol in people with diabetes has been little studied. We investigated the effect of a hypoenergetic high-protein high-cholesterol (HPHchol) diet compared to a similar amount of animal protein (high-protein low-cholesterol, HPLchol) on plasma lipids, glycaemic control and cardiovascular risk markers in individuals with type 2 diabetes. A total of sixty-five participants with type 2 diabetes or impaired glucose tolerance (age 54·4 (sd 8·2) years; BMI 34·1 (sd 4·8) kg/m2; LDL-cholesterol (LDL-C) 2·67 (sd 0·10) mmol/l) were randomised to either HPHchol or HPLchol. Both hypoenergetic dietary interventions (6-7 MJ; 1·4-1·7 Mcal) and total carbohydrate:protein:fat ratio of 40:30:30 % were similar but differed in cholesterol content (HPHchol, 590 mg cholesterol; HPLchol, 213 mg cholesterol). HPHchol participants consumed two eggs per d, whereas HPHchol participants replaced the eggs with 100 g of lean animal protein. After 12 weeks, weight loss was 6·0 (sd 0·4) kg (P < 0·001). LDL-C and homocysteine remained unchanged. All the subjects reduced total cholesterol ( - 0·3 (sd 0·1) mmol/l, P < 0·001), TAG ( - 0·4 (sd 0·1) mmol/l, P < 0·001), non-HDL-cholesterol (HDL-C, - 0·4 (sd 0·1) mmol/l, P < 0·001), apo-B ( - 0·04 (sd 0·02) mmol/l, P < 0·01), HbA1c ( - 0·6 (sd 0·1) %, P < 0·001), fasting blood glucose ( - 0·5 (sd 0·2) mmol/l, P < 0·01), fasting insulin ( - 1·7 (sd 0·7) mIU/l, P < 0·01), systolic blood pressure ( - 7·6 (sd 1·7) mmHg, P < 0·001) and diastolic blood pressure ( - 4·6 (sd 1·0) mmHg; P < 0·001). Significance was not altered by diet, sex, medication or amount of weight loss. HDL-C increased on HPHchol (+0·02 (sd 0·02) mmol/l) and decreased on HPLchol ( - 0·07 (sd 0·03) mmol/l, P < 0·05). Plasma folate and lutein increased more on HPHchol (P < 0·05). These results suggest that a high-protein energy-restricted diet high in

  9. Effects of glucogenic and ketogenic feeding strategies on splanchnic glucose and amino acid metabolism in postpartum transition Holstein cows.

    PubMed

    Larsen, M; Kristensen, N B

    2012-10-01

    Nine periparturient Holstein cows catheterized in major splanchnic vessels were used in a complete randomized design with repeated measurements to investigate effects of glucogenic and ketogenic feeding strategies on splanchnic metabolism of glucose and amino acids. At parturition, cows were assigned to 1 of 3 feeding strategies: a glucogenic diet (GLCG) based on sodium hydroxide treated wheat grain (56.5% of diet dry matter); a ketogenic diet (KETO) based on fodder beets (40.5% of diet dry matter); or an alfalfa-glucogenic strategy (ALF-GLCG) supplying 100% alfalfa (Medicago sativa L.) haylage at the day of parturition, followed by a 6-d linear shift to the GLCG diet. Samples were obtained 14 d before expected parturition as well as at 4, 15, and 29 d in milk (DIM). The net portal release of glucose was greatest with GLCG, reflecting the higher intake of ruminal escape starch with GLCG, as compared with a lower starch intake with KETO. Postpartum, the portal recovery of feed starch was greater (28 ± 3%, mean ± SEM) with KETO as compared with GLCG (15 ± 4%). At 4 DIM, the net hepatic release of glucose was greatest with KETO and least with ALF-GLCG, whereafter it increased as lactation progressed with ALF-GLCG and GLCG, but not with KETO. The high alfalfa haylage allowance at 4 DIM with the ALF-GLCG treatment induced the lowest net release of nutrients from the splanchnic tissues at 4 DIM. The hepatic removal of lactate as percent of total influx (mean ± SEM) increased from 27 ± 3% prepartum to 56 ± 3% at 4 DIM. The hepatic removal of lactate as percent of net portal release increased from 144 ± 10% prepartum to 329 ± 17% at 4 DIM with ALF-GLCG and KETO as compared with 242 ± 20% in GLCG. No clear evidence for an amino acid sparing effect in splanchnic tissues from increasing small intestinal glucose absorption was observed. In conclusion, the glucogenic feeding strategy induced the highest glucogenic status among the tested feeding strategies due to

  10. The effect of an energy restricted low glycemic index diet on blood lipids, apolipoproteins and lipoprotein (a) among adolescent girls with excess weight: a randomized clinical trial.

    PubMed

    Rouhani, Mohammad Hossein; Kelishadi, Roya; Hashemipour, Mahin; Esmaillzadeh, Ahmad; Azadbakht, Leila

    2013-12-01

    Some studies focused on the effect of the dietary glycemic index on lipoproteins and apolipoproteins in adults; however, little evidence exists among adolescents regarding the effect of a low glycemic index (LGI) diet on apolipoproteins and lipoprotein (a) (Lpa). This study was conducted to evaluate the effect of an LGI diet on the lipid profile, apolipoproteins and Lpa among overweight and obese adolescent girls. For this parallel designed randomized clinical trial, 50 healthy overweight/obese girls at pubertal ages were randomly allocated to an LGI or a healthy nutritional recommendations (HNR) based diet. Equal macronutrient distributed diets were prescribed to both groups. Biochemical measurements included lipid profile, apolipoprotein A, apolipoprotein B and Lpa were conducted before and after 10 weeks of intervention. Forty one adolescent girls completed the study. The dietary glycemic index in the LGI group was 42.67 ± 0.067. There were no differences in the mean of blood lipid indices baseline and after intervention between two groups. There were no significant differences between the two groups regarding lipid profiles, apolipoproteins and Lpa. There were no significant differences in lipid profiles, apolipoproteins and Lpa between the LGI diet and the HNR-based diet and the impact of these two diets on lipid profile was equal in this trial.

  11. Long-term Effects of Two Levels of Caloric Restriction on Body Composition, and Diet Satisfaction in CALERIE, a One Year Randomized Controlled Trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is little information on whether the extent of dietary energy restriction in a weight loss program influences long-term weight change. We examined the effects of two levels of caloric restriction (CR) over 12 months on body weight and fat loss, total energy expenditure (TEE), resting metabolic...

  12. Dairy Foods in a Moderate Energy Restricted Diet Do Not Enhance Central Fat, Weight, and Intra-Abdominal Adipose Tissue Losses nor Reduce Adipocyte Size or Inflammatory Markers in Overweight and Obese Adults: A Controlled Feeding Study

    PubMed Central

    Van Loan, Marta D.; Keim, Nancy L.; Adams, Sean H.; Souza, Elaine; Woodhouse, Leslie R.; Thomas, Anthony; Witbracht, Megan; Gertz, Erik R.; Piccolo, Brian; Bremer, Andrew A.; Spurlock, Michael

    2011-01-01

    Background. Research on dairy foods to enhance weight and fat loss when incorporated into a modest weight loss diet has had mixed results. Objective. A 15-week controlled feeding study to determine if dairy foods enhance central fat and weight loss when incorporated in a modest energy restricted diet of overweight and obese adults. Design. A 3-week run-in to establish energy needs; a 12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and obese adults randomly assigned to diets: ≤1 serving dairy/d (low dairy, LD) or ≤4 servings dairy/d (adequate dairy, AD). All foods were weighed and provided by the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT), subcutaneous adipose tissue (SAT) macrophage number, SAT inflammatory gene expression, and circulating cytokines were measured. Results. No diet differences were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There was a significant increase (P = 0.02) in serum 25-hydroxyvitamin D in the AD group. Conclusion. Whether increased dairy intake during weight loss results in greater weight and fat loss for individuals with metabolic syndrome deserves investigation. Assessment of appetite, hunger, and satiety with followup on weight regain should be considered. PMID:21941636

  13. Dairy Foods in a Moderate Energy Restricted Diet Do Not Enhance Central Fat, Weight, and Intra-Abdominal Adipose Tissue Losses nor Reduce Adipocyte Size or Inflammatory Markers in Overweight and Obese Adults: A Controlled Feeding Study.

    PubMed

    Van Loan, Marta D; Keim, Nancy L; Adams, Sean H; Souza, Elaine; Woodhouse, Leslie R; Thomas, Anthony; Witbracht, Megan; Gertz, Erik R; Piccolo, Brian; Bremer, Andrew A; Spurlock, Michael

    2011-01-01

    Background. Research on dairy foods to enhance weight and fat loss when incorporated into a modest weight loss diet has had mixed results. Objective. A 15-week controlled feeding study to determine if dairy foods enhance central fat and weight loss when incorporated in a modest energy restricted diet of overweight and obese adults. Design. A 3-week run-in to establish energy needs; a 12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and obese adults randomly assigned to diets: ≤1 serving dairy/d (low dairy, LD) or ≤4 servings dairy/d (adequate dairy, AD). All foods were weighed and provided by the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT), subcutaneous adipose tissue (SAT) macrophage number, SAT inflammatory gene expression, and circulating cytokines were measured. Results. No diet differences were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There was a significant increase (P = 0.02) in serum 25-hydroxyvitamin D in the AD group. Conclusion. Whether increased dairy intake during weight loss results in greater weight and fat loss for individuals with metabolic syndrome deserves investigation. Assessment of appetite, hunger, and satiety with followup on weight regain should be considered.

  14. Thermoregulation and water balance as affected by water and food restrictions in Sudanese desert goats fed good-quality and poor-quality diets.

    PubMed

    Ahmed, Muna M M; El Kheir, I M

    2004-02-01

    Nine desert goats were used in a 3 x 3 Latin square design in which they were subjected to (a) ad libitum water and food (control), (b) ad libitum food and water restricted to about 40% of the control, and (c) ad libitum water and restricted food (same amount as given to group b). Parameters measured were dry matter intake (DMI), water intake, rectal temperature (Tr), respiration rate (RR), water balance and body weight (BW) changes. The acute effects of the above treatments on these parameters were monitored during the dry summer using two types of feed. The ratio of DMI to water intake decreased (p < 0.01) due to water restriction but increased (p < 0.01) with Lucerne hay compared to grass hay. With both feeds, BW decreased (p < 0.01) with water restriction, with a further decrease (p < 0.01) observed with food restriction. The control group showed a higher (p < 0.01) gain with Lucerne hay than grass hay. Tr and RR increased (p < 0.01) from morning to afternoon; Tr decreased due to food restriction during both morning and afternoon with Lucerne hay (p < 0.05) and grass hay (p < 0.05), whereas RR decreased (p < 0.01) with both types of feeds. For all groups of animals, Tr was higher (p < 0.05) with Lucerne hay than with grass hay, this effect being more pronounced (p < 0.01) with the control group. With both feeds, water restriction decreased (p < 0.01) water turnover rate and evaporative losses, with decreased (p < 0.05) faecal losses observed in the water-restricted groups on Lucerne hay but higher (p < 0.05) losses of urine. The tolerance of desert goats to thermal stress and their coping with shortage of water and food depended on their capacity to lose heat through panting and cutenaous evaporation as well as their ability to concentrate urine.

  15. Calorie Restriction in Overweight SeniorS: Response of Older Adults to a Dieting Study: The CROSSROADS Randomized Controlled Clinical Trial

    PubMed Central

    Haas, Marilyn C.; Bodner, Eric V.; Brown, Cynthia J.; Bryan, David; Buys, David R.; Keita, Akilah Dulin; Flagg, Lee Anne; Goss, Amy; Gower, Barbara; Hovater, Martha; Hunter, Gary; Ritchie, Christine S.; Roth, David L.; Wingo, Brooks C.; Ard, Jamy; Locher, Julie L.

    2014-01-01

    We conducted a study designed to evaluate whether the benefits of intentional weight loss exceed the potential risks in a group of community-dwelling, obese, older adults who were at increased risk for cardiometabolic disease. The CROSSROADS trial used a prospective randomized controlled design to compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition and adipose tissue deposition (Specific Aim #1: To compare the effects of changes in diet composition alone or combined with weight loss with an exercise only control intervention on body composition, namely visceral adipose tissue (VAT)), cardiometabolic disease risk (Specific Aim #2: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on cardiometabolic disease risk), functional status and quality of life (Specific Aim #3: To compare the effects of a change in diet composition alone or combined with weight loss with an exercise only control intervention on functional status and quality of life). Participants were randomly assigned to one of three groups: Exercise Only (Control) Intervention, Exercise + Diet Quality + Weight Maintenance Intervention, or Exercise + Diet Quality + Weight Loss Intervention. CROSSROADS utilized a lifestyle intervention approach consisting of exercise, dietary, and behavioral components. The development and implementation of the CROSSROADS protocol, including a description of the methodology, detailing specific elements of the lifestyle intervention, assurances of treatment fidelity, and participant retention; outcome measures and adverse event monitoring; as well as unique data management features of the trial results, are presented in this article. PMID:25424512

  16. Meta-Analysis of Attention-Deficit/Hyperactivity Disorder or Attention-Deficit/Hyperactivity Disorder Symptoms, Restriction Diet, and Synthetic Food Color Additives

    ERIC Educational Resources Information Center

    Nigg, Joel T.; Lewis, Kara; Edinger, Tracy; Falk, Michael

    2012-01-01

    Objective: The role of diet and of food colors in attention-deficit/hyperactivity disorder (ADHD) or its symptoms warrants updated quantitative meta-analysis, in light of recent divergent policy in Europe and the United States. Method: Studies were identified through a literature search using the PubMed, Cochrane Library, and PsycNET databases…

  17. Peripheral blood mononuclear cell gene expression profile in obese boys who followed a moderate energy-restricted diet: differences between high and low responders at baseline and after the intervention.

    PubMed

    Rendo-Urteaga, Tara; García-Calzón, Sonia; González-Muniesa, Pedro; Milagro, Fermín I; Chueca, María; Oyarzabal, Mirentxu; Azcona-Sanjulián, M Cristina; Martínez, J Alfredo; Marti, Amelia

    2015-01-28

    The present study analyses the gene expression profile of peripheral blood mononuclear cells (PBMC) from obese boys. The aims of the present study were to identify baseline differences between low responders (LR) and high responders (HR) after 10 weeks of a moderate energy-restricted dietary intervention, and to compare the gene expression profile between the baseline and the endpoint of the nutritional intervention. Spanish obese boys (age 10-14 years) were advised to follow a 10-week moderate energy-restricted diet. Participants were classified into two groups based on the association between the response to the nutritional intervention and the changes in BMI standard deviation score (BMI-SDS): HR group (n 6), who had a more decreased BMI-SDS; LR group (n 6), who either maintained or had an even increased BMI-SDS. The expression of 28,869 genes was analysed in PBMC from both groups at baseline and after the nutritional intervention, using the Affymetrix Human Gene 1.1 ST 24-Array plate microarray. At baseline, the HR group showed a lower expression of inflammation and immune response-related pathways, which suggests that the LR group could have a more developed pro-inflammatory phenotype. Concomitantly, LEPR and SIRPB1 genes were highly expressed in the LR group, indicating a tendency towards an impaired immune response and leptin resistance. Moreover, the moderate energy-restricted diet was able to down-regulate the inflammatory 'mitogen-activated protein kinase signalling pathway' in the HR group, as well as some inflammatory genes (AREG and TNFAIP3). The present study confirms that changes in the gene expression profile of PBMC in obese boys may help to understand the weight-loss response. However, further research is required to confirm these findings.

  18. Maternal low protein diet restricted to the preimplantation period induces a gender-specific change on hepatic gene expression in rat fetuses.

    PubMed

    Kwong, Wing Yee; Miller, Daniel J; Wilkins, Adrian P; Dear, Mark S; Wright, J Neville; Osmond, Clive; Zhang, Junlong; Fleming, Tom P

    2007-01-01

    It has been shown previously that maternal low protein diet (LPD) throughout rat gestation altered hepatic gene expression and enzyme activities in offspring. Here, we investigate the effect of maternal LPD (9% casein vs. 18% control) exclusively during the preimplantation period (switched diet group) or provided throughout gestation on hepatic gene expression in day 20 fetuses. Using quantitative competitive PCR, we found that switched diet induced a two-fold increase (P = 0.008) in hepatic gene expression of phosphoenolpyruvate carboxykinase (PEPCK, a rate limiting enzyme for gluconeogenesis) in male fetuses and a 17% increase (P = 0.005) in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1, acts primarily as a reductase to produce active glucocorticoid) in female liver compared with control fetuses. Maternal LPD administered throughout gestation increased 11beta-HSD1 expression in male fetal liver by 27% (P = 0.042) compared with controls. However, maternal LPD fed for either period did not affect fetal hepatic insulin receptor (IR), glucocorticoid receptor (GR), glycogen synthase (GS) nor placental glucose transporter 1 (Glut1) and 3 (Glut3) transcript levels. The alteration in fetal hepatic gene expression could not be attributed specifically to known regulators including insulin or glucose concentrations in fetal blood nor alteration in cAMP in fetal liver, although a combination of these regulatory factors may be responsible. Fetal hepatic glycogen level was unaffected by maternal diet. The present findings show that the long term potential of the preimplantation embryo is sensitive to maternal LPD such that basal levels of hepatic gene expression in day 20 fetuses are altered in a gender-specific manner.

  19. Extensive Reorganization of Primary Afferent Projections into the Gustatory Brainstem Induced by Feeding a Sodium-Restricted Diet during Development: Less Is More

    PubMed Central

    Mangold, Jamie E.; Hill, David L.

    2008-01-01

    Neural development is especially vulnerable to environmental influences during periods of neurogenesis and rapid maturation. In fact, short periods of environmental manipulations confined to embryonic development lead to significant changes in morphology and function. A guiding principal emerging from studies of sensory systems is that experimentally induced effects are most dramatic in higher neural levels (e.g., cortex) and primarily involve postnatal synaptic refinements. In contrast to other sensory systems, the gustatory system is particularly susceptible to the effects of deprivation much earlier and with profound changes evident in the brainstem. Here we show that feeding pregnant rats a custom diet featuring a low-sodium content for 9 d before the tongue appears in the fetus produces extensive restructuring of the gustatory brainstem. Rats born to mothers fed the custom diet from embryonic day 3 (E3) to E12 have terminal field volumes of the greater superficial petrosal, chorda tympani, and glossopharyngeal nerves at adulthood that are expanded as much as 10 times beyond that found in rats fed a standard rat chow. The widespread alterations are not attributable to increased numbers of nerve cells, increased target size, or obvious changes in peripheral taste function. Moreover, we show that the limited period of feeding the custom diet has much larger effects than if rats were fed the diet to postweaning ages. Our results suggest that early periods of altered experience, especially during nucleus of the solitary tract neurogenesis, leads to a restructuring of the gustatory brainstem, which in turn may impact the control of sensory and homeostatic processes. PMID:17460078

  20. Serum Polychlorinated Biphenyls Increase and Oxidative Stress Decreases with a Protein-Pacing Caloric Restriction Diet in Obese Men and Women.

    PubMed

    He, Feng; Zuo, Li; Ward, Emery; Arciero, Paul J

    2017-01-10

    The purposes were to compare the effects of a: (1) 12-week P-CR weight loss (WL) diet (Phase 1) between obese men and women and; (2) 52-week modified P-CR (mP-CR) vs. heart healthy (HH) weight maintenance (WM) diet (Phase 2) on serum PCBs and oxidative stress biomarkers (thiobarbituric acid reactive substances, TBARS; total antioxidant capacity, TAC) in 40 obese participants (men, n = 21; women, n = 19). Participants received dietary counseling and monitoring of compliance. PCBs, TBARS, and TAC were assessed at weeks -1 (CON), 12 (WL), and 64 (WM). Following WL (Week 12), concomitant with reductions in TBARS (0.24 ± 0.15 vs. 0.18 ± 0.11 µM; p < 0.01), PCB serum concentrations (86.7 ± 45.6 vs. 115.6 ± 65.9 ng/g lipid; p < 0.01) and TAC (18.9 ± 2.6 vs. 19.9 ± 2.3 nmol/mL; p < 0.02) were increased similarly in men and women. At the end of WM (Week 64), a significant effect of time × group interaction was observed for % change in PCB 170 and 187; whereby mP-CR values were higher compared to HH (PCB170: 19.31% ± 26.48% vs. -6.61% ± 28.88%, p = 0.02; PCB187: -3.04% ± 17.78% vs. -21.4% ± 27.31%, p = 0.04). PCB changes were positively correlated with TBARS levels (r > 0.42, p < 0.05) and negatively correlated with body weight, fat mass, and abdominal fat (r < -0.46, p < 0.02). Our results support mobilization of stored PCBs as well as enhanced redox status following a 12-week P-CR WL diet. Additionally, a 52-week mP-CR WM diet demonstrated an advantage in preventing weight gain relapse accompanied by an increase in circulating PCBs compared to a traditional HH diet.

  1. Serum Polychlorinated Biphenyls Increase and Oxidative Stress Decreases with a Protein-Pacing Caloric Restriction Diet in Obese Men and Women

    PubMed Central

    He, Feng; Zuo, Li; Ward, Emery; Arciero, Paul J.

    2017-01-01

    The purposes were to compare the effects of a: (1) 12-week P-CR weight loss (WL) diet (Phase 1) between obese men and women and; (2) 52-week modified P-CR (mP-CR) vs. heart healthy (HH) weight maintenance (WM) diet (Phase 2) on serum PCBs and oxidative stress biomarkers (thiobarbituric acid reactive substances, TBARS; total antioxidant capacity, TAC) in 40 obese participants (men, n = 21; women, n = 19). Participants received dietary counseling and monitoring of compliance. PCBs, TBARS, and TAC were assessed at weeks −1 (CON), 12 (WL), and 64 (WM). Following WL (Week 12), concomitant with reductions in TBARS (0.24 ± 0.15 vs. 0.18 ± 0.11 µM; p < 0.01), PCB serum concentrations (86.7 ± 45.6 vs. 115.6 ± 65.9 ng/g lipid; p < 0.01) and TAC (18.9 ± 2.6 vs. 19.9 ± 2.3 nmol/mL; p < 0.02) were increased similarly in men and women. At the end of WM (Week 64), a significant effect of time × group interaction was observed for % change in PCB 170 and 187; whereby mP-CR values were higher compared to HH (PCB170: 19.31% ± 26.48% vs. −6.61% ± 28.88%, p = 0.02; PCB187: −3.04% ± 17.78% vs. −21.4% ± 27.31%, p = 0.04). PCB changes were positively correlated with TBARS levels (r > 0.42, p < 0.05) and negatively correlated with body weight, fat mass, and abdominal fat (r < −0.46, p < 0.02). Our results support mobilization of stored PCBs as well as enhanced redox status following a 12-week P-CR WL diet. Additionally, a 52-week mP-CR WM diet demonstrated an advantage in preventing weight gain relapse accompanied by an increase in circulating PCBs compared to a traditional HH diet. PMID:28075418

  2. Long-term, calorie-restricted intake of a high-fat diet in rats reduces impulse control and ventral striatal D2 receptor signalling - two markers of addiction vulnerability.

    PubMed

    Adams, Wendy K; Sussman, Jacob L; Kaur, Sukhbir; D'souza, Anna M; Kieffer, Timothy J; Winstanley, Catharine A

    2015-12-01

    High impulsivity, mediated through ventral striatal dopamine signalling, represents an established risk factor for substance abuse, and may likewise confer vulnerability to pathological overeating. Mechanistically, the assumption is that trait impulsivity facilitates the initiation of maladaptive eating styles or choices. However, whether consumption of appetitive macronutrients themselves causes deficits in impulse control and striatal signalling, thereby contributing to cognitive changes permissive of overeating behaviour, has yet to be considered. We examined the effects of chronic maintenance on restricted equicaloric, but high-fat or high-sugar, diets (48 kcal/day; 60 kcal% fat or sucrose) on rats' performance in the five-choice serial reaction time task, indexing impulsivity and attention. Markers of dopamine signalling in the dorsal and ventral striatum, and plasma insulin and leptin levels, were also assessed. Rats maintained on the high-fat diet (HFD) were more impulsive, whereas the high-sugar diet (HSD) did not alter task performance. Importantly, body weight and hormone levels were similar between groups when behavioural changes were observed. Maintenance on HFD, but not on HSD, reduced the levels of dopamine D2 receptor (D2 R), cAMP response element-binding protein (CREB) and phosphophorylated CREB (Ser133) proteins in the ventral, but not dorsal, striatum. D2 R expression in the ventral striatum also negatively correlated with impulsive responding, independently of diet. These data indicate that chronic exposure to even limited amounts of high-fat foods may weaken impulse control and alter neural signalling in a manner associated with vulnerability to addictions - findings that have serious implications for the propagation of uncontrolled eating behaviour in obesity and binge-eating disorder.

  3. The moderate essential amino acid restriction entailed by low-protein vegan diets may promote vascular health by stimulating FGF21 secretion.

    PubMed

    McCarty, Mark F

    2016-02-12

    The serum total and LDL cholesterol levels of long-term vegans tend to be very low. The characteristically low ratio of saturated to unsaturated fat in vegan diets, and the absence of cholesterol in such diets, clearly contribute to this effect. But there is reason to suspect that the quantity and composition of dietary protein also play a role in this regard. Vegan diets of moderate protein intake tend to be relatively low in certain essential amino acids, and as a result may increase hepatic activity of the kinase GCN2, which functions as a gauge of amino acid status. GCN2 activation boosts the liver's production of fibroblast growth factor 21 (FGF21), a factor which favorably affects serum lipids and metabolic syndrome. The ability of FGF21 to decrease LDL cholesterol has now been traced to at least two mechanisms: a suppression of hepatocyte expression of sterol response element-binding protein-2 (SREBP-2), which in turn leads to a reduction in cholesterol synthesis; and up-regulated expression of hepatocyte LDL receptors, reflecting inhibition of a mechanism that promotes proteasomal degradation of these receptors. In mice, the vascular benefits of FGF21 are also mediated by favorable effects on adipocyte function - most notably, increased adipocyte secretion of adiponectin, which directly exerts anti-inflammatory effects on the vasculature which complement the concurrent reduction in LDL particles in preventing or reversing atherosclerosis. If, as has been proposed, plant proteins preferentially stimulate glucagon secretion owing to their amino acid composition, this would represent an additional mechanism whereby plant protein promotes FGF21 activity, as glucagon acts on the liver to boost transcription of the FGF21 gene.

  4. Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy

    PubMed Central

    Schoeler, Natasha E.; Leu, Costin; White, Jon; Plagnol, Vincent; Ellard, Sian; Matarin, Mar; Yellen, Gary; Thiele, Elizabeth A.; Mackay, Mark; McMahon, Jacinta M.; Scheffer, Ingrid E.; Sander, Josemir W.; Cross, J. Helen; Sisodiya, Sanjay M.

    2015-01-01

    In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF) > 0.01, using PLINK. Response to KDT in individuals with variants with MAF < 0.01 was evaluated. 303 Individuals had KCNJ11 and 246 individuals had BAD sequencing data and diet response data. Six SNPs in KCNJ11 and two in BAD had MAF > 0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAF < 0.01. No significant results were obtained from association analyses, with either KDT response phenotype. P-values were similar when accounting for ethnicity using a stratified Cochran–Mantel–Haenszel test. There did not seem to be a consistent effect of rare variants on response to KDT, although the cohort size was too small to assess significance. Common variants in KCNJ11 and BAD do not predict response to KDT for epilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes. PMID:26590798

  5. Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy.

    PubMed

    Schoeler, Natasha E; Leu, Costin; White, Jon; Plagnol, Vincent; Ellard, Sian; Matarin, Mar; Yellen, Gary; Thiele, Elizabeth A; Mackay, Mark; McMahon, Jacinta M; Scheffer, Ingrid E; Sander, Josemir W; Cross, J Helen; Sisodiya, Sanjay M

    2015-12-01

    In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥ 50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF)>0.01, using PLINK. Response to KDT in individuals with variants with MAF<0.01 was evaluated. 303 Individuals had KCNJ11 and 246 individuals had BAD sequencing data and diet response data. Six SNPs in KCNJ11 and two in BAD had MAF>0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAF<0.01. No significant results were obtained from association analyses, with either KDT response phenotype. P-values were similar when accounting for ethnicity using a stratified Cochran-Mantel-Haenszel test. There did not seem to be a consistent effect of rare variants on response to KDT, although the cohort size was too small to assess significance. Common variants in KCNJ11 and BAD do not predict response to KDT for epilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes.

  6. Diet-induced ketosis improves cognitive performance in aged rats.

    PubMed

    Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O; Tsipis, Constantinos P; Puchowicz, Michelle A; LaManna, Joseph C

    2010-01-01

    Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1alpha levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions.

  7. The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans.

    PubMed Central

    Walford, R L; Harris, S B; Gunion, M W

    1992-01-01

    Biosphere 2 is a 3.15-acre space containing an ecosystem that is energetically open (sunlight, electric power, and heat) but materially closed, with air, water, and organic material being recycled. Since September 1991, eight subjects (four women and four men) have been sealed inside, living on food crops grown within. Their diet, low in calories (average, 1780 kcal/day; 1 kcal = 4.184 kJ), low in fat (10% of calories), and nutrient-dense, conforms to that which in numerous animal experiments has promoted health, retarded aging, and extended maximum life span. We report here medical data on the eight subjects, comparing preclosure data with data through 6 months of closure. Significant changes included: (i) weight, 74 to 62 kg (men) and 61 to 54 kg (women); (ii) mean systolic/diastolic blood pressure (eight subjects), 109/74 to 89/58 mmHg (1 mmHg = 133 Pa); (iii) total serum cholesterol, from 191 +/- 11 to 123 +/- 9 mg/dl (mean +/- SD; 36% mean reduction), and high density lipoprotein, from 62 +/- 8 to 38 +/- 5 (risk ratio unchanged); (iv) triglyceride, 139 to 96 mg/dl (men) and 78 to 114 mg/dl (women); (v) fasting glucose, 92 to 74 mg/dl; (vi) leukocyte count, 6.7 to 4.7 x 10(9) cells per liter. We conclude that drastic reductions in cholesterol and blood pressure may be instituted in normal individuals in Western countries by application of a carefully chosen diet and that a low-calorie nutrient-dense regime shows physiologic features in humans similar to those in other animal species. PMID:1454844

  8. Both Food Restriction and High-Fat Diet during Gestation Induce Low Birth Weight and Altered Physical Activity in Adult Rat Offspring: The “Similarities in the Inequalities” Model

    PubMed Central

    Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called “Similarities in the Inequalities”, in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the “similarities in the inequalities” phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam’s habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The “similarities in the inequalities” effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms. PMID:25738800

  9. Protein Diet Restriction Slows Chronic Kidney Disease Progression in Non-Diabetic and in Type 1 Diabetic Patients, but Not in Type 2 Diabetic Patients: A Meta-Analysis of Randomized Controlled Trials Using Glomerular Filtration Rate as a Surrogate

    PubMed Central

    Rughooputh, Mahesh Shumsher; Zeng, Rui; Yao, Ying

    2015-01-01

    Background/ Objective Studies, including various meta-analyses, on the effect of Protein Diet Restriction on Glomerular Filtration Rate (GFR) in Chronic Kidney Disease (CKD) have reported conflicting results. In this paper, we have provided an update on the evidence available on this topic. We have investigated the reasons why the effect has been inconsistent across studies. We have also compared the effect on GFR in various subgroups including type 1 diabetics, type 2 diabetics and non-diabetics. Method We searched for Randomized Controlled Trials on this intervention from MEDLINE, EMBASE, and other information sources. The PRISMA guidelines, as well as recommended meta-analysis practices were followed in the selection process, analysis and reporting of our findings. The effect estimate used was the change in mean GFR. Heterogeneity across the considered studies was explored using both subgroup analyses and meta-regression. Quality assessment was done using the Cochrane risk of bias tool and sensitivity analyses. Results 15 randomized controlled trials, including 1965 subjects, were analyzed. The pooled effect size, as assessed using random-effects model, for all the 15 studies was -0.95 ml/min/1.73m2/year (95% CI: -1.79, -0.11), with a significant p value of 0.03. The combined effect estimate for the non-diabetic and type 1 diabetic studies was -1.50 ml/min/1.73m2/year (95% CI: -2.73, -0.26) with p value of 0.02. The effect estimate for the type 2 diabetic group was -0.17 ml/min/1.73m2/year (95% CI: -1.88, 1.55) with p value of 0.85. There was significant heterogeneity across the included studies (I2 = 74%, p value for Q < 0.0001), explained by major variations in the percentage of type 2 diabetic subjects, the number of subjects and overall compliance level to diet prescribed. Conclusion Our findings suggest that protein diet restriction slows chronic renal disease progression in non-diabetic and in type 1 diabetic patients, but not in type 2 diabetic patients

  10. Considerations for the use of restricted, soaked grass hay diets to promote weight loss in the management of equine metabolic syndrome and obesity.

    PubMed

    Argo, Caroline McG; Dugdale, Alexandra H A; McGowan, Catherine M

    2015-11-01

    The addition of hay soaking to current nutritional advice for weight loss management for equine obesity lacks clinical evidence. Twelve overweight/obese horses and ponies were used to test the hypothesis that feeding soaked hay at 1.25% of body mass (BM) daily as dry matter (DM) before soaking would elicit weight losses within the target 0.5-1.0% of BM weekly. Six animals were used to evaluate the impact of nutrient-leaching on the digestibility and daily intakes of dietary energy and nutrients. Soaked hay DM was corrected in accordance with the 'insoluble' ADF content of fresh and soaked hays. The ADF-based method was validated using a test-soaking protocol. Animals fed soaked hay for 6 weeks lost 0.98 ± 0.10% of BM weekly. The most weight loss sensitive animal lost ~2% of BM weekly. Soaking hay did not alter DM gross energy concentrations, incurred losses of water soluble carbohydrates (WSC) and ash and increased acid detergent fibre (ADF) concentrations. Digestibilities of GE, DM, ash and WSC were unaltered but soaking increased uncorrected values for crude protein (+12%) and ADF (+13.5%) digestibility. Corrected DM provision was only 1% of BM daily, providing 64% of maintenance DE requirements, a 23.5% increase in the intended magnitude of energy restriction. Hay soaking leached nutrients, reduced DM and DE provision and was associated with accelerated weight losses over those expected had fresh-hay been fed to the same level. The ADF-based method will allow the predictive evaluation of individual hays to direct feeding management and prevent inadvertently severe DM and energy restriction.

  11. Arylesterase activity is associated with antioxidant intake and paraoxonase-1 (PON1) gene methylation in metabolic syndrome patients following an energy restricted diet.

    PubMed

    de la Iglesia, Rocio; Mansego, Maria L; Sánchez-Muniz, Francisco J; Zulet, M Angeles; Martinez, J Alfredo

    2014-01-01

    The arylesterase (ARE) activity linked to the paraoxonase-1 (PON1) gene is known to protect lipoproteins from oxidation and provide defense against metabolic syndrome (MetS) and cardiovascular diseases. The epigenetic regulation of enzymatic activities is gaining importance nowadays. This research aimed to assess the potential relationships between the ARE activity with the methylation levels of the PON1 gene transcriptional regulatory region, anthropometrics, biochemical markers and antioxidant dietary components. Forty-seven subjects (47 ± 10 y.o; BMI 36.2 ± 3.8 kg/m(2); 46.8 % female) with MetS features, who followed a six-month energy-restricted dietary weight-loss intervention, were included in this study (www.clinicaltrials.gov; NCT01087086). Anthropometric, biochemical, enzymatic and dietary data were assessed using validated procedures. PON1 transcriptional regulatory region methylation was analyzed by a microarray technical approach. Volunteers reduced ARE activity in parallel with body weight (p = 0.005), BMI (p = 0.006), total fat mass (p = 0.020), diastolic blood pressure (p = 0.018), mean blood pressure (p = 0.022) and triglycerides (p = 0.014). Methylation levels of some CpG sites of the PON1 gene correlated negatively with ARE activity (p < 0.05). Interestingly, dietary vitamin C (p = 0.001), tocopherols (p = 0.009) and lycopene (p = 0.038) were positively associated with ARE activity and showed an inverse correlation (p = 0.004, p = 0.029 and p = 0.021, respectively) with the methylation of some selected CpG sites of the PON1 gene. In conclusion, ARE activity decreased in parallel with MetS-related markers associated to the energy restriction, while dietary antioxidants might enhance the ARE activity by lowering the PON1 gene methylation in patients with MetS features.

  12. Arylesterase activity is associated with antioxidant intake and paraoxonase-1 (PON1) gene methylation in metabolic syndrome patients following an energy restricted diet

    PubMed Central

    de la Iglesia, Rocio; Mansego, Maria L.; Sánchez-Muniz, Francisco J.; Zulet, M. Angeles; Martinez, J. Alfredo

    2014-01-01

    The arylesterase (ARE) activity linked to the paraoxonase-1 (PON1) gene is known to protect lipoproteins from oxidation and provide defense against metabolic syndrome (MetS) and cardiovascular diseases. The epigenetic regulation of enzymatic activities is gaining importance nowadays. This research aimed to assess the potential relationships between the ARE activity with the methylation levels of the PON1 gene transcriptional regulatory region, anthropometrics, biochemical markers and antioxidant dietary components. Forty-seven subjects (47 ± 10 y.o; BMI 36.2 ± 3.8 kg/m2; 46.8 % female) with MetS features, who followed a six-month energy-restricted dietary weight-loss intervention, were included in this study (www.clinicaltrials.gov; NCT01087086). Anthropometric, biochemical, enzymatic and dietary data were assessed using validated procedures. PON1 transcriptional regulatory region methylation was analyzed by a microarray technical approach. Volunteers reduced ARE activity in parallel with body weight (p = 0.005), BMI (p = 0.006), total fat mass (p = 0.020), diastolic blood pressure (p = 0.018), mean blood pressure (p = 0.022) and triglycerides (p = 0.014). Methylation levels of some CpG sites of the PON1 gene correlated negatively with ARE activity (p < 0.05). Interestingly, dietary vitamin C (p = 0.001), tocopherols (p = 0.009) and lycopene (p = 0.038) were positively associated with ARE activity and showed an inverse correlation (p = 0.004, p = 0.029 and p = 0.021, respectively) with the methylation of some selected CpG sites of the PON1 gene. In conclusion, ARE activity decreased in parallel with MetS-related markers associated to the energy restriction, while dietary antioxidants might enhance the ARE activity by lowering the PON1 gene methylation in patients with MetS features. PMID:26417268

  13. Improved metabolic response after 16 weeks of calorie-restricted low-glycaemic index diet and metformin in impaired glucose tolerance subjects.

    PubMed

    Macedo da Costa, Teresa Helena; Pires da Silva, Fábio Vinícius; Gonçalves Reis, Caio Eduardo; Augusto Casulari, Luiz

    2014-05-01

    Objetivo: Este estudio analizaba los efectos metabólicos del consejo dietético de seguir una dieta con restricción calórica y un índice glucémico bajo junto con Metformina en individuos con sobrepeso / obesidad y tolerancia alterada a la glucosa. Métodos: Se siguió mensualmente durante 16 semanas a 16 individuos con un índice de masa corporal entre 27-38 kg/m² y se les trató con Metformina (1 g/día) y una prescripción dietética con un índice glucémico bajo y una reducción del energía del 25-30 ¡% de su gasto energético total. Se midieron el metabolismo de la glucosa, el perfil lipídico, la composición antropométrica y corporal y los parámetros de consumo de alimentos antes y después del tratamiento. Se emplearon las pruebas t pareadas y de Wilcoxon para comparar las diferencias con respecto al basal, con un criterio de significación estadística de p ≤0,05. Resultados: Hubo reducciones significativas en los parámetros de composición corporal y antropométricos, una disminución en las concentraciones de HOMA2-% y e triglicéridos y un aumento del índice de Cederholm. Estos resultados muestran una mejora de la sensibilidad periférica a la insulina y una conservación de la función de las células beta pancreáticas. Conclusión: la dieta con restricción calórica y un índice glucémico bajo junto con Metformina fueron beneficiosas para los parámetros metabólicos y antropométricos en individuos con sobrepeso/obesidad y una tolerancia a la glucosa alterada.

  14. Alternate‐day versus daily energy restriction diets: which is more effective for weight loss? A systematic review and meta‐analysis

    PubMed Central

    Garcia‐Alvarez, A.; Alzahrnai, A. H.; Karanxha, J.; Stretchberry, D. R.; Contrera, K. J.; Utria, A. F.; Cheskin, L. J.

    2016-01-01

    Summary Background Alternate‐day‐fasting (ADF) has been proposed as an effective dieting method. Studies have found that it also can increase life span in rodents, and reduce inflammation in humans. The aim of this paper was to systematically review the efficacy of ADF compared to very‐low‐calorie dieting (VLCD) in terms of weight loss, and reduction of fat mass and fat‐free mass. Methods Systematic review: PubMed literature searches were performed. Fixed review procedures were applied. Studies were evaluated for quality. Twenty‐eight studies were included. Meta‐analysis: 10/28 studies (four ADF and six matched VLCD) were further analyzed. Results After adjustment for BMI and duration, there was no significant difference in mean body weight loss (VLCD 0.88 kg more weight loss than ADF, 95% CI: −4.32, 2.56) or fat‐free mass (VLCD 1.69 kg more fat‐free mass loss than ADF, 95% CI: −3.62, 0.23); there was a significant difference observed in fat mass (ADF 3.31 kg more fat mass loss than VLCD, 95% CI: 0.05, 6.56). Meta‐analysis showed that, among ADF studies, the pooled change in body weight, fat mass and fat‐free mass was 4.30 kg (95% CI: 3.41, 5.20), 4.06 kg (95% CI: 2.99, 5.13) and 0.72 kg (95% CI: −0.07, 1.51), respectively, while among VLCD studies, the pooled change was 6.28 kg (95% CI: 6.08, 6.49), 4.22 kg (95% CI: 3.95, 4.50) and 2.24 kg (95% CI: 1.95, 2.52), respectively. Conclusions Our results from both the systematic review and the meta‐analysis suggest that ADF is an efficacious dietary method, and may be superior to VLCD for some patients because of ease of compliance, greater fat‐mass loss and relative preservation of fat‐free mass. Head‐to‐head randomized clinical trials are needed to further assess relative efficacy of these two approaches. PMID:27708846

  15. Low-carbohydrate diets.

    PubMed

    Last, Allen R; Wilson, Stephen A

    2006-06-01

    Americans spend dollar 33 billion annually on weight loss products and services, and a large portion of this money is spent on low-carbohydrate diets. Because of their higher protein and fat content and lower fiber and carbohydrate content, concerns have been raised about the potential health consequences of low-carbohydrate diets. Published long-term data are lacking. Short-term studies comparing traditional low-fat diets with low-carbohydrate diets found lower triglyceride levels, higher high-density lipoprotein cholesterol levels, similar low-density lipoprotein cholesterol levels, and lower A1C levels in persons on low-carbohydrate diets. These diets induce greater weight loss at three and six months than traditional low-fat diets; however, by one year there is no significant difference in maintained weight loss. Weight loss is directly related to calorie content and the ability to maintain caloric restriction; the proportions of nutrients in the diet are irrelevant. Low-carbohydrate diets had lower dropout rates than low-fat diets in several studies, possibly because of the high protein content and low glycemic index, which can be appetite suppressing. Data indicate that low-carbohydrate diets are a safe, reasonable alternative to low-fat diets for weight loss. Additional studies are needed to investigate the long-term safety and effectiveness of these and other approaches to weight loss.

  16. Use of a computerized tracking system to monitor and provide feedback on dietary goals for calorie-restricted diets: the POUNDS LOST study.

    PubMed

    Anton, Stephen D; LeBlanc, Eric; Allen, H Raymond; Karabetian, Christy; Sacks, Frank; Bray, George; Williamson, Donald A

    2012-09-01

    The use of self-monitoring as a tool to facilitate behavioral modification is common in many lifestyle-based weight loss interventions. Electronic tracking programs, including computer-based systems and smart phone applications, have been developed to allow individuals to self-monitor their behavior digitally. These programs offer an advantage over traditional self-report modalities in that they can provide users with direct feedback about dietary and/or physical activity adherence levels and thereby assist them in real-time decision making. This article describes the use of an Internet-based computerized tracking system (CTS) that was developed specifically for the POUNDS LOST study, a 2-year randomized controlled trial designed to test the efficacy of four macronutrient diets for weight and fat reduction in healthy, overweight men and women (body mass index range = 25.0-39.9 kg/m(2)). The CTS served many functions in this study, including data collection, dietary and exercise assessment and feedback, messaging system, and report generation. Across all groups, participants with high usage of the CTS during the initial 8 weeks lost greater amounts of weight than participants with low usage (8.7% versus 5.5% of initial body weight, respectively; p < .001) at week 32. Rates of CTS utilization were highest during the first year of this 2-year intervention, and utilization of the CTS declined steadily over time. The unique features of the CTS combined with technological developments, such as smart phone applications, offer significant potential to improve the user's self-monitoring experience and adherence to health promotion programs designed specifically for individuals with obesity and type 2 diabetes.

  17. Restrictive cardiomyopathy

    MedlinePlus

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy; Idiopathic myocardial fibrosis ... In a case of restrictive cardiomyopathy, the heart muscle is of normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does ...

  18. 5 Ways to Spot a Fad Diet

    MedlinePlus

    ... thing they slim down is your wallet. Some diet pills contain laxatives or diuretics that force a person's body to eliminate more water. Just like restricted-calorie diets, the weight lost with these supplements is mostly ...

  19. Bland diet

    MedlinePlus

    Heartburn - bland diet; Nausea - bland diet; Diarrhea - bland diet; Peptic ulcer - bland diet ... changes to help treat ulcers, heartburn, nausea, vomiting, diarrhea, and gas. You may also need a bland ...

  20. Long-term follow-up of children treated with the modified Atkins diet.

    PubMed

    Chen, Wendy; Kossoff, Eric H

    2012-06-01

    The modified Atkins diet has been studied in mostly short-term clinical trials and case series. No studies have systematically examined the long-term benefits and side effects. The modified Atkins diet was started without prior ketogenic diet use in 87 children at the Johns Hopkins Hospital since 2002, of which 54 continued for more than 6 months. Children who had not been seen within the past 2 years were contacted by phone and email. At their most recent point during the modified Atkins diet (mean 19.9 months), 30 of 54 (55%) children with diet durations of more than 6 months achieved >50% improvement; 19 (35%) were seizure-free. Using an intent-to-treat analysis, at 12 months, 33 of 87 (38%) had >50% seizure reduction; 16 (18%) were seizure-free. These results are similar to published data for short-term modified Atkins diet and long-term ketogenic diet use. Side effects were predominantly elevations in lipid profile and gastrointestinal upset.

  1. The mTORC1-Signaling Pathway and Hepatic Polyribosome Profile Are Enhanced after the Recovery of a Protein Restricted Diet by a Combination of Soy or Black Bean with Corn Protein

    PubMed Central

    Márquez-Mota, Claudia C.; Rodriguez-Gaytan, Cinthya; Adjibade, Pauline; Mazroui, Rachid; Gálvez, Amanda; Granados, Omar; Tovar, Armando R.; Torres, Nimbe

    2016-01-01

    Between 6% and 11% of the world’s population suffers from malnutrition or undernutrition associated with poverty, aging or long-term hospitalization. The present work examined the effect of different types of proteins on the mechanistic target of rapamycin (mTORC1)-signaling pathway in: (1) healthy; and (2) protein restricted rats. (1) In total, 200 rats were divided into eight groups and fed one of the following diets: 20% casein (C), soy (S), black bean (B), B + Corn (BCr), Pea (P), spirulina (Sp), sesame (Se) or Corn (Cr). Rats fed C or BCr had the highest body weight gain; rats fed BCr had the highest pS6K1/S6K1 ratio; rats fed B, BCr or P had the highest eIF4G expression; (2) In total, 84 rats were fed 0.5% C for 21 day and protein rehabilitated with different proteins. The S, soy + Corn (SCr) and BCr groups had the highest body weight gain. Rats fed SCr and BCr had the highest eIF4G expression and liver polysome formation. These findings suggest that the quality of the dietary proteins modulate the mTORC1-signaling pathway. In conclusion, the combination of BCr or SCr are the best proteins for dietary protein rehabilitation due to the significant increase in body weight, activation of the mTORC1-signaling pathway in liver and muscle, and liver polysome formation. PMID:27657118

  2. The mTORC1-Signaling Pathway and Hepatic Polyribosome Profile Are Enhanced after the Recovery of a Protein Restricted Diet by a Combination of Soy or Black Bean with Corn Protein.

    PubMed

    Márquez-Mota, Claudia C; Rodriguez-Gaytan, Cinthya; Adjibade, Pauline; Mazroui, Rachid; Gálvez, Amanda; Granados, Omar; Tovar, Armando R; Torres, Nimbe

    2016-09-20

    Between 6% and 11% of the world's population suffers from malnutrition or undernutrition associated with poverty, aging or long-term hospitalization. The present work examined the effect of different types of proteins on the mechanistic target of rapamycin (mTORC1)-signaling pathway in: (1) healthy; and (2) protein restricted rats. (1) In total, 200 rats were divided into eight groups and fed one of the following diets: 20% casein (C), soy (S), black bean (B), B + Corn (BCr), Pea (P), spirulina (Sp), sesame (Se) or Corn (Cr). Rats fed C or BCr had the highest body weight gain; rats fed BCr had the highest pS6K1/S6K1 ratio; rats fed B, BCr or P had the highest eIF4G expression; (2) In total, 84 rats were fed 0.5% C for 21 day and protein rehabilitated with different proteins. The S, soy + Corn (SCr) and BCr groups had the highest body weight gain. Rats fed SCr and BCr had the highest eIF4G expression and liver polysome formation. These findings suggest that the quality of the dietary proteins modulate the mTORC1-signaling pathway. In conclusion, the combination of BCr or SCr are the best proteins for dietary protein rehabilitation due to the significant increase in body weight, activation of the mTORC1-signaling pathway in liver and muscle, and liver polysome formation.

  3. [Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review].

    PubMed

    Araya-Quintanilla, F; Celis-Rosati, A; Rodriguez-Leiva, C; Silva-Navarro, C; Silva-Pinto, Y; Toro-Jeria, B

    2016-05-16

    Introduccion. La epilepsia es una patologia cerebral que afecta tanto a niños como a adultos. Desde los años veinte, la dieta cetogenica ha ganado prestigio como otra opcion de tratamiento en pacientes con epilepsia refractaria. Sujetos y metodos. Se realiza una sintesis de la evidencia a traves de una revision sistematica de ensayos clinicos aleatorizados que hayan comparado una dieta cetogenica sola con otros tipos de dieta para el tratamiento de estos pacientes. Objetivo. Determinar la efectividad de la dieta cetogenica en la disminucion de los episodios de convulsiones en pacientes con epilepsia refractaria. La estrategia de busqueda incluyo ensayos clinicos aleatorizados y ensayos clinicos controlados. Las bases de datos usadas fueron: Medline, LILACS, Central y CINAHL. Resultados. Se obtuvieron seis articulos que cumplian con los criterios de elegibilidad. Conclusiones. Existe evidencia limitada de que la dieta cetogenica en comparacion con la dieta de trigliceridos de cadena media es mas efectiva en disminuir la frecuencia de las convulsiones. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta gradual (2,5:1 y 3:1) es mas efectiva para disminuir las crisis epilepticas. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta Atkins es mas efectiva para disminuir la frecuencia de convulsiones en tres meses. La decision de aplicar este tipo de dietas tambien debe basarse en costes, preferencias y seguridad del tratamiento. Ademas, debe considerarse la probabilidad de que algunos estudios, por problemas de indizacion, hayan quedado fuera de la revision.

  4. [The use of the ketogenic diet as treatment for refractory epilepsy in the paediatric age].

    PubMed

    Pablos-Sánchez, Tamara; Oliveros-Leal, Liliana; Núñez-Enamorado, Noemí; Camacho-Salas, Ana; Moreno-Villares, José Manuel; Simón-De las Heras, Rogelio

    2014-01-16

    Introduccion. El 23-25% de los niños epilepticos son refractarios a farmacos antiepilepticos. El interes por la dieta cetogenica como tratamiento en estos pacientes no candidatos a otras opciones terapeuticas ha resurgido ultimamente. Objetivo. Valorar la eficacia y seguridad del tratamiento con dieta cetogenica en un importante numero de pacientes pediatricos con epilepsia refractaria en nuestro centro y determinar si los resultados obtenidos corroboran otros de publicacion reciente. Pacientes y metodos. Se revisaron retrospectivamente las historias clinicas de 41 niños con epilepsia refractaria que fueron tratados con dieta cetogenica entre 1998 y 2011, la mayoria con dieta tipo Radcliffe II. La mediana de edad al inicio de la dieta fue de 3,92 años. Resultados. A los seis meses del inicio de la dieta se redujeron las crisis en al menos un 50% en un 36,84% de la muestra (el 10,53% de los niños alcanzo mas de un 90% de reduccion y un 5,26% quedo sin crisis). Aproximadamente un 50% por grupo de edad en los mas pequeños respondio de manera positiva. Un 58,54% de los pacientes presento algun efecto secundario, tolerable y transitorio, principalmente elevacion de los niveles de colesterol y estreñimiento, sin observarse variacion en los parametros antropometricos. Conclusiones. La dieta cetogenica supone una buena alternativa terapeutica en los casos de epilepsia refractaria en la edad pediatrica, con mayor probabilidad de beneficio cuanto menor sea la edad del niño al inicio de la dieta. En general, es bien tolerada. Son de gran importancia en estos pacientes las revisiones periodicas con control nutricional.

  5. HEPATIC FATTY ACID PROFILE OF RATS FED A TRIHEPTANOIN-BASED KETOGENIC DIET.

    PubMed

    Vieira de Melo, Ingrid Sofia; Da Rocha Ataide, Terezinha; Lima de Oliveira, Suzana; Bezerra Bueno, Nassib; Duarte de Freitas, Johnnatan; Goulart Sant'Ana, Antônio Euzébio

    2015-07-01

    Objetivo: el objetivo de este estudio fue evaluar la influencia del consumo de una dieta cetogénica complementada con triheptanoína, un triacilglicerol de cadena media y anaplerótico, en el perfil de ácidos grasos del hígado de ratones Wistar. Métodos: tres grupos de ratones Wistar machos (n = 10) fueron sometidos durante 60 días a una dieta AIN-93 de control, una dieta cetogénica basada en triheptanoína o una dieta cetogénica a base de aceite de soja. Los hígados fueron escindidos y sometidos a extracción de lípidos y metilación para obtener los ésteres metílicos de ácidos grasos, que se sometieron a cromatografía de gas-espectrometría de masa. Resultados y discusión: en comparación con los ratones alimentados con la dieta de control, los de ambas dietas cetogénicas mostraron una reducción significativa en las concentraciones de los ácidos grasos 9-hexadecenoico y 9-octadecenoico, mientras que los alimentados con triheptanoína mostraron niveles de ácido octadecenoico aumentados. Conclusión: los cambios en los perfiles de ácidos grasos del hígado de los ratones alimentados con dietas cetogénicas no están relacionados con la fuente de grasa de la dieta (triheptanoína o aceite de soja), sino más bien con la concentración total de lípidos.

  6. CONVULSIVE DISORDERS IN CHILDREN WITH REFERENCE TO TREATMENT WITH KETOGENIC DIET.

    ERIC Educational Resources Information Center

    KEITH, HADDOW M.

    WRITTEN FOR THE MEDICAL PROFESSION, THIS BOOK PROVIDES INFORMATION ON CHILDHOOD CONVULSIONS (EPILEPSY) AND METHODS OF TREATMENT. VARIOUS CONVULSIVE DISORDERS, INCLUDING HYPSARHYTHMIA, AUTONOMIC SEIZURES, SYMPTOM COMPLEXES, FEBRILE CONVULSIONS, AND "PHOTOGENIC" DISORDERS, ARE DISCUSSED IN TERMS OF CAUSES, SYMPTOMS, AND TREATMENT.…

  7. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

    PubMed

    Bielohuby, Maximilian; Sisley, Stephanie; Sandoval, Darleen; Herbach, Nadja; Zengin, Ayse; Fischereder, Michael; Menhofer, Dominik; Stoehr, Barbara J M; Stemmer, Kerstin; Wanke, Rüdiger; Tschöp, Matthias H; Seeley, Randy J; Bidlingmaier, Martin

    2013-11-01

    Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.

  8. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial

    PubMed Central

    Henderson, Samuel T; Vogel, Janet L; Barr, Linda J; Garvin, Fiona; Jones, Julie J; Costantini, Lauren C

    2009-01-01

    Background Alzheimer's disease (AD) is characterized by early and region-specific declines in cerebral glucose metabolism. Ketone bodies are produced by the body during glucose deprivation and are metabolized by the brain. An oral ketogenic compound, AC-1202, was tested in subjects with probable AD to examine if ketosis could improve cognitive performance. Methods Daily administration of AC-1202 was evaluated in 152 subjects diagnosed with mild to moderate AD in a US-based, 90-day, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were on a normal diet and continued taking approved AD medications. Primary cognitive end points were mean change from Baseline in the AD Assessment Scale-Cognitive subscale (ADAS-Cog), and global scores in the AD Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC). AC-1202 was compared to Placebo in several population groups, including: intention-to-treat (ITT), per protocol, and dosage compliant groups. Results were also stratified by APOE4 carriage status (a predefined analysis based on the epsilon 4 (E4) variant of the apolipoprotein E gene). This trial was registered with ClinicalTrials.gov, registry number NCT00142805, information available at Results AC-1202 significantly elevated a serum ketone body (β-hydroxybutyrate) 2 hours after administration when compared to Placebo. In each of the population groups, a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45: 1.9 point difference, p = 0.0235 in ITT; 2.53 point difference, p = 0.0324 in per protocol; 2.6 point difference, p = 0.0215 in dosage compliant. Among participants who did not carry the APOE4 allele (E4(-)), a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45 and Day 90. In the ITT population, E4(-) participants (N = 55) administered AC-1202 had a significant 4.77 point difference in mean change

  9. Glucose transporter type 1 deficiency syndrome effectively treated with modified Atkins diet.

    PubMed

    Haberlandt, Edda; Karall, Daniela; Jud, Veronika; Baumgartner, Sara Sigl; Zotter, Sibylle; Rostasy, Kevin; Baumann, Matthias; Scholl-Buergi, Sabine

    2014-04-01

    This is a report on the successful treatment of a 6-year-old girl with genetically proven glucose transporter type 1 deficiency syndrome (GLUT1-DS) with modified Atkins diet (MAD). GLUT1-DS is an inborn disorder of glucose transport across the blood-brain barrier, which leads to energy deficiency of the brain with a broad spectrum of neurological symptoms including therapy-resistant epilepsy. Usually classical ketogenic diet (KD) is the standard treatment for patients with GLUT1-DS. Treatment with MAD, a variant of KD, for an observation period of 17 months resulted in improvement of seizures, alertness, cognitive abilities, and electroencephalography in this patient.

  10. Meal replacements and fibre supplement as a strategy for weight loss. Proprietary PGX® meal replacement and PGX® fibre supplement in addition to a calorie-restricted diet to achieve weight loss in a clinical setting.

    PubMed

    Reichert, Ronald G; Reimer, Raylene A; Kacinik, Veronica; Pal, Sebely; Gahler, Roland J; Wood, Simon

    2013-01-01

    Meal replacements and viscous soluble fibre represent safe and sustainable aids for weight loss. Our purpose was to determine if PGX® meal replacements and PGX(®) fibre complex in combination with a calorie-restricted diet would aid in weight loss in a clinical setting. Fifty-two overweight and obese participants (49 women, 3 men; average age 47.1 years) with a mean body mass index (BMI) of 33.8 ± 6.4 kg/m(2) consumed 57 g of proprietary PGX® meal replacement product at breakfast and another 57 g at lunch for 12 weeks. In addition to the meal replacements, they were also asked to consume 5 g/day of PGX® fibre in the form of granules, powder or capsules together with 250 mlwater. A registered dietician recommended low-fat, low-glycaemic-index foods for snacks and the dinner menus such that each volunteer was consuming a total of 1200 kcal/day. All participants (n = 52) lost a significant amount of weight from baseline (-4.69 ± 3.73 kg), which was further reflected in the reductions in their waist (-7.11 ± 6.35 cm) and hip circumference (-5.59 ± 3.58 cm) over the 12-week study (p < 0.0001). BMI scores (n = 51) were reduced by 1.6 ± 1.4 kg/m(2). The use of PGX® meal replacements and PGX(®) fibre along with a controlled dietary caloric intake is of benefit for short-term weight loss.

  11. Vegetarian Diet

    MedlinePlus

    ... animal products The lacto vegetarian diet, which includes plant foods plus dairy products The lacto-ovo vegetarian diet, which includes both dairy products and eggs People who follow vegetarian diets can get ...

  12. Comparison of Methods to Reduce Myocardial 18F-FDG Uptake in Mice: Calcium Channel Blockers versus High-Fat Diets

    PubMed Central

    Cussó, Lorena; Vaquero, Juan José; Bacharach, Stephen; Desco, Manuel

    2014-01-01

    Purpose Besides its application in oncology, 18F-FDG PET-CT imaging is also useful in the diagnosis of certain lung infections, inflammatory diseases, and atherosclerotic plaques. Myocardial uptake of 18F-FDG may hamper visualization of the lesions caused by these diseases. Two approaches have been proposed for reducing myocardial uptake in preclinical studies, namely, calcium channel blockers (verapamil) and high-fat diets such as commercial ketogenic diets and sunflower seed diets. The objective of this study was to compare the efficacy of these approaches in reducing myocardial uptake of 18F-FDG in mice. Methods We performed two experiments. In experiment A, each animal underwent four 18F-FDG PET/CT scans in the following order: baseline, after administration of verapamil, after two days on ketogenic diet and after two days on sunflower seeds. PET scans were performed 60 minutes after injection of 18.5 MBq of 18F-FDG. In experiment B, the best protocol of the three (ketogenic diet) was evaluated in a lung inflammation model to assess the efficacy of reducing myocardial uptake of 18F-FDG. Results Compared with baseline (SUV 2.03±1.21); the greatest reduction in uptake of 18F-FDG was with ketogenic diet (SUV 0.79±0.16; p = 0.008), followed by sunflower seeds (SUV 0.91±0.13; p = 0.015); the reduction in myocardial uptake produced by verapamil was not statistically significant (SUV 1.78±0.79; p = NS). In experiment B, complete suppression of myocardial uptake noticeably improved the visualization of inflamed areas near the heart, while in the case of null or partial myocardial suppression, it was much harder to distinguish lung inflammation from myocardial spillover. Conclusion A high-fat diet appeared to be the most effective method for decreasing myocardial uptake of 18F-FDG in healthy mice, outperforming verapamil. Our findings also demonstrate that ketogenic diet