Effect of a High-Fat Ketogenic Diet on Plasma Levels of Lipids, Lipoproteins, and Apolipoproteins in Children

Kwiterovich, Peter O.; Vining, Eileen P.G.; Pyzik, Paula L.; Skolasky, Richard L.; Freeman, John M.

doi:10.1001/jama.290.7.912

Cited by 260 publications

(188 citation statements)

References 35 publications

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“…In previous short-term studies, increased plasma cholesterol levels were observed after 9 wk of diet (2), whereas at that time point plasma triglyceride levels were lower. Also, in both adults and children with refractory epilepsy, KD was associated with increased plasma cholesterol and triglyceride levels (24,38). Furthermore, the increased plasma cytokine concentrations in our study suggest a systemic proinflammatory state in longterm KD-fed mice.…”

Section: Discussionsupporting

confidence: 51%

Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

Ellenbroek

Dijck

Töns

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

124

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Ellenbroek JH, van Dijck L, Töns HA, Rabelink TJ, Carlotti F, Ballieux BE, de Koning EJ. Long-term ketogenic diet causes glucose intolerance and reduced ␤-and ␣-cell mass but no weight loss in mice. Am J Physiol Endocrinol Metab 306: E552-E558, 2014. First published January 7, 2014 doi:10.1152/ajpendo.00453.2013.-High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term effects on pancreatic endocrine cells are unknown. In this study we investigate the effects of long-term KD on glucose tolerance and ␤-and ␣-cell mass in mice. Despite an initial weight loss, KD did not result in weight loss after 22 wk. Plasma markers associated with dyslipidemia and inflammation (cholesterol, triglycerides, leptin, monocyte chemotactic protein-1, IL-1␤, and IL-6) were increased, and KD-fed mice showed signs of hepatic steatosis after 22 wk of diet. Long-term KD resulted in glucose intolerance that was associated with insufficient insulin secretion from ␤-cells. After 22 wk, insulin-stimulated glucose uptake was reduced. A reduction in ␤-cell mass was observed in KD-fed mice together with an increased number of smaller islets. Also ␣-cell mass was markedly decreased, resulting in a lower ␣-to ␤-cell ratio. Our data show that long-term KD causes dyslipidemia, a proinflammatory state, signs of hepatic steatosis, glucose intolerance, and a reduction in ␤-and ␣-cell mass, but no weight loss. This indicates that long-term high-fat, lowcarbohydrate KD lead to features that are also associated with the metabolic syndrome and an increased risk for type 2 diabetes in humans. pancreatic islet; ketogenic diet; glucose intolerance; ␤-cell; ␣-cell

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Section: Discussionsupporting

confidence: 51%

Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

Ellenbroek

Dijck

Töns

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

124

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“…KD may cause hypercholesterolemia, hypertriglyceridemia, and elevation of apolipoprotein B-containing lipoprotein. 27 The long-term effect of KD-induced dyslipidemia on vascular structure and atheroma formation remains unclear. Although it appears to have no effect on the carotid intima-media thickness and elastic properties after 12 months of KD treatment, 28 Doppler studies and echocardiogram may be necessary in the presence of chronic dyslipidemia and to screen for cardiomyopathy.…”

Section: Dyslipidemia and Cardiovascular Complicationsmentioning

confidence: 99%

The Ketogenic Diet: A Practical Guide for Pediatricians

Luat¹,

Coyle²,

Kamat³

2016

Pediatr Ann

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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.]

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“…The longterm effects of a high-fat diet in mice have not been thoroughly investigated. In humans, the KD has been associated with increased risk of coronary heart disease (Best et al, 2000;Bergqvist et al, 2003;Dashti et al, 2003;Kwiterovich et al, 2003) among other adverse effects. It is unclear whether such adverse events played a role in the eventual death of KD fed Aldh5a1 −/− mice.…”

Section: Lifespanmentioning

confidence: 99%

A ketogenic diet rescues the murine succinic semialdehyde dehydrogenase deficient phenotype

Nylen

Velázquez

Likhodii

et al. 2008

Experimental Neurology

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Succinic semialdehyde dehydrogenase (SSADH) deficiency is an heritable disorder of GABA degradation characterized by ataxia, psychomotor retardation and seizures. To date, there is no effective treatment for SSADH deficiency. We tested the hypothesis that a ketogenic diet (KD) would improve outcome in an animal model of SSADH deficiency, the SSADH knockout mouse (Aldh5a1 −/− ). Using a 4:1 ratio of fat to combined carbohydrate and protein KD we set out to compare the general phenotype, in vivo and in vitro electrophysiology and [ 35 S]TBPS binding in both Aldh5a1 −/− mice and control (Aldh5a1 +/+ ) mice. We found that the KD prolonged the lifespan of mutant mice by >300% with normalization of ataxia, weight gain and EEG compared to mutants fed a control diet. Aldh5a1 −/− mice showed significantly reduced mIPSC frequency in CA1 hippocampal neurons as well as significantly decreased [ 35 S]TBPS binding in all brain areas examined. In KD fed mutants, mIPSC activity normalized and [ 35 S]TBPS binding was restored in the cortex and hippocampus. The KD appears to reverse toward normal the perturbations seen in Aldh5a1 −/− mice. Our data suggest that the KD may work in this model by restoring GABAergic inhibition. These data demonstrate a successful experimental treatment for murine SSADH deficiency using a KD, giving promise to the idea that the KD may be successful in the clinical treatment of SSADH deficiency.

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Effect of a High-Fat Ketogenic Diet on Plasma Levels of Lipids, Lipoproteins, and Apolipoproteins in Children

Cited by 260 publications

References 35 publications

Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

The Ketogenic Diet: A Practical Guide for Pediatricians

A ketogenic diet rescues the murine succinic semialdehyde dehydrogenase deficient phenotype

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