Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level

Dashti, H.; Al-Zaid, N. S.; Mathew, T.C.; Al-Mousawi, Mahdi; Hussain, T.; Asfar, Sami; Behbahani, Abdulla I.

doi:10.1007/s11010-005-9001-x

Cited by 133 publications

(124 citation statements)

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“…A number of studies (10,11,51) have shown that dieting subjects eating a high-fat, low-carbohydrate diet tend to lose more weight more rapidly than subjects eating a low-fat, high-carbohydrate diet, leading to the speculation that high-fat diets might enhance weight loss by attenuating the decrease in energy expenditure typically seen with dieting. However, such an effect has not been demonstrated in either humans or rodents.…”

Section: Discussionmentioning

confidence: 99%

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

Kennedy

Pissios

Otu

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

367

380

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A high-fat, ketogenic diet induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab 292: E1724 -E1739, 2007. First published February 13, 2007; doi:10.1152/ajpendo.00717.2006.-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.liver; gene expression OVER THE PAST FEW DECADES the rates of obesity have risen substantially worldwide. Paradoxically, the increases in body weight, particularly in Western countries, occurred during a period of emphasis on diets low in fat as a means for avoiding weight gain. These dietary recommendations were based largely on the concept that high-fat diets were less satiating (39) and that reducing dietary fat reduced risk for cardiovascular disease by lowering circulating fat and cholesterol (5). As a result of the perceived failure of traditional dietary advice, attention shifted to alternative dietary regimes, including lowglycemic-index diets and very-low-carbohydrate ketogenic diets. Interest in these diets derives in part from the theoretical effects of dietary composition on energy expenditure. Although a small number of human studies have found such diets to be more effective in short-term weight loss and without adverse effects on glucose, insulin, lipids, or blood pressure (7,14,42,49,51), reports on metabolic effects remain inconclusive (8,38). Thus the precise effects of macronutrient diet composition on energy balance remain controversial.Studies of the physiological effects of dietary composition are intrinsically difficult in human populations because of problems achieving both compliance and accurate dietary reporting. Therefore, we developed a mouse model to examine the effect of diet composition on physiology, with particular reference to energy expenditure and metab...

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Section: Discussionmentioning

confidence: 99%

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

Kennedy

Pissios

Otu

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

367

380

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“…Multiple authors [29] highlighted the misleading nature of this article, pointing out that insufficient detail was provided to enable correct evaluation of the case report. Further criticism of Atkins style diets focuses on the consequences for cardiovascular health, since many of these diets contain high levels of saturated fat [8]. In vivo, dietary fat is transported to the liver by chylomicrons, where triglycerides are repackaged and secreted as nascent VLDL, which, via.…”

Section: The Atkins Dietmentioning

confidence: 99%

The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress

McPherson

McEneny

2011

J Physiol Biochem

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Ketogenesis is the branch of mammalian metabolism concerned with the synthesis of ketone bodies. In this process, the small, water-soluble compounds acetoacetate, D-3-β-hydroxybutyrate and propanone are produced by the liver in response to reduced glucose availability. Although ketone bodies are always present at a low level in healthy individuals, dietary manipulation and certain pathological conditions can increase the levels of these compounds in vivo. In some instances, such as in refractory epilepsy, high levels of ketone bodies can be beneficial-in this instance, by exerting an anticonvulsant effect. Conversely, if the levels of ketones rise to supraphysiological levels, as can occur in diabetes mellitus, a state of ketoacidosis can occur, which has serious consequences for cellular function. More recently, research has identified a possible link between ketogenesis and free radical-mediated pathologies, highlighting the potential application of ketogenic diets to the treatment of conditions such as Alzheimer's disease. Overall, an understanding of ketone body metabolism and its links to human disease may prove to be vital in developing new regimens for the treatment of human disease.

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“…However, two recent studies have shown that the longterm use of a low-carbohydrate diet (6-14 months) has a favorable effect on serum cholesterol, lipoprotein subfractions, and high-sensitivity C-reactive protein despite the increased intake of dietary fat. 8,9 However, the use of a low-carbohydrate diet does result in increased serum levels of chylomicrons and chylomicron remnants, both of which are capable of contributing to vascular plaque formation. 8 A theoretical concern exists that increased hepatic lipid oxidation as a result of decreased dietary carbohydrate intake could exacerbate the inflammatory milieu via enhanced freeradical production.…”

mentioning

confidence: 99%

A low-carbohydrate diet rapidly and dramatically reduces intrahepatic triglyceride content

et al. 2006

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During November of 2005, a 42-year-old white woman taking conjugated estrogen since age 16 was seen for evaluation of right upper quadrant pain of 6 months' duration. She was obese with mixed hyperlipidemia but had no evidence of diabetes mellitus or impaired fasting glucose. Initial workup indicated hepatomegaly (craniocaudal dimension: 26 cm) with an increased serum alanine aminotransferase concentration (55 U/L). Viral and autoimmune serologies were negative, and no heritable or environmental (i.e., ethanol) cause of liver disease was identified. Ultrasound examination of the liver was consistent with diffuse fatty infiltration of the liver. A diagnosis of non-alcoholic fatty liver disease (NAFLD) was confirmed by liver proton magnetic resonance spectroscopy, which demonstrated a liver triglyceride content of 44.6% (normal: Յ5.5%) 1 (Fig. 1). Discontinuation of conjugated estrogen was unsuccessful at relieving symptoms, and because of the patient's body mass index (32.2 kg/m 2 ), dietary therapy was initiated to promote weight loss. The diet chosen was the Atkins diet, emphasizing the selection of healthy sources of protein and fat. 2 At day 7 of the diet, she was ketotic with a urinary ketone concentration of 150 mg/dL. Liver biopsy was performed at this visit and showed pan-lobular macrovesicular steatosis without evidence of inflammatory activity or fibrosis. At day 14 of the diet, she remained ketotic with a respiratory quotient of 0.72 by indirect calorimetry. Body mass index had fallen to 30.9 kg/m 2 (Ϫ6.4 kg) with a modest decrement in abdominal pain. Dietary composition over this 2-week period was 54% protein, 41% fat, and 5% carbohydrate with an estimated daily caloric intake of approximately 1,000 kcal. Saturated, monounsaturated, and polyunsaturated fats accounted for 57%, 35%, and 8% of fat intake, respectively.The relative contribution to hepatic glucose production from all sources (glycogen, glycerol, phosphoenolpyruvate) was determined by nuclear magnetic resonance spectroscopy of monoacetone-glucose after ingestion of deuterium oxide in this patient. 3 Glycogenolysis accounted for only 25% of hepatic glucose produced, whereas glycerol gluconeogenesis accounted for 6%. In contrast, glycogenolysis accounts for 53% and glycerol gluconeogenesis for only 3% of newly formed glucose on a Western diet. 3 The patient was instructed to continue dieting and initiate a low-impact exercise regimen.Five weeks after initiating the diet, her body mass index was 29.9 kg/m 2 (Ϫ9.1 kg), her abdominal discomfort was significantly improved, and her serum alanine aminotransferase level was normal (32 U/L). Her exercise regimen consisted of the use of an elliptical machine and low-weight strength training for 30 minutes 3 times per week. Repeat proton magnetic resonance spectroscopy demonstrated a nearly fourfold reduction in liver triglyceride content to 11.9% (Fig. 1).This report shows the dramatic effect of a low-carbohydrate diet and moderate exercise on hepatic steatosis. Triglycerides were rapidly mobilized fr...

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Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level

Cited by 133 publications

References 40 publications

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

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

The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress

A low-carbohydrate diet rapidly and dramatically reduces intrahepatic triglyceride content

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