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Beneficial effects of ketogenic diet in obese diabetic subjects

URL: https://link.springer.com/article/10.1007%2Fs11010-007-9448-z

Journal: Molecular and Cellular Biochemistry

Publication Date: 04/2007

Summary: Obesity is closely linked to the incidence of type II diabetes. It is found that effective management of body weight and changes to nutritional habits especially with regard to the carbohydrate content and glycemic index of the diet have beneficial effects in obese subjects with glucose intolerance. Previously we have shown that ketogenic diet is quite effective in reducing body weight. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. In this study the effect of ketogenic diet in obese subjects with high blood glucose level is compared to those with normal blood glucose level for a period of 56 weeks. A total of 64 healthy obese subjects with body mass index (BMI) greater than 30, having high blood glucose level and those subjects with normal blood glucose level were selected in this study. The body weight, body mass index, blood glucose level, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, urea and creatinine were determined before and at 8, 16, 24, 48, and 56 weeks after the administration of the ketogenic diet. The body weight, body mass index, the level of blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P < 0.0001), whereas the level of HDL-cholesterol increased significantly (P < 0.0001). Interestingly these changes were more significant in subjects with high blood glucose level as compared to those with normal blood glucose level. The changes in the level of creatinine were not statistically significant. This study shows the beneficial effects of ketogenic diet in obese diabetic subjects following its long-term administration. Furthermore, it demonstrates that in addition to its therapeutic value, low carbohydrate diet is safe to use for a longer period of time in obese diabetic subjects.

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Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum

URL: https://academic.oup.com/ajcn/article/87/1/44/4633256

Journal: American Journal of Clinical Nutrition

Publication Date: 01/2008

Summary: Altering the macronutrient composition of the diet influences hunger and satiety. Studies have compared high- and low-protein diets, but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake. We aimed to compare the hunger, appetite, and weight-loss responses to a high-protein, low-carbohydrate [(LC) ketogenic] and those to a high-protein, medium-carbohydrate [(MC) nonketogenic] diet in obese men feeding ad libitum. Seventeen obese men were studied in a residential trial; food was provided daily. Subjects were offered 2 high-protein (30% of energy) ad libitum diets, each for a 4-wk period-an LC (4% carbohydrate) ketogenic diet and an MC (35% carbohydrate) diet-randomized in a crossover design. Body weight was measured daily, and ketosis was monitored by analysis of plasma and urine samples. Hunger was assessed by using a computerized visual analogue system. Ad libitum energy intakes were lower with the LC diet than with the MC diet [P=0.02; SE of the difference (SED): 0.27] at 7.25 and 7.95 MJ/d, respectively. Over the 4-wk period, hunger was significantly lower (P=0.014; SED: 1.76) and weight loss was significantly greater (P=0.006; SED: 0.62) with the LC diet (6.34 kg) than with the MC diet (4.35 kg). The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma (P=0.036 from baseline; SED: 0.62) and 2.99 mmol/L in urine (P<0.001 from baseline; SED: 0.36). In the short term, high-protein, low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein, medium-carbohydrate nonketogenic diets.

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The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus.

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633336/

Journal: Nutrition and Metabolism

Publication Date: 12/2008

Summary: Dietary carbohydrate is the major determinant of postprandial glucose levels, and several clinical studies have shown that low-carbohydrate diets improve glycemic control. In this study, we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus. Eighty-four community volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate, ketogenic diet (<20 g of carbohydrate daily; LCKD) or a low-glycemic, reduced-calorie diet (500 kcal/day deficit from weight maintenance diet; LGID). Both groups received group meetings, nutritional supplementation, and an exercise recommendation. The main outcome was glycemic control, measured by hemoglobin A1c. Forty-nine (58.3%) participants completed the study. Both interventions led to improvements in hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group had greater improvements in hemoglobin A1c (-1.5% vs. -0.5%, p = 0.03), body weight (-11.1 kg vs. -6.9 kg, p = 0.008), and high density lipoprotein cholesterol (+5.6 mg/dL vs. 0 mg/dL, p < 0.001) compared to the LGID group. Diabetes medications were reduced or eliminated in 95.2% of LCKD vs. 62% of LGID participants (p < 0.01). Dietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes. The diet lower in carbohydrate led to greater improvements in glycemic control, and more frequent medication reduction/elimination than the low glycemic index diet. Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes.

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Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome.

URL: https://www.sciencedirect.com/science/article/abs/pii/S0163782708000167?via%3Dihub

Journal: Progress in Lipids Research

Publication Date: 09/2008

Summary: Abnormal fatty acid metabolism and dyslipidemia play an intimate role in the pathogenesis of metabolic syndrome and cardiovascular diseases. The availability of glucose and insulin predominate as upstream regulatory elements that operate through a collection of transcription factors to partition lipids toward anabolic pathways. The unraveling of the details of these cellular events has proceeded rapidly, but their physiologic relevance to lifestyle modification has been largely ignored. Here we highlight the role of dietary input, specifically carbohydrate intake, in the mechanism of metabolic regulation germane to metabolic syndrome. The key principle is that carbohydrate, directly or indirectly through the effect of insulin, controls the disposition of excess dietary nutrients. Dietary carbohydrate modulates lipolysis, lipoprotein assembly and processing and affects the relation between dietary intake of saturated fat intake and circulating levels. Several of these processes are the subject of intense investigation at the cellular level. We see the need to integrate these cellular mechanisms with results from low-carbohydrate diet trials that have shown reduced cardiovascular risk through improvement in hepatic, intravascular, and peripheral processing of lipoproteins, alterations in fatty acid composition, and reductions in other cardiovascular risk factors, notably inflammation. From the current state of the literature, however, low-carbohydrate diets are grounded in basic metabolic principles and the data suggest that some form of carbohydrate restriction is a candidate to be the preferred dietary strategy for cardiovascular health beyond weight regulation.

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Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet

URL: https://link.springer.com/article/10.1007/s11745-008-3274-2

Journal: Lipids

Publication Date: 12/2008

Summary: We recently proposed that the biological markers improved by carbohydrate restriction were precisely those that define the metabolic syndrome (MetS), and that the common thread was regulation of insulin as a control element. We specifically tested the idea with a 12-week study comparing two hypocaloric diets (~1,500 kcal): a carbohydrate-restricted diet (CRD) (%carbohydrate:fat:protein = 12:59:28) and a low-fat diet (LFD) (56:24:20) in 40 subjects with atherogenic dyslipidemia. Both interventions led to improvements in several metabolic markers, but subjects following the CRD had consistently reduced glucose (−12%) and insulin (−50%) concentrations, insulin sensitivity (−55%), weight loss (−10%), decreased adiposity (−14%), and more favorable triacylglycerol (TAG) (−51%), HDL-C (13%) and total cholesterol/HDL-C ratio (−14%) responses. In addition to these markers for MetS, the CRD subjects showed more favorable responses to alternative indicators of cardiovascular risk: postprandial lipemia (−47%), the Apo B/Apo A-1 ratio (−16%), and LDL particle distribution. Despite a threefold higher intake of dietary saturated fat during the CRD, saturated fatty acids in TAG and cholesteryl ester were significantly decreased, as was palmitoleic acid (16:1n-7), an endogenous marker of lipogenesis, compared to subjects consuming the LFD. Serum retinol binding protein 4 has been linked to insulin-resistant states, and only the CRD decreased this marker (−20%). The findings provide support for unifying the disparate markers of MetS and for the proposed intimate connection with dietary carbohydrate. The results support the use of dietary carbohydrate restriction as an effective approach to improve features of MetS and cardiovascular risk.

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Effects of a low carbohydrate weight loss diet on exercise capacity and tolerance in obese subjects.

URL: https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2009.134

Journal: Obesity

Publication Date: 09/2012

Summary: Dietary restriction and increased physical activity are recommended for obesity treatment. Very low carbohydrate diets are used to promote weight loss, but their effects on physical function and exercise tolerance in overweight and obese individuals are largely unknown. The aim of this study was to compare the effects of a very low carbohydrate, high fat (LC) diet with a conventional high carbohydrate, low fat (HC) diet on aerobic capacity, fuel utilization during submaximal exercise, perceived exercise effort (RPE) and muscle strength. Sixty subjects (age: 49.2 ± 1.2 years; BMI: 33.6 ± 0.5 kg/m2) were randomly assigned to an energy restricted (∼6–7 MJ, 30% deficit), planned isocaloric LC or HC for 8 weeks. At baseline and week 8, subjects performed incremental treadmill exercise to exhaustion and handgrip and isometric knee extensor strength were assessed. Weight loss was greater in LC compared with HC (8.4 ± 0.4% and 6.7 ± 0.5%, respectively; P = 0.01 time × diet). Peak oxygen uptake and heart rate were unchanged in both groups (P > 0.17). Fat oxidation increased during submaximal exercise in LC but not HC (P < 0.001 time × diet effect). On both diets, perception of effort during submaximal exercise and handgrip strength decreased (P ≤ 0.03 for time), but knee extensor strength remained unchanged (P > 0.25). An LC weight loss diet shifted fuel utilization toward greater fat oxidation during exercise, but had no detrimental effect on maximal or submaximal markers of aerobic exercise performance or muscle strength compared with an HC diet. Further studies are required to determine the interaction of LC diets with regular exercise training and the long‐term health effects.

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Systematic review of randomized controlled trials of low‐carbohydrate vs. low‐fat/low‐calorie diets in the management of obesity and its comorbidities

URL: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X.2008.00518.x

Journal: Obesity Reviews

Publication Date: 12/2008

Summary: There are few studies comparing the effects of low‐carbohydrate/high‐protein diets with low‐fat/high‐carbohydrate diets for obesity and cardiovascular disease risk. This systematic review focuses on randomized controlled trials of low‐carbohydrate diets compared with low‐fat/low‐calorie diets. Studies conducted in adult populations with mean or median body mass index of ≥28 kg m−2 were included. Thirteen electronic databases were searched and randomized controlled trials from January 2000 to March 2007 were evaluated. Trials were included if they lasted at least 6 months and assessed the weight‐loss effects of low‐carbohydrate diets against low‐fat/low‐calorie diets. For each study, data were abstracted and checked by two researchers prior to electronic data entry. The computer program Review Manager 4.2.2 was used for the data analysis. Thirteen articles met the inclusion criteria. There were significant differences between the groups for weight, high‐density lipoprotein cholesterol, triacylglycerols and systolic blood pressure, favouring the low‐carbohydrate diet. There was a higher attrition rate in the low‐fat compared with the low‐carbohydrate groups suggesting a patient preference for a low‐carbohydrate/high‐protein approach as opposed to the Public Health preference of a low‐fat/high‐carbohydrate diet. Evidence from this systematic review demonstrates that low‐carbohydrate/high‐protein diets are more effective at 6 months and are as effective, if not more, as low‐fat diets in reducing weight and cardiovascular disease risk up to 1 year. More evidence and longer‐term studies are needed to assess the long‐term cardiovascular benefits from the weight loss achieved using these diets.

 

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A carbohydrate-restricted diet during resistance training promotes more favorable changes in body composition and markers of health in obese women with and without insulin resistance

URL: https://www.ncbi.nlm.nih.gov/pubmed/21673483

Journal: The Physician and Sports Medicine

Publication Date: 05/2011

Summary: To determine whether sedentary obese women with elevated levels of homeostatic model assessment (HOMA) insulin resistance (ie, > 3.5) experience greater benefits from an exercise + higher-carbohydrate (HC) or carbohydrate-restricted weight loss program than women with lower HOMA levels. 221 women (age, 46.5 ± 12 years; body weight, 90.3 ± 16 kg; body mass index, 33.8 ± 5 kg/m(2)) participated in a 10-week supervised exercise and weight loss program. The fitness program involved 30 minutes of circuit-style resistance training 3 days per week. Subjects were prescribed low-fat (30%) isoenergetic diets that consisted of 1200 kcals per day for 1 week (phase 1) and 1600 kcals per day for 9 weeks (phase 2) with HC or higher protein (HP). Fasting blood samples, body composition, anthropometry, resting energy expenditure, and fitness measurements were obtained at 0 and 10 weeks. Subjects were retrospectively stratified into lower (LH) or higher (HH) than 3.5 HOMA groups. Data were analyzed by multivariate analysis of variance with repeated measures and are presented as mean ± standard deviation changes from baseline. Baseline HOMA levels in the LH group were significantly lower than those in the HH group (LH, 0.6 ± 0.7; HH, 6.3 ± 3.4; P = 0.001). Diet and training significantly decreased body weight (-3.5 ± 3 kg), fat mass (-2.7 ± 3 kg), blood glucose (-3%), total cholesterol (-4.5%), low-density lipoproteins (-5%), triglycerides (-5.9%), systolic blood pressure (-2.6%), and waist circumference (-3.7%), while increasing peak aerobic capacity (7.3%). Subjects in the HP group experienced greater weight loss (-4.4 ± 3.6 kg vs -2.6 ± 2.9 kg), fat loss (-3.4 ± 2.7 kg vs -1.7 ± 2.0 kg), reductions in serum glucose (3% vs 2%), and decreases in serum leptin levels (-30.8% vs -10.8%) than those in the HC group. Participants in the HH (-14.1%) and HP-HH (-21.6%) groups observed the greatest reduction in serum blood glucose. A carbohydrate-restricted diet promoted more favorable changes in weight loss, fat loss, and markers of health in obese women who initiated an exercise program compared with a diet higher in carbohydrate. Additionally, obese women who initiated training and dieting with higher HOMA levels experienced greater reductions in blood glucose following an HP diet.

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Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076656/

Journal: American Journal of Clinical Nutrition

Publication Date: 05/2011

Summary: Individuals with nonalcoholic fatty liver disease (NAFLD) have excess intrahepatic triglycerides. This is due, in part, to increased hepatic synthesis of fat from carbohydrates via lipogenesis. Although weight loss is currently recommended to treat NAFLD, little attention has been given to dietary carbohydrate restriction. The aim of this study was to determine the effectiveness of 2 wk of dietary carbohydrate and calorie restriction at reducing hepatic triglycerides in subjects with NAFLD. Eighteen NAFLD subjects (n = 5 men and 13 women) with a mean (±SD) age of 45 ± 12 y and a body mass index (in kg/m2) of 35 ± 7 consumed a carbohydrate-restricted (<20 g/d) or calorie-restricted (1200–1500 kcal/d) diet for 2 wk. Hepatic triglycerides were measured before and after intervention by magnetic resonance spectroscopy.  Mean (±SD) weight loss was similar between the groups (−4.0 ± 1.5 kg in the calorie-restricted group and −4.6 ± 1.5 kg in the carbohydrate-restricted group; P = 0.363). Liver triglycerides decreased significantly with weight loss (P < 0.001) but decreased significantly more (P = 0.008) in carbohydrate-restricted subjects (−55 ± 14%) than in calorie-restricted subjects (−28 ± 23%). Dietary fat (r = 0.643, P = 0.004), carbohydrate (r = −0.606, P = 0.008), posttreatment plasma ketones (r = 0.755, P = 0.006), and respiratory quotient (r = −0.797, P < 0.001) were related to a reduction in liver triglycerides. Plasma aspartate, but not alanine, aminotransferase decreased significantly with weight loss (P < 0.001). Two weeks of dietary intervention (≈4.3% weight loss) reduced hepatic triglycerides by ≈42% in subjects with NAFLD; however, reductions were significantly greater with dietary carbohydrate restriction than with calorie restriction. This may have been due, in part, to enhanced hepatic and whole-body oxidation.

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Effects of Dietary Composition During Weight Loss Maintenance: A Controlled Feeding Study

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564212/

Journal: JAMA

Publication Date: 06/2012

Summary: Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied. To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss. A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children’s Hospital Boston and Brigham and Women’s Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings. After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks. Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components. Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged. Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet.