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Nutrition and Alzheimer’s disease: The detrimental role of a high carbohydrate diet

URL: https://www.ejinme.com/article/S0953-6205(11)00004-5/fulltext

Journal: European Journal of Internal Medicine

Publication Date: 04/2011

Summary: Alzheimer’s disease is a devastating disease whose recent increase in incidence rates has broad implications for rising health care costs. Huge amounts of research money are currently being invested in seeking the underlying cause, with corresponding progress in understanding the disease progression. In this paper, we highlight how an excess of dietary carbohydrates, particularly fructose, alongside a relative deficiency in dietary fats and cholesterol, may lead to the development of Alzheimer’s disease. A first step in the pathophysiology of the disease is represented by advanced glycation end-products in crucial plasma proteins concerned with fat, cholesterol, and oxygen transport. This leads to cholesterol deficiency in neurons, which significantly impairs their ability to function. Over time, a cascade response leads to impaired glutamate signaling, increased oxidative damage, mitochondrial and lysosomal dysfunction, increased risk to microbial infection, and, ultimately, apoptosis. Other neurodegenerative diseases share many properties with Alzheimer’s disease, and may also be due in large part to this same underlying cause.

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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.

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Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes

URL: https://www.sciencedirect.com/science/article/abs/pii/S0899900712000731?via%3Dihub

Journal: Nutrition

Publication Date: 10/2012

Summary: Effective diabetic management requires reasonable weight control. Previous studies from our laboratory have shown the beneficial effects of a low-carbohydrate ketogenic diet (LCKD) in patients with type 2 diabetes after its long term administration. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. These studies have indicated that, in addition to decreasing body weight and improving glycemia, LCKD can be effective in decreasing antidiabetic medication dosage. Similar to the LCKD, the conventional low-calorie, high nutritional value diet is also used for weight loss. The purpose of this study was to understand the beneficial effects of LCKD compared with the low-calorie diet (LCD) in improving glycemia. Three hundred and sixty-three overweight and obese participants were recruited from the Al-Shaab Clinic for a 24-wk diet intervention trial; 102 of them had type 2 diabetes. The participants were advised to choose LCD or LDKD, depending on their preference. Body weight, body mass index, changes in waist circumference, blood glucose level, changes in hemoglobin and glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea and creatinine were determined before and at 4, 8, 12, 16, 20, and 24 wk after the administration of the LCD or LCKD. The initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. The LCD and LCKD had beneficial effects on all the parameters examined. Interestingly, these changes were more significant in subjects who were on the LCKD as compared with those on the LCD. Changes in the level of creatinine were not statistically significant. This study shows the beneficial effects of a ketogenic diet over the conventional LCD in obese diabetic subjects. The ketogenic diet appears to improve glycemic control. Therefore, diabetic patients on a ketogenic diet should be under strict medical supervision because the LCKD can significantly lower blood glucose levels.

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Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679496/

Journal: Current Opinions in Clinical Nutrition and Metabolic Care

Publication Date: 07/2012

Summary: Obesity-associated nonalcoholic fatty liver disease (NAFLD) is highly prevalent, for which weight loss is the generally recommended clinical management. Low-carbohydrate ketogenic diets have been successful in promoting weight loss, but variations in the range of metabolic responses to these diets indicate that the effects of altering macronutrient content are not completely understood. This review focuses on the most recent findings that reveal the relationship between low-carbohydrate diets and NAFLD in rodent models and humans. Low-carbohydrate diets have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity. These ketogenic diets also provoke weight loss in rodents. However, long-term maintenance on a ketogenic diet stimulates the development of NAFLD and systemic glucose intolerance in mice. The relationship between ketogenic diets and systemic insulin resistance in both humans and rodents remains to be elucidated. Because low-carbohydrate ketogenic diets are increasingly employed for treatment of obesity, NAFLD, and neurological diseases such as epilepsy, understanding the long-term systemic effects of low-carbohydrate diets is crucial to the development of efficacious and safe dietary interventions.

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Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845365/

Journal: Metabolism

Publication Date: 12/2013

Summary: High fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity. Obese subjects (29.0–44.6 kg/m2) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n=26) or HFLC (n=29) diet for 12 weeks. The age range of subjects was 21–62 years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2 h oral glucose tolerance test did not differ (P>0.05) between diets after 12 weeks. The HFLC group had greater mean decreases in serum triglyceride (P=0.07), and hs-CRP (P=0.03), and greater mean increases in HDL cholesterol (P=0.004), and total adiponectin (P=0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet. Relative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets.

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Improvements in Glucose Metabolism and Insulin Sensitivity with a Low-Carbohydrate Diet in Obese Patients with Type 2 Diabetes

URL: https://www.ncbi.nlm.nih.gov/pubmed/24015695

Journal: Journal of the American College of Nutrition

Publication Date: 04/2013

Summary: The optimal diet for weight loss in type 2 diabetes remains controversial. This study examined a low-carbohydrate, high-fat diet with detailed physiological assessments of insulin sensitivity, glycemic control, and risk factors for cardiovascular disease. Fourteen obese patients (body mass index [BMI] 40.6 ± 4.9 kg/m2) with type 2 diabetes were recruited for an “Atkins”-type low-carbohydrate diet. Measurements were made at 0, 12, and 24 weeks of weight, insulin sensitivity, HbA1c, lipids, and blood pressure. Twelve completers lost a mean of 9.7 ± 1.8 kg over 24 weeks attributable to a major reduction in carbohydrates and resultant reduction in total energy intake. Glycemic control significantly improved (HbA1c −1.1 ± 0.25%) with reductions in hypoglycemic medication. Fasting glucose, homeostasis model assessment (HOMA), and area under the curve (AUC) glucose (intravenous glucose tolerance test [IVGTT]) were significantly reduced by week 12 (p < 0.05). There were nonsignificant improvements in insulin sensitivity (SI) at week 12 ( p = 0.19) and week 24 ( p = 0.31). Systolic blood pressure was reduced (mean −10.0 mmHg between weeks 0 and 24, p = 0.13). Mean high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol all increased. The ratio of total: HDL cholesterol and triglycerides was reduced. A low-carbohydrate diet was well tolerated and achieved weight loss over 24 weeks in subjects with diabetes. Glycemic control improved with a reduction in requirements for hypoglycemic agents.

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Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base

URL: https://www.sciencedirect.com/science/article/pii/S0899900714003323?via%3Dihub

Journal: Nutrition

Publication Date: 01/2015

Summary: The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndromewithout significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.

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Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers in overweight postmenopausal women: a randomized crossover trial.

URL: https://www.ncbi.nlm.nih.gov/pubmed/26178720

Journal: American Journal of Clinical Nutrition

Publication Date: 09/2015

Summary: Heart associations recommend limited intake of saturated fat. However, effects of saturated fat on low-density lipoprotein (LDL)-cholesterol concentrations and cardiovascular disease risk might depend on nutrients and specific saturated fatty acids (SFAs) in food. We explored the effects of cheese and meat as sources of SFAs or isocaloric replacement with carbohydrates on blood lipids, lipoproteins, and fecal excretion of fat and bile acids. The study was a randomized, crossover, open-label intervention in 14 overweight postmenopausal women. Three full-diet periods of 2-wk duration were provided separated by 2-wk washout periods. The isocaloric diets were as follows: 1) a high-cheese (96-120-g) intervention [i.e., intervention containing cheese (CHEESE)], 2) a macronutrient-matched nondairy, high-meat control [i.e., nondairy control with a high content of high-fat processed and unprocessed meat in amounts matching the saturated fat content from cheese in the intervention containing cheese (MEAT)], and 3) a nondairy, low-fat, high-carbohydrate control (i.e., nondairy low-fat control in which the energy from cheese fat and protein was isocalorically replaced by carbohydrates and lean meat (CARB). The CHEESE diet caused a 5% higher high-density lipoprotein (HDL)-cholesterol concentration (P = 0.012), an 8% higher apo A-I concentration (P < 0.001), and a 5% lower apoB:apo A-I ratio (P = 0.008) than did the CARB diet. Also, the MEAT diet caused an 8% higher HDL-cholesterol concentration (P < 0.001) and a 4% higher apo A-I concentration (P = 0.033) than did the CARB diet. Total cholesterol, LDL cholesterol, apoB, and triacylglycerol were similar with the 3 diets. Fecal fat excretion was 1.8 and 0.9 g higher with the CHEESE diet than with CARB and MEAT diets (P < 0.001 and P = 0.004, respectively) and 0.9 g higher with the MEAT diet than with the CARB diet (P = 0.005). CHEESE and MEAT diets caused higher fecal bile acid excretion than did the CARB diet (P < 0.05 and P = 0.006, respectively). The dominant type of bile acids excreted differed between CHEESE and MEAT diets. Diets with cheese and meat as primary sources of SFAs cause higher HDL cholesterol and apo A-I and, therefore, appear to be less atherogenic than is a low-fat, high-carbohydrate diet. Also, our findings confirm that cheese increases fecal fat excretion.