John Mavropoulos

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

ObjectiveDietary 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.Research design and methodsEighty-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.ResultsForty-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).ConclusionDietary 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.

The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age and is associated with obesity, hyperinsulinemia, and insulin resistance. Because low carbohydrate diets have been shown to reduce insulin resistance, this pilot study investigated the six-month metabolic and endocrine effects of a low-carbohydrate, ketogenic diet (LCKD) on overweight and obese women with PCOS.ResultsEleven women with a body mass index >27 kg/m2 and a clinical diagnosis of PCOS were recruited from the community. They were instructed to limit their carbohydrate intake to 20 grams or less per day for 24 weeks. Participants returned every two weeks to an outpatient research clinic for measurements and reinforcement of dietary instruction. In the 5 women who completed the study, there were significant reductions from baseline to 24 weeks in body weight (-12%), percent free testosterone (-22%), LH/FSH ratio (-36%), and fasting insulin (-54%). There were non-significant decreases in insulin, glucose, testosterone, HgbA1c, triglyceride, and perceived body hair. Two women became pregnant despite previous infertility problems.ConclusionIn this pilot study, a LCKD led to significant improvement in weight, percent free testosterone, LH/FSH ratio, and fasting insulin in women with obesity and PCOS over a 24 week period.

The Effects of Varying Dietary Carbohydrate and Fat Content on Survival in a Murine LNCaP Prostate Cancer Xenograft Model

Purpose: Numerous dietary factors elevate serum levels of insulin and insulin-like growth factor I (IGF-I), both potent prostate cancer mitogens. We tested whether varying dietary carbohydrate and fat, without energy restriction relative to comparison diets, would slow tumor growth and reduce serum insulin, IGF-I, and other molecular mediators of prostate cancer in a xenograft model. Experimental Design: Individually caged male severe combined immunodeficient mice (n = 130) were randomly assigned to one of three diets (described as percent total calories): very high-fat/no-carbohydrate ketogenic diet (NCKD: 83% fat, 0% carbohydrate, 17% protein), low-fat/high-carbohydrate diet (LFD: 12% fat, 71% carbohydrate, 17% protein), or high-fat/moderate-carbohydrate diet (MCD: 40% fat, 43% carbohydrate, 17% protein). Mice were fed to maintain similar average body weights among groups. Following a preliminary feeding period, mice were injected with 1 × 106 LNCaP cells (day 0) and sacrificed when tumors were ≥1,000 mm3. Results: Two days before tumor injection, median NCKD body weight was 2.4 g (10%) and 2.1 g (8%) greater than the LFD and MCD groups, respectively (P < 0.0001). Diet was significantly associated with overall survival (log-rank P = 0.004). Relative to MCD, survival was significantly prolonged for the LFD (hazard ratio, 0.49; 95% confidence interval, 0.29-0.79; P = 0.004) and NCKD groups (hazard ratio, 0.59; 95% confidence interval, 0.37-0.93; P = 0.02). Median serum insulin, IGF-I, IGF-I/IGF binding protein-1 ratio, and IGF-I/IGF binding protein-3 ratio were significantly reduced in NCKD relative to MCD mice. Phospho-AKT/total AKT ratio and pathways associated with antiapoptosis, inflammation, insulin resistance, and obesity were also significantly reduced in NCKD relative to MCD tumors. Conclusions: These results support further preclinical exploration of carbohydrate restriction in prostate cancer and possibly warrant pilot or feasibility testing in humans.

Effect of intermittent fasting with or without caloric restriction on prostate cancer growth and survival in SCID mice

Caloric restriction (CR) delays cancer growth in animals, though translation to humans is difficult. We hypothesized intermittent fasting (i.e., intermittent extreme CR), may be better tolerated and prolong survival of prostate cancer (CaP) bearing mice.

Clinical experience of a carbohydrate-restricted diet: effect on diabetes mellitus.

OUR OBJECTIVE was to assess the effect of a carbohydrate-restricted dietary approach on diabetes mellitus. The rationale for using a carbohydrate-restricted diet for diabetes mellitus derives from the known effect of dietary carbohydrate on insulin secretion.1 For type 1 diabetes, less dietary carbohydrate will lead to a lower requirement for insulin to control postprandial blood glucoses. For type 2 diabetes, less dietary carbohydrate will lead to lower insulin levels and less insulin resistance—if insulin resistance is an adaptive response to high insulin levels. Less insulin resistance will then lead to improved glycemic control.

A NO CARBOHYDRATE DIET SIGNIFICANTLY PROLONGS SURVIVAL IN A PROSTATE CANCER XENOGRAFT MODEL VIA IGF-1 AND GLOBAL GENE EXPRESSION CHANGES

. RESULTS: At two days prior to tumor injection, median NCKD body weight was 2.4g (10%) and 2.1g (8%) greater than the LFD and WD groups, respectively (p<0.0001). Diet was significantly associated with overall survival (log-rank:p=0.004). Relative to WD, survival was significantly prolonged for LFD (hazard ratio=0.49, 95% CI 0.29-0.79, p=0.004) and NCKD (hazard ratio=0.59, 95% CI 0.37-0.93, p=0.02). Serum insulin, IGF-1, IGF-1:IGFBP-1 ratio, and IGF-1:IGFBP-3 ratio were significantly reduced in the NCKD group. The phospho-AKT:total-AKT ratio and pathways associated with anti-apoptosis, inflammation, insulin- resistance, and obesity were also significantly reduced in NCKD tumors. CONCLUSIONS: In this mouse xenograft model, despite heavier body weights, a carbohydrate restricted diet significantly prolonged survival. These results support further exploration of carbohydrate restriction in future preclinical trials and warrant the possibility of pilot/ feasibility testing in humans.