ClinicalTrials.gov Identifier: NCT00099151.

IMPORTANCE Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy.OBJECTIVE To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTSA single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois.INTERVENTIONS Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase. MAIN OUTCOMES AND MEASURESThe primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease. RESULTS Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group.CONCLUSIONS AND RELEVANCE Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00960505

OBJECTIVE-Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation.RESEARCH DESIGN AND METHODS-Oxygen partial pressure (AT pO 2 ) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay.RESULTS-AT pO 2 was lower in overweight/obese subjects than lean subjects (47 Ϯ 10.6 vs. 55 Ϯ 9.1 mmHg); however, this level of pO 2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO 2 was negatively correlated with percent body fat (R ϭ Ϫ0.50, P Ͻ 0.05). Compared with lean subjects, overweight/ obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator-activated receptor ␥1 and higher collagen VI mRNA expression, which correlated with AT pO 2 (P Ͻ 0.05). Of clinical importance, AT pO 2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1␣ secretion (R ϭ Ϫ0.58, R ϭ Ϫ0.79, P Ͻ 0.05), suggesting that lower AT pO 2 could drive AT inflammation in obesity.CONCLUSIONS-Adipose tissue rarefaction might lie upstream of both low AT pO 2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity. Diabetes 58:718-725, 2009 B oth insulin resistance and ␤-cell failure are present in individuals with type 2 diabetes. Insulin resistance is closely linked to adiposity with a central or visceral pattern, providing a greater risk of insulin resistance and metabolic dysfunction. Adipose tissue (AT) serves as an endocrine organ secreting a variety of autocrine, paracrine, and endocrine factors that can produce or prevent insulin resistance (1). The failure of AT to adequately proliferate and/or differentiate to sequester lipids away from liver, skeletal muscle, and the pancreatic ␤-cell has been proposed as a precursor to type 2 diabetes, broadening the number of potential mechanisms linking obesity to insulin resistance (2).The increase in body fat in obesity should be accompanied by an increase in vascularization, in order to provide adequate oxygen and nutrients (3). In contrast to expectations, obese mice have lower AT capillary density (rarefaction, also known as capillary drop out) and decreased vascular endothelial growth factor (VEGF), the most potent angiogenic factor (4,5). Consistent with this model, preclinical studies suggest that obese AT is hypoxic (6); however, the hypothesis that AT rarefaction might lead to hypoxia remains untested.In humans, short-term whole-body hypoxia decreases i...

Background The possible advantage for weight loss of a diet that emphasizes protein, fat, or carbohydrates has not been established, and there are few studies that extend beyond 1 year. Methods We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content. Results At 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels. Conclusions Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize. (ClinicalTrials.gov number, NCT00072995.