Intermittent fasting (IF) is a term used to describe a variety of eating patterns in which no or few calories are consumed for time periods that can range from 12 hours to several days, on a recurring basis. Here we focus on the physiological responses of major organ systems, including the musculoskeletal system, to the onset of the metabolic switch – the point of negative energy balance at which liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 hours after cessation of food intake). Emerging findings suggest the metabolic switch from glucose to fatty acid-derived ketones represents an evolutionarily conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage to mobilization of fat through fatty acid oxidation and fatty-acid derived ketones, which serve to preserve muscle mass and function. Thus, IF regimens that induce the metabolic switch have the potential to improve body composition in overweight individuals. Moreover, IF regimens also induce the coordinated activation of signaling pathways that optimize physiological function, enhance performance, and slow aging and disease processes. Future randomized controlled IF trials should use biomarkers of the metabolic switch (e.g., plasma ketone levels) as a measure of compliance and the magnitude of negative energy balance during the fasting period.

Objective To evaluate the safety and tolerability of alternate-day fasting (ADF) and to compare changes in weight, body composition, lipids, and insulin sensitivity index (Si) to those produced by a standard weight loss diet, moderate daily caloric restriction (CR). Methods Adults with obesity (BMI ≥30 kg/m2, age 18-55) were randomized to either zero-calorie ADF (n=14) or CR (-400 kcal/day, n=12) for 8 weeks. Outcomes were measured at the end of the 8-week intervention and after 24 weeks of unsupervised follow-up. Results No adverse effects were attributed to ADF and 93% completed the 8-week ADF protocol. At 8 weeks, ADF achieved a 376 kcal/day greater energy deficit, however there were no significant between-group differences in change in weight (mean±SE; ADF -8.2±0.9 kg, CR -7.1±1.0 kg), body composition, lipids, or Si. After 24 weeks of unsupervised follow-up, there were no significant differences in weight regain, however changes from baseline in % fat mass and lean mass were more favorable in ADF. Conclusions ADF is a safe and tolerable approach to weight loss. ADF produced similar changes in weight, body composition, lipids and Si at 8 weeks and did not appear to increase risk for weight regain 24 weeks after completing the intervention.

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A growing body of evidence indicates that time restricted feeding (TRF), a popular form of intermittent fasting, can activate similar biological pathways as caloric restriction, the only intervention consistently found to extend healthy lifespan in a variety of species. Thus, TRF may have the potential to also improve function in older adults. Given the challenges many individuals have in following calorie restriction regimens over long-time periods, evaluation of alternative approaches that may produce weight loss and improve function in overweight, older adults is important. Ten overweight, sedentary older adults (≥65 years) at risk for, or with mobility impairments, defined by slow gait speed (<1.0 m/s) participated in this trial. All participants received the intervention and were instructed to fast for approximately 16 h per day over the entire four-week intervention. Outcomes included changes in body weight, waist circumference, cognitive and physical function, health-related quality of life, and adverse events. Adherence levels were high (mean = 84%) based on days goal was met, and mean weight loss was 2.6 kg (p < 0.01). Since body composition was not measured in this study, it is unclear if the observed weight loss was due to loss of fat mass, muscle mass, or the combination of fat and muscle mass. There were no significant changes in other outcomes; however, there were clinically meaningful changes in walking speed and improvements in quality of life, with few reported adverse events. The findings of this pilot study suggest that time restricted feeding is an acceptable and feasible eating pattern for overweight, sedentary older adults to follow.