Intermittent fasting: from calories to time restriction

Abstract

The global human population has recently experienced an increase in life expectancy with a mounting concern about the steady rise in the incidence of age-associated chronic diseases and socio-economic burden. Calorie restriction (CR), the reduction of energy intake without malnutrition, is a dietary manipulation that can increase health and longevity in most model organisms. However, the practice of CR in day-to-day life is a challenging long-term goal for human intervention. Recently, daily fasting length and periodicity have emerged as potential drivers behind CR's beneficial health effects. Numerous strategies and eating patterns have been successfully developed to recapitulate many of CR's benefits without its austerity. These novel feeding protocols range from shortened meal timing designed to interact with our circadian system (e.g., daily time-restricted feeding) to more extended fasting regimens known as intermittent fasting. Here, we provide a glimpse of the current status of knowledge on different strategies to reap the benefits of CR on metabolic health in murine models and in humans, without the rigor of continuous reduction in caloric intake as presented at the USU State of the Science Symposium.

Keywords: Calorie restriction; Calories; Fasting; Intermittent Fasting; Time Restricted Feeding.

Fig. 1

Various forms of dietary interventions. Daily caloric restriction (CR) and four forms of intermittent fasting (IF) are depicted: alternate-day fasting (ADF) with 3 days of feeding interspaced with 4 days of fasting, 5:2 cycle consists of 5 days of feeding followed by 2 consecutive days of fasting, time-restricted feeding where the feeding window is limited to 4 h (TRF-4) or 8 h (TRF-8) over a 24-h period, and the fasting mimicking diet (FMD) comprised of 4 days of low caloric intake followed by 10 days of ad libitum feeding. Respiratory exchange ratio (RER) in mice with unlimited food access (AL, dashed pink line) or CR (solid orange line). The RER trajectories of mice subjected to ADF, TRF-4, TRF-8, or FMD (solid green line for the low-calorie portion of the cycle “ON” and AL portion “OFF” depicted by dashed pink line) are shown. The weekly percentage of fed vs. fasted periods on the different dietary regimens, with the FMD portion spanning 2 weeks (4 days “ON” and 10 days “OFF”). Mice fed AL eat around the clock and, therefore, do not experience significant periods of fasting. Daily CR can improve markers of health span and lifespan. Similarly, different forms of IF confer health benefits and possibly improvement in long-term survival in mice, non-human primates, and humans