Impact of intermittent fasting on health and disease processes

Abstract

Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.

Keywords: Alzheimer’s disease; Blood pressure; Cardiovascular disease; Diabetes; Insulin resistance; Intermittent fasting; Ketone bodies; Obesity.

Published by Elsevier B.V.

Figures

Fig. 1

Examples of the influence of eating patterns on levels of glucose at ketones in the blood. The red arrows indicate the time of food consumption/meals during a 2 day period of time. A. This is an example of the typical eating pattern in most industrialized countries. Every day the person eats breakfast, lunch and dinner and a late evening snack. With each meal, glucose levels are elevated and then return towards baseline over a period of several hours. Ketone levels remain low, because liver glycogen stores are never depleted. B. This is an example of fasting one day, followed by a three-meal feeding day. During the fasting day, glucose levels remain in the low normal range, and ketone levels (β-hydroxybutyrate and acetoacetate) rise progressively, and then fall when the first meal is consumed on the 2nd day. C. This is an example of an eating pattern in which all food is consumed within a 6h time window each day. Glucose levels are elevated during and for several hours after the 6h period of food consumption and then remain low for the subsequent 16 h until food is consumed the next day. Ketones are elevated during the last 6–8 h of the 18 h fasting period.

Fig. 2

Patterns of energy intake in subject on either the ‘5:2′ intermittent energy restriction (IER) diet or continuous (daily) energy restriction (CER). Based on Harvie et al., 2011.

Fig. 3

Examples of effects of intermittent fasting on different organ systems. Abbreviations;: 30HB, 3-hydroxybutyrate; CRP, C-reactive protein; IGF-1, insulin-like growth factor 1; IL-6, interleukin 6; TNFα, tumor necrosis factor α