Meal frequency and timing in health and disease

Abstract

Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.

Keywords: circadian rhythm; feeding behavior; metabolism; obesity; time-restricted feeding.

Fig. 1.

The rising tide of obesity is strongly associated with daily calorie intake and sedentary lifestyle-promoting transportation (refs. –; www.earth-policy.org/data_center/C23). *US, approximate value. ^#Worldwide auto production.

Fig. 2.

A metabolic shift to ketogenesis that occurs with fasting bolsters neuronal bioenergetics. Liver glycogen stores are typically depleted within 10–12 h of fasting, which is followed by liberation of fatty acids from adipose tissue cells into the blood. The fatty acids are then transported into liver cells where they are oxidized to generate Acetyl-CoA. Acetyl-CoA is then converted to 3-hydroxy-3-methylgluaryl-CoA, which is in turn used to generate the ketones acetoacetate and β-hydroxybutyrate (β-OHB). The ketones are released into the blood and are transported into various tissues, including the brain, where they are taken up by neurons and used to produce acetyl-CoA. Acetyl-CoA enters the tricarboxylic acid (TCA) cycle to generate ATP.

Fig. 3.

Patterns of daily and weekly food consumption. The upper illustration shows five different patterns of food consumption during a 24-h period. A: Eating three large meals plus snacks spread throughout a 16-h period of wakefulness; this is the common eating pattern of food consumption upon which the epidemic of obesity, diabetes, and associated chronic diseases has emerged. B–D: Examples if time-restricted eating patterns in which food is consumed as three (B) or two (C) regular size meals, or three small meals (D). E: Complete fast. Examples of weekly eating schedules are shown in the lower right. ER, energy restriction; IER, intermittent energy restriction; TRF, time-restricted feeding.