The diet restriction paradigm: a brief review of the effects of every-other-day feeding

Abstract

It has been known since the early 1900s that restriction of dietary intake relative to the ad libitum (AL) level increases stress resistance, cancer resistance, and longevity in many species. Studies investigating these phenomena have used three paradigms for dietary restriction. In the first, the AL intake of a control group is measured, and an experimental group is fed less than that amount in a specified proportion, e.g., 40%. In the second, food is provided AL to both the control and experimental groups: however, the experimental group is subjected to periods of fasting. Recent studies using this paradigm provide food every other day (EOD). Both of these paradigms have been in use since the early 1900s. A third paradigm that combines them was developed in the early 1970s: one or more days of fasting separate the provision of a limited amount of food. It was assumed for many years that the physiological responses to these paradigms were due exclusively to a net decrease in energy intake. Recently, however, it was found that some species and strains of laboratory animals, when fed AL every other day, are capable of gorging so that their net weekly intake is not greatly decreased. Despite having only a small deficit in energy intake relative to control levels, however, these animals experience enhanced longevity and stress resistance in comparison to AL controls as much as in animals enduring daily restriction of diet. These observations warrant renewed interest in this paradigm and suggest that comparisons of the paradigms and their effects can be used to determine which factors are critical to the beneficial effects of caloric restriction.Many species age more quickly with an ad libitum food intake than with one that is restricted, and the mechanism underlying this effect remains unidentified

Ketone bodies as signaling metabolites

“…Surprisingly, the health benefits of intermittent fasting do not require overall reduced caloric intake. Mice fed every-other-day have increased longevity [62], and mice fed only during 8 hours at night are resistant to diet-induced obesity [63], both without altering overall calorie intake. With our growing understanding of the non-energy functions of βOHB, βOHB might be an intermediary of some of the benefits of energy-restricted states.…”

Caloric restriction

“…Compared with restricting intake in a nematode or a fly, one might imagine that restricting the caloric intake of a mammal would be a rather straightforward procedure, however, there are a number of complexities and practical difficulties that have spawned a diversity of protocols (Anson et al, 2005). These protocol differences may not be trivial.…”

Calorie restriction in rodents: Caveats to consider

“…The results are impressive, indicating beneficial effects on a wide range of function and conditions(Anson et al, 2005). For example, systematic studies from the National Institute on Aging have focused on effects on cardiovascular function.…”