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

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 is enhanced in comparison to AL controls as much 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.