Dose effects of alternate‐day fasting (ADF) regimens on in vivo cell proliferation and plasma insulin like growth factor‐1 levels in mice

Reduced cell proliferation is associated with lower cancer risk. ADF, defined as alternating 24 h periods of ad-lib feeding and fasting, decreases cell proliferation rates. The effect of modified regimens of ADF on cell proliferation has not been examined. This study measured the dose effects of ADF on prostate and splenic T-cell proliferation and insulin-like growth factor-1 (IGF-1) levels in mice. In a 4-week trial, 24 male C57BL/6J mice were randomized to 1 of 4 interventions: ADF-25% (25% calorie restriction [CR] on fast day), ADF-50% (50% CR on fast day), ADF-100% (100% CR on fast day), control. Body weight of the ADF-100% group was less (P < 0.005) than that of the ADF-25% and ADF-50% group post-treatment. On the “feast” day, the ADF-100% and ADF-50% groups ate 85% and 45% more food, respectively, than controls, indicating a hyperphagic response to fasting. Proliferation rates of splenic T-cells were 6% and 30% lower (P < 0.05) in the ADF-50% and ADF-100% groups, respectively, relative to controls. Prostate cell proliferation was reduced (P < 0.05) only in the ADF-100% group (49%). IGF-1 levels were reduced only in the ADF-100% group (40% lower, P < 0.05 relative to controls). These findings confirm the beneficial effects of ADF-100% on cancer risk, by decreasing both cell proliferation and circulating IGF-1 levels, and suggest that modified ADF regimens comprising 25–50% CR on the fast day do not replicate these effects.