The relationship between circulating levels of IGF-1 and in vivo cell proliferation rates was also examined.Īt 8 wk of age, the mice were randomized to one of four intervention groups ( n = 6 per group). Accordingly, the objectives of the present study were to measure the dose effects of modified ADF regimens on in vivo proliferation rates of prostate and splenic T-cells and on plasma IGF-1 concentrations in mice. Moreover, how different doses of ADF affect circulating IGF-1 levels and how these changes relate to cell proliferation rates also remain uncertain. In particular, a key question that has yet to be addressed is whether 100% CR is required on the fast day in an ADF regimen, or, more specifically, what degree of CR can be alternated with ad libitum feeding and still achieve beneficial effects? The availability of a sensitive, rapidly responsive biomarker of energy restriction, i.e., cell proliferation rates ( 14), enables different regimens or “doses” of ADF to be compared. Several questions regarding the effect of ADF on cancer risk remain unresolved. Since elevated concentrations of circulating IGF-1 have been implicated in cancer development ( 17, 36), in part by augmenting cell proliferation rates, it is possible that reductions in IGF-1 levels by ADF may beneficially modulate cancer risk. Decreases in insulin-like growth factor-1 (IGF-1) levels ( 33) have also been reported as a result of ADF, although inconsistently ( 2). The proliferation rate of cells (mitogenesis) represents a central element in the promotional phase of carcinogenesis ( 36), so a reduction in global cell proliferation rates may represent a mechanism for the anti-cancer effects of ADF. ( 14) recently demonstrated reductions in epidermal, T-cell, and mammary epithelial cell proliferation rates after short-term ADF in mice.
Complementary to these findings, Hsieh et al. In the few studies that exist to date, ADF has been shown to increase survival rate after tumor inoculation ( 31), decrease lymphoma incidence ( 10), and inhibit hepatic pre-neoplastic lesion development ( 29) in rodents. Although a large body of evidence exists supporting the anti-carcinogenic effects of classic CR ( 16), much less data are available concerning the effects of ADF. Alternate-day fasting (ADF) consists of alternating 24-h periods of ad libitum feeding and fasting, i.e., where food is consumed ad libitum on the feast day, alternating with a day where food is withheld or reduced (fast day). Another dietary restriction paradigm has also been employed, although less commonly. Most dietary restriction studies have implemented the classic calorie restriction (CR) approach, wherein the amount of total food energy consumed is decreased by a certain percentage daily. These findings confirm the beneficial effects of ADF-100% on cancer risk by decreasing cell proliferation and IGF-1 levels and suggest that modified ADF regimens comprising 25–50% CR on the fast day do not replicate these effects.ĭietary restriction has been shown to decrease the risk of certain age-associated diseases, such as cardiovascular disease, Type 2 diabetes, and cancer, in a variety of animal models ( 16, 21, 25). IGF-1 levels were reduced ( P < 0.05) by 40%, relative to controls, in the ADF-100% group. Prostate cell proliferation was reduced ( P < 0.05) by 49% in the ADF-100% group, relative to controls, but did not change in the other groups. Proliferation rates of T-cells were 6% and 30% lower ( P < 0.05) in the ADF-50% and ADF-100% groups, respectively, relative to controls. 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. Body weight of the ADF-100% group was less ( P < 0.005) than that of the ADF-25% and ADF-50% groups posttreatment. In a 4-wk study, 24 male C57BL/6J mice were randomized to one of four interventions: 1) ADF-25%, 2) ADF-50% (50% CR on fast day), 3) ADF-100% (100% CR on fast day), and 4) control. This study measured the effects of modified ADF regimens on prostate and splenic T-cell proliferation and circulating insulin-like growth factor-1 (IGF-1) levels in mice. The effect of modified regimens of ADF on cell proliferation, however, has not been examined. Alternate-day fasting (ADF), defined as alternating 24-h periods of ad libitum feeding and fasting, decreases cell proliferation. Reduced cell proliferation is associated with lower cancer risk.
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