Fasting/CR, cell growth, insulin-like growth factor-1

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Is it the fasting or the CR that accounted for the cancer risk benefit for the higher alternate-day fasting (ADF) regimens? The below paper is pdf-availed. From Fig. 2 mean grams daily food intake data, the values were 2.95^a for control ad libitum mice, 3.75^a for the 25% ADF mice, 4.3^b for the 50% ADF mice and 5.1b for the 100% ADF mice, where different letters are significantly different, p <0.05. The prostate cells from the 25% ADF mice grew not significantly more than those from ad libitum, control mice. Ditto for the Fig. 4 25% and 50% insulin-like growth factor-1 level heights. Therefore, 100% fasts on ADFs appear to be desirable. Varady KA, Roohk D, Hellerstein MK.Dose effects of modified alternate-day fasting regimens on in vivo cell proliferation and plasma insulin-like growth factor-1 in mice.J Appl Physiol. 2007 May 10; [Epub ahead of print] PMID: 17495119

Reduced cell proliferation is associated with lower cancer risk. Alternate-day fasting (ADF), defined as alternating 24 h periods of ad libitum feeding and fasting, decreases cell proliferation. The effect of modified regimens of ADF on cell proliferation, however, has not been examined. 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. In a 4-week study, 24 male C57BL/6J mice were randomized to 1 of 4 interventions: 1) ADF-25% (25% calorie restriction [CR] on fast day), 2) ADF-50% (50% CR on fast day), 3) ADF-100% (100% CR on fast day), and 4) control. Body weight of the ADF-100% group was less (P < 0.005) than that of the ADF-25% and ADF-50% groups 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 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) by 49% in the ADF-100% group, relative to controls, but did not change in the other groups. IGF-1 levels were reduced (P < 0.05) by 40%, relative to controls, in the ADF-100% group. 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. ... Seven-week old C57BL/6J male mice ... At 8 weeks of age, the mice were randomized to 1 of 4 intervention groups (n = 6 per group). The firstintervention group (ADF-25%) was fed the semi-purified AIN-93M diet ad libitum on the feast day, and a25%

calorie-restricted diet on alternate days (fast day). The second group (ADF-50%) was fed the AIN-93M diet ad libitum on the feast day, and a 50% calorie-restricted diet on the fast day. The third group (ADF-100%) was fed the AIN-93M diet ad libitum on the feast day, and underwent a complete fast on alternate days. The fourth group acted as the control, and was fed the AIN-93M diet ad libitum each day. Food was provided or taken away at 13.00 h each day. ... ... in Figure 1. All groups weighed approximately the same during acclimation, and all gained weight at the same rate during weeks 1 and 2. By week 3, however, the ADF-100% group did not continue to gain weight at the same rate as the other groups, and by week 4, the ADF-100% group weighed significantly less (P < 0.05) than the ADF-50% group. By the end of the study, the ADF-100% group weighed less (P < 0.005) than both the ADF-25% and ADF-50% groups. Overall, all groups gained

weight (P < 0.05) from the beginning to the end of the study. Food intake During acclimation, all mice consumed, on average, approximately 3.5 g/d of food. The ADF-100% group ate ~11% less (P < 0.001) and ~16% less (P < 0.0001) than the other treatment groups during weeks 1 and 2, respectively, indicating an acute inability of the ADF-100% group to compensate fully on the feast day for the lack of food consumption on the fast day. Mean weekly food intake of the ADF-100% group increased during week 3 and no significant differences were observed between groups. During week 4, however, the amount of food consumed by the ADF-100% group fell to ~25% less (P < 0.001) than that of the other treatment groups. Hyperphagic response to food restriction A hyperphagic response on the feast day to food restriction on the fast day (P < 0.05) was noted

in each of the ADF intervention groups at week 1 (Figure 2). During week 1, the mean daily food intake on the feast day was 3.4 g/d, 3.9 g/d, 4.7 g/d in the ADF-25%, ADF-50% and ADF-100% groups, respectively. The hyperphagic response persisted throughout the study, as the ADF-50% and ADF-100% groups consumed ~45% and ~85% more (P < 0.05) food, respectively, on feast days than the control group. This hyperphagic response, however, did not persist after the first week in the ADF-25% group. In vivo splenic T-cell and prostate 175 cell proliferation Splenic T-cell and prostate cell proliferation rates after 4 weeks of ADF are shown in Figure 3. At the end of the study, splenic T-cell proliferation was 6% and 29% lower (P < 0.05 for each) in the ADF-50% and ADF-100% groups, respectively, relative to controls. Prostate cell proliferation was 49% lower (P < 0.05) in the ADF-100% group compared to controls.

Thus, restricting food completely on the fast day resulted in significant reductions in proliferation of both cell types. Restricting food by 50% on the fast day reduced splenic T-cell proliferation modestly. Insulin like growth factor-1 Circulating IGF-1 levels are shown in Figure 4. Plasma IGF-1 concentrations were markedly reduced (P < 0.01) in the ADF-100% group when compared to all other groups. Relative to controls, IGF-1 levels were 40% lower in the ADF-100% group. IGF-1 concentrations were not significantly different in the ADF-25% or ADF-50% groups compared to controls. Plasma IGF-1 levels exhibited positive, though only moderate, correlations with in vivo proliferation rates of both splenic T-cell (r = 0.48, P = 0.02) and prostate cells (r = 0.43, P = 0.04). ... In summary, these findings suggest that true ADF-100% results in reductions in cell proliferation rates

and plasma IGF-1 levels, but that modified regimens of ADF (e.g., 25-50% reductions in food intake on the fast days) do not. The ability of ADF to decrease these cancer risk parameters was shown to be both potent and rapid, as reductions were shown after only 4 weeks of diet. ... -- Al Pater, alpater@...

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