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. 2008 Jun;22(6):2090-6.
doi: 10.1096/fj.07-098178. Epub 2008 Jan 9.

Modified Alternate-Day Fasting Regimens Reduce Cell Proliferation Rates to a Similar Extent as Daily Calorie Restriction in Mice

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Modified Alternate-Day Fasting Regimens Reduce Cell Proliferation Rates to a Similar Extent as Daily Calorie Restriction in Mice

K A Varady et al. FASEB J. .
Free PMC article

Abstract

Calorie restriction (CR) and alternate-day fasting (ADF) reduce cancer risk and reduce cell proliferation rates. Whether modified ADF regimens (i.e., allowing a portion of energy needs to be consumed on the fast day) work, as well as true ADF or CR to reduce global cell proliferation rates, remains unresolved. Here, we measured the effects of true ADF, modified ADF, and daily CR on cell proliferation rates in mice. Thirty female C57BL/6J mice were randomized to one of five interventions for 4 wk: 1) CR-25% (25% reduction in daily energy intake), 2) ADF-75% (75% reduction on fast day), 3) ADF-85% (85% reduction on fast day), 4) ADF-100% (100% reduction on fast day), and 5) control (ad libitum intake). Body weights of the ADF groups did not differ from controls, whereas the CR-25% group weighed less than all other groups posttreatment. Epidermal cell proliferation decreased (P<0.01) by 29, 20, and 31% in the CR-25%, ADF-85% and ADF-100% groups, respectively, relative to controls. Proliferation rates of splenic T cells were reduced (P<0.01) by 37, 32, and 31% in the CR-25%, ADF-85%, and ADF-100% groups, respectively, and mammary epithelial cell proliferation was 70, 65, and 62% lower (P<0.01), compared with controls. Insulin-like growth factor-1 levels were reduced (P<0.05) in the CR-25% and ADF-100% groups only. In summary, modified ADF, allowing the consumption of 15% of energy needs on the restricted intake day, decreases global cell proliferation similarly as true ADF and daily CR without reducing body weight.

Figures

Figure 1
Figure 1
Mean body weight throughout the 4 wk study. Values are means ± SE. Mean body weight in each group was similar during wk 1 of the study. By wk 2, the CR-25% group weighed less than all other groups, and this lower body weight persisted until the last day of the study. There were no differences in body weight between the ADF and control groups throughout the 4 wk study. One-way ANOVA with Tukey's post hoc test was used for all between-group analyses; *P < 0.05.
Figure 2
Figure 2
Mean daily food intake throughout the 4 wk study. Values are means ± SE. Each intervention group ate less than control during wk 1, 2, and 4. During wk 3, the CR-25% group ate less than all the other groups. One-way ANOVA with Tukey's post hoc test was used for all between-group analyses; *P < 0.0001, **P < 0.01.
Figure 3
Figure 3
Hyperphagic response on the feed day to food restriction on the restricted (fast) day. Values are means ± SE. Means not sharing a common superscript letter are significantly different (P<0.05). One-way ANOVA with Tukey's post hoc test was used for all between-group analyses.
Figure 4
Figure 4
Effect of 4 wk of CR or ADF on epidermal cell, splenic T-cell, and mammary epithelial cell proliferation. Values are means ± SE. ADF-85% and ADF-100% produced similar reductions (P<0.01) in epidermal cell, T cell, and mammary epithelial cell proliferation as CR-25%. One-way ANOVA with Tukey's post hoc test was used for all between-group analyses; means not sharing a common letter are significantly different (P<0.05).

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