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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^*,1, D. J. Roohk^*, B. K. McEvoy-Hein^*, B. D. Gaylinn, M. O. Thorner and M. K. Hellerstein^*,1

^* Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, California, USA; and

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia, USA

¹Correspondence: Nutritional Sciences and Toxicology, University of California at Berkeley, Morgan Hall, Rm. 308, Berkeley, California, 94720-3104 USA. E-mail: K.A.V., kvarady{at}nature.berkeley.edu; M.K.H., march{at}nture.berkeley.edu

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.—Varady, K. A., Roohk, D. J., McEvoy-Hein, B. K., Gaylinn, B. D., Thorner, M. O., Hellersteinm M. K. Modified alternate-day fasting regimens reduce cell proliferation rates to a similar extent as daily calorie restriction in mice.

Key Words: cancer • insulin-like growth factor-1 • insulin-like growth factor binding protein-3