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      Effect of intermittent fasting with or without caloric restriction on prostate cancer growth and survival in SCID mice.

      The Prostate
      Animals, Body Composition, physiology, Body Weight, Cell Growth Processes, Fasting, Insulin-Like Growth Factor Binding Proteins, blood, Insulin-Like Growth Factor I, metabolism, Male, Mice, Mice, SCID, Pilot Projects, Proportional Hazards Models, Prostatic Neoplasms, pathology, Random Allocation, Survival Analysis

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          Caloric restriction (CR) delays cancer growth in animals, though translation to humans is difficult. We hypothesized intermittent fasting (i.e., intermittent extreme CR), may be better tolerated and prolong survival of prostate cancer (CaP) bearing mice. We conducted a pilot study by injecting 105 male individually-housed SCID mice with LAPC-4 cells. When tumors reached 200 mm(3), 15 mice/group were randomized to one of seven diets and sacrificed when tumors reached 1,500 mm(3): Group 1: ad libitum 7 days/week; Group 2: fasted 1 day/week and ad libitum 6 days/week; Group 3: fasted 1 day/week and fed 6 days/week via paired feeding to maintain isocaloric conditions to Group 1; Group 4: 14% CR 7 days/week; Group 5: fasted 2 days/week and ad libitum 5 days/week; Group 6: fasted 2 day/week and fed 5 days/week via paired feeding to maintain isocaloric conditions to Group 1; Group 7: 28% CR 7 days/week. Sera from mice at sacrifice were analyzed for IGF-axis hormones. There were no significant differences in survival among any groups. However, relative to Group 1, there were non-significant trends for improved survival for Groups 3 (HR 0.65, P = 0.26), 5 (0.60, P = 0.18), 6 (HR 0.59, P = 0.16), and 7 (P = 0.59, P = 0.17). Relative to Group 1, body weights and IGF-1 levels were significantly lower in Groups 6 and 7. This exploratory study found non-significant trends toward improved survival with some intermittent fasting regimens, in the absence of weight loss. Larger appropriately powered studies to detect modest, but clinically important differences are necessary to confirm these findings.

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