Abstract #313: Effect of intermittent fasting on prostate cancer tumor growth in a mouse model

Introduction: Caloric restriction is a well established approach to slow tumor growth in animal models. However, this approach is limited in humans due to poor compliance with weight loss regiments. Therefore, we previously investigated intermittent fasting (i.e. intermittent severe caloric restriction) as a means to slow prostate cancer growth in a xenograft model. In our pilot study, we found trends for mice that were fasted 2 days/week and fed ad libitum the other 5 days to have delayed tumor growth while maintaining normal body weight. Herein we sought to validate these findings using a larger sample size and better powered study. Methods: One Hundred male SCID mice (~8 weeks old) were subcutaneously implanted with 1x105 LAPC-4 cells. All mice were initially fed ad libitum Western diet (40% calories from fat; 45% from simple carbohydrates). When tumor volumes reached 200 mm3, mice were randomized to ad libitum feeding or intermittent fasting 2 days/week with ad libitum feeding on the non-fasting days. To date, 32 mice have been randomized to ad libitum feeding and 31 to intermittent fasting. Mice body weights and tumor volumes were measured twice per week. At the conclusion of each fasting day and prior to refeeding, urinary ketone levels for both ad libitum fed and fasted mice were measured. Comparisons of body weight and tumor volumes between groups were performed using the rank sum test. Results: By day 14 after randomization (longest point of follow-up to date), there was no difference in body weights (p=0.81) or tumor volumes (p=0.24) between ad libitum fed and intermittently fasted mice. Intermittently fasted mice were initially ketotic on day 0 after randomization with moderate (~40ng/ml) levels of post-fasting ketonuria. However, by Day 14 after randomization, post-fasting urine ketone levels had decreased to trace levels (~5ng/ml). Ad libitum fed mice had trace to no detectable urinary ketone levels at any time point (<=5ng/ml). Conclusion: To date, there was no difference in tumor volumes or body weights between ad libitum fed and fasted mice. As fasted mice have become progressively less ketotic after each fasting cycle, this suggests that mice are adapting to intermittent fasting by reducing ketone levels possibly via optimizing glucose utilization. To date, intermittent fasting has not translated into delayed tumor growth as seen in our pilot study, however the current study is still in progress.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 313.