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Background: Dietary factors are likely to be very important in prostate cancer development and progression. Specifically, insulin, insulin-like-growth factor-1 (IGF-1), and caloric intake, which can all be affected by diet, are important in prostate cancer biology. We tested the hypothesis that an isocaloric low-carbohydrate ketogenic diet (LCKD), which in humans lowers insulin and IGF-1 levels, would delay prostate cancer growth in a xenograft model. Methods: 75 male SCID mice were housed in individual cages and fed one of 3 diets: low-fat (12% kcal from fat), high-fat (40% kcal from fat), or a LCKD (85% kcal from fat, 0% kcal from carbohydrates). Mice were fed on a modified paired feeding protocol to maintain equal calories among the groups. After a 3-week run-in period, all mice were injected subcutaneously in the flank with 1 x 10^5 LAPC-4 cells in Matrigel. Tumor volumes were recorded and mice sacrificed when tumors approached 1cc or when mice appeared lethargic with ruffled fur. Results: Mice fed the LCKD, despite initially consuming equal calories, lost significant amounts of weight (up to 15% of body weight) relative to the low-fat and high-fat fed mice. Mice on the LCKD were then fed extra calories to prevent further weight loss and to increase body weight to the weight among the other dietary groups. Mice fed the LCKD had significantly longer survival than mice fed a high-fat diet (log-rank, p=0.008). There was trend for longer survival among men fed the LCKD relative to a low-fat diet (log-rank, p=0.06), but this did not reach statistical significance. There was a non-significant trend for mice fed the low-fat diet to have longer survival than mice fed a high-fat diet (log-rank, p=0.33). Tumors volumes at the time sacrifice were similar among the 3 groups (ANOVA, p=0.61) Conclusions: In a mouse xenograft model, despite consuming more calories, a LCKD significantly prolongs survival relative to a high-fat diet and demonstrates a trend toward improved survival relative to a low-fat diet.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]