Carbohydrate restriction, prostate cancer growth, and the insulin‐like growth factor axis

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Abstract
BACKGROUND: Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no‐carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low‐fat diets in a xenograft model.METHODS: Seventy‐five male SCID mice were fed a NCKD (84% fat–0% carbohydrate–16% protein kcal), low‐fat (12% fat–72% carbohydrate–16% protein kcal), or Western diet (40% fat–44% carbohydrate–16% protein kcal). Low‐fat mice were fed ad libitum and the other arms fed via a modified‐paired feeding protocol. After 24 days, all mice were injected with LAPC‐4 cells and sacrificed when tumors approached 1,000 mm3.RESULTS: Despite consuming equal calories, NCKD‐fed mice lost weight (up to 15% body weight) relative to low‐fat and Western diet‐fed mice and required additional kcal to equalize body weight. Fifty‐one days after injection, NCKD mice tumor volumes were 33% smaller than Western mice (rank‐sum, P = 0.009). There were no differences in tumor volume between low‐fat and NCKD mice. Dietary treatment was significantly associated with survival (log‐rank, P = 0.006), with the longest survival among the NCKD mice, followed by the low‐fat mice. Serum IGFBP‐3 was highest and IGF‐1:IGFBP‐3 ratio was lowest among NCKD mice while serum insulin and IGF‐1 levels were highest in Western mice. NCKD mice had significantly decreased hepatic fatty infiltration relative to the other arms.CONCLUSIONS: In this xenograft model, despite consuming more calories, NCKD‐fed mice had significantly reduced tumor growth and prolonged survival relative to Western mice and was associated with favorable changes in serum insulin and IGF axis hormones relative to low‐fat or Western diet. Prostate 68: 11–19, 2008.

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