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

Prostate. 2008 Jan 1;68(1):11-9. doi: 10.1002/pros.20683.

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 mm(3).

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Weight
  • Cell Line, Tumor
  • Diet, Carbohydrate-Restricted
  • Diet, Fat-Restricted
  • Dietary Carbohydrates / pharmacology*
  • Dietary Fats / pharmacology
  • Energy Intake
  • Fatty Liver / diet therapy
  • Humans
  • Insulin / blood
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Kaplan-Meier Estimate
  • Ketones / blood
  • Male
  • Mice
  • Mice, SCID
  • Prostatic Neoplasms / diet therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Dietary Carbohydrates
  • Dietary Fats
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • Ketones
  • Insulin-Like Growth Factor I