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

Stephen J. Freedland, John Mavropoulos, Amy Wang, Medha Darshan, Wendy Demark-Wahnefried, William J. Aronson, Pinchas Cohen, David Hwang, Bercedis Peterson, Timothy Fields, Salvatore V. Pizzo, William B Isaacs

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalProstate
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2008

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Somatomedins
Ketogenic Diet
Prostatic Neoplasms
Carbohydrates
Growth
Fats
Fat-Restricted Diet
Insulin-Like Growth Factor Binding Protein 3
Tumor Burden
Insulin-Like Growth Factor I
Heterografts
Arm
Serum
Body Weight
Insulin
Proteins
SCID Mice
Neoplasms

Keywords

  • Carbohydrate
  • Diet
  • Fat
  • IGF-1
  • Insulin
  • Ketogenesis
  • Prostatic neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Freedland, S. J., Mavropoulos, J., Wang, A., Darshan, M., Demark-Wahnefried, W., Aronson, W. J., ... Isaacs, W. B. (2008). Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. Prostate, 68(1), 11-19. https://doi.org/10.1002/pros.20683

Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. / Freedland, Stephen J.; Mavropoulos, John; Wang, Amy; Darshan, Medha; Demark-Wahnefried, Wendy; Aronson, William J.; Cohen, Pinchas; Hwang, David; Peterson, Bercedis; Fields, Timothy; Pizzo, Salvatore V.; Isaacs, William B.

In: Prostate, Vol. 68, No. 1, 01.01.2008, p. 11-19.

Research output: Contribution to journalArticle

Freedland, SJ, Mavropoulos, J, Wang, A, Darshan, M, Demark-Wahnefried, W, Aronson, WJ, Cohen, P, Hwang, D, Peterson, B, Fields, T, Pizzo, SV & Isaacs, WB 2008, 'Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis', Prostate, vol. 68, no. 1, pp. 11-19. https://doi.org/10.1002/pros.20683
Freedland SJ, Mavropoulos J, Wang A, Darshan M, Demark-Wahnefried W, Aronson WJ et al. Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. Prostate. 2008 Jan 1;68(1):11-19. https://doi.org/10.1002/pros.20683
Freedland, Stephen J. ; Mavropoulos, John ; Wang, Amy ; Darshan, Medha ; Demark-Wahnefried, Wendy ; Aronson, William J. ; Cohen, Pinchas ; Hwang, David ; Peterson, Bercedis ; Fields, Timothy ; Pizzo, Salvatore V. ; Isaacs, William B. / Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. In: Prostate. 2008 ; Vol. 68, No. 1. pp. 11-19.
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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.",
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