Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis.
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.
Freedland
Stephen J
SJ
Department of Surgery, Durham VA Medical Center, Durham, North Carolina 27710, USA. steve.freedland@duke.edu
Mavropoulos
John
J
Wang
Amy
A
Darshan
Medha
M
Demark-Wahnefried
Wendy
W
Aronson
William J
WJ
Cohen
Pinchas
P
Hwang
David
D
Peterson
Bercedis
B
Fields
Timothy
T
Pizzo
Salvatore V
SV
Isaacs
William B
WB
D000818:Animals; D001835:Body Weight; D045744:Cell Line, Tumor; D050528:Diet, Carbohydrate-Restricted; D018752:Diet, Fat-Restricted; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology; D002149:Energy Intake; D005234:Fatty Liver / Q000178:diet therapy; D006801:Humans; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D007659:Ketones / Q000097:blood; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007659:Ketones; D007334:Insulin-Like Growth Factor I