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

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 ¼ 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 ¼ 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.

Preoperative weight change and risk of adverse outcome following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital database

“…17 In animals, dietary-induced increased serum IGF-I and insulin levels are associated with increased PC growth. [18][19][20] Moreover, elevated insulin levels are also linked with BPH, another prostate-related disease. 21 Among men with PC, those with C-peptide concentrations (a marker of insulin) in the highest quartile had a 2.4-fold increased PC death vs men in the lowest quartile.…”

1444 the Effect of Carbohydrate Restriction on Prostate Cancer Tumor Growth in a Castrate Mouse Xenograft Model

“…However, we have previously shown that a NCKD slows tumor growth across different models [11,12]. As such, we hypothesize that the lack of a dose-effect among low-carbohydrate diets and the overall benefit of low-carbohydrate diet are generalizable, though this requires formal testing in future studies.…”

“…While traditionally a low fat diet was thought to be optimal, we previously hypothesized that a reduced carbohydrate diet was likewise beneficial [10]. In a prior study we found that mice consuming a no-carbohydrate ketogenic diet (NCKD) had increased overall survival and slower tumor growth, compared to mice on a western diet, a benefit not observed in mice consuming a low fat diet [11]. These findings were then replicated in a similar xenograft model with the finding that a low-fat diet was also beneficial [12].…”

Lipid Metabolism, Metabolic Syndrome, and Cancer

“…However, controversial results have also been reported about the role of high fat diet in carcinogenicity [71,72]. This is largely due to the complexity of the diet, not only the fat components such as SFA, MUFA, and PUFA may vary among people in different regions, but also other non-fat nutrients may also alter the function of fat.…”