Previous studies indicate that carbohydrate intake influences prostate cancer biology, as mice fed a no-carbohydrate ketogenic diet (NCKD) had significantly smaller xenograft tumors and longer survival than mice fed a Western diet. As it is nearly impossible for humans to consume and maintain NCKD, we determined whether diets containing 10% or 20% carbohydrate kcal showed similar tumor growth as NCKD. A total of 150 male severe combined immunodeficient mice were fed a Western diet ad libitum, injected with the human prostate cancer cell line LAPC-4, and then randomized 2 weeks later to one of three arms: NCKD, 10% carbohydrate, or 20% carbohydrate diets. Ten mice not injected were fed an ad libitum low-fat diet (12% fat kcal) serving as the reference in a modified-paired feeding protocol. Mice were sacrificed when tumors reached 1,000 mm3. Despite consuming extra calories, all mice receiving low-carbohydrate diets were significantly lighter than those receiving a low-fat diet (P < 0.04). Among the low-carbohydrate arms, NCKD-fed mice were significantly lighter than the 10% or 20% carbohydrate groups (P < 0.05). Tumors were significantly larger in the 10% carbohydrate group on days 52 and 59 (P < 0.05), but at no other point during the study. Diet did not affect survival (P = 0.34). There were no differences in serum insulin-like growth factor-I or insulin-like growth factor binding protein-3 at sacrifice among the low-carbohydrate arms (P = 0.07 and P = 0.55, respectively). Insulin was significantly lower in the 20% carbohydrate arm (P = 0.03). LAPC-4 xenograft mice fed a low-carbohydrate diet (10–20% carbohydrate kcal) had similar survival as mice consuming NCKD (0% carbohydrate kcal).

To our knowledge these results provide the first evidence of an association between exercise and prostate cancer risk as well as grade at diagnosis in men scheduled to undergo prostate biopsy. Specifically moderate exercise was associated with a lower risk of prostate cancer and in men with cancer, lower grade disease. Further investigation using an objective measure of exercise in a larger sample size is required to confirm these findings.

BACKGROUNDNo‐ and low‐carbohydrate diets delay tumor growth compared to western diet (WD) in prostate cancer (PCa) xenograft studies. The effect of these diets in concert with androgen deprivation is unknown.METHODSA total of 160 male SCID mice were injected with 1× 105 LAPC‐4 human PCa cells. Of these, 150 mice were castrated and randomized to an ad libitum WD or fed via a paired‐feeding protocol with a no‐carbohydrate ketogenic diet (NCKD), 10% carbohydrate diet, or 20% carbohydrate diet. The remaining 10 mice were not castrated and were fed an ad libitum WD. The mice were sacrificed once volumes reached 1,000 mm3 and survival tested using the log‐rank test. Serum from the median surviving 8 mice/group was assayed for insulin, IGF‐1, and IGFBP‐3.RESULTSBody weights were roughly equal among groups. The 10 non‐castrated mice experienced accelerated tumor growth. Among castrated mice, WD had the most rapid tumor growth; 20% carbohydrate diet the slowest (P = 0.046). Survival was not significantly different among the various carbohydrate restricted groups (P = 0.51). When pooled, there was a non‐significant trend (P = 0.11) in improved survival among the carbohydrate restricted diets versus WD. No significant difference in serum insulin, IGF‐1, and IGFBP‐3 levels was noted among all groups at pre‐randomization or at sacrifice. CONCLUSIONSA 20% carbohydrate diet slowed tumor growth versus a WD. Though the benefit of carbohydrate restriction was somewhat less than in prior studies in non‐castrate mice, these data still suggest diets achievable in humans may play a role in PCa management. Prostate 73: 449–454, 2013. © 2012 Wiley Periodicals, Inc.

Our meta-analysis suggests that breast cancer patients will benefit from statin intake, however from these cohorts we are unable to differentiate between various statins in terms of effectiveness and duration of use. We highly propose conducting randomized clinical trials.

Purpose Previous mouse studies suggesting that low-fat diets slow prostate cancer (PCa) growth often used corn oil (ω-6), which enhances PCa growth, as their primary fat. Alternatively, using a saturated-fat-based diet, we previously found no significant difference in tumor growth between low-fat- and high-fat-fed SCID mice xenografted with LAPC-4 cells. Whether similar results would hold in a castration model is unclear. Materials and Methods A total of 80 male SCID mice were fed a Western diet (40% fat, 44% carbohydrate) and injected with LAPC-4 human PCa cells. When tumors reached 200mm3, mice were castrated and randomized to either an isocaloric Western or low-fat diet (12% fat, 72% carbohydrate). Animals were euthanized when tumors reached 1,000mm3. Serum was collected and assayed for PSA, insulin, IGF-1, and IGFBP-3. Tumors were assayed for total- and phosphorylated-Akt levels. Results Mice weights were equivalent across groups. Overall, dietary group was not significantly associated with survival (log-rank, p=0.32). There were no statistically-significant differences in PSA (p=0.53), IGF-axis parameters (all p>0.05), or p-Akt:t-Akt ratios (p=0.22) between groups at sacrifice. Conclusions In this xenograft model, we found no difference in tumor growth or survival between low-fat- vs. Western-fed mice, when the fat source was saturated fat. Given these results conflict from those when corn oil is used in which low-fat diets have been shown to delay PCa growth, these findings suggest type of fat may be as important as amount of fat in the setting of PCa.

Caloric restriction (CR) has been shown to have anti-cancer properties. However, CR may be difficult to apply in humans secondary to compliance and potentially deleterious effects. An alternative is intermittent CR, or in the extreme case intermittent fasting (IF). In a previous small pilot study, we found 2 days per week of IF with ad libitum feeding on the other days resulted in trends toward prolonged survival of mice bearing prostate cancer xenografts. We sought to confirm these findings in a larger study. A total of 100 (7- to 8-week-old) male severe combined immunodeficiency mice were injected subcutaneously with 1 × 10(5) LAPC-4 prostate cancer cells. Mice were randomized to either ad libitum Western Diet (44% carbohydrates, 40% fat and 16% protein) or ad libitum Western Diet with twice-weekly 24 h fasts (IF). Tumor volumes and mouse bodyweights were measured twice weekly. Mice were killed when tumor volumes reached 1000 mm(3). Serum and tumor were collected for analysis of the insulin/insulin-like growth factor 1 (IGF-1) hormonal axis. Overall, there was no difference in mouse survival (P=0.37) or tumor volumes (P ≥ 0.10) between groups. Mouse body weights were similar between arms (P=0.84). IF mice had significantly higher serum IGF-1 levels and IGF-1/IGFBP-3 ratios at killing (P<0.001). However, no difference was observed in serum insulin, IGFBP-3 or tumor phospho-Akt levels (P ≥ 0.39). IF did not improve mouse survival nor did it delay prostate tumor growth. This may be secondary to metabolic adaptations to the 24 h fasting periods. Future studies are required to optimize CR for application in humans.

BACKGROUND:We examined the relationship between weight change in the year before radical prostatectomy (RP) and biochemical recurrence (BCR) and adverse pathology. METHODS:We abstracted data from 359 men undergoing RP in the SEARCH (Shared Equal Access Regional Cancer Hospital) database between [2001][2002][2003][2004][2005][2006][2007]. Logistic regression and Cox proportional hazards models were used to test the association between weight change in the year before surgery and adverse pathology and BCR, respectively. RESULTS:In all, 152 (42%) men gained weight, 193 (54%) lost weight and 14 (4%) had the same weight. Among weight gainers, median gain was 2.4 kg and among weight losers, median loss was 2.7 kg. As a continuous variable, weight change was not associated with adverse pathology or BCR (all P40.05). In secondary analysis, on multivariate analysis, men gaining X2.5 kg were at higher BCR risk (hazards ratio ¼ 1.65, 95% confidence interval (CI): 1.03-2.64, P ¼ 0.04) while weight loss X2.5 kg was not associated with BCR (hazards ratio ¼ 0.83, 95% CI: 0.54-1.29, P ¼ 0.41). CONCLUSIONS:As a continuous variable, weight change was not associated with outcome. In secondary hypothesisgenerating analyses, weight gain X2.5 kg in the year before surgery, regardless of final body mass index, was associated with increased BCR following RP. If validated, these data suggest weight gain X2.5 kg may promote prostate cancer progression.

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