Purpose: A low carbohydrate diet (LCD) was shown to suggestively slow prostate cancer (PC) growth. In noncancer patients, LCDs improve metabolic syndrome (MetS) without weight loss. However, concerns about negative impact on cardiovascular disease (CVD) risk remain. The objective of this secondary analysis is to determine the impact of an LCD on risk of MetS and estimated CVD risk in patients with PC. Materials and Methods: Pooled data were analyzed from 2 randomized trials testing LCD vs control on 1) preventing insulin resistance after starting hormone therapy (CAPS1) and 2) slowing PC growth in recurrent PC after failed primary treatment (CAPS2). Both trials included a usual care control vs LCD intervention in which patients were instructed to limit carbohydrate intake to 20 gm/day, and in CAPS1 only, to walk for !30 minutes/day for !5 days/week. MetS components (hypertension, high triglycerides, low high-density lipoprotein cholesterol, central obesity and diabetes), 10-year CVD risk estimated using the Framingham Score with either body mass index (BMI) or lipids, and remnant cholesterol were compared between arms using mixed models adjusting for trial. Results: LCD resulted in a significantly reduced risk of MetS (p[0.004) and remnant cholesterol (p <0.001). Moreover, LCD resulted in significantly lower estimated CVD risk using BMI (p[0.002) over the study with no difference in estimated CVD risk using lipids (p[0.14). Conclusions: LCD resulted in a significantly reduced risk of MetS and remnant cholesterol, and a significantly lower estimated CVD risk using BMI. By comparison, there was no difference in estimated CVD risk using lipids. Study limitations include small sample size, short followup, and inability to distinguish effects of carbohydrate restriction and weight loss. Long-term studies are needed to confirm this finding.

Objectives Both weight loss and low-carbohydrate diets (LCDs) have been shown to slow prostate cancer (PC) growth in animal models. Given the significant weight loss and purported metabolic benefits of LCDs to lower insulin and glucose (two key cancer growth factors), there is growing interest in using them in cancer patients. However, critics point to potentially increased cardiovascular disease (CVD) as a major risk. The objective of this study is to examine the effect of an LCD on estimated CVD risk within the context of randomized trials of LCD in PC patients. Methods Carbohydrate and Prostate Cancer (CAPS) 1 and CAPS2 studies were randomized clinical trials testing 6 mo. of an LCD vs. control (asked to make no diet changes) in overweight PC patients. CAPS1 included 34 men starting androgen deprivation therapy (ADT) and tested whether LCD prevents insulin resistance. CAPS2 included 45 men with recurrent PC after primary treatment and tested whether LCD slows PC growth. Primary results have been presented. In this post-hoc analysis, we calculated 10-year risk of CVD at baseline, 3 mo., and 6 mo. in each study based on a CVD risk model developed from the Framingham Heart Study. This score accounts for age, diabetes, smoking, treated and untreated systolic blood pressure and BMI. Comparisons between arms were made using t-tests. A mixed model was used to test longitudinal changes in CVD risk combining data from both studies but adjusting for study. Results In CAPS1, the 10-year estimated CVD risk was unchanged from baseline to 6 mo. at 29% in controls but decreased from 31% to 23% in the LCD arm (p = 0.23). In CAPS2, CVD risk increased from 34% to 35% in controls but decreased from 32% to 28% in the LCD arm (p = 0.005). When data from the two studies were combined, the LCD was associated with a lower 10-year estimated CVD risk vs. control over the study period (p &lt; 0.001). Conclusions Across two prospective randomized trials, an LCD in men with PC was associated with a lower estimated 10-year risk of CVD than control patients making no diet changes. These data support the safety of LCDs for men with PC. Given CVD is the number one cause of death in men with PC and pre-clinical data supporting anti-PC activity, further research on LCDs using long-term PC and CVD end-points is warranted. Funding Sources Atkins Foundation, American Urological Association, National Institute of Health/National Cancer Institute.