A Lifestyle Intervention of Weight Loss Via a Low-Carbohydrate Diet Plus Walking to Reduce Metabolic Disturbances Caused by Androgen Deprivation Therapy among Prostate Cancer Patients: Carbohydrate and Prostate Study 1 (CAPS1) Randomized Controlled Trial.

Purpose The objective of this study was to test a low-carbohydrate diet (LCD) plus walking to reduce androgen deprivation therapy (ADT)-induced metabolic disturbances. Materials and methods This randomized multi-center trial of prostate cancer (PCa) patients initiating ADT was designed to compare an LCD (≤20g carbohydrate/day) plus walking (≥30 min for ≥5 days/week) intervention vs. control advised to maintain usual diet and exercise patterns. Primary outcome was change in insulin resistance by homeostatic model assessment at 6 months. To detect 20% reduction in insulin resistance, 100 men were required. The study was stopped early after randomizing 42 men due to slow accrual. Secondary outcomes included weight, body composition, lipids, and prostate-specific antigen (PSA). Changes from baseline were compared between arms using rank-sum tests. Results At 6 months, LCD/walking reduced insulin resistance by 4% vs. 36% increase in control ( p = 0.13). At 3 months, vs. control, LCD/walking arm significantly lost weight (7.8kg; p <0.001), improved insulin resistance (↑36%; p = 0.015), hemoglobin A1c (↓3.3%; p = 0.01), high-density lipoprotein (HDL) (↑13%; p = 0.004), and triglyceride (↓37%; p = 0.036). At 6 months, weight loss (10.6kg; p <0.001) and HDL (↑27%; p = 0.003) remained significant. LCD/walking preserved total body bone mineral count ( p = 0.025), reduced fat mass ( p = 0.002), lean mass ( p = 0.036), and percent body fat ( p = 0.004). There were no differences in PSA. Limitations include the effect of LCD, weight loss vs. walking instruction are indistinguishable, and small sample size. Conclusions In an underpowered study, LCD/walking did not improve insulin sensitivity at 6 months. Given most secondary outcomes were improved at 3 months with some remaining improved at 6 months and a secondary analysis showed that LCD/walking reduced insulin resistance over the study, supporting future larger studies of LCD/walking intervention to reduce ADT-induced disturbances.