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

• Published in: Prostate cancer and prostatic diseases Vol. 22; no. 3; pp. 428 - 437
• Main Authors: Freedland, Stephen J., Howard, Lauren, Allen, Jenifer, Smith, Jordan, Stout, Jennifer, Aronson, William, Inman, Brant A., Armstrong, Andrew J., George, Daniel, Westman, Eric, Lin, Pao-Hwa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2019; Nature Publishing Group
• Subjects: 631/67/1059; 692/699/67/1059; Aged; Androgen Antagonists - adverse effects; Androgen suppression therapy; Androgens; Antigens; Biomedical and Life Sciences; Biomedicine; Body composition; Body Composition - physiology; Body fat; Body Weight - physiology; Body weight loss; Bone mass; Cancer Research; Carbohydrates; Care and treatment; Causes of; Complications and side effects; Deprivation; Diet; Diet, Carbohydrate-Restricted; Disturbances; Drug therapy; Health aspects; Healthy Lifestyle; Hemoglobin; High density lipoprotein; Humans; Insulin; Insulin resistance; Intervention; Lipids; Low carbohydrate diet; Male; Metabolic diseases; Metabolic Syndrome - chemically induced; Metabolic Syndrome - metabolism; Metabolic Syndrome - therapy; Metabolism; Methods; Middle Aged; Nutrient deficiency; Prostate cancer; Prostate-specific antigen; Prostatic Neoplasms - drug therapy; Randomization; Secondary analysis; Testing; Therapy; Treatment Outcome; Triglycerides; Walking; Walking - physiology; Weight loss; Weight Loss - physiology; United States
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/s41391-019-0126-5

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.