Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications

Background: Capsinoids from the Capsicum genus of plants are nonpungent capsaicin-related substances with effects on metabolism and body weight in animals. Objectives: Our objectives were to explore the safety and efficacy of capsinoids taken orally (6 mg/d) for weight loss, fat loss, and change in metabolism and to examine whether candidate genes are predictors of capsinoid response. Design: This was a 12-wk, placebo-controlled, double-blind, randomized study. Eligibility criteria included a body mass index (BMI; in kg/m(2)) of 25-35. Body weight was measured, and dualenergy X-ray absorptiometry, indirect calorimetry (men only), and genotyping were conducted. Results: Forty women and 40 men with a mean (+/- SD) age of 42 +/- 8 y and BMI of 30.4 +/- 2.4 were randomly assigned to a capsinoid or placebo group. Capsinoids were well tolerated. Mean (+/- SD) weight change was 0.9 +/- 3.1 and 0.5 +/- 2.4 kg in the capsinoid and placebo groups, respectively (P = 0.86). There was no significant group difference in total change in adiposity, but abdominal adiposity decreased more (P = 0.049) in the capsinoid group (-1.11 +/- 1.83%) than in the placebo group (-0.18 +/- 1.94%), and this change correlated with the change in body weight (r = 0.46, P, < 0.0001). Changes in resting energy expenditure did not differ significantly between groups, but fat oxidation was higher at the end of the study in the capsinoid group (least-squares mean difference: 21.0 mg/min; P = 0.06). Of 13 genetic variants tested, TRPV1 Val585Ile and UCP2 -866 G/A correlated significantly with change in abdominal adiposity. Conclusions: Treatment with 6 mg/d capsinoids orally appeared to be safe and was associated with abdominal fat loss. Capsinoid ingestion was associated with an increase in fat oxidation that was nearly significant. We identified 2 common genetic variants that may be predictors of therapeutic response. Am J Clin Nutr 2009; 89: 45-50.