Subject terms
Weight loss, weight loss, WL
BLIND
Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/mGenotype patterns may modify diet effects on weight loss, with greater weight loss on genotype-concordant diets. Here, the authors show that with the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater weight loss on genotype-concordant diets.