Lessons Learned from the POUNDS Lost Study: Genetic, Metabolic, and Behavioral Factors Affecting Changes in Body Weight, Body Composition, and Cardiometabolic Risk.

Purpose of Review: This paper reviews the genetic and non-genetic factors that provided predictions of, or were associated with, weight loss and other metabolic changes in the POUNDS Lost clinical trial of weight loss. This trial randomized 811 individuals who were overweight or obese to one of four diets that contained either 15% or 25% protein and 20% or 40% fat in a 2 × 2 factorial design. A standard behavioral weight loss program was available for all participants who were followed for 2 years with an 80% completion rate.
Recent Findings: Nineteen genes and five genetic risk scores were used along with demographic, behavioral, endocrine, and metabolic measurements. Genetic variations in most of the genes were associated with weight loss, but this association often varied with the dietary assignment. A number of demographic and behavioral factors, including attendance at behavioral sessions and food cravings were predictive of weight changes. A high baseline level of free triiodothyronine or free thyroxine predicted the magnitude of weight loss. Several perfluoroakyl compounds predicted more rapid weight regain. Genetic evidence from POUNDS Lost provides guidance toward selection of a personalized weight loss diet and improvement in metabolic profile. There is still room for additional research into the predictors of weight loss.