The Personalized Nutrition Study: Evaluation of a Genetically-informed Weight Loss Approach

Obesity and its comorbidities are major public health challenges. To combat the obesity pandemic, many weight-loss strategies have been studied, often emphasizing either high carbohydrate (low fat) diets or high fat (low carbohydrate) diets. Mean weight loss differences between high-carbohydrate and high-fat diets that induce equal caloric deficits have been reported to be small; however, the individual weight loss response varies substantially within diet groups, suggesting that different individuals react differently to high-carbohydrate or high-fat diets. This assumption is supported by retrospective data showing that participants with carbohydrate-responsive polymorphisms lost 2-3 times more weight when assigned to a high-carbohydrate diet compared to a high-fat diet, and vice versa for those with dietary fat-responsive polymorphisms. Conversely, a recent randomized clinical trial aimed to determine the effect of a healthy high-fat diet (high in unsaturated fats) vs. a healthy high-carbohydrate diet (high in whole-grain foods) on 12-month weight change but did not find significant differences between the two groups and failed to find the hypothesized association between genotype patterns and weight loss induced by diets that varied in fat and carbohydrate content. However, an important caveat of their approach is that the single nucleotide polymorphisms selected by the investigators had not been previously associated with obesity or with dietary responses, which may explain their lack of predictive value in identifying differences in inter-individual responses. In addition, the fat composition of the diets was relatively high in both high- and low-fat groups. The inconsistent findings in the literature indicate a need for further research to determine if genetic factors affect weight loss when exposed to diets that vary in carbohydrates and dietary fats.

The purpose of this randomized controlled parallel arm trial is to test the following hypotheses.

Hypothesis 1 will test if participants assigned to the diet that corresponds to their genotype lose more weight than those assigned to a diet inconsistent with their genotype.

Hypothesis 2 will analyze the fat responders and carbohydrate responders separately.

• Hypothesis 2a: Fat responders will lose more weight on the high-fat diet vs. the high-carbohydrate diet.
• Hypothesis 2b: Carbohydrate responders will lose more weight on the high-carbohydrate diet vs. the high-fat diet.