Metabolic Phenotyping Identifies Responders to Sustainable Healthy Diets: Analysis from the MyPlanetDiet Randomized...

Understanding interindividual variation is critical for developing strategies to improve health. Metabolic phenotypes impact how individuals respond to dietary change. Although literature has examined responses to dietary interventions between metabolic phenotypes, none have yet considered sustainable healthy diets.

Exploratory, hypothesis-generating, post hoc secondary analysis from the MyPlanetDiet randomized controlled trial is used to examine subgroup response to sustainable healthy diets. The aim is to identify metabolic phenotype subgroups (MPs) within the MyPlanetDiet sample population and examine if MPs responded differently to dietary change.

The MyPlanetDiet study was a 12-wk randomized controlled trial testing the impacts of more sustainable healthy diet advice relative to advice from food-based dietary guidelines. Dietary assessments, fasting serum samples, and anthropometry were collected at baseline and endpoint. k-means cluster analysis of baseline serum metabolic health markers identified MPs. Metabolomic profiles, dietary intakes, and changes in metabolic health over time were compared between MPs using partial least squares discriminant analysis and analysis of covariance.

Three distinct MPs were identified with significantly different metabolomic profiles despite comparable baseline dietary intakes. Metabolic phenotype 1 (MP1) was categorized as the most metabolically unhealthy, metabolic phenotype 2 (MP2) was mostly female with the lowest anthropometry and high total cholesterol, and metabolic phenotype 3 (MP3) was the youngest with the healthiest blood lipid concentrations. There were significant time × group interactions for total cholesterol (P = 0.001), high-density lipoprotein cholesterol (P < 0.001), triglycerides (P = 0.002), and C-reactive protein (P = 0.043) between MPs. Significant decreases in total cholesterol within MP1 (5.92 ± 0.88 mmol/L to 5.74 ± 0.83 mmol/L, P = 0.006) and MP2 (5.81 ± 0.86 mmol/L to 5.64 ± 0.94 mmol/L, P = 0.018) were observed, but no significant difference was observed in MP3 (P = 0.146). Increased intakes of fruit and vegetables and whole grains were associated with decreased total cholesterol in MP1 and MP2 (all P < 0.05).

Metabolic phenotyping shows interindividual variation in metabolic response to dietary change. Metabolic phenotyping could be a valuable tool for informing personalized nutrition strategies to improve diet and metabolic health.This trial was registered at clinicaltrials.gov as NCT05253547.