Dairy Intake in 2 American Adult Cohorts Associates with Novel and Known Targeted and Nontargeted Circulating Metabolites

The role of dairy in health can be elucidated by investigating circulating metabolites associated with intake. Objectives: We sought to identify metabolites associated with quantity and type of dairy intake in the Framingham Heart Study Offspring and Third Generation (Gen3) cohorts.

Dairy in 2 American adult cohorts associated with numerous circulating metabolites. Reports about diet-metabolite relations and confirmation of previous findings might be limited by specificity of dietary intake and breadth of measured metabolites.

Dairy intake (total dairy, milk, cheese, yogurt, and cream/butter) was analyzed in relation to targeted (Offspring, n = 2205, 55.1 ± 9.8 y, 52% female, 217 signals; Gen3, n = 866, 40.5 ± 8.8 y, 54.9% female, 79 signals) and nontargeted metabolites (Gen3, ∼7031 signals) in a 2-step analysis including orthogonal projections to latent structures with discriminant analysis (OPLS-DA) in discovery subsets to identify metabolites distinguishing between high and low intake; and linear regression in confirmation subsets to assess putative associations, subsequently tested in the total samples. Previously reported associations were also investigated.

OPLS-DA in the Offspring targeted discovery subset resulted in a variable importance in projection (VIP) >1 of 65, 60, 58, 66, and 60 metabolites for total dairy, milk, cream/butter, cheese, and yogurt, respectively, of which 5, 3, 1, 6, and 4 metabolites, respectively, remained after confirmation. In the Gen3 targeted discovery subset, OPLS-DA resulted in a VIP >1 of 17, 15, 13, 7, and 6 metabolites for total dairy, milk, cream/butter, cheese, and yogurt, respectively. In the Gen3 nontargeted discovery subset, OPLS-DA resulted in a VIP >2 of 203, 503, 78, 186, and 206 metabolites, respectively. Combining targeted and nontargeted results in Gen3, significant associations of 7 (6 unannotated), 2, 12 (11 unannotated), 0, and 61 (all unannotated) metabolites, respectively, remained. Candidate identities of unannotated signals included fatty acids and food flavorings. Results supported relations previously reported for C14:0 sphingomyelin, and marginal associations for deoxycholates. Conclusions: Dairy in 2 American adult cohorts associated with numerous circulating metabolites. Reports about diet-metabolite relations and confirmation of previous findings might be limited by specificity of dietary intake and breadth of measured metabolites.