Adela Hruby1, Courtney Dennis2, Paul F Jacques1. 1. Nutritional Epidemiology, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA, USA. 2. Metabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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.
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