Salmon food-specific compounds and their metabolites increase in human plasma and are associated with cardiometabolic health indicators following a Mediterranean diet intervention

Authors: HILL, EMILY - University Of Colorado; REISDORPH, RICHARD - University Of Colorado; RAJERY, SAKAIZA - University Of Colorado; MICHEL, COLE - University Of Colorado; KHAJEH-SHARAFABADI, MOBIN - University Of Colorado; DOENGES, KATRINA - University Of Colorado; WEAVER, NICHOLAS - University Of Colorado; QUINN, KEVIN - University Of Colorado; SUTLIFF, AIMEE - University Of Colorado; TANG, MINGHUA - University Of Colorado; BORENGASSER, SARAH - University Of Colorado; FRANK, DANIEL - University Of Colorado; O'Connor, Lauren; CAMPBELL, WAYNE - Purdue University; KREBS, NANCY - University Of Colorado; HENDRICKS, AUDREY - University Of Colorado; REISDORPH, NICOLE - University Of Colorado

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/19/2023
Publication Date: 10/31/2023
Citation: Hill, E.B., Reisdorph, R.M., Rajery, S.R., Michel, C., Khajeh-Sharafabadi, M., Doenges, K.A., Weaver, N., Quinn, K., Sutliff, A.K., Tang, M., Borengasser, S.J., Frank, D.N., O'Connor, L.E., Campbell, W.W., Krebs, N.F., Hendricks, A.E., Reisdorph, N.A. 2023. Salmon food-specific compounds and their metabolites increase in human plasma and are associated with cardiometabolic health indicators following a Mediterranean diet intervention. Journal of Nutrition. 154:26-40. https://doi.org/10.1016/j.tjnut.2023.10.024.
DOI: https://doi.org/10.1016/j.tjnut.2023.10.024

Interpretive Summary: Nutrimetabolomics is a comprehensive analysis of compounds in foods and human biospecimens to identify potential biomarkers of intake and associations with health. Salmon, a food recommended as part of an omnivorous healthy dietary pattern, contains hundreds of compounds which may provide cardiometabolic benefits. We used a metabolomics-based approach to identify salmon food-specific compounds and their predicted metabolites that increased in plasma after consuming a salmon-containing Mediterranean-style dietary pattern and were associated with changes in cardiometabolic health indicators in 41 participants in a human feeding intervention. We identified 237 compounds that were unique to salmon and 143 of those compounds were also detected in human plasma after salmon consumption as part of the Mediterranean-style dietary pattern. A data-driven nutrimetabolomics approach like suggest strong potential for this comprehensive, metabolomics-based approach to the identification and testing of food biomarkers.

Technical Abstract: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds that may provide cardiometabolic benefits. We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored. For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with 2 servings of salmon per week for 2 5-wk periods. CHIs were assessed, and fasting plasma was collected pre- and postintervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to postintervention and associations with changes in CHIs. Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (false discovery rate <0.05). Increases in 2 annotated salmon FSCs and 2 metabolites were associated with improvements in CHIs, including total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for the discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health.