Metabolite patterns of B vitamin–dependent pathways associated with metabolic syndrome in older adults from the Bushehr elderly health study

Abstract Metabolic syndrome (MetS) is a major global health challenge associated with increased risks of cardiovascular disease, type 2 diabetes, and mortality, particularly among older adults. B vitamins are essential cofactors in the homocysteine–methionine, folate, and tryptophan–kynurenine pathways, which regulate inflammation, oxidative stress, and glucose metabolism. This study investigated associations between B vitamin–related metabolites and MetS in 400 adults aged ≥ 60 years from the Bushehr Elderly Health (BEH) program. Demographic, lifestyle, and clinical data were collected, and fasting blood samples were analyzed using GC-MS/MS and LC-MS/MS. MetS was defined according to International Diabetes Federation criteria. Principal component analysis (PCA) identified metabolite patterns, and logistic regression assessed their associations with MetS. MetS was present in 45.8% of participants. Individuals with MetS had higher levels of total cysteine and several folate-related metabolites, nicotinamide and kynurenine pathway metabolites, whereas serine levels were lower. Factor 1, identified by PCA and consisting of kynurenine, quinolinic acid, kynurenic acid, 3-hydroxykynurenine, cystathionine, anthranilic acid, neopterin, and total cysteine, was associated with 36% higher odds of MetS after adjustment for covariates. These findings indicate significant alterations in B vitamin–related metabolic pathways and suggest potential biomarkers and therapeutic targets for MetS management.