A causal relationship between antioxidants, minerals and vitamins and metabolic syndrome traits: a Mendelian randomization study.

Background: The available evidence regarding the association of antioxidants, minerals, and vitamins with the risk of metabolic syndrome (MetS) traits is currently limited and inconsistent. Therefore, the purpose of this Mendelian randomization (MR) study was to investigate the potential causal relationship between genetically predicted antioxidants, minerals, and vitamins, and MetS.

Methods: In this study, we utilized genetic variation as instrumental variable (IV) to capture exposure data related to commonly consumed dietary nutrients, including antioxidants (β-carotene, lycopene, and uric acid), minerals (copper, calcium, iron, magnesium, phosphorus, zinc, and selenium), and vitamins (folate, vitamin A, B6, B12, C, D, E, and K1). The outcomes of interest, namely MetS (n = 291,107), waist circumference (n = 462,166), hypertension (n = 463,010), fasting blood glucose (FBG) (n = 281,416), triglycerides (n = 441,016), and high-density lipoprotein cholesterol (HDL-C) (n = 403,943), were assessed using pooled data obtained from the most comprehensive genome-wide association study (GWAS) available. Finally, we applied the inverse variance weighting method as the result and conducted a sensitivity analysis for further validation.

Results: Genetically predicted higher iron (OR = 1.070, 95% CI 1.037-1.105, P = 2.91E-05) and magnesium levels (OR = 1.130, 95% CI 1.058-1.208, P = 2.80E-04) were positively associated with increased risk of MetS. For each component of MetS, higher level of genetically predicted selenium (OR = 0.971, 95% CI 0.957-0.986, P = 1.09E-04) was negatively correlated with HDL-C levels, while vitamin K1 (OR = 1.023, 95% CI 1.012-1.033, P = 2.90E-05) was positively correlated with HDL-C levels. Moreover, genetically predicted vitamin D (OR = 0.985, 95% CI 0.978-0.992, P = 5.51E-5) had a protective effect on FBG levels. Genetically predicted iron level (OR = 1.043, 95% CI 1.022-1.064, P = 4.33E-05) had a risk effect on TG level.

Conclusions: Our study provides evidence that genetically predicted some specific, but not all, antioxidants, minerals, and vitamins may be causally related to the development of MetS traits.