High Folate Intake Linked to Low Incidence of Metabolic Syndrome


The relationship between metabolic syndrome and some B vitamins, such as vitamin B12, was only observed among participants who took B12 supplements.

New data link incidence of metabolic syndrome (MetS) with insufficient folate, vitamin B6, and vitamin B 12 intake, according to a longitudinal cohort study with a 30-year follow-up published in JAMA Network Open.

Women who were older and White were more likely to have a higher intake of folate, vitamin B6, and vitamin B 12. Those with sufficient intake were also more likely to have a better quality diet, higher educational level, be non-smokers, have lower alcohol consumption, and be active.

“Serum concentrations of the 3 B vitamins were inversely associated with incident MetS,” the study authors wrote.

The data showed that folate—which is a nutrient that comes from diet or folic acid (FA)—was

the onlyvitamin that is inversely associated with all individual components of MetS. It was associated with a 61% lower incidence of MetS overall.

Folate, vitamin B6, and vitamin B 12 are essential for nucleic acid synthesis and the production of methyl groups. Data suggest that low amounts of B vitamins can lead to adiposity, dyslipidemia, vascular endothelial dysfunction, glucose intolerance, and insulin resistance—and any of these conditions may contribute to or reflect the development of MetS, according to the study authors.

No previous study has directly linked MetS with B vitamin concentration, which led researchers to conduct the Coronary Artery Risk Development in Young Adults (CARDIA) study. CARDIA studied the diets of 4414 young Black and White adults in the United States from 1985 (enrollment) to 2016, hypothesizing that higher intakes and serum concentrations of folate, vitamin B6 and vitamin B12 were associated with lower incident of MetS.

Using a validated diet history, the enrollees’ diets were analyzed at years 0, 7, and 20, and B vitamin serum concentrations were analyzed at years 0, 7, and 15 in a patient subset.

Upon measuring MetS occurrence and analyzing the data from 2020 to 2021, researchers observed that incidence of MetS was 39% lower in participants who had ample vitamin B6 intake. Additionally, incidence rates of MetS were 26% lower among those with sufficient B12 intake.

Vitamin B6 may be a positive agent against MetS because it has favorable effects on adiposity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated blood pressure (BP). Although separate clinical trials examined the relationship between adequate B vitamin intake on BP, insulin resistance, and lipid metabolic profiles that indicate the formation of MetS, this was the first to link this relationship, according to the study.

The study contains some limitations, the first of which being that the researchers cannot rule out residual confounding because it was an observational study. Further, researchers did not examine the potential outcomes of genetic risk factors and their possible influence on B vitamin metabolism.

“Adequate intakes of these B vitamins should be recommended for prevention of MetS. Lower serum concentrations of these B vitamins may be indicators of higher risk of MetS. Further investigations are needed to confirm our findings and establish causal inference,” the study authors wrote.


Zhu, Jie, Chen, Cheng, Lu, Liping, et al. Folate, Vitamin B6, and Vitamin B12 Status in Association With Metabolic Syndrome Incidence. Accessed January 13, 2023. JAMA Netw Open. 2023;6(1):e2250621. doi:10.1001/jamanetworkopen.2022.50621

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