Background and Objectives:
Folic acid, vitamin B6 and vitamin B12 are essential nutrients for nucleic acid synthesis and methyl production. Folic acid in the diet or folic acid (FA) in supplements can provide a carbon group for homocysteine (Hcy), which can be methylated to methionine or degraded to cysteine, and vitamins B6 and B12 act as essential coenzymes for Hcy metabolism. Low levels of B vitamins have been shown to contribute to obesity, dyslipidemia, vascular endothelial dysfunction, glucose intolerance, and insulin resistance, all of which are implicated in the pathogenesis of metabolic syndrome (MetS).
Several randomized clinical trials (RCTs) have found that vitamin B supplementation can reduce components associated with metabolic syndrome. FA supplementation alone or with vitamin B6 and/or vitamin B12 lowers blood pressure (BP), improves insulin resistance, and has a favorable effect on lipid metabolism. However, these studies focused on older cohorts or those at high risk of cardiovascular disease and were not directly associated with MetS for analysis. Therefore, this study intends to use CARDIA data to explore the relationship between folate, vitamin B6 and vitamin B12 intake and serum concentrations and the incidence of MetS in black and white young adults in the United States.
Way:
The CARDIA study recruited black people between the ages of 18 and 30 in the United States (Birmingham, Alabama, Chicago, Illinois, Minneapolis, Minnesota, and Oakland, California) from 1985 to 1986 (0 years). Eight follow-up examinations were performed at the 2nd, 5th, 7th, 10th, 15th, 20th, 25th and 30th years. Subjects with at least 3 individual abnormalities in MetS (waist circumference, blood pressure, triglycerides, HDL cholesterol, blood glucose) were defined as having MetS.
Dietary information was evaluated at baseline, year 7 and year 20 examinations, measuring total folate consumption, vitamin B6 and vitamin B12 intake. Concentrations of folic acid, vitamin B12 and vitamin B6 in serum samples were measured at years 0, 7 and 15. Energy intake-corrected vitamin B intake is calculated as daily vitamin B intake divided by total daily caloric intake. The Cox proportional hazards regression model was used to analyze the relationship between B vitamin intake and serum concentrations and the incidence of MetS.
Outcome:
A total of 4414 subjects (2225 50.4% black, 2331 52.8% female) with a mean age of 24.9 years at baseline were included, and 1430 subjects participated in the measurement of serum B vitamins. Patients were followed up for 30 years, and a total of 1240 MetS events occurred. Participants with higher total intake of folic acid, vitamin B6, or vitamin B12 tended to be older, female, white, more educated, never smoked, and drank less alcohol, and had better overall diet quality, with lower baseline blood pressure, waist circumference, lipids, and Hcy. See the following table for details:
After adjusting for potential confounders, participants in the highest quintile of total folate intake after energy correction had a 61% lower incidence of MetS compared with the lowest intake group (HR, 0.39; 95% CI, 0.31-0.49; p<0.001). The incidence of MetS was 39% lower with vitamin B6 (HR, 0.61; 95% CI, 0.46-0.81; P=0.002) and the incidence of MetS with vitamin B12 intake was 26% lower (HR, 0.74; 95% CI, 0.58-0.95; P=0.008).
Among 1430 participants with available data, serum concentrations of the three B vitamins were inversely correlated with MetS events (folic acid HR, 0.23; 95% CI 0.17-0.33, P<0.001; vitamin B6 HR, 0.48, 95% CI 0.34-0.67, P<0.001; vitamin B12 HR, 0.70, 95% CI 0.51-0.96, P = 0.01).
Serum concentrations of folic acid, vitamin B6, and vitamin B12 were also inversely correlated with serum Hcy concentrations. The corresponding Spearman correlation coefficients were -0.43, -0.22 and -0.37 (P<0.001). In addition, high serum Hcy is associated with an increased incidence of MetS. The specific results are shown in the table below.
In the analysis of individual risk factors, except for the relationship between vitamin B6 intake and blood glucose, and the relationship between vitamin B12 and blood glucose and blood pressure was not significant, the negative association between other risk factors and B vitamins still existed.
No significant differences were seen in the stratified analysis of age, sex, and ethnicity.
Conclusion:
Dietary intake and serum concentrations of folic acid, vitamin B6 and vitamin B12 were significantly negatively correlated with metabolic syndrome events. Adequate intake of these B vitamins should be recommended to prevent metabolic syndrome. Low serum concentrations of these B vitamins may be an indicator of a higher risk of MetS.
Comments:
This large longitudinal cohort study explored the relationship between total intake of folic acid, vitamin B6 and vitamin B12 and the incidence of metabolic syndrome, with a long follow-up period and a more convincing analysis of serum concentrations and the relationship between participants' B vitamin intake and metabolic syndrome. Current epidemiological studies on B vitamins and risk of metabolic syndrome are inconsistent. Some studies, such as this one, have linked B vitamins to a lower incidence of metabolic syndrome. However, cross-sectional studies have found no association between B vitamin intake and metabolic syndrome. Differences in results may be due to differences in the definition of metabolic syndrome, ethnicity, dietary habits, and follow-up periods. Adequate intake of B vitamins and high dietary quality of subjects indirectly reflected the subjects' daily life and daily health awareness, and therefore reduced the incidence of metabolic syndrome.
Bibliography:
Zhu J, Chen C, Lu L, et al. Folate, Vitamin B6, and Vitamin B12 Status in Association With Metabolic Syndrome Incidence [J]. JAMA Netw Open, 2023, 6(1): e2250621.