Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials

Abstract

Background: There is a growing interest in the considerable benefits of dietary supplementations, such as folic acid, on the glycemic profile. We aimed to investigate the effects of folic acid supplementation on glycemic control markers in adults. Methods: Randomized controlled trials examining the effects of folic acid supplementation on glycemic control markers published up to March 2021 were detected by searching online databases, including Scopus, PubMed, Embase, and ISI web of science, using a combination of related keywords. Mean change and standard deviation (SD) of the outcome measures were used to estimate the mean difference between the intervention and control groups at follow-up. Meta-regression and non-linear dose-response analysis were conducted to evaluate the association between pooled effect size and folic acid dosage (mg/day) and duration of the intervention (week). From 1814 detected studies, twenty-four studies reported fasting blood glucose (FBG), fasting insulin, hemoglobin A1C (HbA1C), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) as an outcome measure. Results: Results revealed significant reductions in FBG (weighted mean difference (WMD): −2.17 mg/dL, 95% CI: −3.69, −0.65, p = 0.005), fasting insulin (WMD: −1.63 pmol/L, 95% CI: −2.53, −0.73, p < 0.001), and HOMA-IR (WMD: −0.40, 95% CI: −0.70, −0.09, p = 0.011) following folic acid supplementation. No significant effect was detected for HbA1C (WMD: −0.27%, 95% CI: −0.73, 0.18, p = 0.246). The dose-response analysis showed that folic acid supplementation significantly changed HOMA-IR (r = −1.30, p-nonlinearity = 0.045) in non-linear fashion. However, meta-regression analysis did not indicate a linear relationship between dose, duration, and absolute changes in FBG, HOMA-IR, and fasting insulin concentrations. Conclusions: Folic acid supplementation significantly reduces some markers of glycemic control in adults. These reductions were small, which may limit clinical applications for adults with type II diabetes. Further research is necessary to confirm our findings.

Diet and Maternal Obesity Are Associated with Increased Oxidative Stress in Newborns: A Cross-Sectional Study

“…This finding may be related to the multiple roles folic acid plays in OS, including its direct antioxidant effect through the regulation of NO levels [31] and through decreasing MDA formation [32]. Importantly, decreased levels of OS markers have been observed when folic acid supplements are given at doses of 0.4 to 10 mg to adult populations [33]. Similarly, the present study showed that lower plasma levels of NO and MDA were present in pregnant women who received folic acid supplementation during the first 20 weeks of pregnancy (Table 4) [19].…”

Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms

“…Folate is an essential vitamin that participates in enzymatic reactions involved in the one-carbon metabolic pathways, regulating DNA methylation, and amino acid and lipid metabolism ( 95 ). Interestingly, epidemiological evidence indicates that diet supplementation with folate improves glycemic control and insulin resistance in patients with MS and T2D ( 95 , 96 ). These lines of evidence let us suggest that arsenic and folate can have antagonistic effects on the same metabolic pathways, influencing the development of insulin signaling.…”

Role of Vitamin B12 and Folate in Metabolic Syndrome

“…Folate supplementation has been established with protective studies in reducing insulin and HOMA-IR; however, inconsistent results have been reported regarding the reduction of fasting blood sugar and HbA1c levels [ 131 ]. The dosage of folate supplementation plays an important role in the reduction of insulin resistance [ 132 ]. The glycemic markers were effectively reduced with a folate dose greater than 5 mg/day [ 132 ].…”

“…The dosage of folate supplementation plays an important role in the reduction of insulin resistance [ 132 ]. The glycemic markers were effectively reduced with a folate dose greater than 5 mg/day [ 132 ]. A systematic review published by Xie et al in 2016 showed that folic acid supplementation in maternal and prenatal animal groups decreased both insulin resistance and obesity significantly [ 133 ].…”