Omid Asbaghi1, Damoon Ashtary-Larky2, Reza Bagheri3, Seyedeh Parisa Moosavian4, Hadi Pourmirzaei Olyaei5, Behzad Nazarian6, Mahnaz Rezaei Kelishadi7, Alexei Wong8, Darren G Candow9, Frédéric Dutheil10, Katsuhiko Suzuki11, Amirmansour Alavi Naeini7. 1. Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1416753955, Iran. 2. Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran. 3. Department of Exercise Physiology, University of Isfahan, Isfahan 8174673441, Iran. 4. Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran. 5. Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran 1584743311, Iran. 6. Student Research Committee, Lorestan University of Medical Sciences, Khorramabad 6813833946, Iran. 7. Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran. 8. Department of Health and Human Performance, Marymount University, Arlington, VA 22207, USA. 9. Faculty of Kinesiology and Health Studies, University of Regina, Regina, SK S4S OA2, Canada. 10. CNRS, LaPSCo, Physiological and Psychosocial Stress, CHU Clermont-Ferrand, University Hospital of Clermont-Ferrand, Preventive and Occupational Medicine, Université Clermont Auvergne, WittyFit, F-63000 Clermont-Ferrand, France. 11. Faculty of Sport Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa 359-1192, Japan.
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.
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.