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

Asbaghi, Omid; Ashtary-Larky, Damoon; Bagheri, Reza; Moosavian, Seyedeh Parisa; Olyaei, Hadi Pourmirzaei; Nazarian, Behzad; Rezaei Kelishadi, Mahnaz; Wong, Alexei; Candow, Darren G.; Dutheil, Frédéric; Suzuki, Katsuhiko; Alavi Naeini, Amirmansour

doi:10.3390/nu13072355

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

by

Omid Asbaghi

¹,

Damoon Ashtary-Larky

²,

Reza Bagheri

³,

Seyedeh Parisa Moosavian

⁴

,

Hadi Pourmirzaei Olyaei

⁵

,

Behzad Nazarian

⁶,

Mahnaz Rezaei Kelishadi

⁷,

Alexei Wong

⁸,

Darren G. Candow

⁹,

Frédéric Dutheil

¹⁰,

Katsuhiko Suzuki

^11,*

and

Amirmansour Alavi Naeini

^7,*

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

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Nutrients 2021, 13(7), 2355; https://doi.org/10.3390/nu13072355

Submission received: 8 June 2021 / Revised: 30 June 2021 / Accepted: 6 July 2021 / Published: 9 July 2021

(This article belongs to the Special Issue Health Benefits of Iron and Folic Acid Supplementation)

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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.

Keywords: folic acid; glycemic control; diabetes; meta-analysis

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MDPI and ACS Style

Asbaghi, O.; Ashtary-Larky, D.; Bagheri, R.; Moosavian, S.P.; Olyaei, H.P.; Nazarian, B.; Rezaei Kelishadi, M.; Wong, A.; Candow, D.G.; Dutheil, F.; et al. Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. Nutrients 2021, 13, 2355. https://doi.org/10.3390/nu13072355

AMA Style

Asbaghi O, Ashtary-Larky D, Bagheri R, Moosavian SP, Olyaei HP, Nazarian B, Rezaei Kelishadi M, Wong A, Candow DG, Dutheil F, et al. Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. Nutrients. 2021; 13(7):2355. https://doi.org/10.3390/nu13072355

Chicago/Turabian Style

Asbaghi, Omid, Damoon Ashtary-Larky, Reza Bagheri, Seyedeh Parisa Moosavian, Hadi Pourmirzaei Olyaei, Behzad Nazarian, Mahnaz Rezaei Kelishadi, Alexei Wong, Darren G. Candow, Frédéric Dutheil, and et al. 2021. "Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials" Nutrients 13, no. 7: 2355. https://doi.org/10.3390/nu13072355

APA Style

Asbaghi, O., Ashtary-Larky, D., Bagheri, R., Moosavian, S. P., Olyaei, H. P., Nazarian, B., Rezaei Kelishadi, M., Wong, A., Candow, D. G., Dutheil, F., Suzuki, K., & Alavi Naeini, A. (2021). Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. Nutrients, 13(7), 2355. https://doi.org/10.3390/nu13072355

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

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