The effects of folate supplementation on glucose metabolism and risk of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Ann Epidemiol. 2018 Apr;28(4):249-257.e1. doi: 10.1016/j.annepidem.2018.02.001. Epub 2018 Feb 10.


Purpose: Observationally, homocysteine is associated with higher risk of diabetes. Folate, which reduces homocysteine, is promising for the prevention and treatment of diabetes. Previous meta-analysis of three trials suggested folate might lower hemoglobin A1c (HbA1c).

Methods: An updated systematic review and meta-analysis of placebo-controlled randomized trials was conducted. We searched PubMed using ("folate" or "folic acid") and trial and ("glucose" or "diabetes" or "insulin" or "hemoglobin A1c" or "HbA1c") in any field until February 3, 2017. We also conducted a bibliographic search of selected studies and relevant reviews. Relative risk of diabetes and mean differences in indicators of glucose metabolism between folate and placebo were summarized in a meta-analysis using inverse variance weighting with random effects. Heterogeneity, publication bias, and risk of bias were also assessed.

Results: Eighteen trials of 21,081 people with/without diabetes were identified. Folate decreased fasting glucose (-0.15 mmol/L, 95% confidence interval [CI] -0.29 to -0.01), homeostatic model assessment-insulin resistance (-0.83, 95% CI -1.31 to -0.34), and insulin (-1.94 μIU/mL, 95% CI -3.28 to -0.61) but had no clear effect on diabetes or HbA1c.

Conclusions: Our study suggests a potential benefit of folate on insulin resistance and glycemic control; the latter requires examination in more high-quality trials.

Keywords: Diabetes; Folate; Insulin resistance; Meta-analysis.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dietary Supplements*
  • Folic Acid / administration & dosage
  • Folic Acid / therapeutic use*
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / drug therapy
  • Insulin / analysis
  • Insulin Resistance
  • Risk Factors


  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Folic Acid