Serum homocysteine, folate, and vitamin B12 levels in patients with vitiligo and their potential roles as disease activity biomarkers: A systematic review and meta-analysis

J Am Acad Dermatol. 2019 Mar;80(3):646-654.e5. doi: 10.1016/j.jaad.2018.08.029. Epub 2018 Aug 28.


Background: Hyperhomocysteinemia and folate and vitamin B12 deficiencies have been reported in patients with vitiligo. Investigating the role of these conditions might shed light on the pathogenesis of vitiligo.

Objective: To perform a systematic review and meta-analysis of studies assessing serum homocysteine, folate, and vitamin B12 levels in vitiligo patients.

Methods: Online databases were searched on May 15, 2018, to identify studies comparing serum homocysteine, folate, and vitamin B12 levels between patients with vitiligo and controls. A random effects model was used.

Results: Twenty-two studies involving a total of 1448 patients with vitiligo were included. Patients with vitiligo had significantly higher serum homocysteine levels (standardized mean difference [SMD] 0.550, 95% confidence interval [CI] 0.262-0.838; I2 87.3%) and lower vitamin B12 levels (SMD -0.430, 95% CI -0.738 to -0.121; I2 85.3%) than controls. Serum folate levels were not significantly different between the 2 groups (SMD -0.240, 95% CI -0.592 to 0.111; I2 85.5%). A subgroup analysis revealed that these findings correlated with disease activity.

Limitations: The included studies were heterogeneous. Serum homocysteine levels could be influenced by various factors.

Conclusion: Patients with vitiligo have higher serum homocysteine levels and lower vitamin B12 levels than individuals without vitiligo.

Keywords: folate; homocysteine; hyperhomocysteinemia; vitamin B(12); vitiligo.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Case-Control Studies
  • Folic Acid / blood*
  • Homocysteine / blood*
  • Humans
  • Severity of Illness Index
  • Vitamin B 12 / blood*
  • Vitiligo / blood*


  • Biomarkers
  • Homocysteine
  • Folic Acid
  • Vitamin B 12