DOI: 10.1093/nutrit/nuad091 ISSN: 0029-6643

A comprehensive review and meta-regression analysis of randomized controlled trials examining the impact of vitamin B12 supplementation on homocysteine levels

Mohammad Hassan Sohouli, Faisal Almuqayyid, Aya Alfardous Alazm, Fateme Ziamanesh, Elma Izze da Silva Magalhães, Seyedeh Elaheh Bagheri, Bianca Rodrigues de Oliveira, Mahmoud Alfardous Alazm, Abdul Rahman Adi, Sara Alomar, Ahmed Abu-Zaid
  • Nutrition and Dietetics
  • Medicine (miscellaneous)



Although some research suggests that vitamin B12 (hereafter, B12) supplements can lower homocysteine (Hcy) levels and treat hyperhomocysteinemia, these results are still ambiguous when B12 is taken as an isolated supplement.


This study sought to determine how existing randomized controlled trials (RCTs) could be used to examine the effects of B12 supplementation on Hcy.

Data Sources

To find pertinent RCTs up to June 2022, databases, including PubMed/Medline, Web of Science, Scopus, Cochrane Library, and Embase, were searched.

Data Extraction

All selected RCTs investigated the impact of B12 supplements on Hcy. A meta-analysis of the eligible studies was performed using the random-effects model.

Data Analysis

This review included a total of 21 RCTs (N = 1625 participants). Hcy levels were significantly lower after B12 supplementation compared with the control group (pooled weighted mean difference, –4.15 μmol/L; 95% confidence interval, –4.86, –3.45; P < 0.001), and this reduction was even greater with intervention durations ≥12 weeks and doses >500 µg/d. Furthermore, the effect of B12 supplementation in the form of hydroxocobalamin on the reduction of Hcy level was greater compared with other forms.


In conclusion, this meta-analysis shows that B12 supplementation has a positive impact on lowering blood Hcy levels, particularly when administered for a longer period and at a larger dose.

Systematic Review Registration

PROSPERO registration no. CRD42022364066

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