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Evidence-Based Supplement Research
Evidence-Based Supplement Research

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

  • 2023-07-26
  • Nutrition reviews 82(6)
    • 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

Study Design

Type
Meta-Analysis
Sample size
n = 1,625
Population
21 RCTs (N = 1625 participants)
Methods
Systematic review and meta-analysis of RCTs; random-effects model used; searched databases up to June 2022

Context

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.

Objective

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.

Conclusion

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.

Research Insights

  • 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)

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    greater than 500 µg/d (for dose subgroup)
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