Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies.

Study answer

What this study found

Overall, blood folate showed an additive genotype pattern of CC > CT > TT when measured by microbiologic assay. Protein-based assays showed a different or reverse pattern, indicating that assay choice materially changed the observed association. The review included 40 eligible studies, with 38 in meta-analyses, and found that cross-assay comparability was limited. The authors concluded that blood folate assay methods should be standardized and that protein-based assays should be interpreted cautiously in this genetic context.

Study & population

Systematic review and meta-analysis of 40 eligible studies in nonpregnant, nonlactating healthy women aged 12-49 years from multiple countries.

Intervention

Across included studies, participants received either natural food folate or folic acid-containing supplements, with daily folate doses ranging from 115 mg DFEs to 6800 mg DFEs over 1 day to 6 months.

Key limitation

Evidence was highly heterogeneous in design, folate exposure, duration, and assay method, and most studies used protein-based assays rather than microbiologic assays.

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Original abstract