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Other Health Benefits and Special Considerations

The enzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the reaction converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a reaction necessary to convert homocysteine to methionine. Several mutations in the gene that codes for the MTHFR enzyme have been identified. One in particular, C677T, has been associated with reducing the activity of the enzyme and modulating the risk for NTDs, certain cancers, and elevated homocysteine concentrations. The prevalence of the homozygous form of the mutation (i.e., both gene alleles contain the mutation) varies based on race and ethnicity, with African-Americans having a low prevalence of ~1%; U.S. whites ~12%; and U.S. Hispanics ~21% (Botto & Yang, 2000).

A large meta-analysis of clinical trials and observational studies reports that the C677T polymorphism is associated with lower blood folate concentrations compared to the normal genotype, which can put women with the mutation at higher risk for having an NTD-affected pregnancy (Tsang et al., 2015). In a meta-analysis of case-control studies, the C677T polymorphism was found to be significantly associated with a 43%, 13% and 26% increased risk of NTD in Asian, European, and American populations, respectively (Yadav et al., 2015).

Studies on colorectal cancer have reported conflicting results. A meta-analysis of 92 studies reported that the TT genotype was protective for colorectal cancer across all included populations, but was associated with an increased risk in Hispanics (Shiao & Yu, 2016). Other subgroup analyses among different racial and ethnic groups did not reveal statistically significant associations. Another meta-analysis of 71 studies reported an increased risk for colorectal cancer with the C677T mutation in Caucasian, Asian, and mixed populations (Teng et al., 2013).  

A meta-analysis of case-control studies reported that the MTHFR C677T polymorphism was associated with an increased risk of myocardial infarction in Caucasians under the age of 50 (Xuan et al. 2011). A meta-analysis showed that the C677T polymorphism is significantly associated with risk of ischemic stroke (Song et al., 2016).

These and earlier studies (Bailey et al., 2001; Chen et al., 1996; Ma et al., 1997 ) suggest that individuals with the C677T mutation may have increased folate requirements and may be at increased risk for disease if folate status is suboptimal.  

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