Many functional medicine practitioners now routinely assess patients' MTHFR status, with particular interest in identifying the C677T or A1298C alleles that can impair enzyme function to the detriment of folate utilization.
Homocysteine, which typically rises when there is a methylation blockage, is another biomarker for methylation status that practitioners commonly measure.
Up until now, it has been widespread practice to recommend supplementation with methylated folate (5-methyltetrahydrofolate) and methylcobalamin (vitamin B12) for patients with methylation deficiencies.
Since 5-mTHF is the normal product of the MTHFR enzyme, supplementing with this form makes sense because it bypasses any enzyme blockage.
Folic acid, the synthetic folate form which has been successful at reducing rates of neural tube defects, is not generally used for methylation support since it would require conversion by the deficient MTHFR enzyme, as well as activation via the enzyme dihydrofolate reductase, which is a somewhat inefficient process, especially if there are any single nucleotide polymorphisms in the DFR gene.
A number of combination supplements geared towards methylation support also include other accessory cofactors such as pyridoxine (vitamin B6), betaine and zinc.
While the increased awareness of the importance of methylation is certainly a positive development, there are a number of potential concerns with methylation support supplements, especially when taken at high doses for indefinite time periods.