MTHFR

What the gene does

MTHFR converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (the form that donates a methyl group to homocysteine for re-methylation to methionine). Variants reduce enzyme activity:

• C677T TT: ~30% activity reduction.
• A1298C CC: smaller activity reduction.
• Compound heterozygotes have intermediate effects.

What the evidence actually shows

• Mild elevations in homocysteine (especially in folate-deficient populations).
• Possible small increase in neural tube defect risk — addressed by folic acid fortification.
• Cardiovascular and dementia risk: small effect sizes; B-vitamin supplementation generally doesn’t produce outcome benefit even when it lowers homocysteine.
• Pregnancy: routine MTHFR testing not recommended by most obstetric guidelines.

What MTHFR testing is over-marketed for

• "Detoxification" capacity: weak biological basis.
• Custom "methylated" supplements at premium prices: legitimate for documented B12/folate deficiency; not specifically required by MTHFR status in folate-replete adults.
• Cancer / autism / chronic fatigue links: not supported by high-quality evidence.

Reasonable interpretation

• TT homozygous + elevated homocysteine + low B12/folate intake: consider methylated forms (5-MTHF, methylcobalamin).
• TT homozygous + normal homocysteine: no action required.
• Routine MTHFR testing not recommended unless specific clinical context.

Related entries

Homocysteine, Vitamin B12, Folate.