MTHFR A1298C is involved in converting 5-methylfolate (5MTHF) to tetrahydrofolate (THF). The gene is compromised by about 70% in MTHFR A1298C (+/+) individuals, and about 30% in people with a heterozygous (+/-) mutation.

Unlike MTHFR C677T, it is not linked to elevated homocysteine levels and instead in linked to lower levels of tetrahydrobiopterin BH4. Low levels of BH4 are linked to low levels of serotonin, dopamine, melatonin, norepinephrine and epinephrine. BH4 plays a major role in the detoxification of ammonia. Ammonia is a by-product of protein metabolism, and therefore high amounts of muscle meats may create too much ammonia in people with this mutation.

BH4 is depleted further by mercury, lead and aluminum. It is very important to reduce these in your diet and environment. Coenzyme Q10 (CoQ10) is a major natural energy source and is synthesized in humans from tyrosine through a cascade of precursors. These precursors require B1,  B2, B3 (niacin) B5, B6, B12, folate and tetrahydrobiopterin (BH4) as their coenzymes in the Kreb’s Cycle.

MTHFR A1298C and BH4

BH4 acts as a rate limiting factor for the production of neurotransmitters and catecholamines including serotonin, melatonin, dopamine, norepinephrine, and epinephrine.


BH4 Cycle, COMT, MAO-A

A MTHFR A1298C + status may cause a decrease in any of these neurotransmitters or catecholamines. BH4 is also a cofactor in the production of nitric oxide. A dysfunctional BH4 enzyme may lead to mental/emotional and/or physical symptoms. Mercury, lead, and aluminum may act as a drain on BH4.

Low BH4 Chart - New Page

Healthy BH4 flow chart - New Page-5