What is the MTHFR A128C Gene?
Unlike MTHFR C677T, MTHFR 1298 is not linked to elevated homocysteine levels unless there is a heterozygous MTHFR 1298 and MTHFR 677 together. Disruptions in both MTHFR genes may lead to lower levels of tetrahydrobiopterin BH4.
The heterozygous MTHFR 1298 gene has a reduced function of approximately 20% and the homozygous MTHFR 1298 gene has a 40% reduction in enzymatic function. This means that there is an increase in the need for methylfolate to offset the reduction in enzymatic function.
MTHFR and BH4 Levels
BH4 structurally resembles folate and has been described to be reduced in endothelial cells when increased levels of homocysteine are present. 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, by-product of protein metabolism, and therefore high amounts of muscle meats may create too much ammonia in people with the homozygous MTHFR 1298 gene.
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.
How BH4 Affects Mental Health
BH4 acts as a rate limiting factor for the production of neurotransmitters and catecholamines including serotonin, melatonin, dopamine, norepinephrine, and epinephrine. Therefore, low BH4 will affect every aspect of mental health.
Mice studies have shown that raising BH4 normalizes serotonin levels and digestive function. In one human study, levels of BH4 in cerebrospinal fluid was 42% lower in children with Autism Spectrum Disorder (ASD). These results give insight into how neurotransmitters are being affected in children with autism.
Below is a detailed diagram of understanding the trickle down effect of low BH4.
Variants in MTHFR A1298C or C677T 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.
MTHFR, Oral Contraceptives and Telomeres
One study in 259 post-menopausal women found that for those with certain genotypes in CYP1B1 (rs1056836), KRAS (rs61764370) and MTHFR (rs1801133 and rs1801131), oral contraceptives and hormone replacement therapy was associated with shorter leukocyte telomere length. Shorter leukocyte telomeres are connected to premature aging, and may increase the risk of cancer, cardiovascular disease, obesity, diabetes, chronic pain, and sensitivity to perceived psychological stress.
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