MTHFR (Methylene-Tetra-Hydro-Folate-Reductase)

Methylation helps convert homocysteine into methionine, and methionine produces glutathione . . . our body’s most potent detoxifier. So proper methylation helps our body get rid of any harmful chemicals we have been exposed to (from food, cosmetics, environmental toxins, etc.).

Genetic variations in the MTHFR gene (677 and 1298) impair the body’s ability to methylate well, which can hinder the above processes and lead to elevated homocysteine levels. Certain medications (like metformin) can also interfere with our ability to effectively methylate. As we age it also becomes more difficult to methylate, so MTHFR abnormalities can have worsening effects as we get older.

Homocysteine is an amino acid that plays an important role in metabolism, but high levels of homocysteine can create a pro-thrombotic environment (higher risk of clotting) and can increase oxidative stress. Oxidative stress occurs when damaging free radicals in the body outnumber the amount of protective antioxidants (which accelerates aging and the development of disease).

High homocysteine levels are correlated with an increased risk of cardiovascular disease, especially stroke. (REF 1-4) In fact, high homocysteine levels have been shown to be as strong of an independent risk factor for cardiovascular disease as smoking, high cholesterol, and high blood pressure. Each increase of 5 umol/L in homocysteine increases the risk of a cardiovascular event by about 20%. On the other hand, lowering homocysteine in patients with known cardiovascular disease or hypertension (typically through a combination of well-absorbed B vitamins) has been shown to significantly reduce the risk of stroke. (REF 5, 6)

In addition to increasing the risk of cardiovascular disease, MTHFR gene abnormalities have also been implicated in contributing to various cancers, many psychiatric disorders (ADHD, anxiety, depression, bipolar, etc.), and even some congenital abnormalities (like autism, cleft palate, and down’s syndrome).

MTHFR abnormalities can also cause problems with the blood vessels, hindering the production of nitric oxide (which helps open the arteries and increase blood flow), and leading to higher levels of adrenalin (which causes a narrowing of the arteries and diminished blood flow). This combination can lead to high blood pressure and increase a patient’s risk of a heart attack or stroke . . . in addition to other health issues such as erectile dysfunction and migraines.

Women of childbearing age need folate to help prevent neural tube and other birth defects. Regular folic acid will not suffice in patients with this gene mutation because they must be able to break down the folic acid in order to absorb it . . . so it is vital these women know their MTHFR status.

We all need active folate and B vitamins in order for our brain to produce neurotransmitters (serotonin, dopamine, and norepinephrine) that help with mood, memory, and general cognitive function. Anyone who struggles with mental health or attention issues should be tested because a simple vitamin may aid in recovery.

*Deplin, a prescription form of active folate, has an FDA approved indication to help treat depression.

MTHFR disorders are often treated with L-methylfolate (the broken down and active form of folic acid), and sometimes also with methylated B6 or B12.

Most people tolerate the treatment well, but occasionally patients may feel dizzy or get a headache when they first start taking the supplements. If this happens, the patient can simply take a smaller dose until his or her body adjusts.

Though everyone responds differently to L-methylfolate, many people notice improvement in how they feel once they have been taking it a couple of months. Some individuals (particularly those with a 1298 variant) may take longer to respond, and may benefit from loading their system with a larger dose for the first three months (then later backing down the dose). Once the methylation pathway is optimized, patients often note they experience more energy, better sleep, improvements in mood, and improvements in memory and concentration.  These supplements can also improve symptoms of neuropathy (nerve pain).

Insurance companies do not often cover the cost of L-methyl folate because it is classified as a “medical food,” but a generic form is available. Currently the best price for the 15mg dose is at Walmart with the WellRx discount code. You can download the WellRx app for free on your phone or simply go to their website to print a coupon. Using this coupon at Walmart brings the cash price down to around $67 for 90 pills. Be careful about cheaper non-prescription substitutes online - they must be L5, 6S, Levomefolic Acid, or Metafolin. The 6R and D forms of folate are not biologically active forms, so they will not be effective.

You can access more information on MTHFR HERE.