The MTHFR gene is responsible for making MTHFR protein, which helps in digesting folate (Vitamin B9). Our body needs folate to make DNA & modify proteins. In young women, it's important to prevent birth defects called neural tube defects.
There are two main variants of MTHFR gene mutation:
677: C→T
1298: A→C
Depending on your results, the ability to process folate can be different. For example, someone with a C677T TT variants might have up to 16% less folate in their blood compared to a CC variant, when both are taking the same amount of supplements or eating similar diets.
This graphic from CDC below shows how MTHFR gene mutations of C677T variant transfer from parents to children and grandchildren in a family.
Source: MTHFR Gene, Folic Acid, and Preventing Neural Tube Defects.
MTHFR gene mutations affect our health in many ways:
C667T and A1298C mutations may lower blood folate concentration, requiring more than the normal daily suggested amount of 400 micrograms.
Hyperhomocysteinemia: High homocysteine levels due to certain MTHFR mutations. Homocysteine is a protein known to cause blood clots, stroke, and heart disease at high levels but Vitamins B6, B9, B12 can break it down.
Neural Tube Defects (NTDs): folic acid deficiency can prevent the neural tubes to close around spine and brain in early stage of pregnancy. MTHFR gene mutation in pregnancy should be carefully monitored.
Methotrexate toxicity: methotrexate is a drug used in rheumatoid arthritis, cancers, and autoimmune diseases and certain mutations might increase the risk of toxicity requiring dose adjustment.
Behavioral health: low folate levels from MTHFR mutations can increase the risk of depression, schizophrenia, bipolar disorder, and lower memory scores.
MTHFR stands for methylenetetrahydrofolate reductase. It is a protein (enzyme) made by the gene of same name, both involved in the processing of folate.
Folate is a general term for Vitamin B9 and folic acid is one of the several forms of folate available in enriched foods and supplements.
The words are used interchangeably but only supplemental form of folate is folic acid. It is more stable at high heat and strong light compared to naturally occurring folate.
Other forms of folate include:
DHF or dihydrofolate
THF or tetrahydrofolate
5-MTHF or 5-methylenetetrahydrofolate
5, 10-MTHF or 5, 10-methylenetetrahydrofolate
Folate is naturally available in green leafy vegetables (e.g., spinach, Brussels sprouts, broccoli, asparagus), beans, peanuts, citrus fruits (lime, lemon, orange), beef liver, and seafoods. We can get about 140 micrograms of folate everyday from such a natural diet in US. See a full list of natural foods with folate.
Best natural sources of folate:
Beef liver (3 oz): 250 mcg (micrograms)
Spinach (half-cup): 130 mcg
Black-eyed peas (half-cup): 105 mcg
Asparagus (4 stalks): 90 mcg
Brussels sprouts (half-cup): 80 mcg
** A daily recommendation for folate is 400 mcg. Those expecting a baby may need 600 mcg or more.
That's why many foods are enriched with folate (mainly with folic acid) to meet the higher daily requirement of about 400 micrograms. These fortified foods include bread, pasta, rice, cereals, corn flour (e.g., in tortilla and tamales).
The supplements may often go up to 1000 micrograms. It may take several weeks or months to reach optimal blood folate levels with supplementation.
The following supplements might benefit those with low folate enzyme activity:
L-5-MTHF or L-5-FTHF (400 microgram to 15 mg) - this active form helps when certain MTHFR gene mutations lower the enzyme activity.
Methylcobalamin (B12) - 500 microgram recommended sublingual to help regenerate the active folate due to the necessary methyl group.
Active B Complex - 10-25 mg Pyridoxal-5'-phosphate (B6), 2.1 mg Riboflavin-5'-phosphate (B2) for other necessary cofactors to support folate generation.
Betaine/Trimethylglycine (TMG) - your doctor might recommend TMG whenever homocysteine levels are high.
N-Acetyl Cysteine (NAC) - helpful in reducing oxidation and release of homocysteine from the receptors; another possible option depending on health condition.
There are some very rare MTHFR gene mutations not discussed here. A doctor may recommend more tests if your symptoms don't match with a regular test.
Smoking: increases homocysteine levels.
Alcohol: lowers folate levels and increases homocysteine levels, which are known to cause blood clots, thrombosis, and stroke.
Folate rich diet: to get daily dose of at least 400 microgram (600 microgram for pregnancy women); dark green leafy vegetables, liver, beans, and enriched grains can help.
5-MTHF: 5-methyltetrahydrofolate supplement can make up for folate deficiency, as it's the metabolically active form of folate. However, folic acid is the only form known to help those at risk of neural tube defects.
Folinic Acid: L-5-formyltetrahydrofolate is the reduced form recommended for those going through therapies involving methotrexate or DHFR (dihydrofolate).
Cobalamin (B12): daily doses over 500 microgram may help break down homocysteine to methionine.
Pyridoxine (B6): 25 mg daily dose may help lower homocysteine levels by breaking down into cystathione.
Riboflavin (B2): doses over 2 mg daily in people with low MTHFR enzyme activity can be helpful.
The MTHFR gene produces an enzyme that helps in processing folate (B9 or folic acid) and regulating homocysteine levels in the body.
Folate is a critical nutrient involved in methylation, DNA synthesis and amino acid metabolism.
Those planning to get pregnant might benefit from knowing their MTHFR gene mutations. And a simple cheek swab can help you plan for a healthy pregnancy after learning about your MTHFR genetic mutations.
Order an MTHFR genetic test kit.
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