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MTHFD1

Do Genes Increase Your Choline and Folate Needs (MTHFD1)?

Written by Aleksa Ristic, MS (Pharmacy) on March 10th, 2020

The MTHFD1 gene is crucial for methylation and folate metabolism. In this post, we explore the link between MTHFD1 variants and dietary folate and choline requirements — gene-based diet tips included!

What is MTHFD1?

The MTHFD1 (Methylenetetrahydrofolate dehydrogenase 1) gene codes for an enzyme that metabolizes tetrahydrofolate (THF). It enables the production of nucleotides and homocysteine methylation [R].

Vitamin B9 or folic acid needs to be “activated” to L-methylfolate to achieve its health effects. Enzymes that play vital roles in this process include MTHFD and MTHFR.

Folate, Choline & Methylation

Folate and choline partake in a complex cycle of methylation reactions, known as the one-carbon metabolism. They both supply methyl groups for the production of methionine from homocysteine. MTHFD1, along with MTHFR, participates in this cycle by creating methyl-THF [R].

Hence, folate and choline dietary status and requirements are closely linked, and they both depend on MTHFD1 activity.

The Link Between MTHFD1 Variants and Dietary Choline & Folate

A study of 54 participants studied the impact of MTHFD1 gene variations on choline dietary requirements. When placed on a low-choline diet, people with the “A” allele at rs2236225 were seven times more likely to develop the signs of choline deficiency, such as fatty liver [R].

The effect was particularly strong in young women, who are otherwise protected from choline deficiency by increased PEMT-mediated production. The “A” allele carriers also deficient in folate were 35 times more susceptible to choline deficiency, and folic acid supplements were able to prevent organ damage [R].

That said, a small number of patients likely exaggerated the impact of this variant.

Given the crucial roles of choline and folate in fetal development, it’s no wonder that MTHFD1 variants correlate with different congenital disabilities, such as [R, R, R, R]:

Neural tube defects
Down’s syndrome
Cleft lip and palate
Congenital heart disease

In another trial of 43 young women, rs2236225 worsened the effects of folate deficiency. Women with the “AA” genotype saw a higher increase in homocysteine levels during a low-folate diet. This variant had no impact during folate treatment (400 and 800μg daily) [R].

Elevated homocysteine (hyperhomocysteinemia) is a potential marker of heart disease, Alzheimer’s, and other chronic conditions [R, R, R, R, R].

Both studies focused on the effects of MTHFD1 on women, so they may want to pay special attention to this variant. This is especially true during pregnancy when choline and folate demands are higher, and deficiencies can be detrimental [R, R].

One MTHFD1 variant, rs2236225-A, is associated with the negative impact of choline and folate deficiencies. Adequate intake of these nutrients can prevent any adverse effects.

How It Works

Among other crucial roles in your body, methylation is responsible for converting homocysteine to methionine via two different pathways: one using folate and vitamin B12, and another using choline and betaine (see the image above) [R].

The presence of the “A” allele at rs2236225 changes one amino acid in the MTHFD1 enzyme, making it less stable and more temperature-sensitive. Adequate levels of magnesium and folate may lessen this effect [R].

Reduced MTHFD1 activity means less methyl-THF, which forces the body to use more choline for homocysteine methylation. When the intake of choline and folate is low, this effect may become significant and contribute to the signs of deficiency [R].

The body has another option for removing homocysteine by converting it to cysteine (see image). This pathway depends on vitamin B6.

Your MTHFD1 Results for Choline and Folate Deficiencies

SNP Table

variant	genotype	frequency	risk allele
rs2236225

SNP Summary and Table

Primary SNP:

MTHFD1 rs2236225:

“G” = not associated with the signs of choline and folate deficiencies
“A” = associated with the signs of choline and folate deficiencies

Population Frequency

Around 66% of Europan, 37% of East Asian, and 30% of African descendants carry at least one copy of the “A” allele.

Recommendations

Diet

Choline

Pay special attention to dietary choline intake. As long as you get enough from food, lower MTHFD1 activity won’t have that much of an impact. In most cases of choline deficiency, reintroducing choline into a diet reversed the signs of organ damage [R].

The Institute of Medicine recommends the following intakes [R]:

Adult men: 550 mg/day
Adult females: 425 mg/day
Pregnant women: 450 mg/day
Nursing women: 550 mg/day

One paper suggested that people may need up to 930 mg/day of choline to remove the impact of MTHFD1 variants. However, excess dietary choline may increase TMAO, a metabolite associated with heart disease. Until more research is done, you may want to stick with the recommended intakes [R, R].

The best food sources of choline include [R, R]:

Beef liver: 356 mg per serving (3 oz)
Eggs: 147 mg per serving (1 large egg)
Chicken breast: 72 mg per serving (3 oz)
Codfish: 71 mg per serving (3 oz)

For example, two ounces of beef liver and two eggs would meet your daily requirements. According to a large survey, people who don’t eat eggs or take supplements are much less likely to get enough choline [R].

Plant foods are much lower in this nutrient. If you are vegan and have the MTHFD1 variant, consider supplementing with choline. Good plant-based food sources are [R, R]:

Shiitake mushrooms: 58 mg per serving (½ cup)
Quinoa: 42.5 mg per serving (1 cup)
Broccoli: 31.3 mg per serving (½ cup)
Peanuts: 18.3 mg per serving (1 oz)

If you have the problematic MTHFD1 variant, make sure to get enough choline from food. The best sources include eggs, beef liver, codfish, chicken, shiitake mushrooms, and quinoa.

Folate

Folate deficiency in people with the MTHFD1 variant contributed to both fatty liver (due to low choline) and homocysteine elevation. To counteract these effects, make sure to get enough folate daily.

The recommended daily folate intake is 400 mcg for adults and 600 mcg for pregnant women. The best food sources include [R, R, R, R]:

Chicken liver: 491 mcg per serving (3 oz)
Beef liver: 215 mcg per serving (3 oz)
Spinach, boiled: 131 mcg per serving (½ cup)
Asparagus, cooked: 89 mcg per serving (4 spears)
Brussels sprouts, boiled: 78 mcg per serving (½ cup)
Romaine lettuce: 64 mcg per serving (1 cup)
Avocado: 59 mcg per serving (½ cup)

Lifestyle

Excess alcohol consumption depletes vitamin B6 and increases the risk of choline deficiency. Limit or avoid drinking alcohol, especially if you carry the “A” allele at rs2236225 [R].

Supplements

Keep in mind that the FDA hasn’t approved some of the below supplements for the prevention or treatment of medical conditions. Consult with your doctor before supplementing.

Choline

If you can’t meet your daily requirements with food, consider taking a choline supplement such as:

They all supply choline, but each one has unique health perks you may prefer. Check out our posts on different choline-containing supplements to find out which one suits you best.

Folate

Folate supplements may help by providing more of this vitamin and enhancing homocysteine methylation, especially in pregnant women and those planning to conceive. Most supplements contain the recommended daily amount of 400 mcg [R, R].

People with specific MTHFR variants can’t produce enough methylfolate, which is the active form. They should supplement with L-methylfolate [R].

Other

Other supplements that may help by supporting MTHFD1 activity and homocysteine methylation include:

Aleksa Ristic

MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More nutrition blogs

The Role of Genes in Choline Deficiency (PEMT) A Surprising Player in Obesity and Diabetes (PEMT) A Heat-Generating Gene Linked to Weight Gain (UCP1) Can Our Genes Make Us Fat? (FTO) Can This Gene Affect Vitamin B12 Levels? (FUT2) The Role Of Amino Acids In Diet, Obesity, & Diabetes (PPM1K) How A Fat Metabolism Gene Affects Nutrition and Cognition (FADS2) The Link Between Diabetes and High-Carb Foods (TCF7L2) How An Insulin Gene Influences Diet and Blood Sugar (GIPR) Can This Fat Metabolism Gene Influence Nutrition and Cholesterol? (FADS1)

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What is MTHFD1? The Link Between MTHFD1 Variants and Dietary Choline & Folate Your MTHFD1 Results for Choline and Folate Deficiencies

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Do Genes Increase Your Choline and Folate Needs (MTHFD1)?

What is MTHFD1?

Folate, Choline & Methylation

The Link Between MTHFD1 Variants and Dietary Choline & Folate

How It Works

Your MTHFD1 Results for Choline and Folate Deficiencies

SNP Table

SNP Summary and Table

Population Frequency

Recommendations

Diet

Choline

Folate

Lifestyle

Supplements

Choline

Folate

Other

Disclaimer

More nutrition blogs

Content

Unlock Personalized Results And So Much More!

DNA & Summer Wellness 30% OFF

Essential Bundle

Essential

Bundle

DNA & Summer Wellness 35% OFF

DNA & Summer Wellness 45% OFF

Ultimate Bundle

Policies

About

Navigation

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