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MTHFD1 and Pregnancy: What Your Genotype Means for Folate, Choline, and Fetal Health

Pregnancy requires precise coordination of DNA synthesis, cell division, and gene regulation to support fetal growth. Key nutrients that support these processes include folate and choline. The MTHFD1 gene produces an enzyme that plays a central role in folate metabolism. Certain genetic variants in MTHFD1 can reduce enzyme stability and change how your body uses folate and choline during pregnancy. Understanding your genotype can help you and your healthcare provider plan nutrition and testing before and during pregnancy.

How MTHFD1 affects folate and choline pathways

The MTHFD1 enzyme helps move one-carbon units through the folate cycle, which is essential for making DNA building blocks and supporting methylation reactions that regulate genes. When enzyme function is reduced, the body may rely more on alternative methyl donors such as choline to maintain these processes. In pregnancy this matters because reduced folate pathway efficiency early in development has been linked to higher risk for some birth defects, including certain congenital heart defects. Regardless of genotype, good nutritional status before conception and during pregnancy supports healthy outcomes.

Practical nutrition and lifestyle recommendations for pregnancy planning

  • Prioritize folate-rich foods: leafy greens, legumes, asparagus, and liver. Dietary folate helps support DNA synthesis and cell growth.
  • Include choline-rich foods: eggs, liver, fish, and soybeans are top sources. Choline supports methylation and brain development.
  • Use a prenatal supplement with methylfolate: consider methylfolate rather than folic acid if recommended by your provider, especially if you carry variants that reduce folate pathway efficiency.
  • Ensure B vitamin support: adequate vitamin B12 and B6 support folate metabolism and homocysteine balance.
  • Aim for recommended folate intake: pregnant people commonly aim for at least 600 mcg dietary folate equivalents daily; your provider can tailor guidance.
  • Avoid alcohol when planning pregnancy and during pregnancy because alcohol interferes with nutrient metabolism and fetal development.
  • Start optimization before conception: nutrient stores and one-carbon metabolism are most important in very early pregnancy when organ systems form.
  • Work with your healthcare provider to tailor supplementation, especially if you have dietary restrictions, prior pregnancy complications, or known genetic changes.

Suggested clinical tests to discuss with your healthcare provider

  • Serum folate and red blood cell folate to assess folate status
  • Vitamin B12 level to ensure adequate cofactor support
  • Plasma homocysteine as a functional marker of one-carbon metabolism
  • Standard prenatal screening and any genetics counseling as indicated based on family history or prior outcomes
AA genotype for rs2236225 — two effect alleles

You carry two copies of the effect allele associated with decreased MTHFD1 enzyme stability. This change can reduce folate pathway efficiency, which may increase dependence on choline as an alternative methyl donor during pregnancy. Studies have linked this genotype with an increased risk for some congenital heart defects in offspring, likely related to reduced folate pathway activity during early fetal development.

Recommendations

  • Maximize intake of folate-rich foods: leafy greens, legumes, and liver.
  • Prioritize choline-rich foods daily: eggs, liver, fish, and soybeans.
  • Consider a prenatal supplement containing methylfolate rather than folic acid, along with adequate B12 and B6.
  • Ensure choline is part of prenatal planning; discuss choline dosage with your provider because prenatal formulations vary.
  • Avoid alcohol and begin nutrient optimization before conception for best outcomes.
  • Discuss monitoring (RBC folate, B12, homocysteine) with your healthcare provider to guide supplementation.
AG genotype for rs2236225 — one effect allele

You carry one copy of the effect allele, which may reduce MTHFD1 enzyme stability to a lesser degree. This can modestly increase reliance on choline during pregnancy. Some studies suggest this genotype may be associated with increased risk for certain congenital heart defects, though the effect is typically smaller than with two effect alleles.

Recommendations

  • Focus on balanced folate intake from foods like leafy greens, legumes, and liver.
  • Include choline-rich foods regularly, such as eggs and fish.
  • Consider a prenatal vitamin with methylfolate, along with B12 and B6 support; discuss options with your provider.
  • Avoid alcohol and begin optimizing nutrient intake before conception.
  • Consider checking folate status and related labs if recommended by your provider.
GG genotype for rs2236225 — zero effect alleles

You carry two copies of the non-effect allele and are expected to have typical MTHFD1 enzyme function. Your folate pathway should maintain normal stability and efficiency, supporting DNA synthesis, methylation, and fetal development. You do not carry the A allele linked to reduced enzyme stability or increased congenital heart disease risk.

Recommendations

  • Continue to meet standard folate recommendations, aiming for at least 600 mcg dietary folate equivalents per day during pregnancy as advised by your provider.
  • Include choline-rich foods such as eggs and liver to support overall methylation and fetal brain development.
  • Use a prenatal supplement that includes folate and B vitamins; choose methylfolate if your provider recommends it.
  • Avoid alcohol and optimize nutrient status before conception to support early fetal development.

Supplement considerations

  • Methylfolate vs folic acid: Methylfolate is the bioactive form of folate used directly by the body. If you have variants that affect folate metabolism, your provider may recommend methylfolate. Do not self-prescribe high dose methylfolate without medical guidance.
  • Choline supplements: Some prenatal vitamins include choline, but many do not. Discuss supplemental choline with your provider to reach recommended intake if dietary sources are insufficient.
  • B12 and B6: These B vitamins support folate-mediated reactions and are commonly included in prenatal formulations.

Lifestyle and timing

  • Begin nutrient optimization before conception. The folate and methylation needs of early pregnancy occur before many people know they are pregnant.
  • Limit exposures that interfere with nutrient metabolism. Avoid alcohol and discuss medication effects on folate metabolism with your provider.
  • Maintain a balanced, varied diet and follow prenatal care recommendations for testing and supplementation.

Final notes and important disclaimer

This information is educational and describes how MTHFD1 variation can influence folate and choline needs during pregnancy. PlexusDx does not provide medical advice. Always consult your healthcare provider or a qualified clinician before starting or changing supplements, interpreting genetic results in the context of personal health, or making pregnancy-related decisions. Your provider can help interpret these results alongside clinical history, lab testing, and prenatal screening to create a personalized plan.