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Understanding DHFR and Folate: What Your Genes Mean for Folate Processing

Folate, also known as vitamin B9, is essential for DNA and RNA production, red blood cell formation, and breaking down homocysteine. These functions support overall health, growth, and a healthy pregnancy. The DHFR gene makes an enzyme called dihydrofolate reductase that converts synthetic folic acid into the active folate forms your body can use. Variations in DHFR can change how efficiently this conversion happens. This article explains how different genotypes at rs1650697 can affect folate status, and offers practical, safe recommendations for diet, supplements, lifestyle, and monitoring.

Why DHFR Matters

When you eat foods containing natural folate or consume fortified foods and supplements with folic acid, the body needs to convert those forms into active folate (such as tetrahydrofolate and L-methylfolate) to support cellular processes. Reduced DHFR activity can mean lower active folate availability and a greater chance of unmetabolized folic acid appearing in the bloodstream. That may impact red blood cell production, DNA synthesis, and homocysteine metabolism.

Practical Takeaways

  • Focus on whole foods rich in natural folate.
  • Consider active folate supplements if you have reduced DHFR activity, after discussing with your healthcare provider.
  • Limit high intake of synthetic folic acid from supplements unless advised by a clinician.
  • Monitor related health markers with your healthcare provider when needed.

Genetic Interpretation (rs1650697)

Two effect alleles (AA) — decreased DHFR expression

If you have the AA genotype, you carry two copies of the effect allele. This genotype is associated with decreased DHFR expression and reduced ability to convert synthetic folic acid into active folate. Potential implications include lower levels of active folate and accumulation of unmetabolized folic acid when exposed to high amounts of folic acid from supplements or fortified foods.

Diet Recommendations

  • Prioritize natural folate sources: dark leafy greens (spinach, kale), legumes (lentils, chickpeas), asparagus, broccoli, avocado, and citrus fruits.
  • Favor whole foods over fortified processed foods when possible.
  • Pair folate-rich foods with vitamin C sources to enhance absorption.

Supplement Recommendations

  • Discuss switching from high-dose folic acid supplements to an active form such as L-methylfolate with your healthcare provider.
  • A low-dose B-complex containing active folate may be appropriate if clinically indicated.
  • Avoid unnecessary high-dose folic acid unless prescribed, because conversion may be impaired.

Lifestyle and Monitoring

  • Maintain regular exercise and manage stress to support overall nutrient metabolism.
  • Limit alcohol intake, which can interfere with folate absorption and status.
  • Consider blood tests: serum folate, red blood cell folate, and homocysteine levels if recommended by your clinician.
One effect allele (AG) — moderately decreased DHFR expression

If you have the AG genotype, you carry one copy of the effect allele. This is associated with moderately decreased DHFR expression. Your capacity to convert synthetic folic acid to active folate may be reduced but typically not as much as with two effect alleles.

Diet Recommendations

  • Emphasize folate-rich whole foods: leafy greens, beans, peas, nuts, seeds, citrus fruits, and fortified whole grains in moderation.
  • Include a variety of B vitamin foods such as lean proteins, eggs, and dairy to support overall B vitamin status.

Supplement Recommendations

  • Consider discussing lower-dose active folate (L-methylfolate) with your healthcare provider if you take folic acid supplements or have increased needs, such as pregnancy planning.
  • If taking a multivitamin, check the form of folate and consider switching to a product that contains methylfolate if recommended.

Lifestyle and Monitoring

  • Reduce alcohol intake and maintain a balanced diet to support folate status.
  • Consider periodic blood testing for folate and homocysteine based on clinical context and provider advice.
No effect alleles (GG) — typical DHFR function

If you have the GG genotype, you carry two copies of the non-effect allele. This genotype is associated with typical DHFR enzyme function. You are expected to convert synthetic folic acid from fortified foods and supplements into active folate efficiently. Standard dietary and supplement guidance for folate generally applies.

Diet Recommendations

  • Continue eating a balanced diet with folate-rich foods: leafy greens, legumes, citrus, and whole grains.
  • If pregnant or planning pregnancy, follow standard prenatal folate guidance from your healthcare provider.

Supplement Recommendations

  • Standard folic acid-containing multivitamins and prenatal supplements are generally effective for individuals with typical DHFR function.
  • Talk to your healthcare provider about any special needs or dosing for pregnancy or medical conditions.

Lifestyle and Monitoring

  • Maintain a healthy lifestyle with regular exercise, stress management, and moderate alcohol consumption.
  • Routine monitoring of folate levels is not usually required unless clinically indicated.

When to Talk to Your Healthcare Provider

  • If you are pregnant, planning pregnancy, or of childbearing potential, discuss your folate needs and the best supplement form for you.
  • If you take high-dose folic acid supplements or multiple fortified products, ask whether switching to active folate might be beneficial.
  • If you have symptoms of low folate such as fatigue, pale skin, or if lab tests show low folate or elevated homocysteine, seek medical evaluation.
  • If you have complex medical conditions or take medications that affect folate metabolism, consult your provider before making supplement changes.

Recommended Blood Tests for Monitoring

  • Serum folate to assess short-term folate intake.
  • Red blood cell folate for longer-term folate status.
  • Plasma homocysteine as an indirect marker of functional folate and B vitamin status.
  • Complete blood count if there are symptoms of anemia.

Simple Daily Practices to Support Folate Health

  • Include a serving of leafy greens or legumes most days of the week.
  • Choose whole fruit for vitamin C with meals to help folate absorption.
  • Limit alcohol and avoid smoking, both of which can interfere with folate metabolism.
  • Manage stress with sleep, physical activity, and relaxation techniques to support overall nutrient handling.

PlexusDx provides educational information about genetic predispositions and how they may influence health. This content is for informational purposes only and is not medical advice. Always discuss genetic results, supplements, and changes to your diet or medical care with your healthcare provider before making decisions.