HSA | FSA CARDS ARE NOW ACCEPTED

Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

Choline, Folate and MTHFD1: How These Genes and Nutrients Work Together

Choline is an essential nutrient that supports methylation by feeding the betaine pathway. In the liver and kidney, choline is converted to betaine, which donates a methyl group to remethylate homocysteine through the betaine-homocysteine methyltransferase pathway. This route works independently of folate and vitamin B12 and serves as an important backup to preserve methionine and S-adenosylmethionine or SAMe. By helping keep homocysteine low and maintaining SAMe availability, the choline to betaine pathway supports DNA methylation, neurotransmitter production, and lipid metabolism. It adapts to changes in homocysteine and methionine load and can spare folate and B12 when those nutrients are limited.

The MTHFD1 gene encodes a multifunctional enzyme in the folate cycle that creates and moves one-carbon units needed for DNA synthesis, SAMe production, and repair. A common variant in MTHFD1, rs2236225, affects enzyme efficiency and therefore how much the body relies on folate versus choline-derived methylation. The sections below explain how each genotype affects methylation balance and practical approaches for diet, supplements, lifestyle, and monitoring.

Quick overview of practical goals

  • Support adequate folate status and active folate forms when indicated
  • Include choline-rich foods to supply the betaine backup pathway
  • Ensure supporting B-vitamins: B2 (riboflavin), B6, and B12
  • Monitor homocysteine when clinically appropriate and follow your healthcare provider's advice

Genetic interpretation for rs2236225 (MTHFD1)

Two effect alleles (AA) — higher reliance on choline/betaine

If your genotype is AA you carry two copies of the effect allele. This version of MTHFD1 is linked with lower enzyme efficiency, which means your cells may produce fewer usable folate-derived one-carbon units. As a result your body may rely more on the choline-to-betaine (BHMT) pathway to keep homocysteine and SAMe levels stable.

Potential implications

  • Increased chance of elevated homocysteine under stress, low folate or B12 intake, or during pregnancy
  • Greater need for folate-related nutrients to support DNA synthesis and methylation
  • Higher benefit from dietary choline to support the BHMT backup pathway

Diet recommendations

  • Prioritize choline-rich foods: eggs (yolks), liver, soy products, cruciferous vegetables, legumes, and quinoa
  • Eat folate-rich foods: dark leafy greens, asparagus, Brussels sprouts, beans, lentils, and fortified whole grains
  • Include complete protein sources to support B-vitamin status

Supplement and nutrient strategy

  • Discuss a targeted supplement with your clinician that may include methylfolate plus riboflavin (B2) and vitamin B12
  • Consider a choline supplement if dietary intake is low, especially during pregnancy or lactation after clinician approval
  • Ensure adequate B6 and general B-complex support when recommended

Lifestyle and monitoring

  • Have homocysteine tested if there is clinical concern, especially during pregnancy, when taking medications that affect folate, or with cardiovascular risk
  • Maintain a balanced diet, avoid excessive alcohol which can disrupt folate and choline metabolism, and manage stress
  • Work with a healthcare provider for personalized dosing and monitoring
One effect allele (AG) — moderate reduction in MTHFD1 efficiency

If your genotype is AG you carry one copy of the effect allele. This is associated with a moderate decrease in MTHFD1 activity. Your folate cycle may run a bit less efficiently, which can slightly limit the supply of folate-derived one-carbon units used for remethylating homocysteine and making SAMe.

Potential implications

  • Mild strain on the folate arm of methylation, which can increase need for folate and cofactors
  • Small benefit from additional choline intake as a complementary methyl source

Diet recommendations

  • Include leafy greens, legumes, liver (if acceptable), citrus, and fortified grains for consistent folate intake
  • Add choline-containing foods: eggs, soy, cruciferous vegetables, and nuts
  • Balance meals with protein and healthy fats to support nutrient absorption

Supplement and nutrient strategy

  • Consider ensuring adequate active folate and B12 through diet or clinician-guided supplements
  • Riboflavin (B2) can support folate metabolism and may be helpful in combination with folate

Lifestyle and monitoring

  • Routine attention to diet typically suffices; test homocysteine if symptoms or clinical risk factors appear
  • Avoid chronic alcohol overuse and manage conditions that impair nutrient absorption
No effect alleles (GG) — typical MTHFD1 function

If your genotype is GG you carry two copies of the non effect allele and MTHFD1 activity is expected to be normal. Folate and choline metabolism and the supply of one-carbon units should function efficiently, supporting balanced homocysteine remethylation and SAMe production.

Potential implications

  • Lower genetic risk for folate-related bottlenecks in methylation
  • Still dependent on adequate dietary intake of folate, choline, and B-vitamins

Diet recommendations

  • Maintain a varied diet with leafy greens, beans, eggs, soy, and liver as appropriate
  • Consider a multivitamin if dietary intake is limited or during times of increased need

Supplement and nutrient strategy

  • Supplementation is usually not necessary unless dietary intake or clinical context indicates it
  • Ensure B2, B6, and B12 are adequate for overall methylation support

Lifestyle and monitoring

  • Regular healthy eating, moderate alcohol use, and addressing malabsorption conditions will help preserve methylation balance

When to talk with your healthcare provider

  • If you are pregnant, planning pregnancy, breastfeeding, or experiencing rapid growth periods speak with your clinician about folate, choline, and B12 needs
  • If you have a history of elevated homocysteine, cardiovascular disease, cognitive changes, or symptoms suggesting nutrient deficiency ask about testing and personalized recommendations
  • Before starting any supplements, particularly methylfolate, high dose choline, or B12, consult your healthcare provider to ensure safety and correct dosing

Important disclaimer

This information is educational and relates to genetic predispositions only. PlexusDx does not provide medical advice. Always consult your healthcare provider before making changes to your diet, supplements, or medical care. Genetic results are one piece of your health picture and should be considered alongside clinical factors, personal health history, and professional guidance.

If this genetic variant is present in your PlexusDx results, the following tests and reports are commonly used to explore it further:

🧬 Genetic Tests:

🧪 Blood Tests:

📄 Genetic Report:

Frequently Asked Questions About Cofactors and Choline MTHFD1 rs2236225

How does the MTHFD1 rs2236225 variant affect methylation?

The MTHFD1 rs2236225 variant influences how efficiently your folate cycle produces and moves one-carbon units needed for DNA synthesis and SAMe production. If you carry the effect allele (AG or AA), your cells may generate fewer usable folate-derived one-carbon units, which can shift your methylation balance toward the choline-to-betaine “backup” pathway that helps keep homocysteine and SAMe stable.

What diet supports methylation if I have MTHFD1 rs2236225 AA, AG, or GG?

For AA, prioritize choline-rich foods (eggs/yolk, liver, soy, cruciferous vegetables, legumes, quinoa) plus folate-rich foods (dark leafy greens, asparagus, Brussels sprouts, beans, lentils, fortified grains). For AG, focus on steady folate intake with leafy greens, legumes, and fortified grains, and add complementary choline foods like eggs, soy, cruciferous vegetables, and nuts. For GG, maintain a varied diet with folate and choline sources (leafy greens, beans, eggs, soy, liver if appropriate), since methylation is expected to function efficiently.

When should I test homocysteine or talk to my healthcare provider about supplements?

Consider discussing homocysteine testing with your clinician if there is clinical concern—especially during pregnancy, breastfeeding, rapid growth, cardiovascular risk, a history of elevated homocysteine, cardiovascular disease, cognitive changes, or suspected nutrient deficiency/malabsorption. Before starting methylfolate, high-dose choline, or B12, consult your healthcare provider to ensure safety and correct dosing, since genetic results are only one part of your overall health picture.

What tests can help me learn more about Cofactors and Choline MTHFD1 rs2236225?

The Genetic Methylation Test delivers over 300 genetic insights related to methylation, detoxification, and nutrient processing. The Methylation Pathway Genetic Report translates your results into personalized, actionable guidance. Your healthcare provider can also recommend targeted blood tests based on your specific pathway results and health history to complement your genetic insights with current biomarker data.

Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.