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MTR (rs1805087) and Your Methylation Health: What Your Genotype Means

The MTR gene encodes methionine synthase, a key enzyme that converts homocysteine back into methionine. This reaction is central to the methylation cycle and requires two active nutrients: 5-methyltetrahydrofolate (5-MTHF) as the methyl donor and methylcobalamin (active vitamin B12) as the cofactor. MTR works closely with other genes such as MTHFR and MTRR that regulate folate and B12 metabolism. Variations in MTR can change how efficiently homocysteine is recycled, which can influence methylation balance, DNA integrity, detoxification, and neurotransmitter production.

Why this matters for health

  • Proper MTR activity helps keep homocysteine in a healthy range. Elevated homocysteine is linked to cardiovascular risk and other health concerns.
  • Methylation supports DNA repair, gene regulation, neurotransmitter synthesis, and detoxification pathways.
  • Different rs1805087 genotypes can alter how quickly vitamin B12 is used, potentially increasing nutrient needs or sensitivity to deficiencies.
  • Genetics is only part of the picture. Diet, lifestyle, medications, and other genes influence outcomes.

Quick practical approach

  • Know your rs1805087 genotype and consider baseline blood tests for B12, methylmalonic acid (MMA), serum folate, red blood cell folate, and homocysteine.
  • Support methylation with nutrient-rich foods and, when appropriate, targeted supplementation of active forms: methylcobalamin (B12) and 5-MTHF.
  • Work with your healthcare provider to interpret results, adjust medications, and personalize dosing.
Two effect alleles (GG) — Increased MTR activity

What it means

  • Carrying GG at rs1805087 is associated with greater MTR enzyme activity.
  • This increased activity can use up methylcobalamin faster than usual, potentially placing higher demand on active B12 and 5-MTHF.
  • When nutrient supply is limited, faster B12 turnover can strain the Folate Cycle and Methylation Pathway, which may affect DNA repair, detoxification, and neurotransmitter balance.

Practical recommendations

  • Consider baseline testing: serum B12, methylmalonic acid (MMA), homocysteine, serum folate or RBC folate.
  • Support with active B12: methylcobalamin supplements or sublingual/ injectable forms if clinically indicated.
  • Support with active folate: 5-MTHF rather than folic acid to ensure efficient methyl donation.
  • Include B12-rich foods: fatty fish, shellfish, organ meats, eggs, dairy or fortified foods for those who avoid animal products.
  • Monitor symptoms: fatigue, cognitive fog, numbness or mood changes may indicate B12 insufficiency and warrant testing.
  • Discuss with your provider before starting high-dose supplements, especially if you take medications like metformin or proton pump inhibitors that affect B12 absorption.
One effect allele (AG) — Intermediate MTR activity

What it means

  • Having AG is associated with a modest increase in MTR activity compared with the AA genotype.
  • This may lead to somewhat higher B12 turnover and increased sensitivity to low B12 or low folate status.
  • Many people with AG maintain normal function if diet and lifestyle supply adequate active B12 and folate.

Practical recommendations

  • Assess status with lab tests when possible: serum B12, MMA, homocysteine, serum folate or RBC folate.
  • Ensure dietary intake of methylcobalamin and folate-rich foods or consider low-dose supplementation of methylcobalamin and 5-MTHF if intake is limited.
  • Include balanced protein and leafy greens: legumes, spinach, kale, Brussels sprouts, and fortified whole grains.
  • Lifestyle supports: reduce excessive alcohol, aim for regular meal timing, manage stress and get adequate sleep to support methylation demands.
No effect alleles (AA) — Typical MTR activity

What it means

  • AA at rs1805087 is generally associated with normal MTR enzyme activity and standard B12 usage.
  • With good dietary intake and overall health, methylation balance and homocysteine recycling are likely well supported.

Practical recommendations

  • Maintain a nutrient-rich diet with sources of B12 and folate to support ongoing methylation needs.
  • Routine screening is still useful if you have symptoms, a family history of methylation-related issues, or are taking medications that affect B12 or folate.
  • Continue healthy lifestyle practices: balanced diet, regular physical activity, sleep, and stress management.

Diet and nutrition strategies

  • Prioritize foods with natural B12: fish, shellfish, beef liver, dairy, eggs, or B12-fortified plant foods for vegans.
  • Eat folate-rich foods: dark leafy greens, asparagus, Brussels sprouts, lentils, chickpeas, and avocado. Prefer whole-food sources alongside 5-MTHF if supplemental support is needed.
  • Include choline-containing foods: eggs, soy, and cruciferous vegetables to support one-carbon metabolism and liver methylation demands.
  • Limit alcohol and highly processed foods that can interfere with nutrient absorption and methylation balance.

Targeted supplement considerations

  • Methylcobalamin (active B12): often preferred for direct support of methionine synthase activity. Dosing should be individualized.
  • 5-MTHF (active folate): supports remethylation without relying on metabolic conversion of folic acid.
  • Supportive cofactors: adequate levels of B6, riboflavin (B2), and magnesium support related pathways.
  • Avoid high doses of unmetabolized folic acid when active folate is recommended.
  • Always coordinate supplement use with your healthcare provider, especially if pregnant, breastfeeding, or taking medications.

Lifestyle and follow-up testing

  • Check labs: serum B12, methylmalonic acid, homocysteine, and folate (serum or RBC) to guide supplementation and monitor response.
  • Address medication interactions: metformin, proton pump inhibitors, and some anticonvulsants can decrease B12 or folate status.
  • Stay active, manage stress, and prioritize sleep to support cellular repair and methylation processes.
  • Consider genetic context: MTR works with MTHFR and MTRR. If you have other variants, your nutrient needs and strategy may differ.

Important note and disclaimer

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice. Always consult your healthcare provider or a qualified clinician before making changes to medications, supplements, or treatment plans. Your provider can interpret genetic results together with your medical history, current labs, and other factors to create a personalized plan.