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.

How MTRR and Vitamin B12 Genetics Affect Your Health

Vitamin B12 is an essential nutrient for nerve health, red blood cell formation, and DNA synthesis. Because the body cannot make B12, you must get it from animal foods, fortified products, or supplements. The MTRR gene encodes an enzyme that helps reactivate Vitamin B12 so it can support a key biochemical step that converts homocysteine into methionine. Variations in MTRR can reduce this enzyme's efficiency, which may slow methylation processes, raise homocysteine levels, and make it harder for your body to use B12 effectively even when dietary intake appears adequate.

Why this matters

  • Proper MTRR function helps keep homocysteine at healthy levels and supports methylation, a process important for DNA maintenance, nervous system function, and protein production.
  • Reduced MTRR activity may increase the risk of elevated homocysteine, which can be associated with cardiovascular and neurologic concerns when persistent.
  • Knowing your MTRR genotype can guide nutrition, supplement and lifestyle choices to support B12 use and overall methylation health.

Genetic Interpretation

Two effect alleles — GG (rs1801394)

If your genotype is GG you carry two copies of the effect allele. This is associated with decreased MTRR enzyme activity. The enzyme that regenerates active Vitamin B12 may work less efficiently, which can slow the conversion of homocysteine to methionine. As a result, homocysteine levels could be higher and your body may have more difficulty using B12 even when intake looks adequate.

Practical actions to support B12 and methylation:

  • Emphasize B12-rich foods: meat, fish, eggs and dairy. If you follow a plant-based diet, use reliably fortified foods or supplements.
  • Prefer active B12 forms such as methylcobalamin or hydroxocobalamin over cyanocobalamin when possible.
  • Support folate intake from leafy greens, legumes and fortified foods to help methylation reactions.
  • Consider monitoring fasting homocysteine and serum B12 or methylmalonic acid with your healthcare provider.
One effect allele — AG (rs1801394)

If your genotype is AG you carry one copy of the effect allele. This is associated with moderately decreased MTRR activity. The enzyme may be somewhat less efficient at reactivating B12, which can reduce the conversion of homocysteine to methionine and increase the chance of modestly elevated homocysteine.

Practical actions to support B12 and methylation:

  • Include regular sources of B12: meat, fish, eggs and dairy or fortified alternatives for vegetarian and vegan diets.
  • Consider supplemental methylcobalamin when dietary intake is low or if testing suggests suboptimal B12 status.
  • Eat folate-rich foods and maintain overall nutrient balance including adequate B6, riboflavin and choline to support methylation.
  • Limit excessive alcohol and smoking, which can impair B12 absorption and methylation.
No effect alleles — AA (rs1801394)

If your genotype is AA you carry two copies of the non-effect allele. This genotype is associated with typical MTRR enzyme activity. Your ability to regenerate active Vitamin B12 for the methylation cycle generally functions normally, supporting efficient conversion of homocysteine to methionine. You are not predisposed to decreased enzyme activity from this variant.

Practical actions to maintain status:

  • Maintain a balanced diet with regular sources of B12 from animal foods or fortified products if you limit animal foods.
  • Keep adequate folate intake and follow general healthy lifestyle habits to support methylation and cardiovascular health.
  • Periodic checks of B12 status may be useful if diet changes, digestive issues arise, or symptoms of deficiency appear.

Dietary Recommendations

  • Prioritize whole food sources of B12: beef, poultry, fish, shellfish, eggs and dairy.
  • If you follow a vegetarian or vegan diet, use fortified cereals, plant milks, nutritional yeast labeled with B12, or a supplement to meet needs.
  • Include natural folate sources such as spinach, kale, broccoli, lentils and beans to support methylation.
  • Ensure adequate dietary protein to supply methionine and other amino acids needed for methylation.

Supplement Suggestions

  • Methylcobalamin or hydroxocobalamin are active or easily converted forms of B12 and are often recommended when absorption or methylation is a concern.
  • Consider a B-complex supplement containing folate as 5-methyltetrahydrofolate or folic acid depending on provider guidance.
  • Do not start high dose supplements without consulting your healthcare provider. Discuss appropriate dosing based on blood tests and health history.

Lifestyle and Other Considerations

  • Regular exercise supports overall metabolic health and can indirectly support methylation balance.
  • Limit excessive alcohol consumption and avoid smoking to protect nutrient absorption and liver function.
  • Be aware of medications and gut conditions that can reduce B12 absorption, such as proton pump inhibitors, metformin, gastric surgery or autoimmune gastritis. Review these with your provider.
  • Routine blood tests can track status: serum B12, methylmalonic acid, and homocysteine give useful information when interpreted by a clinician.

When to Talk to Your Healthcare Provider

  • If you have symptoms of B12 deficiency such as numbness, tingling, fatigue, memory changes or unexplained anemia.
  • If you are pregnant, breastfeeding, have gastrointestinal conditions that affect absorption, or take medications that interfere with B12.
  • Before starting any supplements, to determine appropriate type and dose and to arrange relevant blood testing.

Important Disclaimer

PlexusDx provides genetic information for educational purposes only and does not provide medical advice. Use this report to help inform conversations with your healthcare provider. Always consult your healthcare provider before making changes to diet, supplements, medications, or lifestyle based on genetic results.

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 Vitamin B12 and MTRR rs1801394

What does the MTRR rs1801394 variant mean for my Vitamin B12 and homocysteine levels?

The MTRR gene helps reactivate Vitamin B12 so it can support methylation, including the conversion of homocysteine into methionine. Variations in rs1801394 can reduce MTRR enzyme efficiency, which may slow methylation processes and make it harder to use B12 effectively. Depending on whether you have two effect alleles (GG), one effect allele (AG), or no effect alleles (AA), your risk of modestly elevated homocysteine and B12 utilization challenges may differ.

How should I adjust my diet if my MTRR genotype shows decreased B12 reactivation (rs1801394 AG or GG)?

If your rs1801394 genotype is AG or GG, practical nutrition steps focus on ensuring reliable B12 intake and supporting methylation reactions. Emphasize B12-rich foods such as meat, fish, eggs, and dairy, or use fortified foods/supplements if you’re vegetarian or vegan. Where possible, choose active B12 forms like methylcobalamin or hydroxocobalamin rather than cyanocobalamin. Also prioritize folate-rich foods (leafy greens, legumes) to help support methylation pathways.

What tests can help confirm whether my MTRR rs1801394 genotype is affecting B12 status and methylation?

To assess whether genetics may be translating into measurable changes, clinicians often use blood tests such as serum Vitamin B12, methylmalonic acid (MMA), and homocysteine. If you carry the effect allele and want to understand your functional status, asking your healthcare provider about these markers can help guide whether diet or supplement choices (and what type/dose) are appropriate. If you have symptoms of B12 deficiency—such as numbness, tingling, fatigue, memory changes, or unexplained anemia—seek medical guidance and testing.

What tests can help me learn more about Vitamin B12 and MTRR rs1801394?

The Optimal Diet and Weight Loss Genetic Test delivers over 295 genetic insights related to nutrition response, body composition, metabolism, and fitness. The Diet and Nutrition 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.