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How MTRR and Vitamin B12 Affect Your Health

Vitamin B12 is essential for nerve health, brain function, red blood cell formation, DNA synthesis, and energy production. The MTRR gene makes an enzyme called methionine synthase reductase that helps recycle and reactivate Vitamin B12 so it can participate in converting homocysteine into methionine. Variations in MTRR can influence how well this recycling works and may affect homocysteine levels, which are linked to cardiovascular health and methylation-dependent processes in the body.

Why this matters

  • Efficient B12 recycling supports the methylation cycle, which is important for DNA repair, neurotransmitter synthesis, and detoxification.
  • Higher homocysteine levels have been associated with increased cardiovascular risk; better MTRR function tends to help keep homocysteine lower.
  • Diet, age, medications, and gastrointestinal health also influence B12 status—genetics is one part of the picture.

What you can do

  • Prioritize dietary sources of B12: meat, fish, eggs, and dairy. Fortified cereals and plant milks provide B12 for people on vegetarian or vegan diets.
  • Consider supplementation if you are older, have absorption issues, follow a plant-based diet, take medications that reduce B12 absorption, or have clinical signs of low B12.
  • Supportive nutrients: adequate folate and vitamin B6 help the methylation cycle work properly.
  • Monitor blood tests when appropriate: B12, methylmalonic acid (MMA), homocysteine, and a complete blood count (CBC) can clarify status and guide treatment.
  • Discuss genotype-informed strategies with your healthcare provider before starting or changing supplements.

Genetic Interpretation: MTRR rs1805087

2 effect alleles — GG

You carry two copies of the effect allele for rs1805087 (GG). This genotype is associated with enhanced MTRR-related B12 recycling and typically lower homocysteine levels, which is generally favorable for cardiovascular health and methylation processes.

  • Implication: Your MTRR enzyme function likely supports efficient reactivation of Vitamin B12, helping convert homocysteine to methionine effectively.
  • Practical steps: Continue consuming B12-rich foods regularly. Maintain balanced intake of folate and vitamin B6 to support methylation.
  • When to check labs: Routine screening is not usually necessary solely for this genotype, but check B12, MMA, and homocysteine if you have symptoms of deficiency, follow a restrictive diet, are over age 60, or take absorption-impacting medications.
  • Supplement guidance: You may not require extra B12 based on this genotype alone, but supplement if you have risk factors for deficiency. Form options include oral cyanocobalamin or methylcobalamin, sublingual preparations, or intramuscular injections when clinically indicated.
1 effect allele — AG

You carry one copy of the effect allele for rs1805087 (AG). This genotype is associated with a possible tendency toward better B12 recycling and potentially lower homocysteine compared with the non-effect genotype. The effect is modest and interacts with diet and health factors.

  • Implication: Your MTRR enzyme likely functions well, though not as strongly as two effect alleles might suggest. Homocysteine control is probably typical to slightly improved.
  • Practical steps: Ensure steady dietary B12 from animal sources or fortified foods. Keep folate and B6 in your diet for methylation support.
  • When to check labs: Consider testing B12, MMA, and homocysteine if you have symptoms of deficiency, follow a plant-based diet, take medications like metformin or proton pump inhibitors, or are older.
  • Supplement guidance: Consider a low-dose oral B12 supplement when diet may be insufficient. If laboratory tests show deficiency or functional markers are abnormal, your provider may recommend higher-dose oral B12 or injections.
0 effect alleles — AA

You carry two copies of the non-effect allele for rs1805087 (AA). This genotype is associated with typical MTRR enzyme function and standard homocysteine metabolism. It suggests normal capacity for reactivating Vitamin B12 under usual conditions.

  • Implication: Your MTRR enzyme is expected to work within the common range for B12 recycling and homocysteine control.
  • Practical steps: Maintain adequate dietary B12 intake. If you follow a vegetarian or vegan diet, choose fortified foods or supplements to prevent deficiency.
  • When to check labs: Test if you have symptoms of deficiency, are older, have gastrointestinal conditions that impair absorption, or take medications that affect B12 absorption.
  • Supplement guidance: Supplementation is recommended when diet is inadequate or when clinical tests indicate deficiency. Forms include oral cyanocobalamin or methylcobalamin; clinicians sometimes use injections for significant deficiencies or malabsorption.

Diet, Supplements, and Lifestyle Recommendations

Use genetics as one piece of personalized health information. These general strategies support healthy B12 status and optimal methylation regardless of genotype.

  • Dietary sources: Include lean meats, poultry, fish, eggs, and dairy. Choose fortified plant-based milks, cereals, and nutritional yeast if you follow a vegetarian or vegan diet.
  • Supplements: Standard oral doses range from 25 to 100 mcg daily for maintenance; higher doses (500 to 2,000 mcg daily) are used in deficiency or impaired absorption. Methylcobalamin is a bioactive form; cyanocobalamin is stable and widely used. Sublingual and liquid forms may help if absorption is a concern. Intramuscular injections are reserved for significant deficiency or malabsorption and should be directed by a clinician.
  • Supportive nutrients: Adequate folate and vitamin B6 support the methylation cycle. Folate from leafy greens, legumes, and fortified foods is important; consider a folate supplement if intake is low or as directed by a provider.
  • Lifestyle: Reduce excessive alcohol use and stop smoking, as both can impair nutrient status. Maintain a balanced diet, manage chronic conditions, and address gastrointestinal issues that can affect absorption.
  • Medications and conditions: Discuss with your clinician if you take medications such as metformin or proton pump inhibitors, or if you have conditions like atrophic gastritis, celiac disease, or gastric surgery that can reduce B12 absorption.

Recommended Tests to Monitor

  • Serum Vitamin B12: Common screening test but can be normal despite deficiency in some cases.
  • Methylmalonic acid (MMA): A more sensitive marker of functional B12 deficiency.
  • Homocysteine: Elevated levels can indicate impaired methylation and B12 or folate insufficiency.
  • Complete blood count (CBC): Checks for anemia that may accompany B12 deficiency.

Important Disclaimer

PlexusDx provides educational information about genetic predispositions and health. This content is not medical advice. Always consult your healthcare provider before making changes to your diet, starting supplements, adjusting medications, or interpreting laboratory tests. Your healthcare provider can combine genetic information with clinical evaluation, lab results, and personal health history to create a plan tailored to you.