How MTHFR and Vitamin B12 Affect Your Health
Vitamin B12 is essential for DNA synthesis, red blood cell production, nerve health, and energy metabolism. It is found naturally in animal products such as meat, fish, eggs, and dairy. Fortified cereals and nutritional yeast are important sources for vegetarians and vegans. The MTHFR gene makes an enzyme that supports methylation, a chemical process your body uses to activate folate and help use Vitamin B12. Variations in MTHFR can reduce enzyme efficiency, which may lead to higher homocysteine levels and less effective Vitamin B12 function.
Why methylation matters
- Methylation helps convert folate to its active form, L-methylfolate, which works together with Vitamin B12 in key biochemical reactions.
- When methylation is inefficient, homocysteine can rise. Elevated homocysteine is associated with cardiovascular and other health concerns.
- Even with adequate dietary B12, impaired methylation may reduce how well your body uses B12, sometimes resulting in lower functional B12 status.
Practical dietary, supplement, and lifestyle strategies
Whether or not you carry an MTHFR variation, these strategies support methylation, B12 status, and overall health.
Diet
- Prioritize natural folate from leafy greens, asparagus, Brussels sprouts, and legumes.
- Include adequate Vitamin B12 sources: fish, shellfish, poultry, eggs, dairy, or fortified foods for plant-based diets.
- Eat choline-rich foods such as eggs, lean meat, soy, and cruciferous vegetables to support one-carbon metabolism.
- Include methionine sources like fish, poultry, and legumes to support methylation.
- Limit highly processed foods, excessive alcohol, and smoking, which can impair nutrient status and methylation.
Supplements to consider
- L-methylfolate (active folate) instead of folic acid for better support when MTHFR function is reduced.
- Methylcobalamin or hydroxocobalamin forms of Vitamin B12, which are better for methylation than cyanocobalamin for some individuals.
- Consider a B-complex with active forms of B6, B9, and B12 to support methylation and homocysteine conversion.
- Supportive nutrients: magnesium and riboflavin can support methylation enzymes and energy metabolism.
- Have labs checked before starting high-dose supplements and discuss dosing with your healthcare provider.
Lifestyle habits
- Regular physical activity supports healthy metabolism and homocysteine regulation.
- Manage stress through sleep, mindfulness, or relaxation techniques, because chronic stress affects nutrient use and methylation.
- Stay hydrated to support cellular processes.
- Avoid unnecessary exposure to environmental toxins when possible, as detox pathways depend on methylation.
- Discuss routine blood tests for B12, folate, and homocysteine with your healthcare provider to monitor status.
Genetic interpretations for rs1801133 (MTHFR C677T)
2 effect alleles (AA genotype)
You carry two copies of the effect allele. This genotype is associated with a substantial reduction in MTHFR enzyme efficiency, potentially by 70 to 80 percent. Reduced enzyme activity can limit conversion of folate into its active form and impair methylation. As a result, you may have a harder time converting homocysteine into methionine, which can lead to elevated homocysteine levels. Impaired methylation can also reduce how effectively your body uses Vitamin B12, even if you get enough from food.
What may help
- Consider L-methylfolate rather than folic acid to provide the active folate form your body needs.
- Use methylcobalamin or hydroxocobalamin for B12 supplementation if recommended by your clinician.
- Include regular servings of folate-rich vegetables, choline and methionine-containing foods, and B12 sources or fortified foods.
- Ask your healthcare provider about testing serum B12, methylmalonic acid, folate, and homocysteine to track function.
- Discuss appropriate supplement doses with your provider before starting, especially if you are pregnant or taking medications.
1 effect allele (AG genotype)
You carry one copy of the effect allele. This genotype is associated with about a 40 percent reduction in MTHFR enzyme efficiency compared to those without the variant. Reduced enzyme activity can lower the conversion of folate to its active form and make methylation less efficient. This can make it somewhat more difficult to convert homocysteine into methionine and to use Vitamin B12 effectively.
What may help
- Focus on dietary folate from leafy greens and legumes and include reliable B12 sources or fortified foods if you are plant based.
- Consider supplementation with active forms such as L-methylfolate and methylcobalamin if testing shows low functional B12 or elevated homocysteine.
- Support overall methylation with a balanced diet, adequate protein for methionine, and nutrients like riboflavin and magnesium.
- Monitor levels with your healthcare provider to see if intervention is needed.
0 effect alleles (GG genotype)
You carry two copies of the non-effect allele. This is the most common genotype and is associated with standard MTHFR enzyme function. Your body should convert folate into its active form efficiently and support normal methylation. With typical MTHFR function, you are not at increased genetic risk for elevated homocysteine or impaired B12 use related to this variant.
What may help
- Maintain a balanced diet with folate-rich vegetables and adequate B12 from animal sources or fortified foods if you follow a plant-based diet.
- Use routine wellness practices such as exercise, stress management, and hydration to support metabolic health.
- Discuss routine blood work for B12 and folate with your healthcare provider as part of preventive care, especially if you have symptoms suggestive of deficiency.
Important notes and next steps
This information is educational and explains how an MTHFR variant can relate to Vitamin B12 function and methylation. PlexusDx does not provide medical advice. Always discuss genetic results, laboratory testing, and any supplement or medication changes with your healthcare provider before making decisions. Your provider can help interpret these results in the context of your medical history, current medications, and individual needs.

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Vitamin B12 | MTRR (rs1801394)
Vitamin B12 | MTRR (rs1801394)