Folate Cycle | MTHFR (rs1801133)

What this means

• Two copies of the effect allele reduce MTHFR enzyme activity by about 70 to 80 percent.
• This level of reduction can impair conversion of folate to 5-MTHF, limiting methyl group availability for the methionine cycle and methylation reactions.
• Possible consequences include higher homocysteine, lower SAMe, and increased risk factors for cardiovascular disease, certain neurological and mood conditions, reproductive concerns such as neural tube defect risk, and altered detoxification capacity.

What to consider

• Check fasting homocysteine and folate status (serum or RBC folate), B12 (serum and methylmalonic acid if needed), and consider riboflavin status if available.
• Prefer folate as 5-MTHF rather than folic acid supplements when supplementation is indicated.
• Ensure adequate cofactors: riboflavin (B2), pyridoxine (B6), cobalamin (B12), and choline to support alternate methylation pathways and remethylation of homocysteine.
• Address lifestyle factors: limit alcohol, stop smoking, and maintain a balanced diet rich in leafy greens, legumes, and other natural folate sources.

Supplement and diet suggestions

• Consider a supplement containing 5-MTHF at a clinician-guided dose rather than folic acid.
• Include methylation cofactors: B2 (riboflavin), B6 (pyridoxal-5-phosphate preferred), and active B12 (methylcobalamin or hydroxocobalamin as advised).
• Support with choline-rich foods: eggs, soy, cruciferous vegetables, and liver when appropriate.
• Maintain adequate dietary protein for methionine intake and support SAMe production.

Lifestyle and monitoring

• Monitor homocysteine and relevant B vitamin levels after initiating dietary or supplement changes to confirm effective correction.
• Discuss pregnancy planning with your clinician; higher folate requirements may apply for neural tube defect prevention.

What this means

• One copy of the effect allele reduces MTHFR activity by about 40 percent on average.
• Many people with this genotype maintain normal methylation if dietary folate and B12 are adequate; however, a modest increase in homocysteine can occur, especially with low nutrient intake.

What to consider

• Evaluate diet and consider baseline blood tests: homocysteine, folate, B12, and possibly riboflavin and B6 if symptoms suggest deficiency.
• Emphasize natural dietary folates from leafy greens, legumes, and whole foods; consider a low-dose 5-MTHF supplement if levels are borderline or if planning pregnancy.
• Include B2, B6, B12, and choline as part of a supportive nutritional plan.

Supplement and diet suggestions

• Moderate supplementation with 5-MTHF can be useful; dosing guided by a healthcare professional based on labs and clinical context.
• Multivitamin or B-complex that provides riboflavin, B6, and bioavailable B12 is often sufficient for many people.
• Dietary pattern: Mediterranean-style or whole-food focused diets rich in vegetables, legumes, nuts, seeds, and lean protein support methylation and cardiovascular health.

Lifestyle and monitoring

• Routine monitoring may be reasonable if symptoms, pregnancy planning, or other risk factors exist.
• Address modifiable risk factors such as smoking, excess alcohol, poor sleep, and chronic stress which can worsen methylation imbalances.

What this means

• No copies of the effect allele indicate typical MTHFR enzyme activity.
• With sufficient dietary folate and cofactors, methylation function is usually maintained effectively.

What to consider

• Standard healthy nutrition and lifestyle are typically adequate. Focus on balanced folate intake, B12 sufficiency, and overall cardiovascular and neurologic health practices.
• Testing for homocysteine or B vitamin levels is usually not required unless symptoms or clinical concerns arise.

Supplement and diet suggestions

• If using a general multivitamin, standard folate forms are acceptable, but some prefer 5-MTHF for broad support.
• Maintain a diet rich in natural folates: leafy greens, legumes, asparagus, beets, and citrus fruits.

Lifestyle and monitoring

• Prioritize cardiovascular health through regular exercise, healthy weight maintenance, avoidance of tobacco, limited alcohol, and stress management.
• Reassess if new health issues, pregnancy planning, or medications that affect folate metabolism appear.