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MTHFR and Male Fertility: What Your Genotype Means and How to Support Sperm Health

Infertility affects many men and often results from multiple factors. One contributor is variation in the MTHFR gene. MTHFR helps process folate and supports DNA methylation and repair—critical steps for healthy sperm development. Certain MTHFR variants reduce enzyme function, which can increase sperm DNA damage and raise infertility risk, especially when paired with poor nutrition or oxidative stress.

How MTHFR Affects Sperm

  • MTHFR converts folate into forms the body can use for DNA methylation and repair. This is important during spermatogenesis when DNA must be accurately copied and protected.
  • Reduced MTHFR activity can impair DNA methylation, leading to higher rates of sperm DNA fragmentation and abnormal morphology.
  • Environmental factors such as smoking, excessive alcohol, poor diet, and toxin exposure increase oxidative stress and can worsen the effects of reduced MTHFR function.

Practical Steps to Support Fertility

Regardless of genotype, many lifestyle and nutritional steps can support reproductive health. Consider the following:

  • Use a B-complex supplement that provides methylfolate (not folic acid) and methylcobalamin. These active forms bypass common processing steps and support methylation directly.
  • If supplementing, target methylfolate around 400–800 mcg and methylcobalamin 250–1000 mcg unless your healthcare provider advises otherwise.
  • Eat folate-rich foods: leafy greens, legumes, asparagus, avocado, and fortified foods that use methylfolate where available.
  • Include riboflavin (vitamin B2) sources such as eggs, almonds, lean meats, and dairy, which help support one-carbon metabolism.
  • Prioritize antioxidants: vitamin C, vitamin E, selenium, zinc, and dietary sources like berries, nuts, and colorful vegetables help reduce oxidative damage to sperm.
  • Exercise moderately. Regular physical activity supports hormonal balance and circulation but avoid excessive endurance training that may increase oxidative stress.
  • Avoid smoking, limit alcohol, and minimize exposure to environmental toxins like pesticides, heavy metals, and endocrine-disrupting chemicals found in some plastics and personal care products.
  • Discuss monitoring homocysteine levels with your healthcare provider. Elevated homocysteine can indicate impaired folate metabolism and may be correctable with targeted B vitamins.
  • Consider timing: sperm development takes about 72 days. Nutritional and lifestyle changes should be maintained for several months to support new sperm formation.

Genetic Interpretations

Two effect alleles (AA genotype) — Reduced MTHFR function

If your genotype is AA at rs1801133, you carry two copies of the effect allele. This is associated with approximately 70 to 80 percent reduced MTHFR enzyme function and about a 60 percent increased risk of male infertility related to impaired folate metabolism.

What this can mean for you

  • Impaired conversion of folate into methylated forms used for DNA repair and methylation during sperm production.
  • Higher likelihood of sperm DNA damage and abnormal morphology, particularly if oxidative stress or nutrient deficiencies are present.

Actionable recommendations

  • Start a B-complex supplement that includes methylfolate (not folic acid) and methylcobalamin. Consider methylfolate doses in the 400 to 800 mcg range and methylcobalamin 250 to 1000 mcg, after discussing with your provider.
  • Eat folate-rich foods daily: leafy greens, legumes, asparagus, and avocado.
  • Include riboflavin-rich foods such as eggs, almonds, and dairy to support enzyme cofactors.
  • Use antioxidants via diet and supplements as appropriate to reduce oxidative stress.
  • Avoid smoking, limit alcohol, and reduce exposure to environmental toxins.
  • Consider measuring homocysteine levels; elevated values may indicate need for targeted B vitamin support.
  • Work with your healthcare provider or a fertility specialist to personalize testing and supplementation plans.
One effect allele (AG genotype) — Moderately reduced MTHFR function

If your genotype is AG at rs1801133, you carry one copy of the effect allele. This variant is associated with approximately 40 percent reduced MTHFR enzyme function and a likely increased risk of male infertility related to folate metabolism.

What this can mean for you

  • Some reduction in the efficiency of folate processing and DNA methylation during sperm development.
  • Increased sensitivity to oxidative stress and nutrient gaps, which can raise sperm DNA damage risk.

Actionable recommendations

  • Consider a B-complex with methylfolate (400 to 800 mcg) and methylcobalamin (250 to 1000 mcg). Avoid supplements that contain only folic acid.
  • Emphasize folate-rich foods like leafy greens, legumes, and avocado.
  • Add riboflavin-containing foods and antioxidant-rich fruits and vegetables.
  • Adopt lifestyle habits that lower oxidative stress: stop smoking, moderate or avoid alcohol, get adequate sleep, and reduce toxic exposures.
  • Discuss homocysteine testing and follow-up with your healthcare provider if levels are elevated.
No effect alleles (GG genotype) — Typical MTHFR function

If your genotype is GG at rs1801133, you carry two copies of the non-effect allele. This is associated with normal MTHFR enzyme function, supporting typical folate metabolism and DNA methylation processes important for sperm health.

What this can mean for you

  • Your genetic result suggests standard enzyme activity for DNA repair during sperm production and no increased infertility risk from this variant alone.

Actionable recommendations

  • Maintain a balanced diet with folate-rich foods such as leafy greens, legumes, and avocado.
  • Consider a B-complex that includes methylfolate and methylcobalamin to support overall reproductive health, even if your genotype is typical.
  • Continue antioxidant-rich foods, moderate exercise, and avoidance of smoking and excessive alcohol.
  • Minimize exposure to environmental toxins and discuss routine fertility screening with your healthcare provider if you have additional risk factors or concerns.

Testing and Follow-up

If you have fertility concerns, consider discussing the following with your healthcare provider:

  • Comprehensive fertility evaluation including semen analysis and sperm DNA fragmentation testing when appropriate.
  • Blood tests for folate, vitamin B12, homocysteine, and other relevant nutrients.
  • Review of medications and environmental exposures that may affect fertility.
  • Personalized supplement and dietary plan based on lab results and overall health.

Important Notice

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice. Always consult your healthcare provider before starting supplements, changing diet, or making health decisions based on genetic results. Your provider can interpret your genotype in the context of your full medical history, lab tests, and personal needs.