HSA | FSA CARDS ARE NOW ACCEPTED

NOS3 and Male Fertility: What Your Genotype Can Mean for Sperm Health

Infertility affects many men and can involve genetics, environment, and lifestyle. One gene that matters for male reproductive health is NOS3. This gene helps produce nitric oxide, a small molecule that supports blood flow to the testes and protects sperm from oxidative damage. Variations in NOS3 can change nitric oxide production and may influence sperm quality, motility, and overall fertility risk.

How NOS3 Works and Why Nitric Oxide Matters

Nitric oxide helps relax blood vessels and improve circulation. In the testes, healthy blood flow is important for temperature regulation, nutrient delivery, and removal of waste products. Nitric oxide also helps protect sperm from oxidative stress, a form of cellular damage that reduces motility and can harm DNA integrity.

When NOS3 activity is reduced, nitric oxide levels can fall. Lower nitric oxide may lead to poorer testicular blood flow, higher oxidative stress on sperm, and decreases in sperm quality and motility. Knowing your NOS3 genotype can help you choose targeted lifestyle strategies to support nitric oxide production and protect sperm.

Practical Steps to Support Nitric Oxide and Sperm Health

  • Eat nitrate-rich vegetables: Beetroot, arugula, spinach, and other leafy greens contain dietary nitrates that the body can convert to nitric oxide. Include them regularly in meals.
  • Prioritize antioxidants: Vitamin C, CoQ10, and zinc help neutralize oxidative stress and protect sperm. Consider food sources first: citrus fruits and berries for vitamin C, oily fish and organ meats for CoQ10, and oysters, red meat, legumes, or fortified foods for zinc.
  • Consider targeted supplements: L-citrulline (commonly 1 to 2 grams daily) supports nitric oxide production. CoQ10 is often used in fertility support; typical supplement ranges are 100 to 300 mg daily. Zinc dosed according to product labels and provider guidance can help if levels are low. Always consult your healthcare provider before starting supplements.
  • Include omega-3 fats: Fatty fish, walnuts, and flaxseeds supply omega-3s that support sperm membrane health. Aim for regular servings of fatty fish or consider a fish oil supplement if dietary intake is low.
  • Exercise moderately: Regular moderate exercise can improve circulation and metabolic health. Avoid extreme endurance training without medical advice, as overtraining can negatively affect hormones.
  • Avoid smoking and reduce toxin exposure: Smoking and environmental toxins increase oxidative stress and reduce sperm quality. Minimize exposure to nicotine, recreational drugs, and industrial chemicals when possible.
  • Manage weight and blood pressure: Excess weight and high blood pressure are linked to poorer fertility. Healthy body weight and controlled blood pressure support testicular blood flow and hormonal balance.
  • Optimize sleep and stress: Good sleep and stress management support hormone regulation and recovery. Aim for consistent sleep patterns and use stress-reduction tools such as mindfulness, counseling, or relaxation exercises.

Testing and Monitoring

  • Semen analysis: A baseline semen analysis provides essential information about sperm count, motility, and morphology. If you have concerns about fertility, this test is often a first step.
  • Oxidative stress and nutrient labs: In some cases, specialist labs can measure markers of oxidative stress or assess levels of nutrients such as vitamin D, zinc, and CoQ10. Discuss with your healthcare provider whether these tests are appropriate.
  • Blood pressure and metabolic screening: Because circulation and metabolic health affect fertility, routine checks of blood pressure, glucose, and lipid panels can be useful.

Genetic Interpretations for NOS3 Variant rs2070744

2 effect alleles — CC genotype

The CC genotype means you carry two copies of the effect allele and this is associated with reduced NOS3 activity and lower nitric oxide production. This can translate to decreased testicular blood flow and higher oxidative stress on sperm, increasing the risk of poorer sperm motility and quality.

Recommended considerations

  • Increase nitrate-rich foods such as beetroot, arugula, and spinach daily to support nitric oxide production.
  • Prioritize antioxidants: consider vitamin C from food or supplements, CoQ10 supplementation in the 100 to 300 mg range, and zinc if intake or levels are low.
  • L-citrulline 1 to 2 grams daily may help boost nitric oxide pathways.
  • Include omega-3 rich foods or supplements and maintain moderate exercise, healthy weight, and blood pressure.
  • Avoid smoking, reduce exposure to environmental toxins, and practice good sleep hygiene and stress management.
  • Consider semen analysis and discuss nutrient or oxidative stress testing with your healthcare provider.
1 effect allele — CT genotype

The CT genotype means you carry one copy of the effect allele and one copy of the non-effect allele. This is associated with intermediate nitric oxide production and a moderately increased infertility risk compared to the TT genotype. You may experience some reduction in testicular blood flow and increased oxidative stress, which can affect sperm quality and motility.

Recommended considerations

  • Emphasize nitrate-rich vegetables like beetroot, arugula, and spinach several times per week.
  • Support antioxidant intake with vitamin C, CoQ10, and zinc when dietary sources are limited.
  • L-citrulline supplementation (1 to 2 grams daily) can be considered to support nitric oxide production.
  • Include omega-3 fats, maintain regular moderate exercise, avoid smoking and toxins, and manage weight, blood pressure, sleep, and stress.
  • Consider a semen analysis and speak with your healthcare provider about whether nutrient testing or targeted supplements are appropriate.
0 effect alleles — TT genotype

The TT genotype means you carry two copies of the non-effect allele and typically have normal NOS3 activity and nitric oxide production related to this variant. This genotype is associated with a typical fertility risk for this genetic site.

Recommended considerations

  • Maintain a fertility-supporting lifestyle: nitrate-rich foods, antioxidants such as vitamin C and CoQ10, and omega-3 fats.
  • Keep active with moderate exercise, avoid smoking and environmental toxins, and manage weight, blood pressure, sleep, and stress.
  • Consider routine fertility evaluation such as semen analysis if you have difficulty conceiving or other concerns.

Next Steps and When to Seek Help

If you are concerned about fertility or notice changes in semen parameters, begin with a semen analysis and a conversation with your healthcare provider or a reproductive specialist. They can interpret your results, recommend appropriate testing, and advise on supplements or treatments tailored to your situation. Genetic information can guide lifestyle and nutritional choices but is only one part of fertility care.

Important disclaimer: PlexusDx does not provide medical advice. This information is educational and describes genetic predispositions and lifestyle strategies that may influence reproductive health. Always consult your healthcare provider before beginning new supplements, making major lifestyle changes, or interpreting genetic results in the context of clinical care.