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How DIO1 Affects Thyroid Health and Why It Matters

The thyroid gland makes hormones that control energy, metabolism, and reproductive health. One important step in the thyroid hormone pathway is converting the inactive hormone thyroxine (T4) into the active hormone triiodothyronine (T3). The DIO1 gene encodes an enzyme that helps with this conversion. Variations in DIO1 can change how efficiently your body makes T3, which may influence energy, weight, mood, and menstrual regularity even when routine thyroid tests look normal.

What this means in everyday life

  • Reduced conversion of T4 to T3 can lead to lower free T3 and higher reverse T3 (rT3), a metabolically inactive form. That pattern can mimic hypothyroid symptoms.
  • Symptoms to watch for include fatigue, cold intolerance, weight changes, brain fog, low mood, and menstrual irregularities.
  • Standard tests that only measure TSH or total T4 can miss conversion problems. More complete testing may be useful if symptoms persist.

Genetic Interpretation

Two effect alleles — TT (rs11206244)

If you have the TT genotype, you carry two copies of the effect allele linked with reduced DIO1 activity. This commonly results in lower free T3 and higher reverse T3, even when T4 and TSH are within reference ranges. Clinically this can present as fatigue, slowed metabolism, weight shifts, brain fog, and menstrual irregularities.

Consider the following actions:

  • Ask your healthcare provider about expanded thyroid testing including free T3 and reverse T3 in addition to TSH and free T4.
  • Support conversion through diet and nutrients that assist thyroid enzyme activity, especially selenium, iodine, zinc, iron, and vitamin A.
  • Limit excessive intake of raw cruciferous vegetables and concentrated soy if you notice worsened symptoms, and discuss individualized dietary changes with a clinician or dietitian.
  • Prioritize sleep, stress reduction, regular physical activity, and minimizing exposure to environmental toxins like cigarette smoke and certain industrial chemicals.
One effect allele — CT (rs11206244)

If you have the CT genotype, you carry one copy of the effect allele. This is associated with a partial reduction in DIO1 activity and a tendency toward higher rT3 and lower free T3. You may experience milder or intermittent hypothyroid-like symptoms such as fatigue, mental sluggishness, weight changes, or menstrual changes.

Consider the following actions:

  • Monitor symptoms and consider periodic testing of free T3, free T4, and reverse T3 if symptoms are present or changing.
  • Include selenium-rich foods like Brazil nuts and seafood several times per week, and ensure adequate intake of iodine, zinc, iron, and vitamin A through food or under provider guidance.
  • Adopt lifestyle habits that support hormonal balance: consistent sleep, regular moderate exercise, balanced blood sugar, and stress management techniques.
  • Work with your healthcare provider before starting any supplements or making major changes if you have thyroid disease or take thyroid medication.
No effect alleles — CC (rs11206244)

If you have the CC genotype, you carry the common non-effect version of this variant. This is associated with typical DIO1 enzyme function and efficient conversion of T4 to T3. Your genetic risk for elevated rT3 or reduced free T3 due to this variant is low.

Consider the following actions to maintain thyroid health:

  • Continue a balanced diet with adequate selenium and iodine, and maintain overall nutrient sufficiency for zinc, iron, and vitamin A.
  • Keep healthy habits: regular sleep, stress reduction, and routine exercise to support metabolic and reproductive health.
  • Periodic thyroid screening as part of routine care is reasonable, and discuss testing beyond TSH only if symptoms arise.

Diet and Supplement Recommendations

Focus on whole foods that supply nutrients needed for thyroid hormone production and conversion. If you consider supplements, discuss them with your healthcare provider before starting.

  • Selenium: Found in Brazil nuts, seafood, and organ meats. 1 to 2 Brazil nuts per day can supply a practical dose for many people; avoid excessive intake.
  • Iodine: Seafood, iodized salt, and seaweed provide iodine, which is essential for thyroid hormone synthesis. Too much iodine can cause problems, so aim for recommended levels suited to your health status.
  • Zinc and Iron: Meat, shellfish, legumes, and fortified cereals support thyroid function. Iron deficiency can impair thyroid hormone action, especially in menstruating women.
  • Vitamin A: Found in liver, dairy, eggs, and colorful vegetables. Adequate vitamin A supports hormone signaling pathways.
  • Soy and Cruciferous Vegetables: Cooked cruciferous vegetables and moderate soy intake are usually fine for most people. If you have conversion symptoms, reducing raw cruciferous vegetable intake or very high soy consumption may help. Evaluate changes with your clinician.

Lifestyle and Testing Recommendations

  • Testing: If you have symptoms, ask your healthcare provider about testing free T3, free T4, reverse T3, TSH, and thyroid antibodies. These tests together give a clearer picture of hormone production and conversion.
  • Sleep: Aim for consistent, sufficient sleep as sleep deprivation can disrupt hormone balance.
  • Stress management: Chronic stress raises cortisol which can impair conversion of T4 to T3. Techniques like mindfulness, breathwork, and moderate exercise are helpful.
  • Exercise: Regular moderate exercise supports metabolism and hormonal health. Avoid excessive endurance training if you are fatigued, as intense chronic exercise can increase rT3.
  • Environmental exposures: Reduce contact with cigarette smoke and limit exposure to certain industrial chemicals and endocrine-disrupting compounds where possible.

When to Talk to Your Healthcare Provider

See your provider if you have persistent symptoms such as fatigue, unexplained weight changes, cold intolerance, brain fog, or menstrual irregularities. Bring your genetic result and discuss whether expanded thyroid testing or nutrient evaluation is appropriate. Work together before starting supplements or changing thyroid medication.

Important Disclaimer

PlexusDx does not provide medical advice. This information is educational and about genetic predispositions only. Always consult with your healthcare provider before making medical, dietary, or supplement decisions or if you have concerns about your thyroid or reproductive health.