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DIO2 Gene and Thyroid Hormone Conversion: What Your Genotype Means

The thyroid gland releases mostly inactive T4 hormone that must be converted into active T3 in tissues like the brain, heart, and muscles. The DIO2 gene makes an enzyme called deiodinase 2 that performs this conversion. Variations in DIO2 can change how well your body converts T4 into T3, which may affect energy, metabolism, mood, and cognitive function even when standard thyroid blood tests look normal.

Why this matters

  • Active T3 is the hormone cells use to regulate metabolism and brain function.
  • Reduced DIO2 activity can lead to symptoms such as fatigue, brain fog, low mood, or muscle weakness despite normal TSH or T4 levels.
  • Genetics is one factor among diet, nutrients, medications, stress, and environmental exposures that influence thyroid health.

How to support healthy thyroid hormone conversion

  • Eat selenium-rich foods: Brazil nuts, seafood, and some organ meats support deiodinase enzymes.
  • Include zinc sources: Red meat, shellfish, pumpkin and sunflower seeds, and legumes help enzyme function.
  • Maintain balanced iodine: Use iodized salt and include dairy, seafood, and sea vegetables in moderation; avoid both deficiency and excess.
  • Get vitamins A and D: Liver, carrots, leafy greens, fatty fish, eggs, and safe sun exposure support thyroid hormone action.
  • Eat kaempferol-containing foods: Apples, onions, kale, and grapes may support healthy thyroid pathways.
  • Follow an anti-inflammatory Mediterranean-style diet: Plenty of vegetables, fruits, whole grains, healthy fats like olive oil, nuts, seeds, and lean proteins.
  • Avoid endocrine disruptors: Reduce exposure to plastics with BPA, phthalates, and other hormone-active chemicals—choose glass or stainless steel for food and beverage storage when possible.
  • Monitor labs regularly: Include free T3 in addition to TSH and free T4 when assessing symptoms related to conversion efficiency.

Genetic Interpretation for rs225014 (DIO2)

2 effect alleles (CC) — decreased DIO2 activity

Your genotype: CC. You carry two copies of the effect allele associated with lower DIO2 enzyme activity and reduced conversion of T4 into active T3 in peripheral tissues.

What this can look like

  • Higher likelihood of symptoms such as fatigue, cognitive slowing, mood changes, or muscle tiredness even if TSH and T4 are within range.
  • Symptoms may fluctuate based on nutrient status, illness, medications, or environmental exposures.

Practical steps to support conversion

  • Nutrition: Prioritize selenium (Brazil nuts 1–2 per day as a source), seafood, and organ meats in moderation. Add zinc-rich foods like red meat, oysters, pumpkin and sunflower seeds, and legumes.
  • Iodine: Use iodized salt and include iodine-containing foods sensibly; avoid excessive supplementation without medical guidance.
  • Vitamins: Ensure adequate vitamin A from colorful vegetables and liver in small amounts; maintain vitamin D through sun exposure and consider testing levels before supplementing.
  • Phytonutrients: Include kaempferol-rich produce such as apples, onions, kale, and grapes daily.
  • Diet pattern: Adopt an anti-inflammatory Mediterranean-style eating plan to support overall endocrine and metabolic health.
  • Reduce exposures: Limit use of plastics for food storage, avoid microwaving in plastic, choose personal care products with fewer hormone-disrupting chemicals.
  • Monitoring: Ask your healthcare provider to include free T3 and free T4 on thyroid panels when symptoms are present; keep a symptom journal to correlate lab changes and lifestyle interventions.
1 effect allele (CT) — intermediate DIO2 activity

Your genotype: CT. You carry one copy of the effect allele, which is associated with moderately reduced DIO2 activity and somewhat reduced conversion of T4 to T3.

What this can look like

  • You may experience mild or intermittent symptoms such as low energy, difficulty concentrating, or mood shifts, particularly during times of stress, illness, or poor nutrient status.
  • Standard thyroid tests may appear normal while symptoms persist.

Practical steps to support conversion

  • Nutrition: Emphasize selenium sources like Brazil nuts and seafood, and include zinc-rich foods such as seeds, shellfish, and lean meats.
  • Iodine: Maintain balanced intake using iodized salt and food sources; avoid extremes unless advised by a clinician.
  • Vitamins: Support vitamin A and D intake through diet and safe sun exposure; consider testing vitamin D level with your provider.
  • Lifestyle: Follow an anti-inflammatory Mediterranean diet, manage stress, prioritize sleep, and get regular physical activity to support metabolism.
  • Environmental: Minimize exposure to endocrine-disrupting chemicals in plastics and personal care products.
  • Monitoring: Regular thyroid monitoring including free T3 and free T4 can help detect subtle conversion issues and guide interventions.
0 effect alleles (TT) — typical DIO2 activity

Your genotype: TT. You carry two copies of the non-effect allele associated with normal DIO2 enzyme activity and typical conversion of T4 into T3 in tissues.

What this can look like

  • More efficient T4 to T3 conversion supports stable energy, cognitive function, and muscle performance, reducing risk of conversion-related symptoms.
  • This genotype is also associated with a lower genetic risk for some thyroid-related issues compared with carriers of the C allele.

Practical steps to maintain thyroid health

  • Nutrition: Continue a balanced intake of selenium, zinc, iodine, vitamins A and D, and kaempferol-rich produce as part of a varied diet.
  • Healthy habits: Maintain an anti-inflammatory Mediterranean diet, regular exercise, sleep hygiene, and stress management.
  • Environmental: Keep minimizing exposure to endocrine disruptors from plastics and household chemicals to protect long-term hormone balance.
  • Monitoring: Periodic thyroid testing including free T3, free T4, and TSH is still recommended to track changes over time and with life stages.

Additional considerations

  • Medications and supplements can affect thyroid hormone conversion. Always review changes with your healthcare provider.
  • Illness, severe caloric restriction, and chronic stress can lower peripheral T3 levels independent of DIO2 genotype.
  • Targeted nutrient testing and professional guidance can help tailor supplementation if needed. Avoid high-dose iodine or selenium supplements without clinician oversight.

PlexusDx provides genetic information to help you understand predispositions and options for supporting health. This information is educational only and does not constitute medical advice. Always discuss genetic results, symptoms, and any changes to diet, supplements, or treatment plans with your healthcare provider before taking action.