Introduction
T3 – Triiodothyronine is a vital biomarker in the Healthspan Assessment, representing the active form of thyroid hormone that drives metabolism, energy, and brain function. If you’re experiencing fatigue, weight gain, brain fog, or cold intolerance, your T3 levels could provide critical insights. In this chapter, we’ll explore T3 in depth: what it does, why it’s important, optimal ranges, factors that influence it, associated health conditions, and how to optimize it using a functional medicine approach. We’ll also dive into the nutritional biochemistry behind T3, its role in the 12 hallmarks of aging, key physiological axes, and practical steps you can take to feel energized, focused, and metabolically balanced.
What Is T3 – Triiodothyronine and Its Physiological Role?
T3 – Triiodothyronine is the biologically active thyroid hormone, primarily produced by peripheral conversion of thyroxine (T4) via deiodinase enzymes (D1 and D2) in the liver, kidneys, and tissues, with ~20% secreted directly by the thyroid gland [1]. T3 binds nuclear thyroid receptors (TRα and TRβ) to regulate gene expression, increasing basal metabolic rate, protein synthesis, and mitochondrial activity. It supports heart rate, body temperature, digestion, and neurodevelopment. T3 is regulated by the hypothalamic-pituitary-thyroid (HPT) axis, with TSH stimulating T4 release and feedback inhibition. Low T3 impairs energy production and cognition, while high T3 causes palpitations, anxiety, or weight loss [2]. T3 works closely with T4, TSH, reverse T3 (rT3), and selenium to maintain metabolic and neurological health.
Clinical Significance: Why T3 – Triiodothyronine Matters
T3 is a crucial marker because it reflects active thyroid function at the tissue level, often revealing dysfunction missed by TSH alone. Low T3 (non-thyroidal illness syndrome or conversion issues) signals poor energy, weight gain, or depression, while high T3 indicates hyperthyroidism or over-supplementation. Free T3 (unbound) is preferred over total T3 for accuracy. T3 must be interpreted alongside TSH, free T4, rT3, and antibodies to identify root causes like Hashimoto’s or Graves’. For patients, understanding T3 can explain sluggish metabolism, mood issues, or heart symptoms and guide personalized strategies to restore thyroid vitality [3].
Optimal Ranges for T3 – Triiodothyronine
In functional medicine, we focus on optimal T3 ranges to support vibrant health, not just “normal” ranges to avoid disease. For free T3, optimal levels are 3.0–4.2 pg/mL, with functional medicine often preferring upper half (3.5–4.2 pg/mL) for energy and cognition. For total T3, 100–180 ng/dL is ideal [4]. For children, consult a pediatric specialist, as ranges vary by age. Standard lab ranges are broader (free T3: 2.0–4.4 pg/mL; total T3: 80–200 ng/dL), but functional medicine targets tighter ranges for peak health. Always review results with a healthcare provider, as context, such as rT3, iron, or time of day (morning testing), is critical for accurate interpretation.Factors Affecting T3 – Triiodothyronine Levels
Your T3 levels are influenced by diet, lifestyle, and health conditions. Diets low in selenium, zinc, or iodine impair conversion, lowering T3, while nutrient-dense diets with Brazil nuts and seafood support deiodination. Lifestyle factors like chronic stress, calorie restriction, or high-intensity exercise increase rT3 and lower T3, while adequate sleep and moderate exercise optimize conversion. Health conditions, such as gut dysbiosis or leaky gut, reduce T3 via inflammation or poor nutrient absorption. Liver or kidney dysfunction impairs deiodination, while illnesses (euthyroid sick syndrome) divert T4 to rT3. Aging decreases D2 activity, and medications like beta-blockers or amiodarone lower T3 [5].
Your T3 levels are influenced by diet, lifestyle, and health conditions. Diets low in selenium, zinc, or iodine impair conversion, lowering T3, while nutrient-dense diets with Brazil nuts and seafood support deiodination. Lifestyle factors like chronic stress, calorie restriction, or high-intensity exercise increase rT3 and lower T3, while adequate sleep and moderate exercise optimize conversion. Health conditions, such as gut dysbiosis or leaky gut, reduce T3 via inflammation or poor nutrient absorption. Liver or kidney dysfunction impairs deiodination, while illnesses (euthyroid sick syndrome) divert T4 to rT3. Aging decreases D2 activity, and medications like beta-blockers or amiodarone lower T3 [5].
Conditions Associated with Abnormal T3 – Triiodothyronine Levels
Abnormal T3 levels can signal underlying health issues. Low T3 is linked to hypothyroidism (Hashimoto’s), non-thyroidal illness, or conversion defects, causing fatigue, weight gain, or depression. High T3 occurs in Graves’ disease or toxic nodules, leading to anxiety, tremors, or heart palpitations. Chronic gut issues, such as SIBO or celiac, impair selenium absorption, lowering T3, while liver congestion reduces D1 activity. Adrenal dysfunction (high cortisol) inhibits conversion, and inflammation raises rT3 to block T3 action [6].
Nutritional Biochemistry of T3 – Triiodothyronine
T3’s biochemistry centers on its activation from T4 via 5’-deiodinase, requiring selenium as a cofactor. ~80% of T3 is produced peripherally, with D1 (liver/kidney) and D2 (muscle/brain) removing the outer iodine [7]. Gut health is essential: dysbiosis or low bile impairs selenium/iodine absorption, reducing T3, while a healthy microbiome supports enterohepatic circulation of thyroid hormones. Liver health drives 60% of conversion. Key nutrients influence T3: selenium (200 mcg daily) activates deiodinases; zinc supports TR binding; iron is required for TPO enzyme; vitamin A regulates TSH; and omega-3s reduce inflammation. Chronic stress or fasting upregulates D3, producing rT3 to conserve energy, while gut inflammation inhibits D2 via cytokines. Medications like glucocorticoids lower T3, while gut permeability sustains low-grade inflammation blocking conversion [8].
T3 – Triiodothyronine and the 12 Hallmarks of Aging
These are the 12 hallmarks of aging, which I like to relate to the mechanisms of chronic disease and poor cellular function. T3 imbalances contribute to several of these hallmarks, driving long-term health decline. Low T3 impairs DNA repair in metabolic tissues, contributing to genomic instability. It disrupts epigenetic regulation via reduced TR activity, leading to epigenetic alterations. Low T3 impairs mitochondrial biogenesis (PGC-1α), contributing to mitochondrial dysfunction. Deficiency accelerates cell turnover in brain/heart, contributing to telomere attrition. Low T3 disrupts protein synthesis, leading to proteostasis loss. It dysregulates insulin via reduced GLUT4, contributing to nutrient sensing dysregulation. Low T3 induces neuronal senescence, while high T3 overstimulates. Deficiency impairs neural/muscle stem cells, contributing to stem cell exhaustion. Imbalanced T3 disrupts cytokine balance, leading to altered intercellular communication. Low T3 weakens connective tissue, contributing to tissue matrix degradation. Gut dysbiosis impairs nutrient absorption, contributing to microbiome dysbiosis, while low T3 fuels inflammation, tied to immune dysfunction [9]. Optimizing T3 helps mitigate these hallmarks, supporting long-term health.
T3 – Triiodothyronine and Key Physiological Axes
In functional medicine, we view health through interconnected systems or “axes” that influence one another. T3 plays a significant role in the gut-thyroid axis and the gut-brain axis. The gut-thyroid axis involves gut absorption of selenium/iodine and liver conversion of T4 to T3. Dysbiosis, low stomach acid, or inflammation impairs uptake and deiodination, lowering T3, while a healthy gut supports thyroid function [10]. Supporting the gut-thyroid axis involves healing the gut with probiotics, betaine HCl, and selenium-rich foods. The gut-brain axis links gut health to HPT axis and cognition, as T3 regulates neurogenesis and dopamine. Poor gut health reduces T3 availability, contributing to brain fog or depression. Supporting this axis involves optimizing gut health with fiber and managing stress to stabilize T3 for brain function [11]. Addressing these axes through diet, supplements, and lifestyle can optimize T3 and overall health.
Functional Medicine Solutions for T3 – Triiodothyronine
For low T3, focus on selenium-rich foods (2–3 Brazil nuts daily), zinc (15–30 mg), and iodine (150–300 mcg from sea vegetables). Use supplements like selenium (200 mcg), ashwagandha, or guggul under medical supervision to enhance conversion. Test and treat gut dysbiosis, SIBO, or adrenal issues. Avoid goitrogens raw; cook cruciferous veggies. For high T3, reduce iodine, test for Graves’, and use bugleweed or L-carnitine (500–2,000 mg) under supervision to block conversion. Support gut health with fermented foods and anti-inflammatory diet. Test iron, ferritin, and cortisol to rule out blockers [12].
Practical Applications: What You Can Do Today
Take control of your T3 levels by requesting free T3 (and rT3) as part of the Vibrant Wellness Healthspan Assessment, alongside TSH, free T4, and antibodies. Optimize your diet with a meal like wild salmon, seaweed salad, and quinoa this week to support conversion. If T3 is low, eat 2 Brazil nuts daily, discuss selenium with your doctor, and add gentle yoga. Track symptoms like fatigue, cold hands, or hair loss in a journal to monitor improvements. If T3 is high, cut excess iodine, test antibodies, and prioritize sleep. Retest T3 every 3–6 months to track progress.
Conclusion
T3 – Triiodothyronine is the engine of metabolism, energy, and brain health, influencing vitality and long-term wellness. By understanding its role, nutritional biochemistry, connection to the 12 hallmarks of aging, and key physiological axes, you can take targeted steps to optimize it. Whether you’re addressing low T3 to boost energy or managing high levels for calm, functional medicine offers personalized solutions. Start with small changes like adjusting your diet or tracking symptoms, and work with your healthcare provider for a tailored plan. In the next chapter, we’ll explore the next biomarker in your health journey.
References
[1] Bianco, A. C., et al. (2014). Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocrine Reviews, 35(2), 244–280.
[2] Mullur, R., et al. (2014). Thyroid hormone regulation of metabolism. Physiological Reviews, 94(2), 355–382.
[3] Woeber, K. A. (2002). Triiodothyronine production in nonthyroidal illness. Journal of Clinical Endocrinology & Metabolism, 87(3), 1005–1009.
[4] Kharrazian, D. (2013). Why Do I Still Have Thyroid Symptoms? When My Lab Tests Are Normal. Elephant Press.
[5] Peeters, R. P., et al. (2003). Serum 3,3’,5-triiodothyronine (T3) and thyroxine (T4) concentrations in patients with nonthyroidal illness. Journal of Clinical Endocrinology & Metabolism, 88(9), 4143–4148.
[6] Boelen, A., et al. (2008). Interleukin-6 and the cytokine hierarchy in nonthyroidal illness syndrome. Endocrine, 34(1–3), 75–81.
[7] Gereben, B., et al. (2008). Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocrine Reviews, 29(7), 898–938.
[8] Hodges, R. E., & Minich, D. M. (2015). Modulation of metabolic detoxification pathways using foods and food-derived components. Journal of Nutrition and Metabolism, 2015, 760689.
[9] López-Otín, C., et al. (2013). The hallmarks of aging. Cell, 153(6), 1194–1217.
[10] Virili, C., & Centanni, M. (2017). Gut-thyroid axis: How gut microbiota influences thyroid function. Endocrine, 57(3), 353–355.
[11] Bauer, M., et al. (2008). Brain glucose metabolism in hypothyroidism. Journal of Clinical Endocrinology & Metabolism, 93(5), 1749–1755.
[12] Bland, J. (2017). The Disease Delusion. HarperCollins.
[2] Mullur, R., et al. (2014). Thyroid hormone regulation of metabolism. Physiological Reviews, 94(2), 355–382.
[3] Woeber, K. A. (2002). Triiodothyronine production in nonthyroidal illness. Journal of Clinical Endocrinology & Metabolism, 87(3), 1005–1009.
[4] Kharrazian, D. (2013). Why Do I Still Have Thyroid Symptoms? When My Lab Tests Are Normal. Elephant Press.
[5] Peeters, R. P., et al. (2003). Serum 3,3’,5-triiodothyronine (T3) and thyroxine (T4) concentrations in patients with nonthyroidal illness. Journal of Clinical Endocrinology & Metabolism, 88(9), 4143–4148.
[6] Boelen, A., et al. (2008). Interleukin-6 and the cytokine hierarchy in nonthyroidal illness syndrome. Endocrine, 34(1–3), 75–81.
[7] Gereben, B., et al. (2008). Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocrine Reviews, 29(7), 898–938.
[8] Hodges, R. E., & Minich, D. M. (2015). Modulation of metabolic detoxification pathways using foods and food-derived components. Journal of Nutrition and Metabolism, 2015, 760689.
[9] López-Otín, C., et al. (2013). The hallmarks of aging. Cell, 153(6), 1194–1217.
[10] Virili, C., & Centanni, M. (2017). Gut-thyroid axis: How gut microbiota influences thyroid function. Endocrine, 57(3), 353–355.
[11] Bauer, M., et al. (2008). Brain glucose metabolism in hypothyroidism. Journal of Clinical Endocrinology & Metabolism, 93(5), 1749–1755.
[12] Bland, J. (2017). The Disease Delusion. HarperCollins.
