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T2: The Lesser Known Thyroid Hormone

T2: The Lesser Known Thyroid Hormone

TSH, T4, T3 – these are all common buzzwords you might hear come up in discussions about thyroid physiology (TSH is thyroid stimulating hormone, T4 is thyroxine, and T3 is triiodothyronine). We have a plethora of knowledge about these hormones, how they interact with each other, and the role they play in metabolic processes. But most likely you’ve never heard of the thyroid metabolite known as T2, or 3,5-diio-L-thyronine. While scientists have been aware of its existence for many years now, whether or not it has a significant purpose in the body or therapeutic potential as a pharmacological agent has largely remained a mystery until recently.

The obesity epidemic, along with associated diseases like diabetes, has put a tremendous and ever-growing strain on healthcare costs and providers. Based on what we already know about the thyroid’s role in metabolism, exploring lesser understood thyroid metabolites such as T2 is a logical place to look for potential solutions to the metabolic havoc our modern lives have wreaked on our bodies. We know that the “Standard American Diet” (SAD), environmental toxins, and chronic stress are a few of the major contributors to the endocrine and obesity-related disorders we are seeing in astounding proportions. However, research is showing that the addition of T2 to supplements or thyroid treatment may help to ameliorate some of these metabolic changes, particularly those that are related to dietary patterns.

T2 belongs to the family of iodine-dependent thyroid hormones known as iodothyronines, although it is generally considered less active than T4 and T3, as are rT3, 3’3’T2, and 3’T1. It was previously thought to be a catabolite of T3, but studies have shown that T2 is made by the deiodination of T3 and rT3 (possibly more so from rT3) and mimics the effects of T3 on energy metabolism. So while it does appear to be closely related to T3, it has been demonstrated to be metabolically active, possessing its own mechanisms of actions separate from T3. Here are some of the differences that have been found between the two thyroid hormones:

  • T2 appears to be more specific to the mitochondria, as opposed to the DNA-based actions of T3
  • T2 has weaker protein binding potential than T3
  • The conversion of T3 (or rT3) to T2 is not affected by fasting like the T4 to T3 conversion is
  • The main source of T2 is most likely peripheral tissues (rather than the thyroid), partly evidenced by studies showing that skeletal muscle acts as a target for the hormone

This finding that skeletal muscle is a target for T2 and that it helps to prevent fat storage and insulin resistance is significant because it could possibly explain why T2 appears to play a similar but distinctly different role than T3. One theory is that T2 is the peripheral mediator of thyroid hormones’ effects on energy metabolism. Although the exact mechanisms by which T2 exhibits changes on metabolism are not yet completely understood, the following summary of the scientific findings regarding its actions are impressive enough that some healthcare providers have begun to use it in clinical practice:

  • rapidly affects mitochondrial respiratory parameters
  • increases resting metabolic rate (RMR), despite lower circulating T4 and T3
  • decreases adiposity (both in general and specifically abdominal fat) by increasing fat burning
  • decreases triglycerides and cholesterol levels
  • decreases fatty liver markers
  • reduces diet-related weight gain
  • stimulates glucose consumption and growth hormone
  • may relieve diabetic neuropathy
  • may reverse impairments in mitochondria
  • activates SIRT1 and AMPK – important for healthy aging and preventing insulin resistance
  • improves resistance to cold among hypothyroid subjects (in an animal model)
  • increases mitochondrial capacity to import and oxidize fatty acids

*insulin resistance has recently been linked to mitochondrial fatty acid overload/incomplete oxidation

Although many of these same impressive effects on metabolism can be accomplished by T3, there are a few additional findings specific to T2 that have caught the attention of researchers and clinicians. T2 appears to have a significantly more rapid effect on metabolism and is independent of protein synthesis. Additionally, T3 appears to have the opposite/negative effect on SIRT1 (mentioned above), making T2 a possible better choice for achieving certain outcomes.

The studies based on higher dosages of T2 has revealed the need for continuing research to sort out the intricacies of inducing therapeutic change without producing other counterproductive effects long term, such as suppression of TSH (and secondary decrease in circulating T4 and T3), a negative affect on the hypothalamus-pituitary-adrenal-thyroid (HPAT) axis, or increased food intake (which would counteract the metabolic effects). So far, clinicians specializing in thyroid and other endocrine disorders who are utilizing T2 in treatment are reporting safe and effective outcomes.

While diet and lifestyle changes can and should play the biggest role in reversing metabolic disorders, physicians are in need of additional tools in cases where these changes are not enough, particularly in complicated thyroid conditions. It appears that T2 is a promising therapeutic agent helping to fill this need.

References

1. Antonelli, A et al. 3,5-Diiodo-L-Thyronine increases resting metabolic rate and reduces body weight without undesirable side effect. Journal of Biological Regulators & Homeostatic Agents. 2011; 25(4): 655-60.

2. Cavallo, A et al. 3,5-Diiodo-L-Thyronine increases F0F1-ATP synthase activity and cardiolipin level in liver mitochondria of hypothyroid rats. J Bioenerg Biomembr; 2011; 43:349-57.

3. deLange, P et al. (Healthy) Ageing: Focus on Iodothyronines. Int J Mol Sci. 2013; 14: 13873-13892.

4. Goglia, Fernando. The effects of 3,5-diiodothyronine on energy balance. Front Physiol. 13 Jan 2013

5. Hernandez, A. 3,5-Diiodo-L-Thyronine (T2) in Dietary Supplements: What are the Physiological Effects? Endocrinology. Dec. 2014. 156(1): ISSN (online): 1945-7170.

6. Jonas, W et al. 3,5-Diiodo-L-thyronine (3,5-t2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male diet-induced obese mice. Endocrinology. Jan 2015; 156(1): 389-99.

7. Lombardi, A et al. 3,5-Diiodo-L-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement. AJP Endocrinol Metab. 2009; 296: E497-E502.

8. Moreno, M et al. Effect of 3,5-Diiodo-L-Thyronine on Thyroid Stimulating Hormone and Growth Hormone Serum Levels in Hypothyroid Rat. Life Sciences. 1998. 62(26): 2369-2377.

9. Moreno, M et al. 3,5-Diiodo-L-thyronine prevents high-fat-diet-induced insulin resistance in rat skeletal muscle through metabolic and structural adaptations. The FASEB Journal. Oct 2011; 25: 3312-3324.

10. Padron, A.S. et al. Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues. Journal of Endocrinology. 2014; 221(3): 415-427.

11. Pangaro, L et al. Radioimmunoassay for 3,5-Diiodothyronine and Evidence for Dependence on Conversion from 3,5,3-Triiodothyronine. Journal of Clinical Endocrinology and Metabolism. 1980; 50(6): 1075-1081.

12. Papavasiliou, S et al. Thyroid Hormonelike Actions of 3,3,5-L-Triiodothyronine and 3,3-Diiodothyronine. Journal of Clinical Investigation. Dec 1997; 60: 1230-39.

T2: The Lesser Known Thyroid Hormone was last modified: October 24th, 2017 by Holtorf Medical Group

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