3,5-Diiodo-L-thyronine (3,5-T2)

Overview

3,5-Diiodo-L-thyronine (3,5-T2) is a non-peptide endogenous iodothyronine produced by deiodination of T3 and T4. It is not an approved drug and has no registered human clinical trials as a study intervention. The only direct human-administration data come from a single 2-person case report. WADA/anti-doping status for 3,5-T2 specifically is unconfirmed; a 2019 secondary source suggested thyroid hormones as a class were not prohibited, but no current primary WADA citation was found.

Mechanism of Action

3,5-T2 acts largely independently of classical nuclear thyroid hormone receptor (THRβ) genomic signaling, with substantially lower THRβ affinity than T3. The primary mechanism is direct, non-genomic action at mitochondria: 3,5-T2 binds cytochrome-c oxidase subunit Va and abolishes the allosteric inhibition of respiration by ATP, rapidly increasing oxygen consumption. In rodent studies, it activates the AMPK–ACC–malonyl-CoA signaling pathway, increasing mitochondrial fatty-acid oxidation and redirecting lipid partitioning toward oxidation.

Research Summary

No approved human drug or registered interventional clinical trial exists. The only direct human-administration data are from a single 2-person case report: oral 3,5-T2 (~5 μg/kg body weight) for 28 days reportedly raised resting metabolic rate by ~15% and lowered body weight by ~4 kg, with no significant changes in principal clinical parameters and no observed side effects. Endogenous 3,5-T2 has been measured in healthy human serum (~0.22–0.33 nM) and as a metabolite in liothyronine (T3) pharmacokinetic trials. Preclinical rodent studies show 3,5-T2 rapidly increases resting metabolic rate (faster than T3), reduces adiposity in high-fat-diet models by increasing fat oxidation, stimulates liver and skeletal muscle mitochondrial bioenergetics, and activates AMPK in skeletal muscle. One rat regimen (25 μg/100g BW, 4 weeks) showed no HPT-axis suppression or cardiac hypertrophy at that specific dose/duration; however, one mouse model (unsaturated-fat diet) showed no improvement in NAFLD or insulin sensitivity.

Reported Side Effects

• Human safety data extremely limited (only 2-person case report)
• No large-scale toxicology or approved-drug safety label
• Gray-market product purity/identity unverified
• Potential thyroid axis or cardiac effects unknown at scale
• Long-term safety in humans not established

Compare 3,5-Diiodo-L-thyronine (3,5-T2) with Others

Research References

• 3,5-Diiodothyronine, L- (Compound Summary).
• 3,5-Diiodothyronine: A Novel Thyroid Hormone Metabolite and Potent Modulator of Energy Metabolism. 2018.
• 3,5-diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats. 2005. PMID 16014396.
• Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats stimulates bioenergetic parameters in liver mitochondria. 2016. PMID 27854029.

Frequently asked questions

Has 3,5-Diiodo-L-thyronine (3,5-T2) been independently lab-tested?

Disclosed Labs has collected 2 Certificates of Analysis (COA) for 3,5-Diiodo-L-thyronine (3,5-T2) from 2 independent testing labs. 1 vendor has submitted material for testing. Products average 97.4% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/3-5-diiodo-l-thyronine/testing.

How does 3,5-Diiodo-L-thyronine (3,5-T2) work?

3,5-T2 acts largely independently of classical nuclear thyroid hormone receptor (THRβ) genomic signaling, with substantially lower THRβ affinity than T3. The primary mechanism is direct, non-genomic action at mitochondria: 3,5-T2 binds cytochrome-c oxidase subunit Va and abolishes the allosteric inhibition of respiration by ATP, rapidly increasing oxygen consumption. In rodent studies, it activates the AMPK–ACC–malonyl-CoA signaling pathway, increasing mitochondrial fatty-acid oxidation and redirecting lipid partitioning toward oxidation.

What does the research say about 3,5-Diiodo-L-thyronine (3,5-T2)?

No approved human drug or registered interventional clinical trial exists. The only direct human-administration data are from a single 2-person case report: oral 3,5-T2 (~5 μg/kg body weight) for 28 days reportedly raised resting metabolic rate by ~15% and lowered body weight by ~4 kg, with no significant changes in principal clinical parameters and no observed side effects. Endogenous 3,5-T2 has been measured in healthy human serum (~0.22–0.33 nM) and as a metabolite in liothyronine (T3) pharmacokinetic trials. Preclinical rodent studies show 3,5-T2 rapidly increases resting metabolic rate (faster than T3), reduces adiposity in high-fat-diet models by increasing fat oxidation, stimulates liver and skeletal muscle mitochondrial bioenergetics, and activates AMPK in skeletal muscle. One rat regimen (25 μg/100g BW, 4 weeks) showed no HPT-axis suppression or cardiac hypertrophy at that specific dose/duration; however, one mouse model (unsaturated-fat diet) showed no improvement in NAFLD or insulin sensitivity.