T2 and Fat Burning: What the Thyroid Research Really Shows with Dr. Amie Hornaman

What is T2, and why have researchers been investigating its effects on metabolism?

In this episode of the Optimal Protein Podcast, I'm welcoming back Dr. Amie Hornaman to explore 3,5-diiodothyronine, commonly called T2—a lesser-known thyroid hormone derivative studied for its effects on energy expenditure, fatty acid oxidation, and mitochondrial function.

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We walk through research on liver cells, skeletal muscle, and brown fat, unpacking the machinery that helps fatty acids enter the mitochondria and a process called mitochondrial uncoupling, in which energy is released as heat.

We also explore possible connections with ketogenic diets and the question that matters so much to us here: what could these findings mean for losing body fat while preserving muscle?

Much of the research discussed comes from animal studies. We examine a small human report involving just two participants, and Amie shares observations from an uncontrolled group of 14 women who used her T2-containing product. These findings raise interesting questions, but they do not establish that supplemental T2 is a safe or effective approach to fat loss.

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In this episode, we discuss:

What T2 is and how it relates to the better-known thyroid hormones T3 and T4. The 2005 rat study reporting less fat accumulation and greater liver fatty acid oxidation. How the carnitine shuttle helps transport long-chain fatty acids into the mitochondria. AMPK, ACC, and malonyl-CoA—and their roles in regulating fat oxidation. Mitochondrial uncoupling, ATP production, and thermogenesis. Research on T2 and brown fat in animals with low thyroid function. Potential overlaps with ketogenic metabolism. The limited human evidence and the need for larger, controlled studies. Why increased fat burning, lower body weight, and muscle preservation are different outcomes. Protein, resistance training, and body composition during weight loss. Important context for interpreting the research

The approximately 50% lower fat mass reported in the 2005 rat study was a co