Thyroid Hormones: Boosting Energy Metabolism and Muscle Protein Turnover

Thyroid hormones, vital players in our body's regulatory mechanisms, wield significant influence over our energy levels and muscle health. The thyroid, that unassuming gland nestled just below the Adam's apple in your neck, secretes two primary hormones: triiodothyronine (T3) and thyroxine (T4). While T4 serves as a prohormone, most of its potency relies on conversion into T3, a transformation known as outer ring deiodination, primarily occurring outside the thyroid in peripheral tissues. Together, they contribute to a daily production of approximately 88 mcg (113 nmol) of T4 and 28 mcg (43 nmol) of T3 . Interestingly, only about one-fifth of the T3 originates from the thyroid itself, with the remaining four-fifths produced via extrathyroidal T4-to-T3 conversion .

Much like anabolic steroids, thyroid hormones travel through the bloodstream with the help of carrier proteins, with the majority binding to thyroxine-binding globulin (TBG), while the rest finds their place on transthyretin, albumin, and some lipoproteins. Collectively, these proteins bind over 99% of thyroid hormones in circulation, leaving a fraction unbound and available for tissue uptake, thus exerting their effects 

Once thyroid hormones reach peripheral tissues and penetrate a cell's plasma membrane, they spring into action. In the case of T4, it undergoes conversion into T3, essentially functioning as a prohormone. This conversion transpires inside the cell, either near the plasma membrane (from where it quickly equilibrates with blood plasma) or near the cell nucleus—the heart of cellular activities . T3, however, can directly venture into the cell nucleus, home to the intricate process of gene transcription. Just as anabolic steroids do, thyroid hormones primarily exert their effects by modulating gene transcription, achieved through their binding to thyroid hormone receptors predominantly located within the cell nucleus, tightly tethered to DNA.

Thyroid hormones cast their influence far and wide across various tissues, engendering a plethora of effects. For the purposes of this article, we will zoom in on their impact on energy metabolism and protein turnover, two areas of particular interest to our readers.

Energy Metabolism: Powering the Flames

In instances where an individual's thyroid hormone levels fall below the necessary threshold, they may develop hypothyroidism, often accompanied by weight gain. Conversely, an excess of thyroid hormones can lead to hyperthyroidism, characterized by weight loss. These fluctuations in body weight are likely the result of changes in basal metabolic rate, with thyroid hormones being well-known for their role in increasing energy expenditure.

Several mechanisms have been proposed to elucidate how thyroid hormones achieve this feat. In this article, we will delve into the three most noteworthy theories commonly found in scientific literature. The first two mechanisms revolve around the energy required to maintain ion gradients within cells. Cells diligently maintain low intracellular sodium concentrations and high intracellular potassium concentrations relative to the extracellular environment. Achieving this balance relies on specialized pumps embedded within the cell's plasma membrane, known as Na+/K+-ATPases. These pumps tirelessly move sodium ions out of the cell and potassium ions into the cell, a process demanding energy derived from adenosine triphosphate (ATP), the cellular energy carrier molecule. ATP draws its energy from the macronutrients we consume: carbohydrates, fatty acids, and protein (amino acids). Notably, thyroid hormones have been linked to increased sodium and potassium ion permeability of the plasma membrane , resulting in more ions traversing their concentration gradients. This phenomenon forces the sodium-potassium pumps to work harder to maintain the desired intracellular ion concentrations, a process consuming additional energy. Some literature even suggests that T3 can trigger heightened sodium-potassium pump activity across all mammalian tissues .

A similar concept applies to calcium ions within muscle cells , which possess a specialized organelle called the sarcoplasmic reticulum. This structure acts as a reservoir for calcium ions, critical for muscle contractions. The release of calcium ions from the sarcoplasmic reticulum into the cell's interior initiates muscle contractions. To halt contractions, these ions are pumped back into the sarcoplasmic reticulum, a process that demands energy. Fascinatingly, thyroid hormones have been found to regulate the expression of calcium pumps in muscle cells, potentially increasing energy expenditure by sustaining calcium ion storage within the sarcoplasmic reticulum. This action can significantly contribute to heightened energy expenditure.

Lastly, thyroid hormones are believed to "sabotage" oxidative phosphorylation, a process taking place within mitochondria, the cell's powerhouses. Oxidative phosphorylation hinges on the flow of protons (H+) across mitochondrial membranes, a cascade that ultimately fuels the synthesis of ATP, the body's primary energy currency. Here, thyroid hormones come into play by boosting the expression of uncoupling proteins . These proteins, embedded in the inner mitochondrial membrane, allow protons to leak across without passing through ATP synthase, releasing energy as heat instead of converting it into ATP—a fascinating metabolic phenomenon.

Thyroid Hormones and Protein Turnover: A Double-Edged Sword

Inspiration for this article stemmed from a forum discussion on using T3 to enhance protein turnover during a bulking phase. Is it a sound strategy? Not quite. While T3 may indeed accelerate protein turnover, promoting both protein synthesis and breakdown, the latter tends to outpace the former, resulting in net protein degradation.

In one study where subjects received 150 mcg of T3 daily for seven days, protein breakdown surged significantly . Nitrogen excretion, a proxy for protein breakdown, escalated by 45%, while leucine oxidation, another indicator, increased by a substantial 74%. Although whole-body protein synthesis also increased, the magnitude was dwarfed by the rise in protein breakdown. A different study employing 100 mcg of T3 daily for two weeks reported similar findings . While fasting, whole-body protein synthesis increased by 9%, though not statistically significant, whole-body protein breakdown and leucine oxidation exhibited statistically significant increments of 12% and 24%, respectively.

Perhaps more intriguingly, researchers in this study conducted muscle biopsies on the gastrocnemius muscle, measuring various parameters, including muscle fiber cross-sectional area (CSA). The results painted a revealing picture:

In another study, six participants were administered 2 mcg/kg of body weight T4 daily for six weeks, coupled with 1 mcg/kg of body weight T3 daily during the final two weeks . This regimen, equivalent to a supraphysiological thyroid hormone dosage for the initial four weeks, led to suppressed thyroid-stimulating hormone (TSH) levels (from 1. 8 to 0.3 mIU/L) and significant increases in both T4 and T3. While muscle protein kinetics were not measured, the study did assess whole-body protein synthesis and breakdown in the post-absorptive state. Thyroid hormone supplementation amplified both processes, though breakdown exhibited a markedly greater increase. It is reasonable to assume that this pattern reflects what transpires in muscle tissue.

A noteworthy long-term study, utilizing relatively lower dosages compared to prior trials, involved the administration of T3 over two months to a small group of men [16]. The T3 dosing commenced at 75 mcg daily but was gradually reduced to 50 or 62.5 mcg daily when serum T3 levels exceeded 4.6 nmol/L, which occurred in five of the seven participants. Nitrogen balance exhibited significant reductions compared to baseline during the second and third weeks but gradually neared zero afterward, hinting at potential protein-sparing mechanisms at play after the initial few weeks. Additionally, the study observed a significant decrease in lean body mass (1.5 kg) and fat mass (2.7 kg) after six weeks. By the ninth week, lean body mass remained relatively stable (-0.1 kg compared to week six), while fat mass appeared to continue declining (-0.6 kg), although this difference was not statistically significant compared to week six. Protein turnover measures did not yield statistically significant differences, likely due to the study's small sample size.

The question arises: could anabolic steroids mitigate the catabolic effects of thyroid hormones? The answer, though uncertain, leans toward a possibility. Unfortunately, clinical data addressing this specific scenario are lacking. Thus, any conjecture would remain speculative. It is worth pondering whether the modest increase in energy expenditure (typically a few hundred extra calories and a roughly 10-15% boost in resting metabolic rate) justifies the catabolic effects and potential risks associated with this class of drugs.