3,5-Diiodothyronine (3,5-T2) is a naturally occurring thyroid hormone metabolite, structurally related to triiodothyronine (T3). There is growing scientific interest in its role in regulating energy expenditure and fat metabolism. Several preclinical studies in rodents have demonstrated that administration of 3,5-T2 can increase basal metabolic rate, stimulate mitochondrial activity, enhance lipid oxidation, and reduce adiposity, even in the context of high-fat diets. Some evidence suggests that 3,5-T2 exerts these effects without the thyrotoxic side effects commonly associated with T3 or thyroxine (T4), such as cardiac arrhythmias or bone loss.

However, the majority of the data supporting 3,5-T2’s use in fat metabolism comes from animal studies and in vitro experiments. There are very limited clinical trial data in humans. The few small pilot studies that have been conducted suggest a potential for improving metabolic parameters, but they are preliminary and not sufficient for broad clinical recommendations. As such, while there is a scientific basis for the interest in 3,5-T2 and fat metabolism, the quality and quantity of human evidence are low. Thus, the rating is a 2, indicating weak but plausible scientific support that warrants further investigation but does not justify routine clinical use for poor fat metabolism at this time.