Thyroxine is the precursor of T4 and the production of both hormones is signaled in the thyroid gland by TSH or thyroid stimulating hormone.
Thyroid stimulating hormone is released from the pituitary gland and forms a feedback loop with both T3 and T4. Therefore, when the plasma levels of the thyroid hormone falls, TSH production is increased and when the thyroid hormones rise above their normal plasma levels, TSH production is reduced.
The control over the release of TSH itself is found in thyrotropin-releasing hormone (TRH) which is released from the hypothalamus.
T3 is only 20% of the amount of thyroid hormones synthesized. The other 80% is thyroxine.
However, in the plasma T3 is only 2.5% of the circulating thyroid hormones. It does not last as long as thyroxine (the time taken for T3 concentration to reduce to half is 2.5 days while for T4, that time is 6.5 days).
Furthermore, most of the T3 found in circulation are produced from T4.
By simply removing an iodine atom in a specific position on the T4 molecule, T3 is produced. The enzymes responsible for converting T4 to T3 are found in different parts of the body including the thyroid, kidney, liver, adipose tissue, placenta, heart, central nervous system and even the pituitary gland.
Even though T3 can be made from T4, the body still makes triiodothyronine directly. This is done in the lumen of the thyroid gland.
The synthesis proceeds with the addition of iodine atoms to tyrosine for form monoiodotyrosine (MIT) and diiodotyrosine (DIT). These reactions require hydrogen peroxide to proceed.
MIT and DIT then combine together in a reaction catalyzed by an enzyme called thyroid peroxidase. The product of this combination is T3.
What T3 Does and How It Works
The biological effects of T3 are extensive and the hormone contributes to almost all the physiological processes in the human body. For example, T3 affects heart rate, the rate of metabolism, body temperature and growth rate.
In the blood, T3 binds to specific types of carrier proteins: serum albumin (with low affinity) and thyroid-binding globulin (with high affinity).
These molecules increase the stability and longevity of T3 but impede the uptake of the hormone by tissues. For T3 to pass through tissues, it must shed its carrier protein.
To produce its biological effects, T3 binds to thyroid receptors in tissues. In addition, because it is fat-soluble, it can cross into cells through their phospholipid layers.
T3 can be found in most tissues although it is notably absent in the tissues of the testes and spleen.
Its overall effect depends on the part of the body where it acts. However, T3 generally increases the basal metabolic rate.
When T3 increases the rate of metabolism, it does the following:
Increase the amount of oxygen and energy used up by the body
Increase the amount of calories required for normal body processes even when the muscles are rested
Increase the population of sodium/potassium/ATPase, the primary energy-generating complex in the body
Increase the use and breakdown of many nutrient macromolecules produced in the body
On proteins, T3 increases the rate of their production and degradation by increasing the amount of the enzymes, RNA polymerase I and II.
For carbohydrates, T3 increases gluconeogenesis. Gluconeogenesis is the production of glucose from stored glycogen. This effect is mediated by beta adrenergic receptors. By acting on beta adrenergic receptors, T3 can increase heart rate and pulse rate. Specifically, T3 increases systolic blood pressure but decreases diastolic blood pressure.
On lipids, T3 increases the rate of lipolysis. Specifically, it drives the breakdown of cholesterol and increases the number of LDL receptors.
In the brain, T3 increases the production of certain neurotransmitters especially serotonin.
The positive effect of T3 on serotonin is the reason it is now recommended (along with SSRIs or selective serotonin receptor inhibitors) in the treatment of drug-resistance and recurring depression and bipolar disorders. Different studies have established that long-term supplementation with T3 significantly improves the symptoms of (and may even “cure”) these psychological disorders.
T3 (or any of its prodrugs) is also used as a fat loss supplement. It has been proven to increase the metabolism of fatty acid and the breakdown of fat stored in adipose tissue
How T3 Can Promote Weight Loss
The only mechanism by which T3 promotes weight loss is by increasing metabolic rate.
Although it is a one-trick weight loss solution, that one trick is pretty remarkable. T3 increases basal metabolic rate by increasing the rate at which the body breaks down all food groups. It unlocks significant energy for the body to use, and it can produce very dramatic results especially in overweight people with diagnosed or silent hypothyroidism.
When the amount of thyroid hormones produced in the body falls, the rate of metabolism falls with it. In this regard, the amount of circulating T3 is more important than that of T4.
Because of the reduced metabolic rate, low thyroid functioning results in difficulty in reducing body weight. When overweight individuals adopt healthy, low caloric diets and take up regular exercise but still cannot shed weight, the most likely reason is low metabolic rate caused by low T3 levels.
Even a 10% reduction in metabolic rate can make weight loss very difficult. However, available clinical data suggest that most people who find it difficult to lose weight have 15 – 40% reduction in metabolic rate.
For this group of people, T3 is the magic remedy for losing weight.
The ability of T3 to prompting weight loss does not really depend on adopting a low caloric diet. In fact, the usual response to a low-carbohydrate diet is a reduction in the body’s metabolic rate. By supplementing with T3, the body keeps up a high rate of metabolism even with the amount of calories in the diet is reduced.
Exercise, on the other hand, has a more significant effect on the result of T3 supplementation in weight loss. In fact, T3 increases the amount of available energy, and practically encourages the user to exercise.
Unlike stimulants like caffeine and synephrine, T3 increases the rate of metabolism without such side effects as jitters. It does not make the user “hyper”. Instead, it simply energizes the user without the crash that comes from overstimulation with stimulants.
When taking T3 for weight loss, the aim is to increase the levels of T3 to the edge of the upper limit while not stepping over and setting off hyperthyroidism.
To do that, it is important to closely monitor the plasma levels of T3 while taking the supplement.
Where this is not possible, clear signs of hyperthyroidism such as irregular, rapid heartbeats should be the indication to stop T3 supplementation.
In most cases of abnormal weight gain even in the face of dieting and exercise, there is an impairment in the enzymes responsible for converting T4 to T3. Since most of the circulating T3 in the body comes from T4, such impairment makes it important to find another source of T3. This can be done through drugs and supplements that increase T3 levels.
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