Supplement Performance - Does Selenium Affect Thyroid Hormone Metabolism?
Basic Facts about Thyroid Hormones
The principal hormones secreted by the thyroid are thyroxine (T4) and triiodothyronine (T3). T3 is also formed in the peripheral tissues by deiodination of T4. Small amounts of reverse triiodothyronine (RT3) and other compounds are also found in thyroid venous blood. T3 is more active than T4, whereas RT3 is inactive.
The normal total plasma (blood) T4 level in adults is approximately 103 nmol/l and the plasma T3 level is approximately 2.3 nmol/l.1 Large amounts of both are bound to plasma proteins. It’s the free thyroid hormones in plasma that are physiologically active. Normally, 99.98 percent of the T4 in plasma is bound.1 T3 is not bound to quite as great an extent; 0.2 percent is free.1 Diet has a clear-cut effect on conversion of T4 to T3. In fasted individuals, plasma T3 is reduced 10-20 percent in 24 hours and about 50 percent in three to seven days, with corresponding rise in RT3. The decline in T3 conserves calories.
T4 and T3 increase the oxygen consumption (i.e., energy expenditure) of almost all metabolically active tissues. Some of the calorigenic effect of thyroid hormones is due to metabolism of the fatty acids they mobilize. In addition, thyroid hormones increase the activity of the membrane-bound sodium-potassium activated adenosine triphosphatase (Na -K ATPase) in many tissues. Na -K ATPase catalyzes the hydrolysis (breakdown) of ATP to ADP and uses energy to extrude three Na from the cell and take two K into cell for each mole of ATP hydrolyzed. Active transport of Na and K is one of the major energy-using processes in the body. On the average, it accounts for about 24 percent of the energy utilized by cells and in neurons it accounts for 70 percent.2 Thus, it accounts for a large part of the basal metabolism.
Thyroid function is controlled by the thyroid-stimulating hormone (TSH) of the anterior pituitary. The secretion of this hormone is in turn regulated in part by thyrotropin-releasing hormone (TRH) from the hypothalamus and is subject to negative feedback control by high circulating levels of T3 and T4 acting on the anterior pituitary and the hypothalamus. Measurement of TSH is now widely regarded as one of the best tests of thyroid function.1
Basic Facts About Selenium
Selenium is an essential trace nutrient for humans, animals and bacteria. The U.S. recommended dietary allowance (RDA) for selenium is 55 micrograms per day for adult men; the minimum requirement for men has been estimated at 21 micrograms per day. The U.S. Environmental Protection Agency established an “oral reference dose” of five micrograms per kilogram body weight and the National Academy of Sciences has set the maximum safe dietary intake at 400 micrograms per day.
Selenium occurs naturally in foods almost exclusively in the form of organic compounds, primarily selenomethione, selenocystine, selenocysteine, and se-methyl selenomethione.3 Inorganic forms of selenite include selenite and selenate.
These inorganic forms may be found in some vegetables. In addition, in those parts of the world where selenium levels in natural foodstuffs are low, animal feeds are generally supplemented with sodium selenite.3
Adequate selenium may be obtained on a healthful, balanced diet containing a substantial amount of grain products. However, in their review, Drs. Burk and Levander cite evidence that selenium supplementation resulted in a significant reduction in total cancer, most notably prostate, colorectal and lung cancer.4 In a subsequent study, Dr. Clark and co-workers reported selenium supplementation (200 micrograms/day) over a 4.5-year period reduced prostate cancer by 63 percent.5
The results were so significant that the investigators stopped this study prematurately so those receiving the placebo could possibly benefit. Some studies by Dr. Tessler and associates have shown that selenium supplementation will enhance glutathione peroxidase status and reduce lipid peroxidation during prolonged aerobic exercise.6 Although these findings are intriguing, selenium supplementation did not improve actual physical performance. If you decide to take a selenium supplement, most experts agree that a selenium or multivitamin-mineral supplements with no more than 200 micrograms is safe.
Selenium and Thyroid Hormone Metabolism
A major advance in our understanding of selenium´s role in metabolism began with the discovery that type I iodothyrodine deiodinase, the enzyme responsible in humans for most of the peripheral conversion of T4 to T3, is a selenoenzyme. More recently, it was discovered that the type II deiodinase (responsible for T4 conservion to T3 in the brain) and the type III deiodinase (the inner ring deiodinase responsible for deactivating T4 and T3) are also selenoenzymes.
Studies of selenium and thyroid hormone metabolism have been conducted in rats. Unfortunately, studies in rats cannot be extrapolated to humans because circulating T3 is produced mainly by deiodination of T4 in the liver in humans, but comes primarily by release from the thyroid in rats. Most studies of selenium and thyroid hormone have used sodium selenite as the source of dietary selenium. However, selenite is an insignificant source of selenium in human diets (except for some selenium supplements) and possesses potent pharmacological activities unrelated to the nutritional requirement for selenium.
Thus, Dr. Wayne Hawkes and colleagues at the U.S. Department of Agriculture hypothesized that the effects of selenium in food in humans would be different from the reported effects of selenite in rats. They fed 11 men a controlled diet of conventional foods with naturally high or low selenium content for 120 days while confined to a metabolic research unit to identify the metabolic effects in humans of dietary selenium as it occurs naturally in foods. Interestingly, the results of this study suggest that dietary selenium modulates thyroid hormone metabolism and serum (blood) T3 concentrations, which leads to changes in energy metabolism and subsequent changes in body weight and composition. In the high selenium group, decreases in serum T3 and compensatory increases in TSH suggest that a sub-clinical hypothyroid response was induced by the high selenium diet and that decreased energy expenditure caused the observed weight gain.
In the low selenium group, increases in serum T3 and serum triacylglyceroles accompanied by losses of body fat suggest that sub-clinial hyperthyroidism response was induced by the low selenium diet and that increased energy expenditure caused the observed weight loss. According to authors of this study, the increased TSH in the high selenium group and the body fat loss in the low selenium group indicate that these were physiologically important changes in thyroid status.
A simple extrapolation suggests that if the effect of high dietary selenium were to persist, it could cause a weight gain of up to 12 kilograms(26.4 pounds) in five years. However, selenium-induced weight gain might be an unanticipated advantage of selenium treatment in current and proposed clinical trials for AIDS and cancer.
Bottom Line
According to Dr. Hawkes and co-workers, “The results of this study suggest that changes in the activities of selenoenzymes involved in thyroid hormone metabolism led to shifts in circulating T3 concentrations and perturbations of the pituitary-thyroid axis. The resulting sub-clinical hypothyroid and hyperthyroid responses caused changes in the expenditure of metabolic energy leading to gradual changes in body weight and composition, which, over time, might be physiologically important.” However, much more work is required to determine the significance of these observations to the general gym rat population. Also, this study does not suggest that selenium supplements modulate thyroid hormone metabolism.
TRIAC Update
Triiodothyroacetic acid (TRIAC), also known as Tiratricol, is a naturally occurring metabolite of T3. In humans, the amount of TRIAC produced by the liver and other tissues accounts for about 14 percent of T3 metabolism. This production is increased in some situations, such as fasting.
TRIAC has been used with some success as a prescription drug to suppress thyrotropin secretion in patients with non-tumoral pituitary resistance to thyroid hormones. More recently, it has been promoted as a dietary supplement to aid in weight loss. However, the FDA feels TRIAC is not a dietary supplement, but an unapproved new drug containing a potent thyroid hormone, which may cause serious health consequences.
Recently, Dr. Medina-Gomez and colleagues compared the thermogenic action of TRIAC versus T3 in brown fat tissue by studying target genes known to stimulate thermogenic action: uncoupling protein 1 (UCP-1) and type II-5´deiodinase (D2), which provides the T3 required for thermogenesis.8 Interestingly, results indicated that TRIAC is 10-50 times more potent than T3. However, as pointed out by authors, exogenous (supplemental) administration of TRIAC should be avoided due to its TSH-suppressing effects.
