Download Does Selenium Affect Thyroid Hormone Metabolism?

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By Anssi Manninen, MHS
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 semethyl 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.
References
1. Ganong WF (2001) The thyroid gland. In: Review of Medical Physiology. New York: Lange
Medical Books/McGraw-Hill, pp. 307-321.
2. Ganong WF (2001) The general & cellular basis of medical physiology. In: Review of Medical
Physiology. New York: Lange Medical Books/McGraw-Hill, pp. 1-48.
3. Groff JL, Gropper SS (2000) Microminerals. In: Advanced Nutrition and Human Metabolism.
Belmont, CA: Wadsworth, pp. 401-470.
4. Burk RF, Levander OA (1999) Selenium. In: Shils M et al., eds. Modern Nutrition in Health
and Disease. Baltimore: Williams & Wilkins.
5. Clark LC et al. (1998) Decreased incidence of prostate cancer with selenium
supplementation: Results of a double-blind cancer prevention trial. British J Urology, 81:730734.
6. Tessler F et al. (1995) Selenium and training effects on the glutathione system and aerobic
exercise. Med Sci Sports Exerc, 27:390-396.
7. Hawkes WC (2003) Dietary selenium intake modulates thyroid hormone and energy
metabolism in men. J Nutr, 133:3443-3448.
8. Medina-Gomez G et al. (2003) Potent thermogenic action of triiodothyroacetic acid in brown
adipocytes. Cell Mol Life Sci, 60:1957-1967.