Iodine in biology

Iodine is an essential trace element for life, the heaviest element commonly needed by living organisms, and the second-heaviest known to be used by any form of life (only tungsten, a component of a few bacterial enzymes, has a higher atomic number and atomic weight).

The thyroid
Iodine's main role in animal biology is as constituents of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). These are made from addition condensation products of the amino acid tyrosine, and are stored prior to release in an iodine-containing protein called thyroglobulin. T4 and T3 contain four and three atoms of iodine per molecule, respectively. The thyroid gland actively absorbs iodide from the blood to make and release these hormones into the blood, actions which are regulated by a second hormone TSH from the pituitary. Thyroid hormones are phylogenetically very old molecules which are synthesized by most multicellular organisms, and which even have some effect on unicellular organisms.

Thyroid hormones play a basic role in biology, acting on gene transcription to regulate the basal metabolic rate. The total deficiency of thyroid hormones can reduce basal metabolic rate up to 50%, while in excessive production of thyroid hormones the basal metabolic rate can be increased by 100%. T4 acts largely as a precursor to T3, which is (with minor exceptions) the biologically active hormone.

Iodine has a nutritional relationship with selenium. A family of selenium-dependent enzymes called deiodinases converts T4 to T3 (the active hormone) by removing an iodine atom from the outer tyrosine ring. These enzymes also convert T4 to reverse T3 (rT3) by removing an inner ring iodine atom; and convert T3 to 3,3'-Diiodothyronine (T2) also by removing an inner ring atom. Both of the latter are inactivated hormones which are ready for disposal and have essentially no biological effects. A family of non-selenium dependent enzymes then further deiodinates the products of these reactions.

Extrathyroidal iodine
Iodine accounts for 65% of the molecular weight of T4 and 59% of the T3. 15–20 mg of iodine is concentrated in thyroid tissue and hormones, but 70% of the body's iodine is distributed in other tissues, including mammary glands, eyes, gastric mucosa, the cervix, and salivary glands. In the cells of these tissues iodide enters directly by sodium-iodide symporter (NIS). Its role in mammary tissue is related to fetal and neonatal development, but its role in the other tissues is unknown. It has been shown to act as an antioxidant in these tissues.

The US Food and Nutrition Board and Institute of Medicine recommended daily allowance of iodine ranges from 150 micrograms /day for adult humans to 290 micrograms /day for lactating mothers. However, the thyroid gland needs no more than 70 micrograms /day to synthesize the requisite daily amounts of T4 and T3. These higher recommended daily allowance levels of iodine seem necessary for optimal function of a number of body systems, including lactating breast, gastric mucosa, salivary glands, oral mucosa, thymus, epidermis, choroid plexus, etc. Moreover, iodine can add to double bonds of docosahexaenoic acid and arachidonic acid of cellular membranes, making them less reactive to free oxygen radicals.

Iodine and immunity
Iodine has important actions in the immune system. The high iodide-concentration of thymus tissue suggests an anatomical rationale for this role of iodine in the immune system.

Iodine in salivary glands and oral health
The trophic, antioxidant and apoptosis-inductor actions and the presumed anti-tumour activity of iodides might also be important for prevention of oral and salivary glands diseases.

Dietary reference intake and recommended daily allowance
The daily Dietary Reference Intake recommended by the United States Institute of Medicine is between 110 and 130 µg for infants up to 12 months, 90 µg for children up to eight years, 130 µg for children up to 13 years, and 150 µg for adults. Pregnant women have a DRI of 220 µg and lactating mothers require 290 µg.

The United States Recommended Daily Allowance (RDA) is 150 micrograms per day (μg/day) for both men and women, with a Tolerable Upper Intake Level (UL) for adults is 1,100 μg/day (1.1 mg/day). The tolerable upper limit was assessed by analyzing the effect of supplementation on thyroid-stimulating hormone.

Range of observed intakes
Natural sources of iodine include sea life, such as kelp and certain seafood, as well as plants grown on iodine-rich soil. Iodized salt is fortified with iodine.

As of 2000, the median intake of iodine from food in the United States was 240 to 300 μg/day for men and 190 to 210 μg/day for women. In Japan, consumption is much higher due to the frequent consumption of seaweed or kombu kelp.

After iodine fortification programs (e.g. iodized salt) have been implemented, some cases of iodine-induced hyperthyroidism have been observed (so called Jod-Basedow disease). The condition mainly seems to occur in people over forty, and the risk appears higher when iodine deficiency is severe and the initial rise in iodine intake is high.

Deficiency
In areas where there is little iodine in the diet, typically remote inland areas and semi-arid equatorial climates where no marine foods are eaten, iodine deficiency gives rise to hypothyroidism, symptoms of which are extreme fatigue, goitre (swelling in the thyroid gland), mental slowing, depression, weight gain, and low basal body temperatures.

Iodine deficiency is the leading cause of preventable mental retardation, a result which occurs primarily when babies or small children are rendered hypothyroidic by a lack of the element. The addition of iodine to table salt has largely eliminated this problem in the wealthier nations, but as of March 2006, iodine deficiency remained a serious public health problem in the developing world. Iodine deficiency is also a problem in certain areas of Europe. In Germany it has been estimated to cause a billion dollars in health care costs per year.

Iodine may also help prevent diseases of the oral and salivary glands.

Iodine and cancer risk

 * Breast cancer. The breast strongly and actively concentrates iodine into breast-milk for the benefit of the developing infant, and may develop a goiter-like hyperplasia, sometimes manifesting as fibrocystic breast disease, when iodine level are low. Studies indicate that iodine deficiency, either dietary or pharmacologic, can lead to breast atypia and increased incidence of malignancy in animal models, while iodine treatment can reverse dysplasia. Laboratory evidences demonstrate that the effect of iodine on breast cancer is in part independent of thyroid function and that iodine inhibits cancer promotion through modulation of the estrogen pathway. Gene array profiling of estrogen responsive breast cancer cell line shows that the combination of iodine and iodide alters gene expression and inhibits the estrogen response through up-regulating proteins involved in estrogen metabolism. Whether iodine/iodide will be useful as an adjuvant therapy in the pharmacologic manipulation of the estrogen pathway in women with breast cancer has not been determined clinically.


 * Iodine and stomach cancer. Some researchers have found an epidemiologic correlation between iodine deficiency, iodine-deficient goitre and gastric cancer;  a decrease of the incidence of death rate from stomach cancer after implementation of the effective iodine-prophylaxis has been reported also. The proposed mechanism of action is that iodide ion can function in gastric mucosa as an antioxidant reducing species that can detoxify poisonous reactive oxygen species, such as hydrogen peroxide.

Precautions and toxicity of elemental iodine
Elemental iodine is an oxidizing irritant and direct contact with skin can cause lesions, so iodine crystals should be handled with care. Solutions with high elemental iodine concentration such as tincture of iodine and Lugol's solution are capable of causing tissue damage if use for cleaning and antisepsis is prolonged.

Elemental iodine (I2) is poisonous if taken orally in larger amounts; 2–3 grams of it is a lethal dose for an adult human.

Iodine vapor is very irritating to the eye, to mucous membranes, and in the respiratory tract. Concentration of iodine in the air should not exceed 1 mg/m³ (eight-hour time-weighted average).

When mixed with ammonia and water, elemental iodine forms nitrogen triiodide which is extremely shock sensitive and can explode unexpectedly.

Toxicity of iodide ion
Excess iodine has symptoms similar to those of iodine deficiency. Commonly encountered symptoms are abnormal growth of the thyroid gland and disorders in functioning and growth of the organism as a whole. Iodides are similar in toxicity to bromides.

Excess iodine can be more cytotoxic in the presence of selenium deficiency. Iodine supplementation in selenium-deficient populations is theoretically problematic, partly for this reason.

Iodine sensitivity
Some people develop a sensitivity to iodine. Application of tincture of iodine can cause a rash. Some cases of reaction to Povidone-iodine (Betadine) have been documented to be a chemical burn. Eating iodine-containing foods can cause hives. Medical use of iodine (i.e. as a contrast agent, see above) can cause anaphylactic shock in highly iodine sensitive patients. Some cases of sensitivity to iodine can be formally classified as iodine allergies. Iodine sensitivity is rare but has a considerable effect given the extremely widespread use of iodine-based contrast media.