Iodine in biology
Encyclopedia
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).
hormone
s, 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 deiodinase
s 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.
(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.
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
.
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.
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.
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.
gland and disorders in functioning and growth of the organism as a whole. Iodides are similar in toxicity to bromide
s.
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.
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.
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
is an essential trace element
Trace element
In analytical chemistry, a trace element is an element in a sample that has an average concentration of less than 100 parts per million measured in atomic count, or less than 100 micrograms per gram....
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
Tungsten
Tungsten , also known as wolfram , is a chemical element with the chemical symbol W and atomic number 74.A hard, rare metal under standard conditions when uncombined, tungsten is found naturally on Earth only in chemical compounds. It was identified as a new element in 1781, and first isolated as...
, 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 thyroidThyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s, thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
(T4) and triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....
(T3). These are made from addition condensation products of the amino acid tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
, and are stored prior to release in an iodine-containing protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
called thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....
. T4 and T3 contain four and three atoms of iodine per molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
, respectively. The thyroid gland actively absorbs iodide from the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
to make and release these hormones into the blood, actions which are regulated by a second hormone TSH
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
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
Basal metabolic rate
Basal Metabolic Rate , and the closely related resting metabolic rate , is the amount of daily energy expended by humans and other animals at rest. Rest is defined as existing in a neutrally temperate environment while in the post-absorptive state...
. 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
Selenium
Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...
. A family of selenium-dependent enzymes called deiodinase
Deiodinase
Iodothyronine deiodinases are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine , the precursor of 3,5,3’-triiodothyronine is transformed into T3 by deiodinase activity. T3, through binding a nuclear thyroid hormone receptor,...
s 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
3,3'-Diiodothyronine
3,3'-Diiodothyronine is a metabolite of thyroid hormone.It is formed from the breakdown of triiodothyronine. It is an allosteric regulator of the Cytochrome C Oxidase, the complex IV of the electron transport chain. It increases its activity by preventing the interaction of ATP as an allosteric...
(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 symporterSodium-iodide symporter
The sodium/iodide symporter , also known as solute carrier family 5, member 5 is a protein that in humans is encoded by the SLC5A5 gene. The sodium/iodide symporter is a transmembrane glycoprotein with a molecular weight of 87 kDa and 13 transmembrane domains, which transports two sodium cations ...
(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
Docosahexaenoic acid
Docosahexaenoic acid is an omega-3 fatty acid that is a primary structural component of the human brain and retina. In chemical structure, DHA is a carboxylic acid with a 22-carbon chain and six cis double bonds; the first double bond is located at the third carbon from the omega end...
and arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
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 IntakeDietary Reference Intake
The Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...
recommended by the United States Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
is between 110 and 130 µg
Microgram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...
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
Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
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
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
.
Range of observed intakes
Natural sources of iodine include sea life, such as kelpKelp
Kelps are large seaweeds belonging to the brown algae in the order Laminariales. There are about 30 different genera....
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
Kombu
Kombu or konbu , also called dashima or haidai , is edible kelp from the family Laminariaceae widely eaten in East Asia....
kelp.
After iodine fortification programs (e.g. iodized salt) have been implemented, some cases of iodine-induced hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
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 deficiencyIodine deficiency
Iodine is an essential trace element; the thyroid hormones thyroxine and triiodotyronine contain iodine. In areas where there is little iodine in the diet—typically remote inlandareas where no marine foods are eaten—iodine deficiency gives rise to...
gives rise to hypothyroidism, symptoms of which are extreme fatigue, goitre
Goitre
A goitre or goiter , is a swelling in the thyroid gland, which can lead to a swelling of the neck or larynx...
(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
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, 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 atypiaAtypiaAtypia is a clinical term for abnormality in a cell. The term is medical jargon for an atypical cell. Atypia: Etymology: Gk, a + typos, without type; a condition of being irregular or nonstandard....
and increased incidence of malignancy in animal models, while iodine treatment can reverse dysplasiaDysplasiaDysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...
. Laboratory evidences demonstrate that the effect of iodine on breast cancer is in part independent of thyroidThyroidThe thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
function and that iodine inhibits cancer promotion through modulation of the estrogenEstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
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 reducingRedoxRedox reactions describe all chemical reactions in which atoms have their oxidation state changed....
species that can detoxify poisonous reactive oxygen speciesReactive oxygen speciesReactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
, such as hydrogen peroxideHydrogen peroxideHydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
.
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 iodineTincture of iodine
Tincture of iodine is a disinfectant, usually 2–7% elemental iodine, along with potassium iodide or sodium iodide, dissolved in a mixture of ethanol and water. As in the case of Lugol's iodine, the role of iodide and water in the solution is to increase the solubility of the elemental iodine, by...
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
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
, 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
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
and water, elemental iodine forms nitrogen triiodide
Nitrogen triiodide
Nitrogen triiodide is the inorganic compound with the formula NI3. It is an extremely sensitive contact explosive: small quantities explode with a gunpowder-like snap when touched even lightly, releasing a purple cloud of iodine vapor...
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 thyroidThyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
gland and disorders in functioning and growth of the organism as a whole. Iodides are similar in toxicity to bromide
Bromide
A bromide is a chemical compound containing bromide ion, that is bromine atom with effective charge of −1. The class name can include ionic compounds such as caesium bromide or covalent compounds such as sulfur dibromide.-Natural occurrence:...
s.
Excess iodine can be more cytotoxic
Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...
in the presence of selenium deficiency
Selenium deficiency
Selenium deficiency is relatively rare in healthy well-nourished individuals. Few cases have been reported.-Causes:It can occur in patients with severely compromised intestinal function, those undergoing total parenteral nutrition, those who have had gastrointestinal bypass surgery, and also on...
.
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 iodineTincture of iodine
Tincture of iodine is a disinfectant, usually 2–7% elemental iodine, along with potassium iodide or sodium iodide, dissolved in a mixture of ethanol and water. As in the case of Lugol's iodine, the role of iodide and water in the solution is to increase the solubility of the elemental iodine, by...
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.