Iodine in biology

Source: Wikipedia, the free encyclopedia.
Iodine cycle diagram showing various biological uses of Iodine

atomic weight). It is a component of biochemical pathways in organisms from all biological kingdoms, suggesting its fundamental significance throughout the evolutionary history of life.[1]

Iodine is critical to the proper functioning of the vertebrate

endocrine system, and plays smaller roles in numerous other organs, including those of the digestive and reproductive systems. An adequate intake of iodine-containing compounds is important at all stages of development, especially during the fetal and neonatal periods, and diets deficient in iodine
can present serious consequences for growth and metabolism.

Vertebrate functions

Thyroid

In

unicellular
organisms. Thyroid hormones play a fundamental role in biology, acting upon gene
adipocytes to increase carbohydrate absorption and fatty acid release, respectively.[2] A deficiency of thyroid hormones can reduce basal metabolic rate up to 50%, while an excessive production of thyroid hormones can increase the basal metabolic rate by 100%.[3] T4 acts largely as a precursor
to T3, which is (with minor exceptions) the biologically active hormone. Via the thyroid hormones, iodine has a nutritional relationship with
reverse T3 (rT3) by removing an inner ring iodine atom, and also convert T3 to 3,3'-Diiodothyronine
(T2) by removing an inner ring atom. Both of the latter products are inactivated hormones which have essentially no biological effects and are quickly prepared for disposal. A family of non-selenium-dependent enzymes then further deiodinates the products of these reactions.

The total amount of iodine in the human body is still controversial, and in 2001, M.T. Hays published in Thyroid that "it is surprising that the total iodine content of the human body remains uncertain after many years of interest in iodine metabolism. Only the iodine content of the thyroid gland has been measured accurately by fluorescent scanning, and it is now well estimate of 5–15 mg in the normal human thyroid. But similar methods are not available for other tissues and for the extrathyroidal organs. Many researchers reported different numbers of 10–50 mg of the total iodine content in human body".[4][5] Selenium also plays a very important role in the production of glutathione, the body's most powerful antioxidant. During the production of the thyroid hormones, hydrogen peroxide is produced in large quantities, and therefore high iodine in the absence of selenium can destroy the thyroid gland (often described as a sore throat feeling); the peroxides are neutralized through the production of glutathione from selenium. In turn, an excess of selenium increases demand for iodine, and deficiency will result when a diet is high in selenium and low in iodine.[citation needed]

Extrathyroidal iodine

neoplasias.[9]

The U.S. Food and Nutrition Board and Institute of Medicine recommended daily allowance of iodine ranges from 150 micrograms per day for adult humans to 290 micrograms per day for lactating mothers. However, the thyroid gland needs no more than 70 micrograms per day to synthesize the requisite daily amounts of T4 and T3. The higher recommended daily allowance levels of iodine seem necessary for optimal function of a number of other body systems, including lactating breasts, gastric mucosa, salivary glands, oral mucosa, arterial walls, thymus, epidermis, choroid plexus and cerebrospinal fluid, among others.[10][11][12]

Other functions

Iodine and thyroxine have also been shown to stimulate the spectacular

Xenopus laevis has proven to be an ideal model organism for experimental study of the mechanisms of apoptosis and the role of iodine in developmental biology.[13][1][14][15]

Invertebrate functions

It is believed that thyroid hormones evolved in the Urbilaterian well before the development of the thyroid itself and molluscs, echinoderms, cephalochordates and ascidians all use such hormones.[16] Cnidarians also respond to Thyroid hormone despite being parahoxozoans rather than bilaterians.[16][17]

Insects use hormones similar to thyroid hormone using iodine.[18][19][20]

Phosphorylated tyrosines created with tyrosine kinases are fundamental signalling molecules in all animals and in choanoflagellates.[21][22]

Non-animal functions

Iodine is known to be crucial for life in many unicellular organisms[23] Phosphorylated tyrosines created with tyrosine kinases are fundamental signalling molecules in all animals and in Choanoflagellates[21][22] and may be linked to the usage of tyrosine iodine compounds for similar roles.[23] Crockford proposes that iodine was originally used in protecting cell membranes from oxidative damage in photosynthesis and later moved into cytoplasm and became involved with balancing cytoplasmic composition of ions, and later the non enzymatic synthesis of tyrosine in early life.[23]

It is common across all domains of life and uses tyrosine bonded to iodine.[23]

Plants, insects, zooplankton and algae store iodine as mono-iodotyrosine (MIT), di-iodotyrosine (DIT), iodocarbons, or iodoproteins.[24][25][26]

Many plants use thyroid like hormones for regulating growth.[24][27]

Gut-inhabiting bacteria use iodine from host thyroid hormone.[28]

Thyroid-like hormones may be linked to the development of multicellularity.[29][30] Iodotyrosines are highly reactive with other molecules[31] which may have made them important cell signalling molecules early in evolutionary history.[23] They form spontaneously without need for enzymatic catalysts which may have contributed to their early adoption by organisms,[32][33] although enzymes make the yields significantly higher.[34]

The ease of reaction with water may explain why iodine is so common across cell signalling in all domains of life.[35]

Many photosynthetic microbes are able to reduce inorganic

methyl iodide.[41][36][42] Many sulfate-reducing microorganisms and Iron-oxidizing bacteria also reduce iodate to iodide[43][40] as well as many facultative anaerobic organisms[44] suggesting this may be ancestral among anaerobic organisms.[23]

Kelp store large quantities of iodide primarily as iodotyrosines for unknown reasons.[45][46]

Molecular iodine (I2) is toxic to most single-celled organisms by disrupting the cell membrane[47] however Alphaproteobacteria and Choanoflagellates are resistant.[48] Organisms such as Escherichia coli are killed by molecular iodine but require iodine from host thyroid hormone,[28] indicating that not all organisms that need iodine are resistant to the toxic effects of pure iodine.[23]

Dietary recommendations

The

tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. The UL for iodine for adults is 1,100 μg/day. This UL was assessed by analyzing the effect of supplementation on thyroid-stimulating hormone.[8] Collectively, the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes (DRIs).[49]

The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR; AI and UL are defined the same as in the United States. For women and men ages 18 and older, the PRI for iodine is set at 150 μg/day; the PRI during pregnancy or lactation is 200 μg/day. For children aged 1–17 years, the PRI increases with age from 90 to 130 μg/day. These PRIs are comparable to the U.S. RDAs with the exception of that for lactation.[50] The EFSA reviewed the same safety question and set its adult UL at 600 μg/day, which is a bit more than half the U.S. value.[51] Notably, Japan reduced its adult iodine UL from 3,000 to 2,200 µg/day in 2010, but then increased it back to 3,000 µg/day in 2015.[52]

As of 2000, the median observed 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.[49] In Japan, consumption is much higher due to the frequent consumption of seaweed or kombu kelp.[8] The average daily intake in Japan ranges from 1,000 to 3,000 μg/day; previous estimates suggested an average intake as high as 13,000 μg/day.[53]

Labeling

For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of

Daily Value (%DV). For iodine specifically, 100% of the Daily Value is considered 150 μg, and this figure remained at 150 μg in the May 27, 2016 revision.[54][55]
A table of the old and new adult daily values is provided at Reference Daily Intake.

Food sources

Natural sources of iodine include many marine organisms, such as

Iodized salt is fortified with iodine.[57] According to a Food Fortification Initiative 2016 report, 130 countries have mandatory iodine fortification of salt and an additional 10 have voluntary fortification.[citation needed
]

Deficiency

Main article: Iodine deficiency

Worldwide,

hypothyroidic
by a lack of dietary iodine (new hypothyroidism in adults may cause temporary mental slowing, but not permanent damage).

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 also gives rise to hypothyroidism, the most serious symptoms of which are epidemic goitre (swelling of the thyroid gland), extreme fatigue, mental slowing, depression, weight gain, and low basal body temperatures.[59]

The addition of iodine to table salt (so-called

iodized salt) has largely eliminated the most severe consequences of iodine deficiency in wealthier nations, but deficiency remains a serious public health problem in the developing world.[60] Iodine deficiency is also a problem in certain areas of Europe; in Germany, an estimated one billion dollars in healthcare costs is spent each year in combating and treating iodine deficiency.[8]

Iodine and cancer risk

Source:[61]

Precautions and toxicity

Elemental iodine

Elemental iodine is an

phase transfer catalyst
in the tincture. This allows Lugol's iodine to be produced in strengths varying from 2% to 15% iodine.

Elemental iodine (I2) is poisonous if taken orally in large amounts; 2–3 grams is a lethal dose for an adult human.[71][72]

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.

Iodide ion

Compared to the elemental form, potassium iodide has a median lethal dose (LD50) that is relatively high in several animals: in rabbits, it is 10 g/kg; in rats, 14 g/kg, and in mice, 22 g/kg.[73] The tolerable upper intake level for iodine as established by the Food and Nutrition Board is 1,100 µg/day for adults. The safe upper limit of consumption set by the Ministry of Health, Labor and Welfare in Japan is 3,000 µg/day.[74]

The biological half-life of iodine differs between the various organs of the body, from 100 days in the thyroid, to 14 days in the kidneys and spleen, to 7 days in the reproductive organs. Typically the daily urinary elimination rate ranges from 100 to 200 µg/L in humans.[75] However, the Japanese diet, high in iodine-rich kelp, contains 1,000 to 3,000 µg of iodine per day, and research indicates the body can readily eliminate excess iodine that is not needed for thyroid hormone production.[74] The literature reports as much as 30,000 µg/L (30 mg/L) of iodine being safely excreted in the urine in a single day, with levels returning to the standard range in a couple of days, depending on seaweed intake.[76] One study concluded the range of total body iodine content in males was 12.1 mg to 25.3 mg, with a mean of 14.6 mg.[77] It is presumed that once thyroid-stimulating hormone is suppressed, the body simply eliminates excess iodine, and as a result, long-term supplementation with high doses of iodine has no additional effect once the body is replete with enough iodine. It is unknown if the thyroid gland is the rate-limiting factor in generating thyroid hormone from iodine and tyrosine, but assuming it is not, a short-term loading dose of one or two weeks at the tolerable upper intake level may quickly restore thyroid function in iodine-deficient patients.[citation needed]

Excessive iodine intake presents symptoms similar to those of iodine deficiency. Commonly encountered symptoms are abnormal growth of the thyroid gland and disorders in functioning,[78] as well as in growth of the organism as a whole. Iodide toxicity is similar to (but not the same as) toxicity to ions of the other halogens, such as bromides or fluorides. Excess bromine and fluorine can prevent successful iodine uptake, storage and use in organisms, as both elements can selectively replace iodine biochemically.

Excess iodine may also be more cytotoxic in combination with selenium deficiency.[79] Iodine supplementation in selenium-deficient populations is theoretically problematic, partly for this reason.[8] Selenocysteine (abbreviated as Sec or U, in older publications also as Se-Cys)[80] is the 21st proteinogenic amino acid, and is the root of iodide ion toxicity when there is a simultaneous insufficiency of biologically available selenium. Selenocysteine exists naturally in all kingdoms of life as a building block of selenoproteins.[81]

Hypersensitivity reactions

Some people develop a hypersensitivity to compounds of iodine but there are no known cases of people being directly allergic to elemental iodine itself.[82] Notable sensitivity reactions that have been observed in humans include:

Medical use of iodine compounds (i.e. as a

anaphylactic shock in highly sensitive patients, presumably due to sensitivity to the chemical carrier. Cases of sensitivity to iodine compounds should not be formally classified as iodine allergies, as this perpetuates the erroneous belief that it is the iodine to which patients react, rather than to the specific allergen. Sensitivity to iodine-containing compounds is rare but has a considerable effect given the extremely widespread use of iodine-based contrast media; however, the only adverse effect of contrast material that can convincingly be ascribed to free iodide is iodide mumps and other manifestations of iodism.[84]


See also

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