Iodine

Iodine (I) is an essential mineral whose name is derived from the greek term for violet or purple, in reference to the color of the gas it forms in its natural state. Dietary iodine is exclusively found either in the form of iodide (a water soluble anion with the formula of I^-), inorganic iodine (I₂), iodide (the cation), or as a salt such as potassium iodide or sodium iodide.^[1] It is the heaviest nutritional element with an atomic weight of 126.90447g per mole.

Iodine is an essential mineral commonly associated with the thyroid; it has a role in cognitive development

Iodine is commonly found (naturally) in seaweed^[2] due to an ability of seaweed to bioaccumulate and concentrate iodine from the seawater, with some species being known to concentrate iodine up to 30,000-fold higher than that found in the water.^[3]

• Kombu or Kelp, which refers to the genera Laminaria such as Laminaria digitata at 2,353-2,660µg/g when dried^[4][5][6] although on average kelp (all species) average 1,542μg/g by dry weight^[7]
• Wakame, which refers to the Undaria genera such as Undaria pinnatifida at 35-77µg/g^[6][2]
• Nori, which refers to the genera Porphyra such as Porphyra tenera at 12µg/g (fresh weight)^[6] and 43µg/g (dry weight);^[4] the lowest of tested seaweeds^[4]
• Palmaria palmata (Dulse; seaweed) at 44.1µg/g when dried^[4]
• Eisenia bicycli (Arame; seaweed) at 706-721µg/g when dried^[4]
• Alaria esculenta (seaweed) at 100µg/g^[8]
• Dried Hijiki (sea grass) at 391µg/g^[4]
• Kelp Granules (used as a salt substitute) at 67µg/g^[4] although very high levels have been reported in some case studies investigating granules made from Laminaria digitata (8,165+/-373µg/g)^[6]
• Cod (fresh and raw) at 1,050µg/kg^[4]
• Haddock (fresh and raw) at 2,500µg/kg^[4]
• Herring (raw) at 290µg/kg^[4]
• Kippers (raw) at 550µg/kg^[4]
• Mackeral (raw) at 1,380µg/kg^[4]
• Mussels (fresh and boiled) at 1,160µg/kg^[4]
• Plaice (fresh and raw) at 280µg/kg^[4]
• Prawns (frozen) at 210µg/kg^[4]
• Red snapper (fresh) at 650µg/kg^[4]
• Salmon at 590µg/kg^[4]
• Sardines (fresh and raw) at 290µg/kg^[4]
• Rainbow Trout (fresh) at 130µg/kg^[4]
• Tuna (canned) at 140µg/kg^[4]

Distinctions between wet and dry weight for seaweed is crucial since some species of seaweed may swell up to 10 times their weight when fully hydrated, and moisture content is around 70% when hydrated yet only 7-20% when dried.^[9]

Sea products (seaweed and fish) are the highest naturally occurring sources of iodine with seaweed a significantly better source than fish, insofar that the smallest possible difference (Nori versus Haddock) is about 5-fold greater in seaweed and the largest possible difference (Kombu versus Tuna) is 19,000-fold greater in seaweed. Some seaweed products appear to be high enough that they are considered excessive sources that may put one above the tolerable upper limit (TUL) of iodine

Iodine from seaweed is relatively well absorbed, ranging from around 60% to complete absorption.^[10] That being said, iodine can be significantly reduced from kombu via heat treatment (boiling for 15 minutes eliminates up to 99% of iodine) whereas other genera may have lower losses, such as 40% in sargassum,^[7] and this processing of kelp is sometimes associated with application of a dye to result in the products "ao-kombu" or "kizami-kombu" (boiling for 30 minutes in dye and then hang drying).^[7] Due to this processing, some sources have noted variability in Kombu products (in this source, soup) between 660µg/L and 31,000µg/L (or 165-7,750µg per 250mL serving).^[11]

Furthermore, many traditional dishes utilizing seaweed in the Japanese diet tend to also include vegetables with a known goitrogen content (broccoli, cabbage, bok choi and soy)^[7][6] which are known to compete with iodine for uptake into the thyroid^[12][13] or in the case of soy isoflavones reduce the incorporation of iodine into active thyroid hormones;^[14] this attenuates possible thyrotoxicosis from high iodine intake. Furthermore, some species of seaweeds may contain high levels of the nondietary mineral bromide (as bromine)^[15] which also possesses anti-thyroid properties^[16] which may reduce the risk of thyrotoxicosis.

Despite the aforementioned, there are still many cases of iodine induced goitre and thyrotoxicosis associated with high seaweed consumption (mostly Kombu) that is successfully treated with seaweed and iodine restriction.^{[17][11][18][19][20]}

Despite the very high iodine content in seaweed, there are many reasons to explain why dietary inclusion is not completely toxic. These include iodine losses with heat treatment, a trend to consume Nori and Wakame over Kombu, and coingestion of seaweed with goitrogen containing foods; there are still some cases of iodine toxicity, but these are thought to be due to poor processing and even then excessive dietary intake

For other food products, iodine concentrations are around:

• Milk (fortified to an average of 150µg/kg with a range of 40-320µg/kg in Britain^[4])
• Brazil nuts (210µg/kg), cashews (110µg/kg), hazelnuts (170µg/kg), and walnuts (90µg/kg)^[4]
• Frankfurters (180µg/kg)^[4]
• Pork (70µg/kg) and Beef (60µg/kg) sausage^[4]

Other potential dietary and nondietary sources of iodine that add to the iodine content of the body include the red food coloring erythrosine (E127, C.J. 45430, which is 57.7% iodine by weight^[21]) and some medications such as Povidone-iodine.^[22]

Salt is known to contain iodine due to Universal Salt Iodization, where iodine is added to salt either in the form of potassium iodate (KIO₃) or potassium iodide (KI).^[23] The exact content of iodine in salt varies depending on country, but it has been reported to be in the range of 15-25μg/g (15-25ppm) with less than 10μg/g is seen as inadequate^[24] and higher doses up to 40μg/g used selectively in regions where there is less iodine in the diet and iodine deficiency is more prevalent.^[25] In some areas of the world, iodized poppy seed oil (Lipiodol) is used as an iodine supplement.^[26][27]

In regards to other food products, the iodine concentration appears to be low enough that overshooting the tolerable upper limit (lowest estimate being 1,000µg) is unlikely to occur and sufficient enough that consumption of a varied diet is enough to assure sufficiency

Requirements can be explained as how much of a nutrient is either needed outright or recommended, whereas Status refers to how much of a nutrient a population is consuming relative to the requirements. Whereas 100μg may be a requirement, Deficient relative to that requirement is a status

For infants under six months, a daily intake of around 110μg iodine is required as the AI (adequate intake) and after six months this increases to 130μg.^[28][29]

For lactating women, a dietary intake of 290μg is recommended.^[28]

Due to the importance of iodine in proper cognitive function of children, the American Thyroid Association has recommended supplementation of 150μg for lactating women in first world nations (Canada and the US)^[30] which is on the lower range of supplemental intake since most women are sufficient (and the iodine is preventing a worst case scenario of sudden dietary restriction).

The adequate intake of iodine (AI) tends to be in the low 100s to high 200s when measured in micrograms when looking at all age groups.

Iodine deficiency can be detected via urinary iodine concentrations, as up to 97% of dietary iodine is excreted in the urine. The World Health Organization (WHO) recommends a concentration in the range of 150-249μg/L^[31] with less than 100μg/L is seen as deficient^[32][24] and the upper limit being 300μg/L. Urinary iodine is a relatively rapid biomarker, as it can increase from 100μg/L to 30,000μg/L within a single day and return to 100μg/L within a few days^[33] and thus is more reflective of daily habits than it is of bodily iodine storages.

Iodine status of the body can be detected via urinary measurements, although these urinary concentrations change quite rapidly and are more reflective of daily iodine intake and dietary routines than it is of bodily iodine stores

Japanese diets are thought to have a daily iodine intake of 1,000-3,000µg^[7] with some estimates at the lower range.^[5] This is based off of a relatively consistent intake of seaweed (4.3-5.3g daily^[34]) frequently (up to 21% of meals^[35] and 20-38% of the adult population consuming more than five servings a week and only 1-2% 'rarely' consuming seaweed^[36]) which recently has been favoring Wakame and Nori over Kelp (assessed via trends in survey research).^[5][34][37]

British diets appear to have an estimated 166-177µg daily (1985 and 1991 numbers).^[4]

Americans have been noted to have urinary iodine concentrations of 168μg/L (and pregnant women at 173μg/L) in 2001-2002 data,^[30] within the recommended range by the WHO.

First world nations (Japan, Britain, USA) all seem to be, on average, in the sufficient range for dietary iodine intake although the Japanese diet is above the TUL as it is set in other nations (at 1,000µg). This seems to be fine statistically speaking, since the Japanese themselves have a higher TUL of 3,000µg which the national average does not exceed

When looking at third world nations and a global scale, it is thought that up to two billion persons worldwide are at risk for developing iodine deficiency^[38][39] and the world bank suspects that this iodine deficiency precedes a reduciton of up to 10-15 IQ points seen in children born in iodine deficient areas and may contribute to a 5% reduced global market capacity attributed to micronutrient deficiencies.^[40][41]

The Japanese diet appears to have the highest dietary iodine intake, although most other first world nations have diets that are sufficient in dietary iodine. Third world nations are known to be plagued by iodine deficiency, however

Mild iodine deficiency in children is known to contribute to growth retardation, impaired hearing capacity and reduced cognitive function while severe iodine deficiency results in cretinism^[42][43] which can be fully prevented with sufficient maternal iodine prior to conception^[44] and rates of cretinism have seemingly been abolished with the introduction of an iodinized food supply (via table salt).^[45][46]

Severe iodine deficiency in a mother prior to conception results in cretinism of the child (severe and irreversible mental retardation) but cretinism has since been pretty much abolished in first world nations since table salt was iodinized (added iodine) resulting in more exposure to iodine in the food supply

It is still possible that a relative iodine deficiency (not severe enough to result in irreversible cretinism) may result in impaired cognition, and a meta-analysis of trials investigating the IQ of children have noted that areas with higher iodine intakes (relative to iodine deficiency areas) have a pooled higher IQ of 13.5 points.^[47]

A relative deficiency of iodine is known to occur to a relatively higher degree in pregnant women, lactating women, and infants due to high requirements for iodine.^[32] Populations with a low iodine intake relative to a higher thiocyanate intake are at increased risk (due to competitive inhibition of iodine uptake into the thyroid)^[48] as are vegans (who do not consume seaweed)^[49][50][51] and lactovegetarians who do not consume seaweed.^[52] Rates of deficiencies (assessed by urinary iodine below 100μg/L) in vegetarians and vegans have been reported to be as high as 25% and 80%, respectively.^[53]

Intestinal malabsorption states are not associated with a reduced iodine status.^[54]

A relative deficiency (lower than ideal intake but enough to prevent cretinism) appears to be associated with less cognitive potential, and populations at risk for mild iodine deficiency include pregnant and lactating women as well as their infants

For adults, the tolerable upper limit for iodine intake has been recommended to be 1,100μg (Institute of Medicine; IOM) whereas the world health organization (WHO) has a lower TUL of 500μg,^[28] although has recommended an upper intake level of 3,000μg.^[55]

In 4-8 year olds, the TUL has been set at 300μg and 9-13 year old children have a TUL of 600μg.^[28]

The recommended upper intake is in the range of 500-1,100μg when looking at international bodies, while the highest recommended upper limit is 3mg; consumption of seaweed routinely is thought to put people near the highest upper intake level

High iodine intake is suspected in some regions of the world, including China due to high iodine concentrations in the water^[56][57] and in Iceland from animals that are fed fish (and thus retain some of the iodine content).^[58] Countries with confirmed higher than acceptable averages include Brazil, Algeria, Côte d'Ivoire, Zimbabwe, Uganda, and the USA (all above 300μg/L) and both Chile and Congo (above 500μg/L).^[59][60] Intake is also thought to be excessive in Japan, where consumption of seaweed has been noted to cause increases in urinary iodine up to 1,000μg/L.^[59]

Supplementation of 100-300μg iodine in a population of otherwise healthy persons without iodine deficiency for six months is able to cause minor antiinflammatory effects as assesed by a reduction in serum IL-6 and C-reactive protein.^[61]

The changes in cytokines indicate an antiinflammatory effect, but the mechanisms underlying this are not known as the change appears to be very small

Dosages of 250-500μg iodine in otherwise normal men and women has failed to alter serum T3 or T4 concentrations^[62] and failures to increase circulating thyroid hormones have been seen with 5g of Alaria esculenta (a seaweed conferring 500μg iodine),^[8] 75-150μg in pregnant women (24 weeks),^[32] 100-300μg,^[61] and 500μg^[63]. At least one study in persons with subclinical Hashimoto's disease has noted that 500μg was low enough to cause a slightly suppression of T4,^[64] suggesting that those with underlying thyroid diseases are slightly more sensitive.

Higher doses of iodine have a transient suppressive effect on circulating T3 and T4 concentrations, which has been seen with 1,500μg in women,^[62] 50-250mg,^[65] saturating doses of potassium iodide,^[66][67]

1,500μg in women has caused a slight increase in serum TSH^[62] which is also seen in men given 1,500-4,500;^[63] slightly lower doses of iodine (500μg via Alaria esculenta) have been known to cause transient increases in TSH (29.5%)^[8] and this has been noted with 500μg iodine itself albeit in persons with subclinical Hashimoto's disease.^[64]

Higher sensitivity of TSH-release from TRH (thyrotropin releasing hormone) has been noted with 1,500μg iodine in women^[62] and with saturating doses of potassium iodide;^[66] this is thought to be related to the decrease in serum thyroid hormones that occurs with high doses of iodine.^[65]

In euthyroidic persons (those with normal thyroid function), normal doses of iodine do not have any significant effect whereas higher pharmacological doses appear to have a transient suppressive effect

Severe iodine deficiency in children is associated with reduced IGF-1 and IGFBP-3 concentrations in serum.^[68][69]

A deficiency of iodine is known to hinder the function of IGF-1 and other growth factors

Mild iodine deficiencies have been noted to be associated with an elevated hearing threshold in children.^[70]

Iodine deficiency in the mother, transferred to the fetus, is known to induce an irreversible state of mental retardation known as cretinism.^[71] This is mostly prevented with sufficient iodinazation of the food supply^[72][73] although some instances of iodine deficiency have been reported in the first world.^[74]

True iodine deficiencies, as rare as they may be in the first world countries, causes irreversible neurological damage to the fetus resulting in cretinism

In New Zealand women after birth, urinary iodine concentrations have been noted to be in the deficiency range in both the mothers (20-41μg/L) and infants (34-49μg/L) and both 75μg and 150μg are equally effective in increasing urinary iodine to a sufficient range.^[32]

In areas of the world with a sufficient iodine content of the diet, breast milk concentrations of iodine tend to be around 150-180μg/L^[29][75] whereas in deficient areas it may drop to 50μg/L.^[32]

In mothers who receive 75-150μg iodine daily for 24 weeks after childbirth, breast milk concentrations of iodine is dose dependently increased by 30% and 70% relative to unsupplemented control.^[32]

Thiocyanate (a component of many vegetables including broccoli, although third world nations mainly intake cassava as a source of thiocyanates^[48][38]) is a known goitrogen and a competitive inhibitor of the sodium/iodide symporter NIC,^[76] which mediates iodine uptake from the blood into the thyroid for subsequent production of thyroid hormones.^[77][78]

Some populations with a relatively low iodine intake are at greater risk for iodine deficiency when there is also a high dietary intake of thiocyanates,^[48]

Goitre is an enlargening of the thyroid glands from numerous causes. Diffuse goitre (also known as simple or colloid goitre) is an enlargening of the glands without the presence of nodules nor hyperthyroidism, this is the type of goitre most commonly seen with iodine deficiency^[79] and it can be treated with supplemental iodine although it takes a few years to do have some effect^[80] and up to a decade to eradicate it.^[81]

Iodine excess can cause goitre, as has been seen in an 'Endemic coast goitre' in Japan along the coast where excessive daily seaweed consumption (reaching up to 10,000µg daily) has resulted in goitre.^[19]

The term endemic goitre is sometimes used when describing population areas, when over 5% of the population in a certain region has goitre from any cause.^[79]

Both iodine deficiency as well as iodine excess may cause goitre

High acute doses of iodine can acutely suppress hormone synthesis in the thyroid for up to 48 hours (afterwhich the body adapts and normal hormone secretion occurs), a phenomena known as the acute Wolff–Chaikoff effect^[82][83] which is thought to be due to a downregulation of iodine transportation into the thyroid from plasma (which prevents continued suppression of hormone synthesis and thyrotoxic effects).^[84][85]

That being said, thyrotoxicosis has been noted in response to excessive iodine intakes. This is thought to be due to underlying thyroid disorders (hypothyroidism or hyperthyroidism) having altered iodine transportation into the thyroid.^[86][87] In essence, persons in which the Wolff-Chaikoff effect does not occur may experience thyrotoxicosis from high supplementation or food levels^[88] which has been noted in a few case studies involving kelp tea (dosage of iodine not known)^[87] and soup^[89] as well as topical iodine application (via povidone-iodine).^[90]

High iodine intakes may be able to cause thyrotoxicosis in a select few individuals who may be susceptable to this conditions, due to a protective adaptation (Wolff-Chaikoff effect) not occurring in them

In children with an elevated iodine status (urinary iodine of 300-1,000μg/L) it was noted that urinary concentrations exceeding 500μg/L were associated with an increase in thyroid size, as assessed by ultrasound.^[59]

An elevated thyroid size may persist with high iodine intake independent of thyrotoxicosis