Dr. Guy E. Abraham, MD, The history of iodine in medicine Part I of III: from discovery to essentiality

Dr. Guy Abraham MD, published in the Original Internist:

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The history of Iodine in medicine Part I: from discovery to essentiality.

Source: Original Internist

Publication Date: 03/22/2006

Author: Abraham, Guy E.


http://www.accessmylibrary.com/coms2/summary_0286-14996118_ITM


COPYRIGHT 2006 Original Internist, Inc.

The essential element Iodine has been kept in the Dark Ages over the last 60 years after World War II. In order to partially remedy the gross neglect of this essential element by the medical profession, poorly represented in medical textbooks and vilified in endocrine publications, The Original Internist will start a series of publications on the history of Iodine in medicine from discovery to the present. This series of publications is part of a book on the Iodine Project which was implemented by the author six years ago. Over the last four years, a series of publications by the author and collaborators have appeared in The Original Internist, rediscovering iodine as the universal medicine, (1-13) a status iodine held for over 100 years before World War II.

This first installment of this series deals with the history of iodine from discovery to essentiality, covering a period of 100 years. The discovery of the stable halides--chloride, iodide, bromide, and fluoride--seems to have been a French enterprise. All four halides were identified by French scientists, (Table 1) with H. Davy from Great Britain, sharing the discovery of chloride with Gay-Lussac in 1809-1810. (4,14)

Two years prior to the discovery of iodine, Gay-Lussac identified chlorine as a new element in 1809, and subsequently Davy claimed credit a year later in 1810 for this discovery. Of interest is the fact that Faraday was Davy's lab assistant and when Davy traveled abroad, Faraday doubled as his valet.

"Gay-Lussac and Thenard made a fundamental contribution to the realization that so-called oxymuriatic acid contained no oxygen and was an element ... On the previous day, 26 February (1809), Gay-Lussac and Thenard had read a first draft of their memoir. In the first reading the authors had suggested unequivocally that oxymuriatic gas was an element. Their patron, Berthollet, unfortunately persuaded them to alter their remarks to make this not more than a possibility ... Because of the pressure he exerted on Gay-Lussac and Thenard, Davy is usually credited with the discovery of the elementary nature of chlorine, which he announced in 1810." (14)

Bernard Courtois, a French chemist, was a saltpeter (potassium nitrate) manufacturer. Saltpeter was one of the compounds needed for the manufacture of gunpowder. Seaweed ash was used as a valuable source of sodium and potassium salts. Sulfuric acid was added to remove interfering compounds before the salts could be precipitated. One day toward the end of 1811, Courtois added too much acid to the suspension of seaweed ash. The iodides in seaweed were oxidized to iodine, which sublimated and formed a violet vapor above the preparation. The crystals obtained from condensation of the iodine vapor were analyzed by Courtois, and he prepared several Iodide salts. Courtois never published his findings. Some of these crystals ended up in the hands of Gay-Lussac and Ampere who gave some to Davy.

Although Courtois discovered iodine in 1811, it was Gay-Lussac who proved that it was a new element and gave it the name of "iode" from the Greek "ioeides" meaning violet colored. Davy anglicized the name "iode" calling it "iodin" which became "iodine" in the 1930s. (4) By 1813, Gay-Lussac had synthesized several products from iodine and fully characterized this new element, but he gave full credit to Courtois for the discovery of iodine. According to the Dictionary of Scientific Discovery, (14) Davy, in an attempt to eclipse Gay-Lussac in the characterization of iodine, did the unthinkable for a scientist of his rank: "A large part of Davy's claim for the originality of his study of iodine depends on his complete honesty in claiming certain knowledge before that of Gay-Lussac and in particular in dating as 11 December a paper read to the Institute on 13 December (that is the day following Gay-Lussac's publication)."

Courtois did not benefit from his discovery. In 1831, he was awarded a prize of 6,000 francs for his discovery. By this time Courtois had given up the saltpeter business and, from the 1820s, attempted to make a living by preparing and selling iodine and iodine compounds. This enterprise also failed, and he died in poverty. (14)

Fifteen years after the discovery of iodine, Balard discovered bromine serendipitously while developing a method to measure iodine in seaweeds and other plants obtained from the Atlantic Ocean and Mediterranean Sea. (14)

"The discovery of bromine, Balard's first and greatest achievement, actually was a byproduct of his more general chemical investigations of the sea and its life forms. In the course of his studies, Balard devised a reliable test for the presence of iodine, the content of which he was determining in plants taken from the Atlantic and the Mediterranean. Chlorine water was added to the test solution, to which starch and sulfuric acid had already been added. The iodine was manifested by its characteristic blue color at the interface of the test solution and the chlorine water. Then Balard noticed that, in some samples, above the blue layer there appeared a yellow-orange layer, which had its own characteristic odor. He isolated the substance causing the yellow color, which proved to be a red liquid."

Although the names of the two previous halogens were based on their colors, "chloros" meaning greenish yellow for chlorine; and "ioeides" meaning violet colored for iodine, Balard did not choose the red color of liquid bromine but the odor instead, and obviously not a pleasant one, since the Greek word "bromos" means stench. As a side note, "spontaneous generation" iconoclast Louis Pasteur who left his name to "pasteurization" was a student of Balard.

Some 60 years after the discovery of bromine, Moissan survived long enough to characterize the last stable halogen fluorine in 1886. Moissan received the Nobel Prize for chemistry in 1906. Fluorine derives its name from "flux." The isolation of fluorine was a life-threatening endeavor, and many scientists were maimed and killed trying to accomplish this feat. Fluorine is the most reactive of all the elements.

Only eight years after the discovery of iodine from seaweed, a Swiss physician, JF Coindet who previously used burnt sponge and seaweed successfully for the treatment of goiter, reasoned that iodine could be the active ingredient in seaweed. In 1819, he tested tincture of iodine at 250 mg/day, in 150 goiter patients with great success. He could reduce significantly the size of goiter within a week. He published his results in 1820. (15)

During the early 1850s, Chatin (16,17) studied the relationship between the prevalence of goiter and the concentrations of Iodide in the soil, water, and food supplies of different localities. He also studied the effect of iodine supplementation on endemic of goiter. He made the following observations: 1) goiter and cretinism are rare in localities which arc rich in iodine; 2) they do occur frequently, however, in localities which arc poor in iodine; and 3) iodine supplementation is a specific preventative of goiter.

Between 1891 and 1892, a series of publications appeared in the British Medical Journal, reporting for the first lime the effective use of thyroid extracts both parentally and orally in patients with hypothyroidism. (18-20) In 1895, Bauman (21) detected high concentrations of iodine in the thyroid gland and proposed that the active ingredient in the thyroid extracts contains iodine.

By the time Bauman identified large concentrations of iodine in the thyroid gland in 1895, pharmaceutical and apothecary preparations containing iodine, excluding thyroid extracts, were widely used as a panacea for all human ills. To quote Kelley: (22) "In the first flush of enthusiasm for the newcomer, physicians and surgeons tested it and tried it for every conceivable pathological condition. The variety of diseases for which iodine was prescribed in the early years is astonishing--paralysis, chorea, scrofula, lacrimal fistula, deafness, distortions of the spine, hip-joint disease, syphilis, acute inflammation, gout, gangrene, dropsy, carbuncles, whitlow, chilblains, burns, scalds, lupus, croup, catarrh, asthma, ulcers, and bronchitis--to mention only a few. Indeed, tincture of iodine, iodoform, or one of the iodides, was applied to almost every case that resisted the ordinary routine of practice; and between 1820 and 1840 there appeared a remarkable series of essays and monographs testifying to the extraordinary benefits to be achieved by this new and potent remedy."

Unfortunately, these monographs disappeared from US medical libraries. It is now very difficult to review the true history of iodine in medicine in extenso without access to these publications. Some 50 years ago, Nobel laureate Albert Szent Gyorgyi, the physician who discovered vitamin C in 1928 and who was a medical student in the early 1900s, wrote: (23) "When I was a medical student, iodine in the form of KI was the universal medicine. Nobody knew what it did, but it did something and did something good. We students used to sum up the situation in this little rhyme: 'If ye don't know where, what, and why, prescribe ye then K and I.' Our medical predecessors, possessing very few and crude instruments only, had to make use of two given by nature (the use of which has since gone out of fashion): eyes and brains. They were keen observers and the universal application of Iodide might have been not without foundation."

The phenomenal growth of iodine-containing products, from 10 preparations listed in the pharmacopoeias in 1851 to 1,700 approved pharmacopoeial names assigned to iodine-containing products in 1956, is compelling evidence for the widespread applications of iodine in medicine: (22) "In the Great Exhibition at the Crystal Palace in Hyde Park in May 1851, iodine and iodine compounds were publicly shown for the first time by ten pharmaceutical firms,... by 1890, to choose a date at random, the 6th edition of Martindale 's Extra Pharmacopoeia sponsored 30 medicaments derived from iodine; the Iodine Centenary Volume compiled by The Prescriber in 1914 mentions 45 iodine preparations; by 1928 Martindale had extended its coverage to 128 iodine items; and, in an International Index published in 1956, and devoted exclusively to iodine pharmaceuticals, no less than 1,700 approved pharmacopoeial names, proprietary names, synonyms, and alternative designations are alphabetically listed."

By the early 1900s iodine was well-established in medical and surgical practices, as described in the Encyclopedia Britannica 11th Edition published in 1910-1911. (24) In Volume XIV, under iodine, on pages 725-726, one reads: "In medicine iodine is frequently applied externally as a counterirritant, having powerful antiseptic properties. In the form of certain salts iodine is very widely used, for internal administration in medicine and in the treatment of many conditions usually classed as surgical, such as the bone manifestations of tertiary syphilis. The most commonly used salt is the iodide of potassium; the iodides of sodium and ammonium are almost as frequently employed, and those of calcium and strontium are in occasional use. The usual doses of these salts are from five to thirty grains or more. [Author's note: For the reader's information, one grain is approximately 60 mg. Therefore, the daily therapeutic dose was from 300-1,800 mg iodide]. Their pharmacological action is as obscure as their effects in certain diseased conditions are consistently brilliant and unexampled. Our ignorance of their mode of action is cloaked by the term deobstruent, which implies that they possess the power of driving out impurities from the blood and tissues. Most notably is this the case with the poisonous products of syphilis. In its tertiary stages--and also earlier--this disease yields in the most rapid and unmistakable fashion to iodides; so much so that the administration of these salts is at present [Author's note: For the reader's information, this was written in early 1900.] the best means of determining whether, for instance, a cranial tumour be syphilitic or not. No surgeon would think of operating on such a case until iodides had been freely administered and, by failing to cure, had proved the disease to be non-syphilitic. Another instance of the deobstruent power--'alterative,' it was formerly termed--is seen in the case of chronic lead poisoning. The essential part of the medicinal treatment of this condition is the administration of iodides, which are able to decompose the insoluble albuminates of lead which have become locked up in the tissues, rapidly causing their degeneration, and to cause the excretion of the poisonous metal by means of the intestine and the kidneys. The following is a list of the principal conditions in which iodides are recognized to be of definite value: metallic poisonings, as by lead and mercury, asthma, aneurism, arteriosclerosis, angina pectoris, gout, goiter, syphilis, haemophilia, Bright's disease (nephritis), and bronchitis."

In a monograph published in 1940 by Harvard University Press, reviewing the history of iodine in medicine with 588 references, the author, William Thomas Salter (25) expressed his amazement at the surprisingly good results obtained with iodide in tertiary luetic (i.e., syphilitic) lesions and arteriosclerosis using daily amounts of grams of iodide for long periods of time and without any evidence of complications.

"After the discovery of iodine by Courtois in 1811, there was a great vogue for iodine therapy ... Likewise, in the 1820s it was first introduced in the treatment of syphilis, and that use of the medication has continued since. It still is employed in the treatment of various granulomata such as actinomycosis, blastinomycosis, and odd skin disturbances like lupus erythematosus. Occasionally, even today, a gumma is found and the response of such a tertiary luetic lesion to iodide therapy is very surprising ... The dosage used in these disturbances is often very high. Doses of several grams a day have not infrequently been administered for considerable periods ... This form of therapy, however, still remains important in the treatment of sclerotic lesions of the aorta due to syphilis, and has even been used over long periods for the treatment of generalized arteriosclerosis. One cannot help wondering what complication such therapy may produce in the endocrine system, but there is available no very clear-cut evidence of manifest endocrinopathy due to these heroic doses of iodine."

In the same year Salter's monograph on iodine was released by Harvard University Press, (25) Redisch and Perloff (26) published in the Journal of Endocrinology a manuscript entitled, "The medical treatment of hyperthyroidism." The two medical treatment modalities used at that time were iodine alone and x-ray irradiation of the thyroid gland, with iodine alone being by far the most common approach.

In the early 1900s, Professor Kocher came on the scene and had an adverse iodophobic effect on the treatment of hyperthyroidism. Professor Theodore Kocher carried a lot of weight, being the recipient of the Nobel Prize in Medicine and Physiology in 1909 for his work on thyroid surgery, the only Nobel Prize assigned to research on the thyroid gland. The year after Kocher received the Nobel prize, he reported that he suffered from hyperthyroidism following ingestion of iodide. Kocher then became the most famous medicoiodophobe in medical history. He was against the use of iodine/iodide for all forms of hyperthyroidism. (4)

Whether Kocher suffered from Iodophobia Vera, true iodophobia, when the physician, although misguided, is sincere; or Iodophobiae Simulatio, that is simulated io-dophobia with intent to deceive, remains a mystery. The timing was perfect. The Nobel Prize gave world recognition to Kocher who did not waste any time to use his fame in the promotion of iodophobia.

Redisch and Perloff commented: "The relationship between iodine and the thyroid gland, particularly as regards function, was recognized as early as the beginning of the last century by Staub (1819) and Coindet (1820). After the syndrome of Flajani was classically described by Graves and von Basedow, iodine became the basis for treatment, with variable degrees of success, until that time when Kocher first described his hyperthyroidism presumably caused by iodine. This conception of the great Swiss surgeon caused such a sensation that the use of iodine was almost completely abandoned. Today, however, we are skeptical of the validity of Kocher's conclusions." (26)

Cowell and Mellanby in their 1925 publication give a glimpse of Kocher's influence over the thyroidologists of that time, bordering on intimidation: "Kocher taught that the administration of Potassium Iodide must never be carried out in exophthalmic goiter, and on the whole, this advice has been taken. As evidence of this fact may be mentioned the discussion on the treatment of exophthalmic goiter at the Royal Society of Medicine in 1923. No speaker mentioned iodine or any preparation of iodine as being of any value in the treatment of the disease, and it can be inferred that therapy involving the use of iodine has been deliberately avoided." (2)

Kocher's influence divided the clinicians into two groups: the iodine group who favored the use of iodine preparations first in hyperthyroidism, referring the patient for x-ray or surgery only if non-responsive; and the surgical school, discouraging the use of iodine and recommending surgery exclusively for hyperthyroidism. Kocher's influence crossed the Atlantic Ocean, as reported by Redisch and Perloff: "The conception that treatment of Graves' disease ... is primarily surgical, is widespread despite the fact that American, as well as European, literature contains numerous reports of satisfactory results with non-surgical treatment in selected cases." (26)

Under the subheading "Treatment with iodine alone", Redisch and Perloff reported that iodine alone was used extensively by physicians for hyperthyroidism at that time. Clinics in Europe and the US reported very high success rates with iodine alone: "In Biedl's clinic about 10% of the cases with favorable results were completely and permanently cured, 40% entirely symptom-free so long as iodine was administered, and 50% almost symptom-free but still showing some manifestations of the condition. The 'toxic symptoms' of acute Graves' disease (diarrhea, restlessness, insomnia) reacted especially favorably to iodine. The fact that the percentage of cases treated by iodine alone in Means' clinic has increased remarkably during the last three years, shows that the pendulum may be once again swinging towards the medical treatment of hyperthyroidism in this country." (26)

Using iodine alone in patients with hyperthyroidism, Thompson, et al, (27) reported in 1930, a success rate of 88% and Starr, et al, (28) in 1924, reported a success rate of 92% with Lugol solution at daily doses of 6-90 mg.

During the first 100 years following the discovery of iodine, its clinical applications were purely empirical, and the effective dose was arrived at by trial and error. The concept of essential trace elements was not yet established. In 1911, Gabriel Bertrand (1867-1962) proposed the concept of essential trace elements, necessary for normal growth and functions of plants, following a series of publications in the Comptes Rendus de L'Academie des Sciences published between 1894 and 1911.

The evolution of Bertrand's concept of essential elements is described in the Dictionary of Scientific Discoveries: (14) "In the years 1894-1897, Bertrand investigated the process of the darkening and hardening of the latex of lacquer trees. He recognized that the color change was caused by the oxidation of a phenol--laccol in the presence of another substance, laccase. Other phenolic compounds, he found, underwent similar organic oxidation reactions, also in the presence of substances similar to laccase. In 1896, Bertrand first used the term 'oxidase' for these oxidizing enzymes (including tyrosinase, which he had described). During the following year, he published several studies of oxidases. Bertrand made another important advance in the analysis of enzymes when he observed that laccase ash contained a large proportion of manganese. Throughout the last half of the 19th century it had been known that plants contained minerals, and in 1860, it was demonstrated that in artificial situations plants could be grown in a water culture containing only metallic salts. Researchers still accepted the presence of minerals in the plant as incidental, however, and thought them the result of the presence of minerals in the soil. Bertrand's work in 1897, and especially his later claim that a lack of manganese caused an interruption of growth, forced a change in thinking on this matter. He concluded that the metal formed an essential part of the enzyme, and, more generally, that a metal might be a necessary functioning part of the oxidative enzyme. From this and similar research he developed his concept of the trace element, essential for proper metabolism."

Ten years later, Marine applied Bertrand's concept of essential trace elements to the element iodine in human subjects. This was the first and last time an element was demonstrated to be essential for human health based on research performed in human subjects. Interestingly, all the other essential trace elements were studied only in laboratory and farm animals, not human subjects. The only element proven essential for human health based on studies performed in humans, turns out to be the most feared and neglected nutrient.

Based on extensive studies of overall performance and goiter in farm animals, D. Marine estimated the amount of iodide required for human subjects. However, for convenience, the nurses and physicians supervising this project were only concerned with the appearance of simple goiter following implementation of iodine supplementation. Again, for convenience and to keep the cost of supervising personnel to a minimum, the iodide was not given daily but at less frequent intervals using larger amounts of iodide.

Marine chose a population of adolescent school girls from 5th-12th grade between the ages of 10 and 18 years residing in Akron, Ohio, a city with a 56% incidence of goiter. (29,30) His choice was based on the observation that the incidence of goiter was highest at puberty, and six times more common in girls than in boys. (30) He studied two groups of pupils devoid of goiter (thyroid enlargement by palpation) at the beginning of the project. The control group consisted of 2,305 pupils who did not receive iodide supplementation; and 2,190 pupils received a total of 4 g of sodium iodide per year for a period of 2.5 years. The amount of iodide was spread out in two doses of 2 g each during the spring and the fall. This 2-gram dose was administered in daily amounts of 0.2 g of sodium iodide over 10 days. At 4,000 mg of sodium iodide per 365 days, the average daily amount of sodium iodide was 12 mg, equivalent to 9 mg iodide, 60 times the RDA.

After 2.5 years of observation, 495 pupils in the control group developed thyroid enlargement (22%). Only five cases of goiter occurred in the iodine-supplementation group (0.2%). Iodism was observed in 0.5% of the pupils receiving iodide supplementation. Iodism is characterized by the following signs and symptoms: skin eruptions; frontal sinus pressure with rhynorhea (runny nose); brassy taste associated sometimes with dyspepsia. In an area of Switzerland with an extremely high incidence of goiter (82-95%), Klinger, as reported by Marine, administered 10-15 mg of iodine weekly to 760 pupils of the same age group. The daily iodine intake in this group was 1.4-2.0 mg. The initial examination revealed 90% of them had enlarged thyroid. After 15 months of this program, only 28.3% of them still had an enlarged gland. None experienced iodism. In response to these studies, the Swiss Goiter Commission advised the use of iodine supplementation in all cantons. Iodized fat in tablet form containing 3-5 mg iodine per tablet was used for iodine supplementation.

In 1831, French chemist and agronomist JG Boussingault (31) proposed iodized sodium chloride (table salt) as a means of preventing goiter. Such proposal was implemented first in Europe and then in the 1920s in the US. Following Marine's study, absence of goiter, not overall performance was the endpoint relied upon for assessing iodine sufficiency. Iodization of salt gave a false sense of iodine sufficiency and resulted in the public relying on iodized salt for supplementation instead of the previously used forms of iodine and iodide such as the Lugol solution in the recommended daily amount of 0.1-0.3 ml containing 12.5-37.5 mg elemental iodine. (4) In order to ingest 12.5 mg of elemental iodine from salt, one would have to consume 165 g of salt; and obviously three times that amount of salt would be required for supplying 37.5 mg elemental iodine. (3,5) Besides, table salt in the US contains iodide only, not iodine. Iodine is very important for normal function of breast tissue. (3) Therefore, supplementation should contain both forms, iodine and iodide. The evolution of iodine from discovery to essentiality is summarized in Table 2.

The implementation of iodization of table salt in the US was associated with the appearance of autoimmune thyroiditis. In several communities worldwide, an increased incidence of chronic autoimmune thyroiditis was reported following implementation of iodization of sodium chloride. (32) In areas of the US where this relationship has been studied, mainly in the Great Lakes region, a similar trend was reported. In 1966 and 1968, Weaver, et al, (33,34) from Ann Arbor Michigan reported: "The salient histopathological feature of the thyroid glands, removed at operation in a five-year period before iodine prophylaxis (1915-1920), was the paucity of lymphocytes in their parenchyma, and, more importantly, the absence of thyroiditis of any form ... It should be emphasized that the thyroid glands prior to the use of iodized salt were devoid of lymphocytes, and nodular colloid goiters with dense lymphocytic infiltrates were found after the introduction of iodized salt in 1924."

It is of interest to note that prior to iodization of salt, autoimmune thyroiditis was almost non-existent in the US, although Lugol solution and Potassium Iodide were used extensively in medical practice in amounts two orders of magnitude greater than the average daily amount ingested from iodized salt. This suggests that inadequate iodide intake aggravated by goitrogens, not excess iodide, was the cause of this condition. (2) Of interest is the fact that autoimmune thyroiditis cannot be induced by inorganic iodide in laboratory animals unless combined with goitrogens, therefore inducing iodine deficiency. Furszyfer, et al, (35) from the Mayo Clinic, studied the average annual incidence of Hashimoto's thyroiditis among women of Olmsted County, Minnesota during three consecutive periods covering 33 years of observation, from 1935-1967. They found the incidence to be higher in women 40 years and older versus women 39 years and less. However, in both groups, there was a progressive increase in the incidence of Hashimoto's thyroiditis over time. During the three periods evaluated (i.e., 1935-1944; 1945-1954; 1955-1967) the average annual incidence of Hashimoto's per 100,000 population was 2.1, 17.9, and 54.1 for women 39 years and less. For women 40 years and older, the average annual incidence over the same three periods was 16.4, 27.4, and 94.1.

It is important to point out that the Mayo Clinic study started 10-15 years after implementation of iodization of salt in the area. Therefore, even during the first decade of observation, the prevalence of autoimmune thyroiditis was already significant. Again, it must be emphasized that prior to the implementation of iodized salt as observed by Weaver, et al, (32,33) this pathology of the thyroid gland was not reported in the US, even though the Lugol solution and Potassium Iodide was used extensively in medical practice at that time in daily amount two orders of magnitude greater than the average intake of iodide from table salt . (3)

In 1912, pathologist H. Hashimoto (36) published his histological findings in four thyroid glands removed at surgery: numerous lymphoid follicles; extensive connective tissue formation; diffuse round cell infiltration; and significant changes of the acinar epithelium. He called this pathology of the thyroid struma lymphomatosa. This condition became known as Hashimoto's thyroiditis. At the time of his publication in 1912, autoimmune thyroiditis was not observed in the US population until the iodization of salt. Hashimoto's thyroiditis is now classified as goitrous autoimmune thyroiditis because the gland is enlarged, in distinction to atrophic autoimmune thyroiditis where atrophy and fibrosis are predominant. Both conditions are chronic, progressing over time to hypothyroidism in a significant percentage of patients. (4) Both conditions improved following a complete nutritional program emphasizing magnesium combined with iodine supplementation for whole body sufficiency.(4)

Further evidence that iodine deficiency, not excess, is the cause of autoimmune thyroiditis follows. Experimentally induced autoimmune thyroiditis in laboratory animals by acutely administered iodide required the use of antithyroid drugs, essentially goitrogens, to produce these effects. These goitrogens induced thyroid hyperplasia and iodide deficiency. Antioxidants either reduced or prevented the acute iodide-induced thyroiditis in chicks and mice. Bagchi, et al, and Many, et al, proposed that the thyroid injury induced by the combined use of iodide and goitrogens occurs through the generation of reactive oxygen species. (See reference 4 for review.)

A proposed mechanism by the author for the oxidative damage caused by low levels of iodide combined with antithyroid drugs is that inadequate iodide supply to the thyroid gland, aggravated by goitrogens, activates the thyroid peroxydase (TPO) system through elevated TSH, low levels of iodinated lipids, and high cytosolic free calcium, resulting in excess production of [H.sub.2][O.sub.2]. The excess [H.sub.2][O.sub.2] production is evidenced by the fact that antioxidants used in Bagchi's experiments did not interfere with the oxidation and organification of iodide and therefore neutralized only the excess oxidant. This [H.sub.2][O.sub.2] production is above normal due to a deficient feedback system caused by high cytosolic calcium due to magnesium deficiency and low levels of iodinated lipids which require for their synthesis iodide levels two orders of magnitude greater than the RDA for iodine. (4)

Once the low iodide supply is depleted, TPO in the presence of [H.sub.2][O.sub.2] and organic substrate reverts to its peroxydase function which is the primary function of haloper-oxydases, causing oxidative damage to molecules nearest to the site of action--TPO and the substrate thyroglobulin (Tg). Oxydized TPO and Tg elicit an autoimmune reaction with production of antibodies against these altered proteins with subsequent damage to the apical membrane of the thyroid cells, resulting in the lymphocytic infiltration and in the clinical manifestations of Hashimoto's thyroiditis. (4)

Based on this proposed mechanism where deficiencies of magnesium and iodine induce autoimmune thyroiditis, implementations of a complete nutritional program emphasizing magnesium combined with iodine supplementation was effective in patients with this thyroid pathology, including autoimmune hyperthyroidism. Even a patient with atrophic autoimmune thyroiditis responded to this program. (4)

About the Author

Guy E. Abraham, MD, is a former Professor of Obstetrics, Gynecology, and Endocrinology at the UCLA School of Medicine. Some 35 years ago, he pioneered the development of assays to measure minute quantities of steroid hormones in biological fluids. He has been honored as follows: General Diagnostic Award from the Canadian Association of Clinical Chemists, 1974; the Medaille d'Honneur from the University of Liege, Belgium, 1976; the Senior Investigator Award of Pharmacia, Sweden, 1980.

The applications of Dr. Abraham's techniques to a variety of female disorders have brought a notable improvement to the understanding and management of these disorders. Twenty-five years ago, Dr. Abraham developed nutritional programs for women with premenstrual tension syndrome and post-menopausal osteoporosis. They are now the most commonly used dietary programs by American obstetricians and gynecologists. Dr. Abraham's current research interests include the development of assays for the measurement of iodide and the other halides in biological fluids and their applications to the implementation of orthoiodosupplementation in medical practice.

References

1) Abraham GE, Flechas JD, and Hakala JC. "Optimum levels of iodine for greatest mental and physical health." The Original Internist, 2002; 9(3):5-20.

2) Abraham GE, Flechas JD, and Hakala JC. "Measurement of urinary iodide levels by ion-selective electrode: Improved sensitivity and specificity by chromatography on anion-exchange resin." The Original Internist, 2004; 11(4):19-32.

3) Abraham GE, Flechas JD, and Hakala JC. "Orthoiodosupplementation: Iodine sufficiency of the whole human body." The Original Internist, 2002; 9(4):30-41.

4) Abraham GE. "The safe and effective implementation of orthoiodosupplementation in medical practice." The Original Internist, 2004; 11(1):17-36.

5) Abraham GE. "The concept of orthoiodosupplementation and its clinical implications." The Original Internist, 2004; 11(2):29-38.

6) Abraham GE. "The historical background of the iodine project." The Original Internist, 2005; 12(2):57-66.

7) Abraham GE and Brownstein D. "Evidence that the administration of Vitamin C improves a defective cellular transport mechanism for iodine: A case report." The Original Internist, 2005; 12(3):125-130.

8) Abraham GE. "The Wolff-Chaikoff effect: Crying wolf?" The Original Internist, 2005; 12(3):112-118.

9) Abraham GE. "Serum inorganic iodide levels following ingestion of a tablet form of Lugol solution: Evidence for an enterohepatic circulation of iodine." The Original Internist, 2004; 11(3):29-34.

10) Abraham GE, Brownstein D, and Flechas JD. "The saliva/serum iodide ratio as an index of sodium/iodide symporter efficiency." The Original Internist, 2005; 12(4):152-156.

11) Abraham GE and Brownstein D. "Validation of the orthoiodosupplementation program: A rebuttal of Dr. Gaby's editorial on iodine." The Original Internist, 2005; 12(4):184-194.

12) Brownstein D. "Clinical experience with inorganic, nonradioactive iodine/iodide." The Original Internist, 2005; 12(3):105-108.

13) Flechas JD. "Orthoiodosupplementation in a primary care practice." The Original Internist, 2005; 12(2):89-96.

14) Dictionary of Scientific Discoveries. Charles Coulston Gillispie, editor in chief. Simon & Schuster Macmillan, New York.

15) Coindet JF. "Decouverte d'un nouveau remede contre le goitre." Ann Clin Phys, 1820; 15:49.

16) Chatin A. "Existence de l'iode dans les plantes d'eau douce: consequences de ce fait pour le geognosie, la physiologie vegetale, la therapeutique et peut-etre pour l'industrie." Compt Rend Acad Sci, 1850; 30:352.

17) Chatin A. "Un fait dans la question du goiter et du cretinisme." Compt Rend Acad Sci, 1853; 36:652.

18) Murray GR. "Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep." BMJ, 1891; 2:796-797.

19) MacKenzie HW. "A case of myxoedema treated with great benefit by feeding with fresh thyroid glands." BMJ, 1892; 2:940.

20) Fox EL. "A case of myxoedema treated by taking extract of thyroid by the mouth." BMJ, 1892; 2:941.

21) Baumann E. "Ueber das normale Vorkommen von Jod im Thierkorper." Hoppe-Seylers Z Physid Chem, 1895; 21:319-330.

22) Kelly FC. "Iodine in medicine and pharmacy since its discovery--1811-1961." Proc R Soc Med, 1961; 54:831-836.

23) Szent-Gyorgyi A. Bioenergetics. Academic Press, New York, 1957; 112.

24) "Iodine." In: Encyclopedia Britannica, 11th Edition, 1910-1911, Vol. XIV. 725-726.

25) Salter WT. The Endocrine Function of Iodine. Harvard University Press, Cambridge, MA, 1940; 254-255, 261, 268-269.

26) Redisch W and Perloff WH. "The medical treatment of hyperthyroidism." Endocrinology, 1940; 26:221-228.

27) Thompson WO, Thompson PK, Brailey AG, et al. "Prolonged treatment of exophthalmic goiter by iodine alone." Arch Int Med, 1930; 45:481-502.

28) Starr P, Walcott HP, Segall HN, et al. "The effect of iodine in exophthalmic goiter." Arch Int Med, 1924; 34:355-364.

29) Marine D. "Prevention and treatment of simple goiter." Atl Med J, 1923; 26:437-442.

30) Marine D and Kimball BS. "The prevention of simple goiter in man." J Lab Clin Med, 1917; 3:40-48.

31) Boussingault JB. "Recherches sur la cause qui produit le goitre dans les Cordilieres de la Nouvelle-Grenade." Ann Chim Phys, 1831; 48:41.

32) Gaitan E, Nelson NC, and Poole GV. "Endemic goiter and endemic thyroid disorders." World J Surg, 1991; 15:205-215.

33) Weaver DK, Batsakis JG, and Nishiyama RH. "Relationship of iodine to 'Lymphocytic Goiters.'" Arch Surg, 1968; 98:183-186.

34) Weaver DK, Nishiyama RH, Burton WD, et al. "Surgical thyroid disease." Arch Surg, 1966; 92:796-801.

35) Furszyfer J, et al. "Hashimoto's thyroiditis in Olmsted County, Minnesota, 1935 through 1967." Mayo Clin Proc, 1970; 45:586-596.

36) Hashimoto H. "Zur Kenntniss der lymphomatosen Veranderung der Schilddruse (Struma lymphomatosa)." Arch Klin Chir, 1912; 97:219-248.

by Guy E. Abraham, MD



Table 1 The Halides: Discovery in Chronological Order

Halide Year Discoverer Country

Chloride 1809 Gay-Lussac France
1810 H. Davy Great Britain
Iodide 1811 B. Courtois France
Bromide 1826 AJ Balard France
Fluoride 1886 F. Moissan France
Astatin* 1940 Carson USA
McKenzie
Segre

* All isotopes are radioactive; exists naturally in minute amounts.
First isolated as a byproduct of bombardment of a bismuth target with
alpha particles in a 60-inch cyclotron. (4)

Table 2 The Evolution of Iodine from Discovery to Essentiality

1811 Discovery of iodine by Bernard Courtois (14)
1813 Gay-Lussac proved its elementary nature and coined the name
iode, anglicized to iodin by Davy, which became iodine in the
1930s (4)
1850-1853 Chatin (16,17) measured iodine in water, food, and air of
various localities. He studied the effect of iodine
supplementation on prevention of goiter. He made the
following observations:
* Goiter and cretinism are rare in localities which are
rich in iodine.
* They do occur frequently, however, in localities which
are poor in iodine.
* Iodine supplementation is a specific preventative of
goiter.
1895 Baumann reported high concentrations of iodine in the thyroid
gland. (21)
1911 Bertrand proposed the concept of essential trace elements
based on his research on manganese in plants. (14)
1917-1923 Marine applied Bertrand's concept of essential trace element
to iodine in human subjects. The end point evaluated was the
incidence of goiter. (29,30) Marine confirmed Chatin's
observation made 70 years previously. Iodine was the first
trace element reported to be essential for human health.



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