I. Introduction

.For example, potassium iodide has been prescribed safely to pulmonary patients in daily amounts of up to 6.0 gm/day, in large groups of such patients for several years.1-3 It is important, however, to emphasize that this safety record only applies to inorganic, non-radioiodides. Unfortunately, the severe side effects of iodine-containing drugs have been attributed to inorganic iodine/iodide, even though published studies clearly demonstrate that it is the whole organic molecule that is cytotoxic, not the iodine covalently bound to this molecule. To quote Phillipou, et al:4“We can, therefore, conclude that the effect of amiodarone, benziodarone, Na iopanate, and other iodine containing substances with similar effects is due to the entire molecule and not to the iodine liberated. It should be noted that the cytotoxic effect of amiodarone in all cultures is also due to the entire molecule and not to the iodine present in it.” Several forms of iodine are used in clinical medicine (Table 1). Unless otherwise stated, this presentation is concerned only with inorganic, non-radioactive iodine/iodide.

Medical iodophobia is the unwarranted fear of using and recommending inorganic, non-radioactive iodine/iodide within the range known from the collective experience of three generations of clinicians to be the safest and most effective amounts for treating symptoms and signs of iodine/iodide deficiency (12.5-37.5 mg). The range of daily intake of this essential nutrient is hereafter referred to as orthoiodosupplementation because it is the range of iodine/iodide intake required in order to achieve whole body sufficiency for this element based on a recently developed iodine/iodide loading test. (See Section VII for more details on the loading test.) Medicoiodophobes suffer from: A) a split personality which results in iodophobia within the orthoiodosupplementation range previously used safely and successfully in medical practice and iodophylia for megadoses of iodide (up to 12 gm/day); B) double standards, which render those physicians intolerant to the minor side effects of the inorganic forms and extremely tolerant to the severe side effects of the radioactive and organic forms; C) amnesia pertaining to the inorganic, non-radioactive forms when making therapeutic decisions; D) confusion, attributing the severe side effects of organic iodine-containing drugs to inorganic iodine/iodide; and E) an altered state of consciousness, allowing doublethink, doublespeak, and contradictory logic to become acceptable.

Although the factors involved in medical iodophobia are still unknown, decreased cognition seems involved. Since low iodine intake is associated with intellectual impairment, deficiency of this essential element cannot be ruled out, and if present, would create a self-perpetuating phenomenon. Needless to say, medical iodophobia is contagious and can be transmitted to patients and other physicians (iatrogenic iodophobia). Medical iodophobia will remain a syndrome until the causes are discovered and effective therapy implemented. It is very likely however, that medical iodophobia will eventually be classified as an iodine-deficiency disease.

Discovered in Imperial France 5 a century before the concept of essential trace elements was proposed by Gabriel Bertrand,6 the first trace element tested in human subjects and recognized as essential to human health,7,8 the most deficient trace element in the world,9 iodine had the misfortune of attraction the attention of endocrinologists because it is incorporated into some very important hormones of the thyroid gland.10-13 Starting out as a panacea for all human ills,14 iodine, as an essential element, eventually became associated exclusively with the thyroid gland.15 This thyroid fixation resulted in endocrinologists dictating the human needs for this nutrient. All human application of iodine became eventually subservient to the dictates of misinformed endocrinologists.

For example, disaffection of water for human consumption and in swimming pools is far superior, safer, and less expensive with the use of iodine at 1 to 2 ppm, that with the use of chlorine and its derivatives at the same concentrations.16-19 However, unfounded concern about the adverse effects of iodine at these levels on the thyroid gland,20-22 and vide infra has prevented the widespread use of iodine for these applications, with toxic chlorine and its derivatives used by default. All studies published so far favor iodine over chlorine for treatment of municipal waters and swimming pools, “Because of the increasing difficulty experienced by many communities in achieving satisfactory disinfection of public water supplies with acceptable concentrations of chlorine, a feasibility study on the use of iodine for this purpose was undertaken.”19 “The effectiveness, ease of administration and palatability were prime reasons for considering iodine as a disinfectant of community water supplies effective bacteriological control of the water was maintained by all concentrations of iodine used in this study.”17 “At an iodine concentration of 1 mg/liter ( 1 ppm), the water met all standards for safety and palatability (1962 USPHS Drinking Water Standards) During the five years in which this study was conducted no instances of urticaria or iodism were observed.”19 ”

No evidence of iodine induced allergic phenomena was detected during this study.”17 “Comparative data indicate that disinfection of an Olympic-size swimming pool can be accomplished with iodine at half the dose of chlorination Use of the iodinated swimming pool caused no significant changes in either the RAI uptakes or PBI concentrations.”19 The advantage of iodine over chlorine as a disinfectant in the treatment of municipal waters is that it could be used as a disinfectant and also as a source of a very important essential element. It is obvious that the benefits of such an approach would outweigh the risks, based on the studies mentioned above.

When different groups of competitive swimmers were asked about their preference between chlorine and iodine as a disinfectant of swimming pools,19 they overwhelmingly chose iodine. None preferred chlorine. “All members of the swimming teams of five universities who participated in AAWU swimming championships that were held in the Stanford pools were asked to express their opinions of iodine-treated water as compared with chlorine-treated water Seventeen of the 20 freshmen and varsity swimming members expressed a preference for the iodine-treated pool in respect to eye irritation. The other three had no preference, but none preferred the chlorine treatment. Of the championship-swimming contestants, 48 preferred the iodine-treated pool, five had no preference, but none preferred the chlorine-treated pool

Twenty-eight of the subjects who had been exposed to the iodine-treated water for one month were examined by the three physicians of the research staff, each of whom made his observations independently of the others. Twenty-seven of the swimmers examined received a completely negative rating for eye irritation. In only one student was a mild conjunctivitis found on medical examination. This student wears contact lenses and stated that his eye irritation had improved in a miraculous way since the pool had been treated with iodine.”

In the early 1960s, iodine was added to bread as a dough conditioner. One slice of bread contained the full RDA of 150 g.23,24 As would be expected, because of isotope dilution effect, the percent of radioiodide uptake by the thyroid gland decreased from 20-30% to 10-20%. In 1965, London, et al 25 from the National Institute of Health evaluated the amount of iodine present in 32 bakery products from 12 different commercial bakeries. They reported that a typical diet contributed to approximately 1 mg of iodine per day and 726 g came from bakery products. Concern was expressed over the inhibition of thyroid hormone synthesis in thyrotoxic patients at those levels of iodine. The last sentence of their publication read, “One milligram of iodine will suppress the uptake of radioactive iodine by the normal thyroid gland, probably by simple dilution of the dose, and may considerably reduce organic binding of iodine in the thyroid glands of thyrotoxic persons.7” Reference 7 of their manuscript is a study published in 1949 by Stanley 26 one year after the Wolff-Chaikoff Effect was reported in rats.27

The first paragraph of Stanley’s manuscript stated the objective, “The interest of thyroidologists was recently aroused by the demonstration by Wolff and Chaikoff (1) that, with levels of serum iodide higher than 20 to 30 micrograms per cent, organic binding of iodine in the rat thyroid was inhibited. Extension of these observations to man was undertaken.”

The interest of thyroidologists could not have been aroused so quickly by the publication of Wolff and Chaikoff in The journal of Biological Chemistry, 27 a journal involved in publishing research in the basic sciences, not clinical medicine. The thyroidologist with aroused interest was Stanley himself who obviously had insider information in order to publish his manuscript within a year following the Wolff-Chaikoff publication, considering the fact that it takes several months for the review process in peer review journals, and that it would have required several months for him to design and perform his experiments after reading the Wolff-Chaikoff paper. During the year Stanley published his “extension of the Wolff-Chaikoff Effect to man,” he co-authored a paper with Astwood on using goitrogens to manage patients with Graves’ disease as an alternative to using inorganic iodine/iodide. It is a strange coincidence that the investigators who authored the iodophobic publications regarding the so-called inhibition of organic binding of radioactive iodide in the thyroid gland by the administration of inorganic, non-radioactive iodide, were also involved in testing goitrogens in laboratory animals and in normal human subjects and in implementing the use of these goitrogens as an alternative to inorganic iodine/iodide in patients with Graves’ disease (See Section IV).

Stanley concluded, “Thus, the observations of Wolff and Chaikoff in the rat were extended to man.” However, in a review published in 1969, Wolff 28 stated, “The rarity of iodide goiter in the face of the extensive exposure of a great many patients to iodide has not been satisfactorily explained.” Without preconceived ideas, it is easily explained == inorganic, non radioactive iodine/iodide is safe. “The demonstration of the Wolff-Chaikoff Effect in man remains presumptive.” Several researchers erroneously concluded that the rapid decrease in serum thyroxine (T4) following oral ingestion of inorganic iodine/iodide in thyrotoxic patients was due to the Wolff-Chaikoff Effect, that is sustained inhibition of T4 synthesis. However, Wartofsky, et al 29 in 1970, evaluated the effect of Lugol solution, administered at five drops (30 mg iodine/iodide) three times a day in five thyrotoxic patients. Following a well-designed protocol, they concluded that “the rapid decrease in T4 secretion induced by iodine is not the result of an acute sustained inhibition of T4 synthesis (The Wolff-Chaikoff Effect), but rather results from an abrupt decrease in the fractional rate of thyroid T4 release.” Therefore, in hyperthyroidism, iodine/iodide in Lugol at a daily dose of 90 mg induced a physiological trend toward normalization of thyroid function, a beneficial effect.

One can appreciate the thyroid fixation of confused endocrinologists who ignore the rest of the human body in favor of misinterpreted laboratory tests assessing thyroid function. The concern about decreased uptake of radioiodide by the thyroid gland following ingestion of increasing amounts of inorganic, non-radioactive iodide shows a lack of understanding of the physiological interpretation of the iodide tracer. Theoretically, as we previously discussed,30 the uptake of radioactive iodide by the thyroid gland should be zero in order to achieve sufficiency of the thyroid for inorganic, non-radioactive iodide. Decreased thyroid uptake of inorganic radioiodide is an effect to be desired, not avoided. Besides, a low radioiodide uptake by the thyroid resulting from adequate intake of inorganic, non-radioactive iodine/iodide (orthoiodosupplementation) serves as a preventive measure against unexpected exposure to radioactive iodide/iodine.30 Based on a review of the literature, we computed the daily amount of iodine/iodide needed for sufficiency of the thyroid gland and the whole human body. This amount, called orthoiodosupplementation, amounted to 100 times the RDA.30

In the 1980s, thanks to iodophobia, iodine was replaced with bromine in the bread-making process. 31 Bromide is a goitrogen and interferes with iodide utilization by the thyroid gland,32-34 and possibly by the mammary gland also.35 Iodine has an anticarcinogenic effect on the breast.30 The last national nutritional survey showed a trend of decreasing iodine intake by the US population. 30, 31 Currently 15% of the US adult female population excreted in their urine less than 0.05 mg iodide/L, a level classified by the World Health Organization (WHO) as iodine deficiency. One must keep in mind that the amounts of daily intake of iodine set by the WHO were recommended with the goal of preventing simple goiter and stupidity (cretinism), not sufficiency of the whole human body for iodine, an amount we estimated to be 100-fold higher than the recommended daily intake.30 Concurrent with the decreased intake of iodine/iodide and increased intake of bromine in the US population, a trend of increasing prevalence of cancers of the mammary and thyroid glands was reported.30

Velicky, et al 33 in a 1997 publication, reported that rats consuming low levels of bromide, similar to levels presently consumed by human subjects, developed goiter, even though those rats received the normal amount of iodide in their diet. Under histological examinations, increased mitotic activity of the follicular epithelium was observed. The values of the mitotic index increased with increasing intake of bromide. The authors discussing their results, commented, “This finding is important in connection with the data showing an increasing exposure of living organisms to environmental bromine which represents an important environmental factor contributing to the development of endemic goiter; this is caused by a decreased utilization of the consumed iodine which produces a relative iodine deficiency even when the iodine intake is sufficient The transport of iodine and its organification can be blocked by Br- ions due to a mutual competition between bromide and iodide anions This results in a thyroxin and triiodothyronine deficiency, which in turn increases secretion of TSH Each stimulation of cell proliferation is obviously a key factor in the tumor growth of the thyroid (Williams, 1992) and an increased incidence of thyroid carcinoma in humans is higher in regions with iodine deficiency (Gaitan, et al, 1991).”

Shimomura, et al 36 observed that bromine enhances the biological activity of a tumor promoter. Sangster, et al 37 reported a decreased ability to concentrate and sleepiness in normal male subjects ingesting 4 mg sodium bromide/kg bw/day. This hypnotic effect could be due to oxidation and organification of bromide in the central nervous system. Torii, el al 38 tested an organic bromine compound, isolated from the cerebrospinal fluid of patients with bromism. In cats, this organic bromine induced REM sleep. Therefore, bromine has a zombifying potential. Why iodine deficient, even by the very low RDA standard, remains a mystery! Nevertheless, it is a very effective way to keep a nation sick and zombified.

The purpose of this manuscript is to review studies published during the late 1800s and early 1900s describing the effect of oral ingestion of inorganic, non-radioactive iodine/iodide in patients with simple goiter and in Graves’ disease, both conditions due to iodine/iodide deficiency. This physiological approach will be compared with the current non-physiological trend of prescribing to iodine-deficient female patients with hypothyroidism and simple goiter the hormone thyroxine (T4), which increases the risk of breast cancer in those patients (discussed in Section III). In Graves’ disease, the non-physiological trend of prescribing to iodine-deficient female patients with hypothyroidism and simple goiter the hormone thyroxine (T4), which increases the risk of breast cancer in those patients (discussed in Section III). In Graves’ disease, the non-physiological use of goitrogens and radioiodide has replaced iodine/iodide resulting in hypothyroidism of these unfortunate patients. It seems that no matter what your thyroid problem is, you always end up getting T4. In the discussion of published data on iodine-induced hypothyroidism and hyperthyroidism, a clear distinction will be made between inorganic versus organic forms, in order to demonstrate that adverse effects attributed to iodine in most publications were the result of ingestion and injection of organic forms of iodine-containing drugs.

A review of some historical events combined with some physiological aspects of iodide metabolism by the thyroid gland will be discussed in order to demonstrate that inadequate iodine/iodide intake combined with goitrogens, not excess iodide, is the cause of autoimmune thyroiditis. Last, the concept of orthoiodosupplementation is the safest and most effective method of supplementing patients with this essential trace element in amounts for whole body sufficiency. CONTINUED/.