Iodine On My Mind

Health Information

News for your health!
Drs. Brownstein, Abraham, Flechas and TSH Misunderstanding
     
Validation of the orthoiodosupplementation program: A Rebuttal of Dr. Gaby’s Editorial on iodine (download a copy of this discussion)

 

Guy E. Abraham, M.D.1 and David Brownstein, M.D.2


Orthoiodosupplementation is the daily amount of the essential element iodine needed for whole body sufficiency 1 . Whole body sufficiency for iodine is assessed by an iodine/iodide loading test (1,2). The test consists of ingesting 4 tablets of a solid dosage form of Lugol (Iodoral®), containing a total of 50 mg iodine/iodide. Then urinary iodide levels are measured in the following 24 hr collection. The iodine/iodide loading test is based on the concept that the normally functioning human body has a mechanism to retain ingested iodine until whole body sufficiency for iodine is achieved. For consistency and uniformity, the same solid dosage form of Lugol (Iodoral®) is used in the loading test and for orthoiodosupplementation. During orthoiodosupplementation, a negative feedback mechanism is triggered that progressively adjusts the excretion of iodine to balance the intake. As the body iodine content increases, the percent of the iodine load retained decreases with a concomitant increase in the amount of iodide excreted in the 24 hr urine collection. When whole body sufficiency for iodine is achieved, the absorbed iodine/iodide is quantitatively excreted as iodide in the urine. At such time, 90% or more of the iodine load is recovered in the 24 hr urine collection, and the body retains approximately 1.5 gm of elemental iodine (2).

In the August/September 2005 issue of Townsend Letter, Dr. Allen Gaby, M.D. wrote an Editorial on iodine, questioning the validity of the iodine/iodide loading test we use to assess whole body sufficiency for iodine; and the safety and efficacy of the orthoiodosupplementation program in medical practice. Our rebuttal will cover four topics:

  1. The safe and effective use of iodine by our medical predecessors.
  2. The computation of the average daily intake of iodide from seaweed by mainland Japanese.
  3. The validation of the iodine/iodide loading test.
  4. The effectiveness and safety of orthoiodosupplementation in current medical practice.
I. The safe and effective use of iodine by our medical predecessors.

To quote Gaby:

Recently, a growing number of doctors have been using iodine supplements in fairly large doses in their practices. The treatment typically consists of 12 to 50 mg per day of a combination of iodine and iodide, which is 80 to 333 times the RDA of 150 mcg (0.15 mg) per day. The element iodine was used in daily amounts 2 to 3 orders of magnitude greater than the RDA by physicians for over 150 years. Only 8 years after the discovery of iodine from seaweed by French chemist Bernard Courtois in 1811, Swiss physician J.F. Coindet who previously used successfully burnt sponge and seaweed for simple goiter, reasoned that iodine could be the active ingredient in seaweed. In 1819, he tested tincture of iodine at 250 mg/day, an excessive amount by today’s standard, in 150 goiter patients with great success. He published his results in 1820 (3). There is no question that the amount of iodine used by Coindet was excessive. But, Coindet was the first physician to use the newly discovered element iodine in medical practice. Since then, the collective experience of a large number of clinicians from the U.S. over the last century has resulted in the recommended daily amount of 0.1 to 0.3 ml of Lugol (4), containing from 12.5 to 37.5 mg elemental iodine, for iodine/iodide supplementation (1). This range of daily intake for iodine supplementation was based on clinical observation of the patient’s overall wellbeing. These daily amounts of iodine previously recommended by U.S. physicians based on clinical observation, without the availability of tests for thyroid hormones and without any procedure to assess whole body sufficiency for iodine, turned out to be the exact range of iodine needed for whole body sufficiency, based on an iodine/iodide loading test developed recently (1,2).

The Lugol solution was developed by French physician, Jean Lugol in 1829 for treatment of infectious diseases using oral ingestion of his preparation (4). The Lugol solution contains 5% iodine and 10% potassium iodide in water. Iodine is not very soluble in water, with aqueous saturation at 0.33 gm iodine/L. The addition of potassium iodide to an aqueous solution of iodine stabilizes the iodine by forming a complex triodide I3- and increases the aqueous solubility of iodine in the form of a triodide complex 150 times. The recommended daily amount of Lugol was 0.1 ml to 0.3 ml, containing 12.5 to 37.5 mg elemental iodine (1). As late as 1995, the 19th Edition of Remington’s Science and Practice of Pharmacy (5), continued to recommend between 0.1 to 0.3 ml daily of Lugol 5% solution in the treatment of iodine deficiency and simple goiter.

British physicians recommended a similar range of daily intake of iodine in the form of hydrogen iodide as the ranges of iodine recommended by U.S. physicians in the form of Lugol solution. The recommended daily intake of hydriodic acid syrup was 2 to 4 ml (6). The syrup is prepared by the British apothecary from an aqueous stock solution containing 10% hydrogen iodide (HI), which is diluted 10 fold with syrups of different flavors. When hydrogen iodide is dissolved in water, it forms hydriodic acid. The syrup would contain 1% hydrogen iodide equivalent. This would compute to 10 mg iodide per ml. So, the recommended daily amount of elemental iodine was from 20 to 40 mg.

As far back as 100 years ago, U.S. physicians used Lugol solution extensively in their practice for many medical conditions (1). In 1932, physician B.N. Cohn (7) wrote: "…the widespread use of compound solution of iodine, U.S.P., (For the reader’s information, that is Lugol solution) is the result of a paper by Plummer and Boothby, published in that year (1923). Since then compound solution of iodine has been used by nearly every clinician ..."

Lugol solution was called then Liquor Iodi Compositus, (that is Latin for compound solution of iodine). Marine in 1923 (8) used a daily average of 9 mg iodide in the prevention of goiter in adolescent girls, an amount 60 times the current RDA for iodine. In Marine’s study, the prevalence of goiter decreased 100 fold compared to a control group following 2 ½ years of supplementation.

Gaby used the RDA for iodine as his gold standard:

"First is the notion that the optimal daily iodine intake for humans is around 13.8 mg per day, which is about 90 times the RDA and more than 13 times the "safe upper limit" of 1 mg per day established by the World Health Organization."

Does Gaby realize that the RDA for iodine was established very recently in 1980, confirmed in 1989 (9), and based on data supplied by endocrinologists with thyroid fixation ignoring the rest of the body? The goal of the RDA for iodine is the prevention of extreme stupidity (cretinism), iodine-deficiency induced goiter and hypothyroidism, not whole body sufficiency for iodine. In 1930, Thompson et al(10) stated: "The normal daily requirement of the body for iodine has never been determined." This statement is still true today, more than 70 years later. We still don’t know the iodine/iodide requirements for whole body sufficiency. Physician Henry A. Schroeder (11) who did extensive studies on the dietary requirement for trace elements reported in 1975 that iodine in dog food is 20 times higher than iodine in food consumed by humans. The amount of iodine in the food supply of humans, of pets and laboratory animals, expressed as parts per million (PPM) are: for humans 0.12; for rabbits 0.59; for rats 1.17 and for dogs 2.25. Schroeder commented:

"Because it is doubtful that man differs much in his needs from other omnivorous animals, we could build up a good, if very indirect, case that man is not getting enough"

During the period when potassium iodate was used as a dough conditioner (1960-1980), and prior to the introduction of the goitrogen bromate as an alternative to iodate (1), one slice of bread contained the full RDA for iodine (12). During this period, Oddie et al (13) reported the results of a nationwide survey of iodine intake in the U.S. at 133 locations comprising of 30,000 euthyroid subjects. The mean iodine intake in these locations ranged from 240 to 740 ug/day. Correlation between iodine intake and mortality rates from thyroid diseases revealed a highly significant inverse correlation between iodine intake and mortality rates. Oddie et al comment: "Despite this high average, there is still a significant negative correlation (r = - 080) between iodine intake and mortality rate from thyroid diseases". In other words, the mortality rates would have continued to decrease with higher intake of iodine. Gaby blamed iodine for simple goiter in children when in fact iodine is used to prevent and treat childhood goiter. Again, quoting Gaby:

"In a survey of 3,300 children aged 6-12 years from 5 continents, thyroid glands were twice as large in children with high dietary iodine intake (about 750 mcg per day), compared with children with more normal iodine intake. While the significance of that finding is not clear, it suggests the possibility of iodine-induced goiter."

Analysis of the data in Table I of that publication (14) revealed only children from Hokkaido, Japan showed increased thyroid volumes of significance compared to the other groups: 2.16 to 2.59 ml for all the other groups; and 2.86 and 4.91 ml for the 2 groups from Hokkaido. This area of Japan is known to have a high incidence of euthyroid goiter. Suzuki et al (15) who first reported this finding in 1965 did not think that iodine was the cause of this goiter. He commented:

"Considering the paucity of reported cases of iodine goiter with the wide spread usage of iodine medication, we cannot exclude factors other than excessive intake of dietary iodine as a cause of the goiter."

Several other studies confirmed Suzuki’s skepticism regarding the role of iodine in the Hokkaido goiter. For example, Clement (16) in Tasmania, reported that a daily intake of 1.4 mg of potassium iodide (10 times the RDA) by infants and children for 16 years resulted in reduction in the prevalence of goiter, but in some regions, that amount of iodine did not have a significant effect on the rates of goiter. Different amounts of goitrogens in these different regions may explain this discrepancy. In Marine’s study, 9 mg/day of iodide were required to decrease the prevalence of goiter in adolescent girls by 100 fold (8). Currently, in Tasmania, potassium iodate is added to bread at 2 mg per loaf of bread.

"After a preliminary survey in 1949, tablets containing 10 mg potassium iodide had been made available to infants, preschool children, and schoolchildren through schools and child-health centres for weekly consumption for approximately sixteen years. State-wide surveys at five-year intervals showed a slow steady reduction in the prevalence of goiter, but in some regions the rates remained high." (16)

Gaby mentioned the "safe upper limit" of 1 mg/day, established by the WHO. As previously mentioned, prior to World War II, U.S. physicians used routinely 12.5 to 37.5 mg elemental iodine daily for iodine supplementation (1). Based on a review of the literature we previously proposed a daily intake of 12.5 mg elemental iodine for whole body sufficiency (12). However, based on the loading test, as much as four times that amount is required to achieve whole body sufficiency for iodine in some individuals (1,2). The greater demand for iodine may be due to the goitrogen load in these subjects. Large numbers of pulmonary patients were treated safely for years with daily amounts of potassium iodide 2 to 3 orders of magnitude greater than 1 mg. Fradkin and Wolff (17) commented on the safety of relatively large doses of potassium iodide:

"Although there are scattered case reports of IIT (iodide-induced thyrotoxicosis) after the use of KI, these must be considered in the light of over 108 tablets of KI prescribed annually in this country. Reports of experience with KI (1.6-6.4 g/day) in large series of pulmonary patients revealed no hyperthyroidism in 2404 and 502 patients."

The requirement for iodine depends on the goitrogen load. The greater the goitrogen load, the greater the need for iodine. Bromide is a goitrogen that interferes with the uptake and utilization of iodide by target cells (1,2). The U.S. population is exposed to large amounts of the element bromine in its organic and inorganic forms. We have observed a basal mean level of urine bromide at 24 mg/24 hr, four times higher than reported in Western Europe. The United States utilizes two-thirds of the annual world production of bromine (17). The annual world production of bromine is 280,000 tons. At 909 Kg/ton, we have then an annual world production of bromine of approximately 254,520,000 Kg. The U.S. consumes 167,983,200 Kg of bromine annually. Out of that amount, 45,450,000 Kg are used in agriculture (food supply) and 9,090,000 Kg for water sanitation (water supply). The amount of bromine used in our food and water supplies compute to 21% of the total U.S. utilization of this goitrogenic halogen (18). It does not take a rocket scientist to figure out that we, in the U.S., are exposed to high amounts of the goitrogen bromine via our food and water supplies in all its inorganic and organic forms, such as methylbromide in agriculture. Bromine competes with iodine for cellular uptake and utilization; and has goitrogenic, carcinogenic and narcoleptic properties (1). Iodine pulls bromine from storage sites and increases its urinary excretion (2). Chloride also increases the excretion of bromide i n urine (18). For detoxification of bromide, the halides iodide and chloride are the most effective.

The annual world production of iodine in 1981 was 12,000 tons or 10,908,000 Kg (18). Some 20% of the iodine used in the U.S. is for animal feed supplement, and none for human food, except the minimal amount in table salt (19). Between 1960 and 1980, iodate was used in bread with one slice of bread containing the full RDA of 0.15 mg (1). But some 20 years ago, iodophobia resulted in the removal of iodate from bread, replacing it with… you guessed it… bromate. If you wanted to keep a nation sick and zombified, we cannot think of a better way to achieve this goal (1).

Gaby, assuming we evolve from a Big Bang 20 billion years ago, commented:

"Since emerging from the iodine-rich oceans to become mammals, we have evolved in an iodine-poor environment."

Actually, the oceans are very poor in iodine, based on concentration of this element. Although the largest reservoir of iodine is in the oceans, because of their large volume, the concentration of iodate/iodine/iodide in the oceans is only 0.05 PPM, very dilute indeed, compared to bromide at 70 PPM (20). For example, to obtain the RDA for iodine from seawater, you need 3 liters. Sea salt is very low in iodide, much lower than iodide in iodized table salt, actually 50 times lower. It is understandable why someone who believes in the theory of evolution has a problem with such high requirements for iodine in an environment depleted of this element. Unless sometimes in the distant past, the topsoil of planet earth contains significant levels of iodine and meeting these high requirements for iodine sufficiency could then be achieved with any diet.

The theory of evolution does not offer an intellectually satisfying answer to this paradox. However, the Biblical account of the origin of the world through creation 6000 years ago followed by the fall of man and the flood fits very well the current situation. According to the biblical narrative, the Creator declared planet earth and everything in it perfect. Therefore, the original planet earth contained a topsoil rich in iodine, and all elements required for perfect health of Adam, Eve and their descendants. A rebelled archangel was expelled from God’s Habitation for attempting a hostile takeover (Isaiah 14:12-15). His name was Lucifer before the attempt (Isaiah 14:12) and Satan after his expulsion (Luke 10:18). Satan deceived Eve into believing that she could become a goddess by disobeying her Creator (Genesis 3:4,5). A sequence of events followed, culminating in the worldwide flood 4500 years ago. Following this episode, the receding waters washed away the topsoil with all its elements into oceans and seas. The new topsoil became deficient in iodine and most likely other essential elements, whose essentialities are still unknown. Mountainous areas became the most iodine-deficient because the receding waters were the most rapid over the steep slopes, eroding deeper into the soil. The biblical account of the flood fits very well with the finding of high concentrations of iodine in brines, which accompany oil wells and natural gas deposits (9). By 1977, the brines associated with deposits of natural gas in Japan accounted for 56% of the world iodine production (19). The previous existence of iodine-rich living organisms from which came these iodine-rich degradation products strongly suggests that sometime in the distant past, iodine was plentiful on planet earth, and some catastrophic event resulted in washing away the iodine-rich top soil in the oceans. The worldwide flood fits extremely well with the current findings of high iodine concentrations in brines.

The toxicity of iodine depends on the forms of this element. Several forms of iodine prescribed by U.S. physicians are listed in Table I. The manmade organic forms of iodine are extremely toxic, whereas the inorganic non-radioactive forms are extremely safe (2). However, the safe inorganic non-radioactive forms were blamed for the severe side effects of the organic iodine-containing drugs. For example, in reference #14 of Gaby’s editorial, discussing thyrotoxicosis induced by iodine (21), the form of iodine involved is an iodophore, an organic form of iodine. This iodophore interferes with iodine uptake and utilization by the thyroid gland (22). From a publication by Phillippou, et al, published in 1992 (23), it is obvious that the cytotoxicity of the organic iodine-containing drugs is due to the molecule itself, not the iodine released or present in the molecule. "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."

A new syndrome, medical iodophobia, was recently reported (1) with symptoms of split personality, double standards, amnesia, confusion and altered state of consciousness. Medical iodophobia has reached pandemic proportion and it is highly contagious (iatrogenic iodophobia). A century ago, non-radioactive forms of inorganic iodine were considered a panacea for all human ills, but today, they are avoided by physicians like leprosy (2). We have previously discussed the factors involved in this medical iodophobia (24). If iodine deficiency is the cause of medical iodophobia, this syndrome would become self-perpetuating. Unfortunately, physicians are afraid of the element that is, most likely, the cure of their phobia.

II. The computation of the average daily intake of iodide from seaweed by mainland Japanese

Over 95% of the iodine consumed by mainland Japanese comes from seaweed. If you want to prove that the intake of iodine by mainland Japanese is within the same range as consumed by the U.S. population or maybe slightly above, just tell your Japanese study subjects to abstain from seaweed during the study period. It’s that easy and this technique has been used effectively in several publications. As a general rule, mainland Japanese living in the coastal areas of Japan, consume more seaweed than inland dwellers (15,25-27). Among the coastal areas, the inhabitants of Hokkaido ingest the largest amount of seaweed (15). Hokkaido produces 90% of the seaweed consumed in Japan (15), further processed by drying and flattening for sales in food stores. Statistics compiled by the Japanese Ministry of Health is based on the dry form of seaweed (28). Seaweed contains predominantly the inorganic form of the element iodine, mainly iodide (29). Seaweed also concentrates other halides such as bromide, which possess goitrogenic, carcinogenic and narcoleptic properties (1). Seawater is very poor in iodide and relatively rich in bromide with 0.05 PPM iodide and 70 PPM bromide. There is 1400 times more bromide than iodide in seawater.

Mainland Japanese consume large amounts of iodine from seaweed and they are one of the healthiest nations (12). Based on extensive surveys performed by the International Agency for Research on Cancer and published in 1982 (30), mainland Japanese, at least up to 1982, experienced one of the lowest incidences of cancer in general. Mainland Japanese have the longest lifespan in the world (31). Although seaweed has been the main source of iodine for the Japanese population, inorganic iodine/iodide in supplements (liquid or tablets) seems a much purer, safer and more accurate form for supplementation of this essential element than seaweed. It is more difficult to titrate the amount of seaweed needed to achieve whole body sufficiency for iodine than the amount of a pure standardized solid dose form of this essential element. It was not conclusively proven that iodine was the cause of the reported seaweed-induced goiter with normal thyroid functions 40 years ago in Hokkaido, Japan (15). This seaweed-induced goiter eventually disappeared (23). Suzuki et al (15) questioned whether seaweed itself was the cause of this goiter, since much larger amounts of iodide in pulmonary patients did not induce goiter. Suzuki et al commented: "Considering the paucity of reported cases of iodine goiter with the wide spread usage of iodine medication, we cannot exclude factors other than excessive intake of dietary iodine as a cause of the goiter." Also, residents in Tokyo, Japan, who excreted similar levels of iodide in their urine (around 20 mg/24h) did not experience goiter. Contamination of seaweed with bromide is the most likely explanation, since bromide is a goitrogen (1), and there is 1400 times more bromide than iodide in seawater (20). The presence of excess goitrogens in the diet would require greater amounts of ingested iodine to prevent the goitrogenic effect of these substances (2).

Gaby equates urinary iodide excretion with dietary intake of iodine and uses data of urine iodide levels from one group of Japanese thyroidologists to validate his claim of low average daily intake of iodine by mainland Japanese, comparable to iodine consumption in the U.S.

"In studies that have specifically looked at iodine intake among Japanese people, the mean dietary intake (estimated from urinary iodine excretion) was in the range of 330 to 500 mcg per day,(7,8) which is at least 25-fold lower than 13.8 mg per day."

References 7 and 8 quoted by Gaby are from the same group of Japanese thyroidologists. Usually, Japanese thyroidologists trained in the U.S. will encourage their patients to abstain from seaweed when performing radioisotope testing of the thyroid gland in order to obtain results comparable with results obtained from U.S. thyroidologists. The urinary excretions of iodide reported by Ishizuki et al in references 7 and 8 of Gaby’s editorial are obviously from patients who were told to abstain from seaweed. We will quote other studies by Japanese investigators who reported urinary iodide levels 10 to 100 time higher than the values reported by Ishizuki et al .

In assessing the intake of iodine by mainland Japanese based on urinary excretion of iodide, keep in mind that urinary iodide levels are not a good index of intake unless whole body sufficiency for iodine is achieved and the form of iodine consumed is highly bioavailable(1,2). For example, only 10% of sodium iodide present in table salt is bioavailable, due to competition with chloride for intestinal absorption (9). On a molor basis, there is 30,000 times more chloride than iodide in iodized salt. Iodine excreted in the 24 hr. urine collection can be as low as 10% of the ingested amount in iodine-deficient subjects (1), due to body retention of iodine. Therefore, the amount of iodine ingested can be as high as 10 times the amount of iodide recovered in the 24 hr urine collection.

With this in mind, let us review some published data. Konno et al (25) measured iodide in morning urine samples of 2,956 men and 1,182 women, all normal and healthy, residing in Sapporo, Japan. The 95% confidence limits were from 1.14 to 8.93 mg/L with an average 3.3 gm/L. Assuming an average 24 hr. urine volume of 1.5 liters, the daily iodide excretion would range from 1.7 to 13.4 mg with an average of 5 mg. As discussed previously, these amounts are an underestimate of iodine intake. Yabu et al (32) from Osaka measured iodide levels in morning urine samples obtained from 39 male and 88 female local residents. He reported a range of 0.6 to 17.4 mg/L. If those iodine levels are expressed as mg/24 hr. and assuming an average 24 hr. urine volume of 1.5 liter, the range of iodine excretion per 24 hr. would be from 1 to 25 mg in these 163 Japanese subjects.

Gaby mentioned that the calculation we used to estimate the average daily intake of mainland Japanese was based on dry weight whereas the data in Nagataki’s publication (26) on iodine in seaweed was reported per wet weight.  Quoting from that article (26):  "For example, the dry weight of such food as "tangle" (Laminaria) contains 0.3% iodine (1) and this may be eaten in quantities as large as 10 g daily". This daily intake would compute to 30mg of elemental iodine.  However, on page 643 of the same article, Nagataki et al (26) stated: "…according to the statistics of the Ministry of Health and Welfare (13), the average daily intake of seaweed was 4.6 g (wet weight)," when in fact, that Organization confirmed by a phone interview (6/21/05) that their data on seaweed in the 1965 report were expressed as dry weight. For example, in table 8 of Nagataki’s Reference #13, values for seaweed consumption for several years from 1950 to 1963 are listed in gms of dry weight, confirmed by the Japanese Ministry of Health and Welfare. We have compiled some of these data in our Table II, taken from reference 13 of Nagataki’s article. The value of 4.6 g that Nagataki quoted as wet weight was actually expressed as dry weight and Nagataki used the value for the year 1963 only, that is, 4.6 gm. Nagataki et al mentioned correctly dry weight on page 638 at the beginning of their article, and for some unknown reason, they erroneously mentioned wet weight on page 643 of the same publication, which is confusing. We have relied, therefore, on the original information supplied by the Japanese Ministry of Health and Welfare, that is Nagataki’s Reference #13, and our reference #28.

We estimated the average daily intake of iodine by mainland Japanese in 1963 at 13.8 mg, based on information supplied by the Japanese Ministry of Health, which used only dry weight in their calculations, confirmed by a phone interview of one of us (GEA) on June 21, 2005, with officials of this Organization (See Table II). This amount of iodine was confirmed in mainland Japanese based on urine iodide levels in this population, as previously discussed.

One can see that iodine intake was even higher during the years 1954, 1956, 1958 and 1960. The mean value for the 8 amounts of seaweed displayed in Table II is 4.5 gm and at 0.3% iodide, this average daily amount would contain 13.5 mg iodide. Gaby ends his Editorial with a recommendation but without any validating reference.

"Thyroid function should be monitored in patients receiving more than 1 mg of iodine per day."

If 60 million mainland Japanese take Gaby’s recommendation seriously, laboratories performing thyroid function tests in Japan could not keep up with the demand.

We must emphasize that the orthoiodosupplementation program is not based on consumption of iodine by the Japanese population, but on whole body iodine sufficiency assessed by the iodine/iodide loading test, which brings us to our next topic.

Table II

Annual change of intake of food by food groups in Japan

(Except for the calories, all values below are expressed as gms / per capita / day)

Yrs.

1950

1952

1954

1956

1958

1960

1962

1963

Calories

2,098

2,109

2,074

2,092

2,118

2,096

2,080

2,083

Proteins









Total

68

70

69

69.1

70.1

69.7

70.4

70.6

Animal

17

23

22

22.6

23.8

24.7

27.3

27.7

Vegetable

51

47

47

46.5

46.4

45.0

43.2

42.9

Fat

18

20

21

21.8

23.7

24.7

28.3

29.2

Carbohydrate

418

412

403

405

406

399

386

382

Sugars

7.2

14.5

15.6

15.6

12.3

12.3

13.4

14.0

Fats & Oils

2.6

3.9

4.6

5.1

5.7

6.1

7.6

8.1

Beans

53.7

68.4

68.2

72.7

71.0

71.2

70.8

69.4

Milk

6.8

10.2

12.5

19.4

22.0

29.5

35.9

38.8

Milk products


0.4

0.6

2.1

2.6

3.4

5.9

6.3

*Sea weeds (dry weight)

3.0

4.1

4.8

5.0

5.0

4.7

4.5

4.6

Compiled from tables 6 and 8 of the official publication, Nutrition in Japan, 1964, Nutrition Section, Bureau of Public Health, Ministry of Health and Welfare, Tokyo, Japan, March 1965.

* In a phone interview with Guy E. Abraham, M.D., on June 21, 2005, using Miss Hisa Izumi as an interpreter, the interviewees Miss Nichi and Mister Arai at the Japanese Ministry of Health and Welfare confirm that, in the nutritional surveys published in 1965, the average daily amount of seaweed consumed is expressed as gms of dried seaweed.

III. The validation of the iodine/iodide loading test.

Gaby questions the validity of the iodine/iodide loading test and presents some valid arguments.

"Before the iodine-load test can be considered a reliable indicator of tissue iodine levels, it needs to be demonstrated that only negligible amounts of iodine are excreted in the feces after an oral iodine load."

Inorganic iodine is an ideal element for an oral loading test. Inorganic forms of iodine are quantitatively absorbed by the gastrointestinal tract and highly bioavailable. Less than 5% of ingested inorganic iodine/iodide are excreted in the feces and sweat (33), with most of that amount in sweat. The data in reference #9 of Gaby’s paper dealing with low bioavailability of ingested iodine in cows, which are ruminants, should not be extrapolated to humans. Since data obtained with the iodine/iodide loading test revealed that 90 to 100% of the ingested iodine/iodide is recovered in the 24 hr. urine collection when sufficiency is achieved (1,2), it is obvious that the ingested iodine/iodide in the tablets used for the loading test are highly bioavailable. Serum iodide is rapidly cleared by the kidneys with a daily clearance rate of 43.5 liters (9). The renal clearance of iodide remains constant with intake from 0.001 mg to 2,000 mg iodide (34). The gastrointestinal tract has the capacity to absorb quantitatively large amounts of iodine/iodide (34).

Studies performed with a sustained release form of iodine, amiodarone, give further support for the validity of the iodine/iodide loading test. Amiodarone is a benzofuranic derivative containing 75 mg of iodine per 200 mg per tablet. It is widely used for the long-term treatment of cardiac arrhythmias (33-37). Broekhuysen et al (38) using balance studies of amiodarone and the non-amiodarone inorganic iodine released from amiodarone, reported the following: In 2 subjects treated with 300 mg of amiodarone/day containing 112.5 mg iodine, the total amount of iodine measured in urine and feces was very low during the first 3 days, with a mean of 19% and 7% of the total iodine ingested, suggesting that as much as 93% of the iodine ingested was retained in the body, or 105 mg iodine per day was retained by the patient. After 25 to 27 days of therapy with 300 mg amiodarone/day, the mean % iodine excretion of combined urine plus feces in these 2 subjects increased 48% and 75%. Therefore, after approximately one month, the percent of iodine retained by the body had decreased to 25% and 50%. No inorganic iodine/iodide was found in feces, only the organic form, amiodarone, whereas only inorganic iodide was excreted in urine.

In 2 other subjects treated with 300 mg amiodarone/day for 7 weeks, balance studies revealed that at the end of the study, the total excreted iodine in urine and feces averaged 97.4% and 96.9%. Again, only the organic form amiodarone was found in feces and only the inorganic form in urine. Based on the balance studies, the amount of iodine retained by the body following 7 weeks on amiodarone at 300 mg/day containing 112.5 mg iodine, was estimated at 1.5 gm. The authors commented: "These results suggest that iodine is retained in the body until a mechanism is triggered that adjusts the excretion of iodine to balance completely the intake." They estimated that the body retained 1.5 gm of iodine before the ingested iodine in amiodarone is completely excreted, and before therapeutic efficacy.

In 3 patients who eventually died following long-term treatment with amiodarone, the levels of inorganic iodine (not amiodarone) present in various organs and tissues were measured. The total body non-amiodarone iodine content was estimated at approximately 2 gm with the greatest amount found in fat tissues (700 mg) and striated muscle (650 mg). Iodine was present in every tissue examined. The highest concentrations of non-amiodarone iodine were found in descending order: thyroid gland, liver, lung, fat tissues, adrenal glands and the heart. We previously reported a double peak of serum inorganic iodide levels, 8 hours apart, following ingestion of a solid dosage form of Lugol (39). This pattern is indicative of an enterohepatic circulation of inorganic iodine, which could explain the high iodine content of the liver. Human ovaries also concentrate iodine effectively with a value of 741 ug/100 mg wet weight (40). According to Slebodzinski (40), the iodine concentrations in the ovaries are the highest of all other organs, except the thyroid gland. Unfortunately, Broekhuysen et al (38) did not report the levels of iodine in the ovaries of the 2 subjects studied at autopsy. Maybe, there were male subjects.

When a tablet form of Lugol is ingested at a daily amount of 50 mg elemental iodine, whole body sufficiency is achieved in approximately 3 months and the estimated amount of iodine retained in the body is approximately 1.5 gm (9). This is the same amount of iodine retained in patients on amiodarone following 7 weeks at 300 mg/day containing 112.5 mg iodine. Clinical response to amiodarone is observed after the same period of time on amiodarone therapy. Some comparisons between amiodarone, an organic form of iodine, and inorganic iodine/iodide are in order. In the patients who ingested 300 mg amiodarone for 7 weeks, the total amount of iodine ingested is: 112.5 mg × 49 days = 5.5 gm. The patients retained 1.5 gm, that is 1.5 gm / 5.5 gm × 100 = 27% of the total dose. In patients of orthoiodosupplementation at 50 mg elemental iodine/day, sufficiency is achieved usually in 3 months and 1.5 gm of iodine is retained. The total amount of iodine ingested during 3 months at 50 mg/day = 50 mg / day × 90 days = 4.5 gm. The patients retained 1.5 gm, that is 1.5 gm / 4.5 gm × 100 = 33% of the total dose. Roughly 30% of the total dose of iodine is retained at iodine sufficiency in both cases, but the time required to achieve sufficiency decreases as the daily amount of iodine increases. Whether this inverse relationship between the daily dose of iodine and time required for whole body iodine sufficiency will persist with daily intake of iodine greater than 100 mg would require further investigation.

Since iodine mobilizes toxic metals and goitrogenic halides from their storage sites (1,2), it may not be wise to achieve whole body sufficiency for iodine too rapidly since mobilization of these toxic substances may increase their peripheral levels high enough to cause symptoms. A complete nutritional program combined with increased fluid intake will help the body eliminate these toxic elements more safely (1). To be discussed later, in cases of increased mobilization of bromide from storage sites by orthoiodosupplementation and elevated serum bromide levels high enough to cause bromism, the administration of sodium chloride (6-10 gm/day) increases the renal clearance of bromide by as much as 10 fold and minimizes the side effects of bromism (18). If orthoiodosupplementation results in elevated urine lead levels, together with increased bromide, ammonium chloride is preferable to sodium chloride since it is the chloride that increases renal clearance of bromide. The ammonium is metabolized to urea and has an acidifying effect, which increases renal clearance of lead also.

The above comparison of the data obtained from amiodarone administration and orthoiodosupplementation is suggestive of an important role of inorganic iodine released from amiodarone in the therapeutic effect of this drug, and that whole body sufficiency for iodine is a requirement for optimal cardiac function. Since the amount of iodine used in the amiodarone study is twice the amount of iodine used in orthoiodosupplementation, the time required for whole body iodine sufficiency was only 7 weeks for amiodarone and 12 weeks for orthoiodosupplementation. In order to achieve whole body sufficiency for iodine in 6 weeks using orthoiodosupplementation, the daily intake required would be 100 mg.

One more argument in support of the validity of the iodine/iodide loading test follows. Serum inorganic iodide levels measured under steady state conditions are a good index of bioavailability of the iodine preparation in subjects without a defect/damage of the transport of iodine/iodide in target cells. We have previously calculated that the serum levels of inorganic iodide at equilibrium would be the daily amount of iodine ingested divided by 43.5 liters if the form of iodine ingested was completely bioavailable (9). At 50 mg iodine/day, the expected serum inorganic iodide level at equilibrium would be: 50 mg/43.5 L = 1.15 mg/L. In 8 normal subjects who achieved whole body iodine sufficiency, the fasting serum inorganic iodide levels 24 hrs after the last intake of iodine, ranged from 0.85 to 1.34 mg/L.

The mechanism involved in the absorption of iodine/iodide by the gastrointestinal tract is different from the mechanism involved in the transport of iodide inside the target cells (2). A severe cellular transport defect/damage of iodide by target cells can occur in a patient with a very efficient gastrointestinal absorption of iodine/iodide. In such a case, the absorbed iodine/iodide will be excreted quantitatively as iodide in the urine even though the target cells are iodine deficient. We have reported on 3 such cases (2,41). In one instance, the patient was studied with serial blood samples following a load of 50 mg iodine/iodide (4 tablets Iodoral®) prior to and following intervention with administration of oral Vitamin C at 3 gm/day for 3 months. A positive effect of Vitamin C was observed on the iodide cellular transport function (41). In all 3 cases, the serum iodide levels 24 hrs following a load of 50 mg iodine/iodide were very low, compared to the normal subjects : <0.006 mg/L, 0.011 mg/L and 0.016 mg/L. Prior to orthoiodosupplementation, the percent of iodine load excreted in these 3 patients were: 90%, 96% and 102%. The above results suggest that Gaby grossly underestimated the ability of the gastrointestinal tract to absorb ingested iodine/iodide quantitatively in relatively large amounts, when he stated:

"However, the validity of the test depends on the assumption that the average person can absorb at least 90% of a 50-mg dose. It may be that people are failing to excrete 90% of the iodine in the urine not because their tissues are soaking it up, but because a lot of the iodine is coming out in the feces. There is no reason to assume that a 50-mg dose of iodine, which is at least 250 times the typical daily intake, can be almost completely absorbed by the average person."

Several organs beside the thyroid gland can concentrate peripheral iodide against a gradient (41). The salivary glands have this capability and we are now investigating the mixed saliva iodide/serum iodide ratio as a mean of assessing cellular iodide transport efficiency in cases of iodide transport defect/damage prior to and following nutritional intervention.

IV. The effectiveness and safety of orthoiodosupplementation in current medical practice.

Physicians who use holistic therapies are always on the search for safe and effective natural therapies that have minimal adverse effects. The experience of several physicians with iodine/iodide in daily amounts from 6.25 to 50 mg, using a solid dosage form of Lugol (Iodoralâ ) for over three years in several thousands of patients has shown it to be safe and effective, with minimal adverse effect (2).

  1. Effectiveness
  2. The Center for Holistic Medicine in West Bloomfield, MI (office of D. Brownstein, M.D.) has tested over 500 patients for iodine deficiency using the iodine/iodide loading test, developed by one of us (1). Based on the experience of the Center, the loading test provides an accurate and reproducible picture of the iodine status in the body. Retesting many of these patients has shown the changes in the test correlates with the changes in the clinical picture. In other words, as the loading test improves, the clinical picture improves.

    Our experience at the Center for Holistic Medicine has shown that patients with the lowest urinary iodide levels on the loading tests are often the most ill. Many of these patients with very low urine iodide levels following the loading test have severe illnesses such as breast cancer, thyroid cancer or autoimmune thyroid disorders. All of these conditions have been shown in the literature to be associated with iodine deficiency (1). Positive clinical results were seen in most of these patients after supplementation of orthoiodosupplementation within the range of 6.25-50mg of iodine/iodide (1/2 to 4 tablets of Lugol in tablet form).

    One of the most satisfying effects of orthoiodosupplementation has been in the treatment of fibrocystic breasts and thyroid nodules. The treatment of fibrocystic breasts with iodine has been reported for over 100 years. Iodine/iodide supplementation has resulted in significant improvement in fibrocystic breast illness for nearly every patient treated. Thyroid nodules also respond positively to iodine/iodide supplementation. Serial ultrasounds usually show decrease in the size of the thyroid cysts and nodules and eventual resolution of the lesions. When orthoiodosupplementation is combined with a complete nutritional program, it is rare not to see improvement in the palpation and radiological examination of thyroid nodules and cysts following iodine/iodide therapy as described here.

    The effectiveness of orthoiodosupplementation has not been limited to the very ill. In fact, most patients treated with orthoiodosupplementation have quickly experienced positive results although optimal responses are observed when whole body iodine sufficiency is achieved based on the iodine/iodide loading test. Our experience has shown that a wide range of disorders have responded to orthoiodosupplementation including thyroid disorders, chronic fatigue, headaches, fibromyalgia and those with infections. Additionally, our clinical experience has shown that iodine/iodide supplementation has resulted in lower blood pressure in hypertensive patients. The blood pressure-lowering effect is seen when sufficiency of iodine is achieved.

    Occasionally, individuals on thyroid medication will develop signs and symptoms of hyperthyroidism on orthoiodosupplementation. This situation has been easily rectified by lowering or discontinuing the thyroid medication. Of those individuals taking thyroid medication, approximately 1/3 of them will need to discontinue or lower their thyroid medication upon taking iodine/iodide due to increased thyroid function and improved receptor responsiveness (2). The remaining 2/3 of the thyroid treated patients will maintain their thyroid dosages while taking iodine/iodide without side effects.

  3. Safety

Dr. Gaby’s claims that the relatively high doses of iodine/iodide used in orthoiodosupplementation may lead to hypothyroidism, goiter or autoimmune thyroid problems. This just is not the case. A review of the literature revealed that the organic forms of iodine were involved in most of these complications (1). Iodine intake has fallen over 50% in the U.S. over the last 30 years (42). During this same time, increases in diabetes, hypertension, obesity, breast and thyroid cancer, and other thyroid disorders, have been reported. It appears to us that iodine deficiency, not iodine excess may be responsible for the increase of these conditions (1,2).

The clinical experience with orthoiodosupplementation in approximately 4,000 patients at the Center for Holistic Medicine has clearly shown that orthoiodosupplementation at daily dose of 6.25 to 50mg elemental iodine has not been associated with increases in hypothyroidism, goiter and autoimmune thyroid problems. On the contrary, the use of iodine/iodide has been effective at treating the above conditions with minimal adverse effects.

Dr. Gaby points out that "some people are especially sensitive to the adverse effects of iodine". He is correct. Just as some people are sensitive to Vitamin C, some are sensitive to iodine/iodide. Few holistic physicians would deny the effectiveness of mega doses of Vitamin C, in amounts thousands of times greater than the RDA for Vitamin C, in the treatment of wide range of illnesses. Just as with Vitamin C therapies, individualized doses and proper follow-up visits can help minimize adverse effects of iodine/iodide therapies.

Dr. Gaby writes, "The relative absence of side effects may be due to the use of iodine as part of a comprehensive nutritional program." He is correct. With orthoiodosupplementation the best results do occur when used as part of a comprehensive nutritional program, as do all holistic therapies. We favor a magnesium emphasized total nutritional approach (1).

The most common adverse effects of iodine/iodide supplementation observed at the Center for Holistic Medicine has been metallic taste in the mouth and acne. Based on the experience of three clinicians at that Center, with a combined patient population of some 4,000, the prevalence of these side effects is about 1%. This is probably due to a detoxification reaction. The release of bromide may be one cause of this detoxification reaction. Clinical experience has continually shown that iodine/iodide supplementation results in a large urinary excretion of bromide (1,2). When bromide levels begin to decline, the above mentioned adverse effects begin to decline as well. Chloride increases renal clearance of bromide (17) and the use of NaCl or ammonium chloride shortens the time required for bromide detoxification with orthoiodosupplementation. Oral administration of sodium chloride (6 to 10 gm/day) increased the renal clearance of bromide by as much as 10 fold with mean serum half-life of 290 hrs in pre-chloride load subjects and 30-65 hrs after chloride administration. Intravenous sodium chloride gives the same results as the oral route (18,43).

In the practice of medicine, we have seen very few natural therapies as safe and effective as orthoiodosupplementation. In the proper forms of iodine (inorganic non-radioactive forms), in daily amounts of iodine for whole body sufficiency and properly monitored, orthoiodosupplementation is not only safe, it is an effective tool for the clinician. Prior to the availability of assays for thyroid hormones and without any test for assessing whole body sufficiency for iodine, our medical predecessors recommended a range of daily iodine intake from Lugol solution (12.5 – 37.5 mg) exactly within the range required for achieving whole body sufficiency for iodine (1,2). Relying on clinical observation of the patient’s overall wellbeing, our predecessors have given us useful information, which we have discarded in favor of preconceived opinions from self-appointed iodophobic pseudo experts. This has resulted in pandemic iodine deprivation. Iodine deficiency is misdiagnosed and treated with toxic drugs. Orthoiodosupplementation may be the simplest, safest, most effective and least expensive way to help solve the health care crisis crippling our nation (9).

References

  1. Abraham, G.E., The safe and effective implementation of orthoiodosupplementation in medical practice. The Original Internist, 11:17-36, 2004.
  2. Abraham, G.E., The historical background of the Iodine Project. The Original Internist, 12(2):57-66, 2005.
  3. Coindet, J.F., Decouverte d’un nouveau remède contre le goitre. Ann. Clin. Phys., 15:49, 1820.
  4. Lugol, J.G.A., Mémoire sur l’emploi de l’iode dans les maladies scrophuleuses. Paris, 1829. (Published by himself).
  5. Gennaro A.R., Remington: The Science and Practice of Pharmacy, 19th Edition, 1995, Mack Publishing Co., 1267.
  6. Martindale, The Extra Pharmacopoeia 28th edition. J.E.F. Reynolds. Editor: The Pharmaceutical Press, pg. 865, 1982.
  7. Cohn, B.N.E., Absorption of Compound Solution of Iodine from the Gastro-Intestinal Tract. Arch. Intern Med., 49:950-956, 1932.
  8. Marine, D., Prevention and Treatment of Simple Goiter. Atl. Med. J., 26:437-442, 1923.
  9. Abraham, G.E.: The concept of orthoiodosupplementation and its clinical implications. The Original Internist, 11:29-38, 2004.
  10. Thompson, W.O., Brailey, A.G., Thompson, P.K., et al, The Range of Effective Iodine Dosage in Exophthalmic Goiter III. Arch. Int. Med., 45:430, 1930.
  11. Schroeder, H.A., The Trace Elements and Man. The Devin-Adair Co., Old Greenwich, CT, pg. 52,53, 1975.
  12. Abraham, G.E., Flechas, J.D., Hakala, J.C., Orthoiodosupplementation: Iodine sufficiency of the whole human body. The Original Internist, 9:30-41, 2002.
  13. Oddie, T.H., Fisher, D.A., McConahey, W.M., et al, Iodine Intake in the United States: A Reassessment. J. Clin. Endocr. & Metab., 30:659-665, 1970.
  14. Zimmermann, M.B., et al, High thyroid volume in children with excess dietary iodine intakes. Am. J. Clin. Nutr., 81:840-844, 2005.
  15. Suzuki, H., Higuchi, T., Sawa, K., et al, Endemic Coast Goitre in Hokkaido Japan. Acta Endocr., 50:161-176, 1965.
  16. Clements, F.W., Goitre prophylaxis by addition of potassium iodate to bread. The Lancet, 1:489-492, 1970.
  17. Fradkin, J.E., Wolff, J., Iodide-Induced Thyrotoxicosis. Medicine, 62:1-20, 1983.
  18. Sticht, G., Käferstein, H., Bromine. In Handbook on Toxicity of Inorganic Compounds – Seiler HG and Sigel, H Editors, Marcel Dekker Inc, 143-151, 1988.
  19. Bulman, R.A., Iodine. In Handbook on Toxicity of Inorganic Compounds – Seiler HG and Sigel, H Editors, Marcel Dekker Inc, 327-337, 1988.
  20. Neidleman, S.L., Geigert, J., Biohalogenation: Principles, Basic Roles and Applications. Ellis Horwood Limited Publishers, Chichester, Halsted Press, 1986.
  21. Stewart, J.C., Vidor, G.I., Thyrotoxicosis induced by iodine contamination of food-a common unrecognized condition? British Med. J., 1:372-375, 1976.
  22. Furudate, S., Nishimaki, T., Muto, T., 125I Uptake Competing with Iodine Absorption by the Thyroid Gland following Povidone-Iodine Skin Application. Exp. Anim. 46(3), 197-202, 1997.
  23. Phillippou, G., Koutras, D.A., Piperingos, G., et al, The effect of iodide on serum thyroid hormone levels in normal persons, in hyperthyroid patients, and in hypothyroid patients on thyroxine replacement. Clin. Endocr., 36:573-578, 1992.
  24. Abraham, G.E., The Wolff-Chaikoff Effect: Crying Wolf? The Original Internist, 12(3):112-118, 2005.
  25. Konno, N., Yuri, K., Miura, K., et al, Clinical Evaluation of the Iodide/Creatinine Ratio of Casual Urine Samples as an Index of Daily Iodide Excretion in a Population Study. Endocrine Journal, 40(1):163-169, 1993.
  26. Nagataki, S., Shizume, K., Nakao, K., Thyroid Function in Chronic Excess Iodide Ingestion: Comparison of Thyroidal Absolute Iodine Uptake and Degradation of Thyroxine in Euthyroid Japanese Subjects. J. Clin. Endocr., 27:638-647, 1967.
  27. Konno, N. Makita, H., Yuri, K., et al, Association between Dietary Iodine Intake and Prevalence of Subclinical Hypothyroidism in the Coastal Regions of Japan. J. of Clin. Endocr., & Metab., 78:393-397, 1994.
  28. Nutrition in Japan, 1964. Nutrition Section, Bureau of Public Health, Ministry of Health and Welfare, Japan. Printed: Tokyo, Japan, March 1965.
  29. Shaw, T.I., The Mechanism of Iodide Accumulation by the Brown Sea Weed Laminaria digitata. Proc. Roy. Soc. (London), B 150, 356-371, 1959.
  30. Waterhouse, J., Shanmvgakatnam, K., et al, Cancer incidence in five continents. LARC Scientific Publications, International Agency for Research on Cancer, Lyon, France, 1982.
  31. Koga, Y., et al, Recent Trends in Cardiovascular Disease and Risk Factors in the Seven Countries Study: Japan. Lessons for Science from the Seven Countries Study, H. Toshima, et al, eds, Springer, New York, NY, 63-74, 1994.
  32. Yabu, Yukiko, Miyai, K., Hayashizaki, S., et al, Measurement of Iodide in Urine Using the Iodide-selective Ion Electrode. Endocr. Japan, 33:905-911, 1986.
  33. Underwood, E.J., Trace Elements in Human and Animal Nutrition. Academic Press, New York, NY, pg. 271-296, 1977.
  34. Childs, D.S., Keating, F.R., Rall, J.E., et al, The effect of varying quantities of inorganic iodide (carrier) on the urinary excretion and thyroidal accumulation of radioiodine in exophthalmic goiter. J. Clin. Invest., 29:726-738, 1950.
  35. Marcus, F.I., Fontaine, G.H., Frank, R., et al, Clinical pharmacology and therapeutic applications of the antiarrhythmic agent, amiodarone. Am. Heart J., 101:480-493, 1981.
  36. Martino, E., Bartalena, L., Bogazzi, F., et al, The Effects of Amiodarone on the Thyroid. Endocrine Reviews, 22(2):240-254, 2001.
  37. Dusman, R.E., Stanton, M.S., Miles, W.M., et al, Clinical Features of Amiodarone-Induced Pulmonary Toxicity. Circulation, 82:51-59, 1990.
  38. Broekhuysen, J., Laruel, R., Sion, R., Recherches dans la serie des benzofurannes XXXVII. Etude comparee du transit et du metabolisme de l’amiodarone chez diverses especes animals et chez l’homme. Arch. Int. Pharmacodyn., 177(2):340-359, 1969.
  39. Abraham, G.E., Serum inorganic iodide levels following ingestion of a tablet form of Lugol solution: Evidence for an enterohepatic circulation of iodine. The Original Internist, 11(3):29-34, 2004.
  40. Slebodzinski, A.B., Ovarian iodide uptake and triiodothyronine generation in follicular fluid. The enigma of the thyroid ovary interaction. Domest. Anim. Edocrinol. 29(1):97-103, July 2005.
  41. Abraham, G.E., Brownstein, D., Evidence that the administration of Vitamin C improves a defective cellular transport mechanism for iodine: A case report. The Original Internist, 12(3):125-130, 2005.
  42. Hollowell, J.G., Staehling, N.W., Hannon, W.H., et al, Iodine Nutrition in the United States. Trends and Public Health Implications: Iodine Excretion Data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J. of Clin. Endocr. & Metab., 83:3401-3408,1998.
  43. Rauws, A.G., Pharmacokinetics of Bromide Ion-An Overview. Fd. Chem. Toxic., 21:379-382, 1983

Effect of daily ingestion of a tablet containing 5 mg iodine and 7.5 mg iodide as the potassium salt, for a period of 3 months, on the results of thyroid function tests and thyroid volume by ultrasonometry in ten euthyroid Caucasian women.

Guy E. Abraham M.D., Jorge D. Flechas M.D., and John C. Hakala R. Ph.

Note: For the sake of clarity, the element iodine in all its forms will be identified in this manuscript with the letter I, whereas the name iodine will be reserved for the oxidized state [I.sub.2].

Introduction

According to a recent editorial of the Journal of Clinical Endocrinology and Metabolism, (1) one-third of the world's population lives in areas of I deficiency, which is the world's leading cause of intellectual deficiency. (2) I is an essential element, and its essentiality is believed to be due to its requirement for the synthesis of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). The recommended daily intake of I for adults of both sexes in North America and Western Europe varies from 150 to 300 ug. (1) I deficiency results in goiter (enlarged thyroid gland) and hypothyroidism. The recommended levels for daily I intake were chosen with the goal of preventing and correcting endemic goiter and hypothyroidism, assuming that the only role of I in health maintenance is in its essentiality for the synthesis of T4 and T3.

Considering the importance of this element for overall well-being, it is most amazing that no study so far has attempted to answer the very important question: What is the optimal amount of daily I intake that will result in the greatest levels of mental and physical well-being in the majority of a population with a minimum of negative effects? In studies designed to answer this question, consideration should be given to the possibility that I, at levels higher than those required to achieve normal thyroid function tests and absence of simple goiter, may have some very important thyroidal and extrathyroidal (non-T3 ,T4-related) roles in overall well-being.

Some 80 years ago, D. Marine reported the results of his landmark study on the effect of I supplementation in the prevention and treatment of iodine-deficiency goiter. Based on extensive studies of goiter in farm animals, he estimated the amount of I that would be required for human subjects. He chose a population of adolescent school girls from the fifth to twelfth grade between the ages of 10 and 18 years residing in Akron, Ohio, a city with a 56% incidence of goiter. (3) 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. (4) 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 I supplementation; and 2,190 pupils received a total of 4 gm of sodium iodide per year for a period of two and a half years. The amount of I was spread out in two doses of 2 gm each during the spring and during the fal l. This 2 gm dose was administered in daily amounts of 0.2 gm of sodium iodide over 10 days. At 4,000 mg of sodium iodide per 365 days, the daily amount is 12 mg, equivalent to 9 mg I. After two and a half years of observation, 495 pupils in the control group developed thyroid enlargement (22%). Only five cases of goiter occurred in the I-supplementation group (0.2%). Iodism was observed in 0.5% of the pupils receiving I supplementation. In an area of Switzerland with an extremely high incidence of goiter (82-95%), Klinger, as reported by Marine, (3) administered 10-15 mg of iodine weekly to 760 pupils of the same age group. The daily I intake in this group was 1.4-2 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 I supplementation in all cantons. Iodized fat in tablet form containing 3 to 5 mg I per tablet was used for I supplementation.

Due to the large consumption of seaweeds in the Japanese diet, this population ingests several milligrams of I daily without ill effects -- in fact, with some very good results, evidenced by the very low incidence of fibrocystic disease of breast (5) and the low mortality rates for cancers of the female reproductive organs. (6) According to the Japanese Ministry of Health and Welfare, the average daily intake of seaweed is 4.6 gm. At an average of 0.3% I content (range = 0.08-0.45%), that is an estimated daily I intake of 13.8 mg. (7) Japanese living in the coastal areas consume more than 13.8 mg. (7) Studies performed on some of the subjects living in the coastal areas revealed that the thyroid glands exposed to those levels of I organify more I than they secrete as T3 and T4, and the levels of T3 and T4 are maintained within a narrow range. The excess I is secreted as non-hormonal I of unknown chemical composition, mostly as inorganic I. (7) The intake of I in the non-coastal areas of Japan is less. A recen t study of 2,956 men and 1,182 women residing in the non-coastal city of Sapporo, Japan, (8) revealed a urine concentration of I in spot urine samples, with a mean value of 3.4 mg/L, corresponding to an estimated daily intake averaging 5.3 mg. (5) This relatively low I intake by Japanese standard, is more than 30 times the recommended daily amount of I in North America and Europe. (1)

B.V. Stadel, from the National Institutes of Health, proposed in 1976 to test the hypothesis that the lower incidence and prevalence of breast dysfunctions and breast cancer and the lower mortality rate from breast, endometrial and ovarian cancers observed in Japanese women living in Japan versus those women living in Hawaii and the continental US, was due their I intake. (6) He suggested a prospective study with two groups of subjects recruited from the same population with a high incidence of the above pathologies: the control group on intakes of I from a Western diet at RDA levels, and the intervention group receiving I in amounts equivalent to that consumed by Japanese women living in Japan. So far, data from this type of prospective epidemiological research are not available in the published literature.

Data are available, however, regarding the effects of I, ingested in daily amounts of several milligrams, on subjective and objective improvements of fibrocystic disease of the breast (FDB). In 1966, two Russian scientists (9) published their results regarding the effect of oral administration of potassium iodide in daily amounts equivalent to 10-20 mg I, on 200 patients with "dyshormonal hyperphasia of mammary glands." They postulated that this form of mastopathy was due to excess estrogens from ovarian follicular cysts which were caused by insufficient consumption of I. The duration of I supplementation of their patients varied from six months to three years. Within three months, there was significant reduction of swelling, pain, diffuse induration, and nodularity of the breast. Out of 167 patients who completed the program, a positive therapeutic effect was observed in 72% of them. In five patients with ovarian follicular cysts, there was a regression of the cystic ovaries following five months to one year of I supplementation. No side effects of I supplementation was reported in those patients.

Ghent et al (10) extended the Russian study further, using different amounts of different forms of I in women with FDB. Beginning in 1975, these Canadian investigators tested various amounts of various forms of I in three open trials. Lugol 5% solution was used in 233 patients for two years in daily amounts ranging from 3162 mg I. They achieved clinical improvement in 70% of the patients. Thyroid function tests were affected in 4% of the patients and iodism was present in 3% of them. In 588 patients, using iodine caseinate at 10 mg/day for five years, only 40% success rate was achieved. In 1,365 patients, using an aqueous saturated solution of iodine in daily amount based on body weight, estimated at 3-6 mg I/day, 74% of the patients had clinical improvements, both subjectively from breast pain and objectively from breast induration and nodularity. Iodism was present in only 0.1% in this last group. In a double-blind study of 23 patients ingesting aqueous solution of iodine in amounts of 3-6 mg/day for a mean of 191 days, 65% showed objective and subjective improvement, whereas in 33 patients on a placebo, 3% experienced worsening of objective signs and 35% experienced improvement in subjective breast pain. These data are summarized in Table 1. Although the percentage of subjects reporting side effects in Ghent's studies appear high, ranging from 7-10.9%, the authors stated that the incidence of iodism was relatively low, and most complaints were minor, such as increased breast pain at the onset of I supplementation, and complaint about the unpleasant taste of iodine.

When the data from Marine's, Klinger's and Ghent's studies (3,10) were evaluated regarding the incidence of iodism in relation to the daily amount of I ingested, a positive correlation was found between those two parameters: 0% iodism at a daily amount of 1.4-2 mg; 0.1% iodism with 3-6 mg daily; 0.5% with 9 mg and 3% with 31-62 mg (Table 2).

In the 19th edition of Remington's Science and Practice of Pharmacy, published in 1995, (11) the recommended daily oral intake of Lugol 5% solution for I supplementation was 0.1-0.3 ml. This time-tested Lugol solution has been available since 1829, when it was introduced by French physician Jean Lugol. The 5% Lugol solution contains 50 mg iodine and 100 mg potassium iodide per ml, with a total of 125 mg I/ml. The suggested daily amount of 0.1 ml is equivalent to 12.5 mg of I, with 5 mg iodine and 7.5 mg of iodide as the potassium salt. This amount of I is very close to 13.8 mg, the estimated daily intake of I in Japanese subjects living in Japan, based on seaweed consumption. (7) Obviously, this quantity of I present in 4.6 gm of seaweed would have to be consumed daily to maintain the I intake at this level. As quoted by Ghent et al, (10) in 1928 an autopsy series reported a 3% incidence of FDB, whereas in a 1973 autopsy report, the incidence of FDB increased markedly to 89%. (10,12,13) Is it possible that th e very low 3% incidence of FDB reported in the pre-RDA early 1900s (12) was due to the widespread use of the Lugol solution available then from local apothecaries, and the recently reported 89% incidence of FDB (13) is due to a trend of decreasing I consumption (2) with such decreased levels still within RDA limits for I, therefore giving a false sense of I sufficiency?

This lengthy introduction could be justified in the present context by stating that the background information was necessary to set the stage for the present study. If indeed, as suggested by Ghent et al, the amount of I required for breast normality is much higher than the RDA for I which is based on thyroid function tests and thyroid volume, (10) then the next question is: What is the optimal amount of I that will restore and maintain normal breast function and histology, without any significant side effects and negative impact on thyroid functions? From the studies referred to (9,10) and Table 1, the range of daily I intake in the management of FDB was 31-62 mg. From Table 2, we observe that the incidence of iodism increased progressively from 0% at 2 mg to 3% at 31-62 mg.

Our goal was to assess the effect of a standardized, fixed amount of I, within the range of daily amount of I previously used in FDB, on blood chemistry, hematology, thyroid volume and function tests, first in clinically euthyroid women with normal thyroid volume by ultrasonometry, and subsequently in women with FDB if there was no evidence of adverse effects or toxicity on the thyroid gland. The equivalent of 0.1 ml of a 5% Lugol solution, that is 12.5 mg I was chosen, a value close to the average intake of 13.8 mg consumed in Japan, (7) a country with a very low incidence of FDB; (5) slightly higher than the 9 mg amount used in Marine's original study (3) of adolescents, with a very low incidence (0.5%) of iodism following this level of I supplementation; also within the range of 10-20 mg used in the Russian study of FDB, without any side effects reported; (8) and five times less than the largest amount of 62 mg used in Ghent's studies with a 3% iodism reported. (10)

Because administration of I in liquid solution is not very accurate, may stain clothing, has an unpleasant taste, and causes gastric irritation, we decided to use a precisely quantified tablet form containing 5 mg iodine and 7.5 mg iodide as the potassium salt. To prevent gastric irritation, the iodine/iodide preparation was absorbed into a colloidal silica excipient; and to eliminate the unpleasant taste of iodine, the tablets were coated with a thin film of pharmaceutical glaze. Ten clinically euthyroid caucasian women were evaluated before and three months after ingesting a tablet daily. The evaluation included thyroid function tests and assessments of thyroid volume by ultrasonometry. The results suggest that this form and amount of I administered daily for three months to euthyroid women had no detrimental effect on thyroid volume and functions. Some statistically significant changes were observed in the mean values of certain tests of urine analysis, thyroid function, hematology, and blood chemistry fol lowing I supplementation. These mean values were within the reference range, except for mean platelet volume (MPV), with a mean value below the reference range prior to supplementation, but within the normal range following I supplementation. In two subjects, baseline TSH levels were above 5.6 mIU/L, the upper limit for the reference range of the clinical laboratory used in this study. In both subjects, I supplementation markedly suppressed TSH levels.

Subjects and Methods

The female subjects were recruited from the private patients of one of the authors (JDF) and from staff members of a medical clinic. They were ambulatory, without any serious medical problems, clinically euthyroid, and on no medication known to affect thyroid functions. Informed consent was obtained from all subjects. Of 12 subjects recruited, two were dropped from the data analyzed. One subject had a diffusely enlarged thyroid with a volume of 43 ml by ultrasonometry, (14) significantly higher than the upper normal of 18 ml. (14,15) Even though the thyroid function tests were within the normal limits for this subject, we decided to exclude her from this study; however, she was placed on the same I supplementation and reevaluated every three months. The other subject did not return for follow-up. The clinical information on the 10 Women selected are displayed in Table 3. Mastodynia (breast pain) was initially the only symptom evaluated pre- and post-I supplementation. However, some of the subjects volunteered information regarding improvement of restless leg and tremor while on the program, so we included these two symptoms also.

The tablets containing 5 mg iodine and 7.5 mg of iodide as the potassium salt were prepared by one of the authors (JCH). A 5% Lugol solution, prepared with USP grade iodine crystals and potassium iodide powder in purified water, was added to a colloidal silica excipient under mixing, and the preparation was calibrated to contain the above amounts per tablet. The excess water was evaporated under low heat and the resulting dried preparation compressed into tablets which were coated with a thin film of pharmaceutical glaze. There was no loss of I due to evaporation since triplicate analysis by a commercial laboratory (Weber Laboratories, New Port Beach, CA) of tablets taken from the batch used in the present study, revealed quantitative recovery, with I concentrations of 12.5, 12.5 and 12.6 mg per tablet. After initial evaluation, each subject was supplied with a bottle of 90 tablets (registered under the name lodoral[TM]), with instruction to ingest one tablet a day for 90 days and to report any adverse effec ts.

The following laboratory evaluations were performed prior to and after three months of I supplementation: Complete blood count (CBC) was obtained from an Abbott Cell-Dyn[R] 1200; the metabolic panel and thyroid profile were performed by Lab Corporation of America; urine analysis was processed at the clinic with Multistix 10SG Reagent Strips, read on a Clinitek 100 that was calibrated daily. Measurement of thyroid volume by ultrasonometry was performed at the clinic by a registered sonographer using a portable Biosound Esaote Megas System unit with a frequency of 7.5 megaHertz, according to the procedure described by Brunn et al. (14) The volume of each lobe of the thyroid gland was calculated according to the formula: V (mL) = W(cm) x D(cm) x L(cm) x 0.479. (14) The thyroid volume was the sum of the volumes of both lobes, taking 18 ml as the upper limit for normal thyroid volume in women living in a non-endemic goiter area. (16) Body compositional analysis was performed at the clinic by near infrared technol ogy, (17) using a Futrex 5000: muscle mass, fat mass, percent fat, and total body water. The body mass index (BMI) is the ratio of body weight divided by height squared, using the metric units of kilogram (kg) for weight and meter (in) for height. (18) Based on the classification of overweight and obesity by BMI, the normal range is 18.5-24.9 kg/[m.sup.2], with less than 18.5 as underweight; between 25-29.9 as overweight, and 30 and above as obese. The latest NHANES III study (1988-1994) revealed that 25% of American women are overweight and 25% obese. (18) Based on this classification, five subjects were within the normal range, two were overweight, and three were obese (Table 3). Therefore, these subjects are a good representation of our "normal" population. Statistical analysis of the data, comparing pre- and post-I supplementation values within patients, was done by paired data analysis. (19)

Results

Clinically, there were significant improvements of mastodynia (p0.004), tremor (p=0.048), and restless leg (p0.009) (Table 3). There was no statistically significant effect of I supplementation on blood pressure, body temperature and body composition (Table 4). Percent body fat reached a near significant drop (p=0.075).

Regarding laboratory evaluation of the subjects, results of urine analysis were normal in all subjects pre- and post-I supplementation. The only statistically significant effect of I was on urine pH (p0.0 12) with pre- and post-I values (mean [+ or -] SD) respectively of 6.05[+ or -]0.69 and 7.00[+ or -]0.85. (Reference Range: 5.0-8.5). Out of 17 different measurements performed on blood chemistry, nine were affected significantly by I supplementation: a drop in creatinine (p<0.01), calcium (p=0.04), albumin (p><0.01), A/G ratio (p><0.01), alkaline phosphatase (p><0.01); and a rise in sodium (p=0.01), carbon dioxide (p=0.02), globulin (p0.0l), and SGPT levels (p><0.01). However, all those values remained well within the reference ranges for these parameters (Table 5). Three hematological measurements out of the 13 assessed were significantly altered by the intervention: a drop in mean corpuscular volume (MCV) (p><0.01) and mean corpuscular hemoglobin (MCH) (p><0.01); and a rise in mean platelet volume (MPV) (p=0.04 ). Although the above differences were statistically significant, they represented a small percentage of the mean values compared (Table 6). The values for MCH and MCV were within the reference ranges both pre- and post-I supplementation. However, the mean value for MPV ([+ or -] SD) was below the normal range of 8.2-10.3 fl prior to intervention (7.5[+ or -]1.3 fl) and increased to reach the normal range following I supplementation (8.2[+ or -]1.3 fl). Although MPV below 4 fl is an indication of a compromised immune system, this slightly low mean value prior to I supplementation may not be of clinical significance. Nevertheless, the effect of I supplementation was beneficial on this parameter. >

The data on thyroid function tests and thyroid volume are displayed in Table 7. Thyroid volume in all the subjects were below 18 ml, the upper limit of normal values reported, (14, 15) suggesting that their intake of I prior to this study was adequate to prevent enlargement of the thyroid gland, and to maintain normal thyroid hormones, since all these values were within normal limits. Serum T4 levels dropped significantly (p<0.01) from a mean of 8.8 (SD=1.3) to 7.2 ug/dL (SD=1.1). However, all individual values remained within the reference range (Table 7). Mean serum TSH levels decreased following I intake from 4.4 mIU/L to 3.2 mIU/ L. This non-significant decrease was due to the marked fall in subjects #1 and #10, with 16 mIU/L decrease between these two subjects. Using the classification of subclinical hypothyrodism as clinical euthyroidism with normal levels of thyroid hormones but elevated TSH above 6 mIU/L, (20,22) subjects #1 and #10 would be classified as subclinical hypothyroid before I supplementati on. >

Discussion

The goal of this pilot study was to evaluate the effect of I supplementation in American Caucasian women, a population with a high incidence of FDB and breast (23,24,25) cancer, using daily I intake comparable to average daily I consumption in Japanese women living in Japan, a country with a very low incidence of FDB and breast cancer. (25,26) The parameters evaluated were: thyroid volume by ultrasonometry; thyroid function tests; and evidence of toxicity based on urine analysis, hematology, and blood chemistry.

The mean thyroid volume ([+ or -] SD) in our 10 subjects (7.7[+ or -]3.6 ml) is comparable to the mean thyroid volumes measured using the same method, in normal euthyroid women from Sweden (7.7 ml), Holland (8.7 ml), and Hong Kong (8.9 ml); but 60% of the mean thyroid volume from Ireland (12.9 ml) and 47% of the mean thyroid volume from Germany (16.5 ml). (15,16,27) The high mean thyroid volumes observed in Irish and German women could be due to their low I intake and high prevalence of goiter. (15,16) Two subjects (#1 and #10) had an elevated TSH level prior to intervention. In both cases, I supplementation markedly suppressed TSH levels: in subject #1, from 7.8 to 1.4 mIU/L, and in subject #10, from 21.5 to 11.9 mIU/L (Table 7). Subclinical hypothyroidism is defined as clinical euthyroidism with normal levels of thyroid hormones, but with elevated TSH levels above 6 mIU/L. (20,21,22) By this classification, subject #1 would be classified as subclinical hypothyroid before I supplementation, and reclassified as normal three months after starting the ingestion of I in daily amount of 12.5 mg, 80 times the RDA level. It is likely that subject #10, if maintained on this program, would have reached TSH levels within the normal range. It is estimated that close to 8 million American women suffer from subclinical hypothyroidism, (21) which is a risk factor for coronary heart disease and possibly peripheral arterial diseases. (21) If the above findings can be confirmed in a larger group of subjects with subclinical hypothyroidism, the solution to this problem could be very simple: increase daily I intake using I supplements in these individuals to levels consumed from seaweed by Japanese women living in Japan. At the least, a therapeutic trial of I supplementation could identify a subgroup of subclinical hypothyroid subjects who would be responsive to such an approach.

We have reviewed published studies in Russia and Canada showing a beneficial effect of I intake at several milligrams a day on FDB both subjectively (mastodynia) and objectively (breast cysts, nodularity, and induration). (9,10) In the present study, there was a significant improvement in the mean score of mastodynia in seven subjects experiencing this symptom following three months of I supplementation. Of interest is the observation that three months after termination of I intake, the beneficial effect on mastodynia was still present in those subjects. Based on an extensive review of breast cancer epidemiological studies, R.A. Wise-man (28) came to the following conclusions: 92-96% of breast cancer cases are sporadic; there is a single cause for the majority of cases; the causative agent is deficiency of a micronutrient that is depleted by a high fat diet; and if such an agent is detected, intervention studies with supplementation should lead to a decline in the incidence of breast cancer. Several authors h ave proposed that this protective micronutrient is the essential element (5,6,10,29,30) Some of the mechanisms by which I could prevent breast cancer are the antioxidant properties of iodides (31) and the ability of I to markedly enhance the excited singlet to triplet radiationless transition. (32) Reactive oxygen species causing oxidative damage to DNA are usually excited singlets with a high energy content released rapidly and characterized by fluorescence, whereas the corresponding triplet state releases its lower energy at a slower rate expressed as phosphorescence. Such an effect of I would depend on its concentration in the intra- and extracellular fluids. Other possible mechanisms involved were reviewed by Derry: the apoptotic properties of I and its ability to trigger differentiation, moving the cell cycle away from the undifferentiated characteristic of breast cancer--for that matter, of all cancers. The above properties of I are totally independent of thyroid hormones. A recent study in female rats (33) has demonstrated an effect of I deficiency, independent of thyroid hormones, on the response of the hypothalamo-pituitary-adrenal axis to stress. There was an attenuation of this axis to stress following I deficiency, and this attenuation persisted after functional recovery of the thyroid axis.

The significant increase in urine pH following I supplementation, with mean ([+ or -] SD) values of 6.05[+ or -]0.69 and 7.00[+ or -]0.85 for pre- and post-intervention respectively, is suggestive of increased reducing equivalents in biological fluids. This effect could be due to the 7.5 mg of iodide ingested daily. (31) However, an effect of I on the enhancement of singlet [right arrow] triplet transition (32) is to decrease the oxidative burden of the body; such an effect would result also in an increase of urine pH. To our knowledge, this effect of I supplementation on urine pH has not been previously reported.

Although several extrathyroidal organs and tissues have the capability to concentrate and organify I, (34-36) the most compelling evidence for an extrathyroidal function of I is its effects on the mammary gland. Eskin et al have published the results of their extensive and excellent studies on the rat model of FDB and breast cancer and the importance of iodine as an essential element for breast normality and for protection against FDB and breast cancer. (30,37,38) The amount of I required for breast normality in the female rats was equivalent, based on body weight, to the amounts required clinically to improve signs and symptoms of FDB. (9,10) Eskin's findings on the protective effect of iodine against breast cancer in the rat model were recently confirmed by Japanese researchers. (39)

Of interest is the findings of Eskin et al (40) that the thyroid gland preferentially concentrate iodide whereas the mammary gland favors iodine. In the I-deficient female rats, histological abnormalities of the mammary gland were corrected more completely and in a larger number of rats treated with iodine than iodide given orally at equivalent doses. Recent textbooks of endocrinology continue the tradition of the past, reaffirming that iodine is reduced to iodide prior to absorption in the intestinal tract, referring to a study by Cohn, (41) published in 1932, using segments of the gastrointestinal tract of dogs, washed clean of all food particles prior to the application of I in the lumen. However, Thrall and Bull (42) observed that in both fasted and fed rats, the thyroid gland and the skin contained significantly more I when rats were fed with iodide than with iodine; whereas the stomach walls and stomach contents had a significantly greater level of I in iodine-fed rats than iodide-fed animals. Peripheral levels of inorganic I were different with different patterns, when rats were fed with these two forms of I. The authors concluded, "These data lead us to question the view that iodide and iodine are essentially interchangeable." Based on the above findings, I supplementation should contain both iodine and iodide.

The potentially adverse effects of I supplementation at the levels used in the present study are threefold: iodism, I-induced hyperthyroidism (IIH) and I-induced goiter (IIG). Iodism is dose-related, and the symptoms are unpleasant brassy taste, increased salivation, coryza, sneezing, and headache originating in the frontal sinuses. Skin lesions are mildly acneiform and distributed in the seborrheic areas. (11,43) Those symptoms disappear spontaneously within a few days after stopping the administration of I. As of this writing, no iodism, and for that matter, no side effect has been reported in more than 150 subjects who underwent I supplementation at 12.5 mg/day. It was suggested 100 years ago that iodism may be due to small amounts of bromine contaminant in the iodine preparations and trace amount of iodate and iodic acid in the iodide solutions. (43) With greater purity of USP grade materials now available, iodism may no longer be a problem at the level of I used in the present study.

The next potential complication is IIH, which occurs predominately in population with I-deficiency during the early period of I replacement. (45) In the 8th edition of Werner and Ingbar's The Thyroid, published in 2000, Delange (46) stated: "The possible reason for the development of IIH after iodine supplementation has now been identified: iodine deficiency increases thyrocyte proliferation and mutation rates. Possible consequences are the development of hyperfunctioning autonomous nodules in the thyroid ... and hyperthyroidism after iodine supplementation. Therefore, IIH is an IDD (Iodine Deficiency Disorder)." The prevalence of goiter in the United States is about 3.1%. (46) In non-endemic goiter areas, IIH occurs predominantly in elderly subjects with nodular goiter, which could be detected by ultrasonography.

The last of the three adverse effects of I supplementation is I-induced goiter (IIG) and hypothyroidism. Most patients with IIG have received large amounts of I (up to 2 gm per day) for prolonged periods of time, usually as an expectorant for asthma, chronic bronchitis, and emphysema. (11,47) In the 10th edition of Goodman and Gilman's The Pharmacological Basis of Therapeutics, published in 2001, Farwell and Braverman wrote: "In euthyroid individuals, the administration of doses of I from 1.5 to 150 mg daily results in small decreases in plasma thyroxine and triodothyronine concentrations and small compensatory increases in serum TSH values, with all values remaining in the normal range. " (48) However, in patients with underlying thyroid disorders, IIG with hypothyroidism could be induced, mainly by I-containing drugs. Predisposing factors to I-induced hypothyroidism are: treated Graves' disease, Hashimoto's thyroiditis, postpartum lymphocytic thyroiditis, subacute painful thyroiditis, and lobectomy for beni gn nodules. (47) It is not necessary to stress the importance of medical supervision during the implementation of I supplementation for FDB and other conditions. A careful history should reveal previous and current thyroid disorders. Ultrasonography, although not required, is highly recommended prior to I-supplementation to detect abnormal echo patterns. Serum thyroid autoantibodies would supplement finding from history and physical examination. Reevaluation is recommended every three months to assess response to I supplementation and to monitor possible side effects.

The significant decrease in serum T4 observed in the present study, concomitant with the absence of significant changes in the mean values for TSH, FT3 and FT4, following I supplementation at 12.5 mg/day (Table 7), could be due to either a decreased secretion of T4 by the thyroid gland, or it could be due to lower levels of thyroxine-binding globulin (TBG). The synthesis of TBG occurs in the liver and this synthesis is stimulated by estrogens. (48) In the female rat, I deficiency increases the sensitivity of mammary tissue to estrogens. (37) I supplementation to these female rats in amounts equivalent, based on body weight, to amounts of I required in women with FDB for subjective and objective improvement of FDB, (10) had an attenuating effect on estrogen stimulation of the mammary tissue in those female rats, decreasing their response to estrogens. (41) Therefore, the decreased T4 levels following I supplementation could be due to a similar mechanism on hepatic synthesis of TBG, by decreasing the sensitivit y of hepatic receptors to estrogens, resulting in decreased synthesis and release of TBG by the liver and decreased T4 levels. Since we did not include serum TBG levels in our thyroid profile, the explanation for this decrease of serum T4 levels must await future research.

The amount of I used in the present study would be considered physiological by Japanese standard. In the United States, there is a dichotomy regarding the physician's attitude toward I: iodophobia in the physiological range, (49) requiring a leap of faith to move up from RDA microgram amounts to the milligram amounts ingested by Japanese with a very low incidence of FDB and breast cancer, (25,26) and iodophilia in the therapeutic range, prescribing excessively large amounts of I in gram amounts for long periods of time (11,48) as an expectorant in patients with asthma, chronic bronchitis, and emphysema, at least up to 1995.

The ranges of I ingested by human subjects for physiological and therapeutic purposes in different countries are displayed in Figure 1. From the lowest amount observed in areas with severe endemic goiter to the highest amount prescribed, is a millionfold range. Based on the most recently published literature, we have made an attempt in Figure 1 to display the physiological and therapeutic ranges on the right side of the graph. Within the physiological range, we have displayed first the levels of I necessary for normal thyroid functions and control of endemic goiter under all physiological conditions. (1,2) Thyroid sufficiency for I is defined according to Saxena et al (50) as the minimal effective daily dose of I required for either maximal suppression of radioactive I uptake by the normal thyroid gland or for a decrease of radioactive I uptake to approximately 5% of the total dose of radioactive I administered. A daily amount of I from 1.5 to 2 mg/[m.sup.2]/day was required to achieve the 5% goal. These auth ors state, "Thus, for the adult, the minimal effective daily dose of iodide becomes 3 to 4 mg." We have chosen this level of I daily for I sufficiency of the thyroid gland. However, Sternthal et al (51) were able to reduce this mean percent uptake below 5% with higher daily dose of I given for 12 days: 4% at 10 mg; 1.9% at 15 mg; 1.6% at 30 mg; 1.2% at 50 mg; and 0.6% at 100 mg. For breast sufficiency, the average daily consumption of I by Japanese women living in Japan was chosen, a population with the lowest prevalence of FDB and breast cancer. (25,26) This value is also within the range of I supplementation used in published studies of FDB, (9,10) with the limitation that the number of subjects in these studies were relatively small compared to the Japanese female population. The therapeutic range was divided into two parts based on Farwell and Braverman, (47) as quoted in this text: up to 150 mg of I, a range with no adverse effects on the normal thyroid gland, and above that quantity, with a risk for IIG and hypothyroidism, mainly in the presence of thyroid disorders.

The benefits of I supplementation within the range used in FDB outweigh the risks if implemented under medical supervision. We plan to expand this pilot study in order to build a database that could be used to develop a protocol for the implementation of I supplementation in FDB and other conditions, such as subclinical hypothyroidism, by interested physicians. There is a need for assays of serum inorganic I levels to complement urine I levels. Not one of the clinical laboratories contacted offered this service.

TABLES

REFERENCES

(1.) Dunn JT. Editorial: "What's happening to our iodine?" J Clinical Endocrinology and Metabolism, 1998; 83:3398-3400.

(2.) Hollowell J, Staehling N, Hannon W, Flanders D, Gunter E, and Maberly G. "Iodine nutrition in the United States. Trends and public health implications: Iodine excretion data from national health and nutrition examination surveys I and III (1971-1974 and 1988-1994)." J Clinical Endocrinology and Metabolism, 1998; 83:3401-3408.

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

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

(5.) Cann S, Netten J, and Netten C. "Hypothesis: Iodine, selenium and the development of breast cancer." Cancer Causes and Control, 2000; 11:121-127.

(6.) Stadel B. "Dietary iodine and risk of breast, endometrial, and ovarian cancer." The Lancet, 1976; 1:890-891.

(7.) Nagataki S, Shizume K, and Nakao K. "Thyroid function in chronic excess iodide ingestion: Comparison of thyroidal absolute iodine uptake and degradation of thyroxine in euthyroid Japanese subjects." J Clin Endo, 1967; 27:638-647.

(8.) Konno N, Yuri K, Miura K, Kumagai M, and Murakami S. "Clinical evaluation of the iodide/creatinine ratio of casual urine samples as an index of daily iodide excretion in a population study." Endocrine Journal, 1993; 40:163-169.

(9.) Vishnyakova VV and Murav'yeva NL. "On the treatment of dyshormonal hyperplasia of mammary glands." Vestn Akad Med Nauk SSSR, 1966; 21:19-22.

(10.) Ghent W, Eskin B, Low D, and Hill L. "Iodine replacement in fibrocystic disease of the breast." Can J Surg, 1993; 36:453-460.

(11.) Gennaro AR. Remington: The Science and Practice of Pharmacy, 19th edition, Mack Publishing Co, 1995; 976, 1267.

(12.) Sem BC. "Pathologico-anatomical and clinical investigations of fibroadenomatosis cystica mammae and its relations to other pathological conditions in mammae especially cancer." Acta ChirScand, 1928; 10:1-48.

(13.) Kramer WM and Rubin BF. "Mammary duct proliferation in the elderly: A histopathologic study." Cancer, 1973; 31:130-137.

(14.) Brunn J, Riock U, Rui G, and Bon T. "Volumentrioder Schiiddrusenlappen mittela Real-time-Sonographic." Dusche Med, 1981; 106:1338-1340.

(15.) Gutekunst R, Smolarek H, Hasenpusch U, and Stubbe P. "Goitre epidemiology: thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden." Acta Endo, 1986; 112;494-501.

(16.) Smyth P. "Thyroid disease and breast cancer." J Endo Int, 1993; 16:396-401.

(17.) Cassady S. "Reliability of near infrared body composition analysis." Card Pulm Phy Ther, 1996; 7:8-12.

(18.) Amatruda J and Linemeyer D. "Obesity." In: Endocrinology & Metabolism. Felig P and Frohman L, Editors. McGraw-Hill, Inc., 2001; 945-991.

(19.) Goldstein A. "Comparison of paired observations by t-test." In: Biostatistics: An Introductory Text. The Macmillan Co., New York, 1964; 61-63.

(20.) Staub JJ, Noel R, Grani E, and Gemsenjager E. "The relationship of serum thyrotropin (TSH) to the thyroid hormones after oral TSH-releasing hormone in patients with preclinical hypothyroidism." J Clin Endo and Metabolism, 1983; 86:449.

(21.) Staub J, Althaus B, Engler H, and Ryff A. "Spectrum of subclinical and overt hypothyroidism: Effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues." Am J Med, 1992; 92:631-642.

(22.) Muller B, Zulewski H, Huber P, and Ratcliffe G. "Impaired action of thyroid hormone associated with smoking in women with hypothyroidism." NFJM, 1995; 333:964-969.

(23.) Love SM, Gelman RS, and Silen W. "Fibrocystic 'disease' of the breast--a nondisease?" NFJM, 1982; 307:1010-1014.

(24.) Devitt JE. "Abandoning fibrocystic disease of the breast: Timely end of an era" Can Med Assoc J, 1986; 134:217-218.

(25.) Parker S, Tong T, Bolden S, and Wingo PA. "Cancer statistics." CA Cancer J Clin, 1997; 47:6-27.

(26.) Sasano N, Tateno H, and Stemmeermann GN. "Volume and hyperplastic lesions of breasts of Japanese women in Hawaii and Japan." Prey Med, 1978; 7:196-204.

(27.) Kung A, Laot T, Chaut 5, Tams F, and Lowt L. "Goitrogenesis during pregnancy and neonatal hypothyroxinaemia in a borderline iodine sufficient area." Clinical Endo, 2000; 53:725-731.

(28.) Wiseman R. "Breast cancer hypothesis: A single cause for the majority of cases." JEpid Comm Health, 2000; 54:851-858.

(29.) Derry D. Breast Cancer and Iodine, Trafford Publishing, Victoria B.C., 2001; 92.

(30.) Eskin B. "Iodine and mammary cancer." Adv Exp Med Biol, 1977; 91:293-304.

(31.) Venturi S, Donati F, Venturi M, Venturi A, Grossi L, and Guidi A. "Role of iodine in evolution and carcinogenesis of thyroid, breast and stomach." Adv Clin Path, 2000; 4:11-17.

(32.) Kasha M. "Collisional perturbation of spin-orbital coupling and the mechanism of fluorescence quenching. A visual demonstration of the perturbation." The Journal of Chemical Physics, 1952; 20:71-74.

(33.) Nolan LA, Windle RJ, Wood SA, and Kershaw YM. "Chronic iodine deprivation attenuates stress-induced and diurnal variation in corticosterone secretion in female wistar rats." Journal of Neuro, 2000; 12:1149-1159.

(34.) Freinkel N and Ingbar S. "The metabolism of I by surviving slices of rat mammary tissue." Endo, 1956; 58:51-56.

(35.) Schiff L, Stevens CD, Molle WE, Steinberg H, Kumpe C, and Stewart P. "Gastric (and salivary) excretion of radioiodine in man (preliminary report)." JNat Can Inst, 1947; 7:349-356.

(36.) Banerjee R, Bose A, Chakraborty T, De 5, and Datta A. "Peroxidase-catalysed iodotyrosine formation in dispersed cell of mouse extrathyroidal tissues, J Endocr, 1985; 106:159-165.

(37.) Eskin B, Bartuska D, Dunn M, Jacob G, and Dratman M. "Mammary gland dysplasia in iodine deficiency." JAMA, 1967; 200:115-119.

(38.) Eskin B. "Iodine metabolism and breast cancer." Trans New York, Acad of Sciences, 1970; 32:911-947.

(39.) Funahashi H, Imaj T, Tanaka Y, et al. "Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat." Journal of Surgical Oncology, 1996; 61:209-213.

(40.) Eskin B, Grotkowski C, Connolly C, and Ghent W. "Different tissue responses for iodine and iodide in rat thyroid and mammary glands." Biological Trace Element Research, 1995; 49:9-19.

(41.) Cohn B. "Absorption of compound solution of iodine from the gastro-intestinal tract." Arch Intern Med, 1932; 49:950-956.

(42.) Thrall K and Bull LU. "Differences in the distribution of iodine and iodide in the Sprague-Dawley rat." Fundamental and Applied Toxicology, 1990; 15:75-81.

(43.) Peacook L and Davison H. "Observations on iodide sensitivity." Ann Allerg, 1957; 15:158-164,

(44.) The Encyclopedia Britannica: 11th edition; Volume XIV. Encyclopedia Britannica Company, New York, 1910; pg. 726

(45.) Stanbury J, Ermans A, Bourdoux P, Todd C, Oken E, and Tonglet R. "Iodine-induced hyperthyroidism: Occurrence and epidemiology." Thyroid, 1998; 8:83-100.

(46.) Delange FM. "Iodine Deficiency." In: Werner and Ingbar 's The Thyroid. Braverman LE and Utiger RD. Editors. Lippincott Williams and Wilkins, 2000; 295-329.

(47.) Farwell AP and Braverman LE. "Thyroid and antithyroid drugs." In: Goodman and Gilman 's The Pharmacological Basis of Therapeutics. 10th Edition, McGraw-Hill, 2001; 1563-1596.

(48.) Robbins J, Cheng S-Y, Gershengom MC, et al. "Thyroxine transport proteins of plasma: molecular properties and biosynthesis." Recent Prog Horm Res, 1978; 34:477.

(49.) Lee K, Bradley R, Dwyer J, and Lee SL. "Too much or too little: The implication of current iodine intake in the United States." Nutrition Reviews, 1999; 57:177-181.

(50.) Saxena KM. Chapman EM, and Pryles CV. "Minimal dosage of iodide required to suppress uptake of iodine-131 by normal thyroid." Science, 1962; 138:430-431.

(51.) Sternthal E, Lipworth L, Stanley, et al. "Suppression of thyroid radioiodine uptake by various doses of stable iodide." NEIM, 1980; 303:1083-1088.

 


 

Orthoiodosupplementation: Iodine sufficiency of the whole human body

Guy. E. Abraham M.D.1, Jorge D. Flechas M.D.2 and John C. Hakala R.Ph.3

I. Introduction

The essential trace element iodine (I) is the only one required for and in the synthesis of hormones. These I-containing hormones are involved in embryogenesis, differentiation, cognitive development, growth, metabolism, and maintenance of body temperature. I is highly concentrated in one organ, the thyroid gland, which becomes visibly enlarged when there is a deficiency of that element. It is the most deficient trace element in the world with an acknowledged third of mankind functioning below optimal level due to its deficiency (1). Low intake of I is the world’s leading cause of intellectual deficiency (2). Yet, as unbelievable as it may sound, this essential element has suffered from total neglect regarding the amount of it required by the human body for optimal health. In 1930, Thompson et al wrote (3): “The normal daily requirement of the body for iodine has never been determined.” This statement is still true today, more than 70 years later.

At the Children’s Summit held in 1990, the United Nations and heads of state assembled for that occasion, pledged to eliminate I deficiency by the year 2000. Commenting on this meeting, John T. Dunn stated in 1993 (4) “The goal is technically feasible, but many obstacles must be overcome before it is realized.” In the list of obstacles, no mention was made of the greatest obstacle of them all: Our total ignorance regarding sufficiency of the whole human body for I. It is obvious that I deficiency has been equated with the simple goiter, cretinism, and I-deficiency disorders related to its role in thyroidal physiology. Supplementation was considered adequate if such amount prevented cretinism, simple goiter and symptoms of hypothyroidism (1,2,4). The assumption that the only role of I as an essential element is in its essentiality for the synthesis of T3 and T4, became a dogma. With the advent of sensitive assays, Thyroid Stimulating Hormones (TSH) was promoted to queen of tests for thyroid functions (5) and I was forgotten altogether as irrelevant to the point where most endocrinologists and other medical practitioners do not request a single test for urine I concentration, during their whole medical career.

II. Iodophobia and misinformation about I

It is ubiquitous: the fear of using or recommending I (Iodophobia) and misinformation about I are found in books written by laypersons; in books written by physicians for laypersons; and in articles and books written by physicians for physicians. We will use as examples one book written by a famous endocrinologist for laypersons and a textbook of endocrinology written by physicians for physicians, both books recently published.

First, we will quote excerpts from a book published in 1999 and written by Doctor R. Arem M.D. for consumers, with the title: “The thyroid solution: A revolutionary Mind-Body Program that will help you”. As editor of an educational periodical on thyroid disorders, which is read by 25,000 physicians nationwide, Dr. Arem’s views influence a large segment of practicing endocrinologists. Anyone awake will realize that eastern mysticism and New Age occultism have penetrated deeply, although insidiously, into the practice of medicine. On pages 309, 310 of his book, Dr. Arem recommends guided imagery, meditation, yoga and tai chi, without a single reference to validate the effectiveness and lack of adverse effects of those practices. “I encourage men and women to perform tai chi, yoga…”. In a section with the title “Iodine: A Double Edge Sword”, the author stated on page 305: “Research has clearly established that the high dietary iodine content in some areas of the world has resulted in a rise in the prevalence of thyroiditis and thyroid cancer.” One reference is given (7), and when that reference is reviewed, there is no high dietary I intake involved. Essentially, that study evaluated the incidence of thyroiditis and thyroid cancer in areas of Argentina with severe I deficiency, before and after iodization of salt was made available. Urine I was 9.3 ? 1.7 ug/gm creatinine before iodization and 110 ? 82 ug/gm creatinine after iodization. Keep in mind that the RDA for I is 150 ug/day. The incidence of the more invasive form of thyroid cancer did not change, but the incidence of papillary carcinoma was: 0.78/100,000/year before and 0.84/100,000/year after iodization of salt. Obviously, the data available in this publication do not agree with Doctor Arem’s conclusion about the association between high dietary I intake and thyroid cancer. In fact, the available information on this subject, to be discussed later, points to chronic I deficiency as a predisposing factor for thyroid cancer.

The iodophobic misinformation continues with anecdotal stories from Doctor Arem’s archives: A female patient ingested 2-3 gm of kelp daily and developed Grave’s disease which necessitated “destruction of the thyroid gland”. How strange! The mainland Japanese consumed a daily average of 4.6 gm of seaweed and they are one of the healthiest people on earth (10,11,12,22,23). Another iodophobic story follows: NASA consulted Doctor Arem because their ground personnel became “low grade” hypothyroid, whatever that means. Sherlock Arem discovered the cause. The ground personnel were drinking water with 4 gm iodine per liter. That is interesting because the maximum amount of iodine that can be dissolved in water at room temperature is 0.3 gm per liter. Doctor Arem saved the day at NASA: “Alarmed by my warnings about the potential consequences…”. What is the expert’s advice?

“I advise not consuming more than 500 to 600 micrograms a day”. With such iodophobia and misinformation coming from the top, no wonder there is a trend of decreasing I consumption nationwide in the USA.

As we will now demonstrate, this kind of misinformation may have serious consequences. On page 232, Doctor Arem wrote regarding the evaluation of simple goiter: “To determine the cause of your goiter, your physician may order one or several of the following tests”. In that list, no mention was made of urine I levels, when in fact, the most common cause of simple goiter worldwide is I deficiency. However, he may have given the reason for not considering urine I levels in the evaluation of simple goiter, toward the end of the book on page 305: “To function normally, the thyroid requires 150 micrograms a day… In the United States, iodine consumption ranges between 300 and 700 micrograms a day.” This statement has no reference and is inaccurate. The last comprehensive nutritional survey (2) (NHANES III 1988-1994) revealed that the median urine I concentration was 145 ug/L and 15% of the U.S. adult female population suffered from I deficiency (urine I less than 50 ug/L). That is 1 out of every 7 female patients walking in a doctor’s office, interestingly, the same risk ratio for breast cancer in our population, that is 1 in 8 (63). With this high prevalence of I deficiency, including urine I levels in the initial screening of simple goiter is justified. Without the information on urine I levels, the physician will most likely prescribe thyroid hormones to the I-deficient patient.

Hintze et al (8) compared the response of patients with simple goiter to administration of I at 400 ug/day and to the administration of T4 at 150 ug/day for a period of 8 months and 4 months after cessation of therapy. The results definitely favor I over T4. There was a similar suppression of the size of the thyroid gland with I, and with T4. This suppression persisted 4 months after discontinuation of I; whereas the mean thyroid volume in the group receiving T4, returned to pre-T4 level 4 months after stopping T4 administration. The authors concluded: “Our data clearly shows that iodine alone…is at least equally as effective for goiter reduction as levothyroxine alone and offers the further benefit of a sustained effect after cessation of therapy”.

Of greater concern, however, is the possibility that I-deficient women are more prone to breast cancer and depriving them of I is not in their best interest. Based on an extensive review of breast cancer epidemiological studies, R.A. Wiseman (9) came to the following conclusions: 92-96% of breast cancer cases are sporadic; There is a single cause for the majority of cases; The causative agent is deficiency of a micronutrient that is depleted by a high fat diet; If such an agent is detected, intervention studies with supplementation should lead to a decline in the incidence of breast cancer. It is the opinion of several investigators that this protective micronutrient is the essential element I (14,16,19,20,54). Demographic surveys of Japan and Iceland revealed that both countries have a relatively high intake of I, and low incidences of simple endemic goiter and breast cancer, whereas in Mexico and Thailand, just the reverse is observed: a high incidence of both endemic goiter and breast cancer (10). Thomas et al (11,12) has demonstrated a significant and inverse correlation between I intake and the incidence of breast, endometrial and ovarian cancer in various geographical areas. Thyroid volume measured by ultrasonometry and expressed as ml is significantly larger in Irish women with breast cancer than controls with mean values of 12.9 ? 1.2 in controls and 20.4 ? 1.0 in women with breast cancer (13). Intervention studies in female rats by Eskin (14-16) are very suggestive of a facilitating role of I deficiency on the carcinogenic effect of estrogens, and a protective role of I by maintaining normality of breast tissues.

The administration of thyroid hormones to I-deficient women may increase further their risk for breast cancer. In a group of women undergoing mammography for screening purposes (17) the incidence of breast cancer was twice as high in women receiving thyroid medications for hypothyroidism (most likely induced by I deficiency) than women not on thyroid supplement. The mean incidences were 6.2% in controls and 12.1% in women on thyroid hormones. The incidence of breast cancer was twice as high in women on thyroid hormones for more than 15 years (19.5%) compared to those on thyroid hormones for 5 years (10%).

Backwinkel and Jackson (18) have presented as evidence against the association between I deficiency and breast cancer, the fact that in the state of Michigan, between 1924 and 1951, the prevalence of goiter decreased markedly from 38.6% to 1.4%, but no detectable change was observed in the prevalence of breast cancer, during that same interval of time. These authors are making the assumption that the amount of I required to control goiter is the same as that required for protection against breast cancer. Ghent et al (19) and Eskin (20) have estimated, based on their studies, that in both women and female rats, the amount of I required for protection against breast cancer and fibrocystic disease of the breast (FDB), is at least 20 to 40 times the amount required for control of goiter.

Medical textbooks written for physicians contain the same iodophobia and misinformation about I. When I is incorporated into a drug, that drug gets all the credit for the good effects and I is blamed for the side effects. Although there are several I-containing drugs used by physicians for various medical condition (21), we will just cover one of these drugs, from information supplied by Roti and Vagenakis in the latest review on I excess (21). Amiodarone is a benzofuranic derivative containing 75 mg I per 200 mg tablet. It is widely used for the long term treatment of cardiac arrhythmia. It is long acting with 100 days half-life and releases 9 mg I daily in patients ingesting the recommended amount. In the United States, Amiodarone induces hypothyroidism in 20% of patients ingesting it. The authors of that review blamed I for the hypothyroidism although no study has been performed with daily administration of 9 mg of inorganic I in a similar group of patients. It would not be surprising if inorganic I alone in equivalent amount resulted in the same beneficial effects without the side effects, amount them, destructive thyroiditis which require large doses of glucocorticoids and in some cases, thyroidectomy. Actually, there is a large population consuming close to 100 times the RDA almost daily, the Japanese living in Japan. According to the Japanese Ministry of Health, the average daily consumption of seaweed by mainland Japanese is 4.6 gm(22). At an average of 0.3% I in seaweed (range 0.08-0.45%) (22), that would compute to an average daily intake of 13.8 mg I. Overall, the Japanese living in Japan are among the healthiest people in the world, based on cancer statistics (23). They have one of the lowest incidence of I-deficiency goiter and hypothyroidism (10).

In the same review on I excess (21), published in a textbook read by most endocrinologists, and therefore influencing the national trend in the management of thyroid disorders, there is a subsection with the title “Iodine as a Pathogen”. This is an essential trace element that is given the attribute of a Pathogen. Commenting on the latest nutritional survey (NHANES III), the authors stated that this trend of decreasing I intake has resulted in a lower percentage of the U.S. population consuming excess I, defining excess I intake as urine I levels above 500 ug/L (0.5 mg/L): “This trend in iodine consumption has also resulted in a decline in the percentage of the population with excessive iodine intake (>500 ug/L) from 27.8% in the 1971 to 1974 survey to 5.3% in the 1988 to 1994 survey”. With this iodophobic mentality, a cut off point of 0.5 mg I/L of urine has been arbitrarily chosen for excess I intake. What is considered excess I by these authors represents 3% of the average daily I intake by mainland Japanese, a population with a very low incidence of cancer of the female reproduction organs (11,12). This attitude toward I may play an important role in the high incidence of cancer of the female reproductive organs in our population. It would be of interest to compare the prevalence of breast cancer with urine I levels from data available in the last two National Nutritional Surveys.

Currently, the average daily intake of I by the U.S. population is 100 times less than the amount consumed by the mainland Japanese. In the 1960’s, I-containing dough conditioners increase the average daily I intake more than 4 times the RDA (24). One slice of bread contained the full RDA of 150 ug. The risk for breast cancer in our population was then 1 in 20 (63). Over the last 2 decades, food processors started using bromine, a goitrogen (25) instead of I in the bread making process. The risk for breast cancer now is 1 in 8, and it is increasing at 1% per year (63). The rationale for replacing I with a goitrogen in a population already I deficient, is not clear, but definitely not logical and against common sense. In rats on a diet with the rat RDA for I (3 ug), adding thiocyanate, a goitrogen, at 25 mg/day caused hypothyroidism (26). Increasing I intake to 80 times rat RDA prevented this effect. In humans, that would be the equivalent of 12 mg I/day. It is likely that a large percentage of patients receiving T4 for hypothyroidism are I deficient. This I deficiency is worsened by the goitrogens they are exposed to. Prescribing T4 to them increases further their risk for breast cancer (17). What these patients really need is a supply of I large enough for I sufficiency and to neutralize the effect of most of these goitrogens. Based on the studies of Lakshmy et al (26) in rats, that amount of I would correspond to the level of I consumed by mainland Japanese.

For those who trust the food processors to meet their nutritional needs, the last significant source of I is table salt, which contains 74 ug I per gm of NaCl. An editorial in the February 2002 issue of the Journal of Clinical Endocrinology and metabolism (27) exhorted the USA and Canada to decrease the amount of I in table salt by one half. “Most other countries use 20-40 PPM as iodine, and the United States and Canada should consider lowering the level of fortification to this range.” This recommended low level of I fortification between 20-40 PPM had no significant effect on urine I levels and size of goiters in published studies from Germany and Hungary (28,29). Essentially, this amount of I was designed to give a false sense of I sufficiency but to really be ineffective. It is ironic that the title of this editorial is: “Guarding our Nation’s Thyroid Health”. With guardians like that, who needs enemies?

Considering that low I intake is associated with intellectual deficiency, if we continue to lower the supply of I from our food sources, if we continue to disseminate misinformation about I and if we promote iodophobia in Christian America, we will end up with a nation of zombies worshiping Satan as Queen of Heaven.

III. Requirement of the thyroid gland for I

After reviewing the available information in published studies designed to assess the effect of various amounts of I on thyroid physiology, it was possible to arrive at a tentative range of intake that would result in sufficiency of the thyroid gland for that element.

With the availability of radioactive isotopes of I and improved understanding of I metabolism, it became obvious that the thyroid gland concentrates this trace element more than 2 orders of magnitude, compared to most other organs and tissues. The percent of radioiodide uptake by the thyroid gland correlated inversely with the amount of I ingested (30). In areas of severe endemic goiter, it was above 80% (31). The % uptake decreases progressively with increased intake of I, and at RDA levels (150 ug), the % uptake was maintained between 20 and 30% (24). In the 1960’s I added to bread increased the average daily intake 4-5 times RDA levels, with a concomitant decrease in % uptake below 20% (24,32). During the “Cold War” years, the threat of nuclear attack and radioactive fallout became a topic of national interest (33). Attempts were made to estimate the amount of I required to suppress maximally radioiodide uptake by the thyroid (34,37). It is of interest to note that these studies were not performed to assess requirement of the human body for I, but as a crisis management in case of fallout of radioisotopes of I during a nuclear attack or accident. However, we will use these data to assist us in pinpointing the optimal requirement of the human body for I.

The ranges of % radioiodide uptake by the thyroid gland from some selected publications are displayed in Table I. The goal of this selection was to cover a wide range of I intake, from severe goiter to intake of excess I. From the publications by Karmarker et al (31) 3 areas were selected, representing severe, (<25 ug I/day) moderate (25-50 ug/day) and mild (51-100 ug/day) I deficiency. Moving up into the RDA range, the 2 studies of Pittman et al, in 2 groups of normal subjects before and after I was added to bread at a level of 150 ug I/slice of bread (24). The mean I intake in the 2 groups were 2/3 and 4-5 times RDA levels. Going up in the scale of I intake, Saxena et al (34) were the first to attempt a systematic study of the effect of increasing I intake on the % uptake of radioiodide by the thyroid gland in order to find the minimum oral dose of I for maximum suppression of radioactive I uptake by the thyroid gland. These researchers used 63 euthyroid children as subjects and they express the amount of I ingested as mg I/m2/day. The range of I intake covered was from 0.1 to 2.5 mg/m2/day, which would correspond to a range of 0.2 to 5 mg I in the adult. At 0.1 mg, the percent uptake varied from 20 to 30%. On a semilogarythmic graph, there was a linear relationship between the log of I intake and % thyroid uptake of radioiodide. This linearity persisted up to 1.5 mg/m2/day where the % uptake seems to reach a plateau at 5% uptake with oral doses of I up to 2.5 mg/m2/day. Because of the apparent leveled off at 5% thyroidal uptake at 1.5 mg/m2/day (equivalent to 3 mg I in adults), Saxena et al concluded that this percentage represented maximum suppression of radioiodide uptake by the thyroid gland. Six years later, Cuddihy (35) observed a 4% radioiodide uptake when 10 mg I was ingested. Hamilton and Soley (36) in 1940, were able to achieve a mean % uptake of 3.5% when 14 mg I was mixed with the radioactive tracer. In 1980, Sternthal et al (37) used amounts of I from 10 mg to 100 mg/day. At 10 mg, they confirm the 4% uptake observed by Cuddihy, and they were able to achieve near maximum suppression (0.6% radioiodide uptake by the thyroid gland) with a daily I intake of 100 mg.

If these data are plotted on a semilogarithm graph, with % radioiodine uptake on the y-axis and the logarithm of the amount of I ingested on the x-axis, 4 slopes and ranges are observed (Fig. 1). By extending the first 2 slopes A and B to the point where their extensions cross the x-axis at zero % uptake, we can estimate the amount of I required for sufficiency of these 2 “pools” of I. Slope A cross the x-axis at 0.27 mg and slope B, at 6 mg I. The range of intake covering slope A could be called the RDA range, or the goiter control range, since no more uptake of radioactive I was required at .27 mg which is the upper limit (0.3 mg) of the RDA for control of goiter under all physiological conditions (1).

Slope A is very steep, and therefore represents a range of I intake where the I-trapping mechanism of the thyroid gland is very inefficient. Within the linear portion of that range, that is, with intake of I less than 100 ug/day, extrathyroidal tissues would be able to compete effectively with the thyroid for available I. To be discussed latter, the mammary glands possess an I-trapping system similar to that of the thyroid and have certain requirements for I to maintain normality. The larger breast of women would retain more I than men, and there would be less I available for the I-trapping of the thyroid gland. This would result in a greater incidence and prevalence of thyroid dysfunction’s in women than in men, mainly in areas of marginal I intake. Indeed, the prevalence of goiter in endemic areas is 6 times higher in pubertal girls than pubertal boys (38). Subclinical and overt hypo- and hyperthyroidism are more common in women than in men (39,40). The physiological approach in these cases would be to treat them with I supplementation in optimal amounts, not thyroid hormones and anti thyroid drugs.

In the July 2002 issue of Bottom Line Health magazine, there is an article by Dr. R.L. Shames, M.D. entitled “Thyroid Disease Could Be the Cause Of Your Symptoms”. This article is saturated with misinformation: “The thyroid needs iodine to function, but deficiencies of this mineral are largely a thing of the past because of our high consumption of iodized salt. Especially if you live near a coast, you may be getting too much iodine, which is harmful to the thyroid”. Misinformation #1: I deficiency is a thing of the past. Fact #1: The last National Nutritional Survey (NHANES III 1988-1994) revealed that 15% of the U.S. adult female population suffered from I deficiency, defined as urine I level below 50 ug/L (2), which is a very low level by any standard. Misinformation #2: “High consumption of iodized salt prevents I deficiency”. Fact #2: Iodized salt contains 74 ug I/gm salt. The purpose of iodization of salt was to prevent goiter and cretinism, not for optimal level of I required by the human body. For example, to ingest the amount of I needed to control FDB, that is 5 mg I/day (19), you need to consume 68 gm of salt. To reach levels of I ingested by mainland Japanese, a population with a very low prevalence of cancer of the female reproductive organs, you need 168 gm of salt. Misinformation #3: You may be getting too much I if you live near a coast. Fact #3: Kung et al (Clin. Endo 53:725-731, 2000), after investigating I deficiency in Hong Kong, concluded: “Our experience in Hong Kong has shown that it is not safe to assume that iodine insufficiency does not exist in coastal regions”. Misinformation #4: Too much I from coastal areas is harmful to the thyroid. Fact #4: From the study just mentioned, coastal areas do not even supply enough I to prevent I deficiency. The article by Dr. Shames even has a subsection teaching his readers how to reduce I intake! Considering that 15% of his female readers are already I deficient, even by the low RDA standard, what a shame!

Returning now to Fig. 1, slope B corresponds to I sufficiency of the thyroid gland, and represents a range where the efficiency of the I-trapping mechanism by the thyroid is markedly improved over slope A which is steeper, and therefore less efficient. Slope B starts at 0.1 mg, the upper limit for mild deficiency and extends to 6 mg, theoretically, the optimal I intake for sufficiency of the thyroid gland. Slope C is almost horizontal, representing a range of I between 3 mg and 14 mg. The thyroid gland possesses maximal efficiency of the I-trapping mechanism over the range of I intake in slope C. Slope D from 15 mg to 100 mg of iodide could be called the saturation range. In order to refine further the optimal range of I intake, Fig. 2 displays the range of I intake from 0.1 to 100 mg.

The amount of I retained by the thyroid gland was also plotted for each intake levels. The amount retained was computed by multiplying the amount of I ingested by the % uptake of radioiodine by the thyroid gland. The 6 mg point is of interest because not only it is the crossing point of slope B at zero radioiodide uptake on the x-axis, but it represents also the 50% saturation point of the I trapping system of the thyroid gland. A system in a state of dynamic equilibrium would be the most stable at midpoint between the 2 extremes, that is at 50% saturation. The RDA for I corresponds to 5% saturation of the I-trapping mechanism of the thyroid gland, a very unstable position, predisposing to both hypo- and hyperthyroidism. The intake of 14 mg was the maximum amount that did not trigger the autoregulatory mechanism of the thyroid gland. This amount may represent the upper limit of I required for sufficiency of the whole human body. At 15 mg intake, the thyroid gland downregulates the efficiency of the I trapping in an attempt to bring down the amount of I retained to 50% saturation (Fig. 2). Above 15 mg intake, the efficiency of the trapping mechanism increases markedly with greater intake of I to reach saturation at 50 mg intake and 0.6 mg/24 hr of trapped I by the thyroid gland (Fig. 2).

Searching the literature, we found evidence supporting the amount observed in our calculation regarding the saturation of the I trapping by the normal thyroid, that is 0.6 mg/day. For example, Wagner et al (41) observed in an euthyroid subject who received increasing amount of iodide that the maximum trapping of I by the thyroid was 50 ug/2 hrs. This value multiplied by 12 = 600 ug/24 hr. Fisher et al (42) observed in 20 normal subjects receiving different amounts of I, that the computed I accumulation/day by the thyroid gland was highest in 2 subjects with values of 608 and 613 ug/24 hr.

Regarding the optimal I intake of 6 mg/day for sufficiency of the thyroid gland, there are some very interesting observations reported by various investigators, with 6 mg mentioned in connection with various physiological parameters of thyroid function. With optimal intake of I, thyroid functions would be the most stable under adverse conditions, maintaining hormeostatis when pathological conditions tend to destabilize homeostatis in both directions, toward hypo- and hyperactivity of the thyroid gland. Therefore, the optimal intake of I for thyroid sufficiency should have the greatest effect in restoring normal functions under both conditions. The amount 6 mg/day happens to be the daily intake of I that gave the maximum reduction in basal metabolism toward the normal range in most cases of Grave’s disease (hyperthyroidism) (3).

First, let us describe the form of I used in these studies. The Lugol solution contains 5% iodine and 10% potassium iodide (43). It has been available since 1829 when it was introduced by french physician Jean Lugol, and was used extensively in medical practice during the early part of the 20th century. The recommended intake for I supplementation at that time was 2 drops/day corresponding to 12.5 mg I. This recommendation was still mentioned in the 19th Edition of Remington’s Science and Practice of Pharmacy, published in 1995 (43). As quoted by Ghent et al (19), in 1928 an autopsy series reported a 3% incidence of FDB, whereas in a 1973 autopsy report, the incidence of FDB increased markedly to 89%. Is it possible that the very low 3% incidence of FDB reported in the pre-RDA early 1900’s was due to the widespread use of the Lugol solution available then from local apothecaries; and the recently reported 89% incidence of FDB is due to a trend of decreasing I consumption (2) with such decreased levels still within RDA limits for I, therefore giving a false sense of I sufficiency?

The American physician H.S. Plummer was the first in 1923 to use Lugol solution pre- and post- operatively in his management of Grave’s disease (44). He postulated that the hyperthyroidism of Grave’s disease was due to I deficiency and that the high mortality rate associated with the post-operative recovery period could be controlled with I administration pre- and post-operatively. By administering 20-30 drops of Lugol pre-operatively and 10 drops post-operatively, he reported zero mortality rate. His procedure became widely used both in the USA and abroad. In 1930, a systematic study was performed by Thompson et al (3) in patients with Grave’s disease, using a wide range of I intake from Lugol solution, that is from 1/5 drop to 30 drops/day. In 17 hospitalized patients and in 23 outpatients, one drop of Lugol gave the maximum reduction in basal metabolism toward the normal range in the majority of the patients, following a period of bed rest. One drop of Lugol contains a total of 6.25 mg, with 40% iodine and 60% iodide as the potassium salt.

Koutras et al (45) administered increasing amounts of iodide from 0.1 to 0.8 mg to normal subjects over a period of 12 weeks and measured the quantity of I retained by the thyroid gland before an equilibrium with the new plasma inorganic I was reached. With all the doses administered, a total of 6-7 mg I was accumulated by the thyroid gland over a period of weeks before equilibrium was reached. Again, around 6 mg was the amount observed under those physiological manipulations. These authors stated: “From our evidence it appears that, with all the doses we used, the thyroid took up about 6 to 7 mg of iodine before an equilibrium with the new PII (Plasma Inorganic I) was reached. It is of some interest that this is approximately the amount of the intrathyroidal exchangeable iodine”. Based on the above observations and the data displayed in Fig. 2, we would like to propose that the optimal daily intake for I sufficiency of the thyroid gland is 6 mg, with a minimum of 3 mg, Saxena’s minimal daily amount (34).

IV. Requirement of the extrathyroidal tissues for I

In 1954, Berson and Yalow (46) postulated that following initial clearance of an administered dose of radioiodine, the major portion of the radioiodine in the body is distributed between 2 compartments, the thyroidal and extra thyroidal organic I pools which are in dynamic equilibrium. The results obtained from an elegant experimental design, revealed that the total exchangeable organic I pool ranged from 7 to 13 mg. The total organic pool of I observed in Berson and Yalow’s study may correspond to the range of I intake required daily for I sufficiency of the whole human body. The upper limit of 13 mg I is amazingly close to the upper limit of 14 mg observed in slope C (Fig. 2), the maximum intake of I that will not trigger down regulation of the I-trapping mechanism of the thyroid gland.

The amount of I required by the human body for optimal health would not be expected to trigger downregulation of the I trapping system of the thyroid gland. We are proposing that the upper limit of the requirement of the whole human body for I would be 14 mg. If 6 mg I is the optimal amount needed for the thyroid gland, the extra-thyroidal tissues need the difference, that is 14 mg – 6 mg = 8 mg. Although several extrathyroidal organs and tissues have the capability to concentrate and organify I (47-49), the most compelling evidence for an extra thyroidal function of I is its effects on the mammary gland. Eskin et al have published the results of their extensive and excellent studies on the rat model of FDB and breast cancer and the importance of iodine as an essential element for breast normality and for protection against FDB and breast cancer (14-16,19,20). The amount of I required for breast normality in the female rats was equivalent based on body weight, to the amounts required clinically to improve signs and symptoms of FDB. That amount of I was 0.1 mg I/kg body weight/day. For a 50 kg woman, that daily amount would compute to 5 mg I.

Of interest is the findings of Eskin et al (20) that the thyroid gland preferentially concentrate iodide whereas the mammary gland favors iodine. In the I-deficient female rats, histological abnormalities of the mammary gland were corrected more completely and in a larger number of rats treated with iodine than iodide given orally at equivalent doses. This would suggest that iodine is not reduced to iodide during intestinal absorption. Recent textbooks of endocrinology continue the tradition of the past, reaffirming that iodine is reduced to iodide prior to absorption in the intestinal tract, referring to a study by Cohn (50), published in 1932, using segments of the gastrointestinal tract of dogs, washed clean of all food particles prior to the application of I in the lumen. However, Thrall and Bull (51) observed that in both fasted and fed rats, the thyroid gland and the skin contained significantly more I when rats were fed with iodide than with iodine; whereas the stomach walls and stomach contents had a significantly greater level of I in iodine-fed rats than iodide-fed animals. Peripheral levels of inorganic I were different with different patterns, when rats were fed with these 2 forms of I. The authors concluded: “These data lead us to question the view that iodide and iodine are essentially interchangeable”. Based on the above findings, I supplementation should contain both iodine for the mammary tissue and iodide for the thyroid gland.

The mammary glands can effectively compete with the thyroid gland for peripheral I. Eskin et al (52) measured the 24 hr. radioiodide uptake in 57 clinically normal breasts, and in 8 clinically abnormal breasts. The mean ? SD % uptake was 6.9 ? 0.46% in the normal breasts and 12.5 ? 1% in abnormal breasts. These means were statistically significant at p <0.005. Considering that these measurements are representative of a single breast and a woman has 2 breasts, the % uptake per patient is twice these amounts. This brings the 24 hr. radioiodide uptake by the mammary glands of a woman in the same range as the 24 hr. radioiodide uptake by the thyroid gland. The higher % uptake in the abnormal breasts suggests that the abnormal breasts were more I deficient than normal breasts. As previously discussed, endemic goiter is 6 times more common in pubertal girls than pubertal boys (38). This suggests that in areas of marginal I supply, the larger breast of pubertal girls with greater I requirement, would leave less I available for thyroid uptake than in pubertal boys, and the expected outcome would be a greater prevalence of goiter in pubertal girls than boys. The presence of simple goiter in a female patient is an indication of I deficiency of both the thyroid and mammary glands. Treating such patients with T4 instead of I supplementation is non physiological and increases their risk of breast cancer (17).



http://drdavidbrownstein.blogspot.com/2012/01/new-illness-strikes-media-iodophobia.html 

A New Illness Strikes: Media-Iodophobia Folks, a new illness is rampaging the country. It causes extreme anxiety and fear. What is the name of this illness? Media-iodophobia. Media-iodophobia occurs when the news media erroneously reports the results of a medical article which causes anxiety and fear in the lay public.

I knew when I saw the headline in the Reuters article yesterday that I would be busy answering questions about the study. The headline read, “How much iodine is too much?” Even my publisher (whom I enjoy writing for) reported on the study today with the headline, “Too much iodine hurts thyroid function.” Does too much iodine hurt thyroid function?

To answer the question, I pulled the article and dissected it. The scientists studied 256 normal-thyroid adults in a four week, double-blind, placebo-controlled, randomized controlled trial.(1) The patients were randomly assigned to 12 intervention groups with iodine supplemented at doses ranging from 0-2mg/day. The researchers studied the effects of the differing doses of iodine by measuring thyroid function, thyroid size, and urinary iodine.

The authors found that, as compared with the placebo group, all the iodine- supplemented groups responded with significantly increased urinary iodine excretion. Furthermore, the thyroid size decreased in the iodine-supplemented groups. These effects are exactly what you would expect when supplementing with iodine. In fact, a decreased thyroid size is a good sign as iodine helps improve the architecture of the thyroid gland.

The scientists also studied the thyroid function in the different treatment groups. They found that the subjects treated with higher amounts of iodine had slightly elevated TSH (thyroid stimulating hormone) levels. They termed the subjects who had increased TSH levels as suffering from subclinical hypothyroidism. They concluded, “This study showed that subclinical hypothyroidism appeared in the participants who {ingested 800ug iodine per day}… Thus we caution against a total daily iodine intake that exceeds 800ug/day…” This conclusion is the genesis of media-iodophobia as most people do not read research articles and just read the summary.

The conclusion of the article makes it clear that the researchers were also suffering from iodophobia—medical iodophobia. Medical iodophobia is a term coined by my mentor, Dr. Guy Abraham. Unfortunately, in this case, medical iodophobia leads to media-iodophobia. How did I come up with these diagnoses?

The authors of the study concluded that the slightly elevated TSH confers a diagnosis of subclinical hypothyroidism. Nothing could be further from the truth.

Does iodine cause the TSH to rise? The answer is “yes”. Does the elevated TSH mean the thyroid gland is failing? The answer to this question is “no”. It is well known, or should be well known, that iodine is transported into the cell by a transport molecule known as sodium-iodide symporter (NIS). NIS is stimulated by TSH.(2) Therefore, when iodine supplementation is begun, one of the first effects seen is a slight elevation of TSH as the body is trying to produce transport molecules (NIS) to move iodine into the cell. After iodine supplementation begins, it is normal and expected for TSH to elevate slightly. I have been lecturing to doctors and lay people alike about this concept for nearly 10 years. In fact, I have written about this important concept in my book, Iodine: Why You Need It, Why You Can’t Live Without It, 4th Edition.

In this study, subclinical hypothyroidism should not be the correct diagnosis if the other thyroid function tests (T3 and T4 levels) remain normal. In a true hypothyroid condition, TSH will increase and T3 and T4 levels will fall below the reference range.

I have been teaching doctors how to properly use and monitor iodine supplementation in their practice. My experience has shown that many patients do experience a transient increase in TSH levels while maintaining normal levels of the other thyroid hormones—T3 and T4. Furthermore, a vast majority of patients feel significantly better with iodine therapy. In this article, the researchers did not report symptomatic changes with iodine therapy.

The proper conclusion of this study should have read, “This study showed, as expected that iodine therapy resulted in a slightly elevated TSH. This would indicate that the subjects were properly producing NIS in order to transport iodine into the cell. Furthermore, as expected, iodine therapy appeared to improve the architecture of the thyroid gland by decreasing the thyroid gland volume as observed by ultrasonography measurement.”

I have been using iodine effectively in my practice for nearly 10 years. More information about iodine can be found in my book and my newsletters. Please go to www.drbrownstein.com for more information.