The Wolff-Chaikoff effect of increasing iodide intake on the thyroid - Letters to the Editor
Townsend Letter for Doctors and Patients, Dec, 2003 by Guy E. Abraham
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In 1948, Wolff and Chaikoff published a landmark paper, (1) on the thyroid effect of increasing amounts of iodide (Potassium salt), injected intraperitoneally in rats. The authors stated: "Organic binding of iodine within the glands can be almost completely blocked by raising the level of plasma inorganic iodine (PII) above a certain critical level, which for the rat amounts to about 20 to 35 percent." This effect became known as the Wolff-Chaikoff (W-C) Effect.
The W-C Effect was extrapolated to humans, without supporting data reproducing this effect in vivo by either oral ingestion of equivalent amounts of iodide, based on body weight and given daily over a long period of time; or by keeping PII levels above 20% using sufficient amounts of iodide orally to produce those levels. In 1948, there was already evidence that the W-C Effect did not occur in humans. The Lugol solution and SSKI were used extensively in medical practice for patients with asthma. The recommended daily amount was 1,000 -2,000 mg. (2) This amount was used in patients with asthma, chronic bronchitis and emphysema for several years. Hypothyroidism and goiter were not common in this group of patients.
The most quoted reference for the validation of the W-C Effect in humans is not the original 1948 publication, but a review by Wolff in 1969, with the title "Iodide goiter and the pharmacologic effects of excess iodide," published in the American Journal of Medicine. (3) This article was obviously addressed to clinicians and coming from the National Institutes of Health, gave it credibility among clinicians. The expressions "iodide goiter" and "excess iodide" were used effectively by clinical endocrinologists in their publications to create the iodophobic mentality now prevailing in the medical community. (4) For example, what is considered "excess" by endocrinologists represents only 3% of the average daily intake of iodide by 60 million mainland Japanese, a population with a very low incidence of cancer overall and in particular of the female reproductive organs. (4) Just think how healthy our population would be if the average consumption of iodine/iodide by supplementation was in the range consumed by mainland Japanese.
In the first paragraph of the 1969 publication, Doctor Wolff stated the purpose of his review: "This review concerns itself with the effects of excess iodide, i.e., amounts greater than those needed for the production of normal amounts of the thyroid hormones ... a rough estimate of the daily iodide requirement for man would be about 200 ug of iodine per day." So, now we know that Doctor Wolff defined excess iodide as daily intake above 200 ug and with the implication that the only need for iodide by the human body was for the synthesis of thyroid hormones. This review was published before the RDA for iodine was established.
Doctor Wolff (3) arbitrarily defined four degrees of iodide excess:
First degree excess
Iodide levels slightly above 200 ug/day. Potential problem: "Positive iodine balances may be prolonged and lead to considerable increases in hormone stores." In 1964, 5 years before Wolff published his review, Koutras et al. (5) from Scotland published a very well designed study to look into that possibility. They administered potassium iodide to normal subjects for 12 weeks in daily amounts of 100 ug, 200 ug and 800 ug. There was a proportional increase in iodide uptake by the thyroid gland, but not greater than 6-7 mg iodide over the 12 week period. Peripheral thyroid hormone (PBI) did not change appreciably. The authors stated: "From our evidence, it appears that, with all the doses used, the thyroid took up about 6-7 mg of iodine before an equilibrium with the new PII (Plasma inorganic iodide) was reached." Regarding the W-C Effect, the authors stated: "There is no evidence that the same mechanism is also responsible for the decreased iodide utilization which accompanies small increases in the PII levels." Wolff made no reference to Koutras' paper, although it was published in the Journal of Clinical Endocrinology, not an obscure journal.
Second degree excess
"A larger amount which can inhibit iodine release from the thyrotoxic human thyroid gland." What is wrong with that? Before the discovery of thiocarbamide drugs, the Lugol solution and potassium iodide were used extensively during the early and mid-1900's in medical practice for that purpose and with good results. (6-9) Best results were achieved with 6 mg/day. (7) The effect of iodine supplementation was usually a normalization of thyroid function in mild hyperthyroidism.
Third degree excess
"A slightly greater intake which leads to inhibition of organic iodine formation and which probably causes iodide goiter. This is the so-called Wolff-Chaikoff Effect." In the same review, Doctor Wolff seems to contradict himself. "The rarity of iodide goiter in the face of the extensive exposure of a great many patients to iodide has not been satisfactorily explained. The demonstration of the Wolff-Chaikoff Effect in man remains presumptive."
Concerning iodide goiter, Doctor Wolff stated: "The most common form of iodide goiter is that seen in Hokkaido." The Japanese authors investigating the Hokkaido goiter did not think iodide was the cause of the thyroid enlargement since Japanese subjects from Tokyo without goiter excreted similar levels of iodide in their urine. (10) Excess goitrogens in the diet of those subjects could explain their normal thyroid function in the presence of goiter and this problem has since been solved. In 1994, 27 years after the original publication by Nagatani et al., (10) Konno et al. (11) stated: "Kelp-induced endemic goiter was reported to occur in the coastal regions of Hokkaido nearly 30 years ago. Such goiter has now disappeared." Please note that Konno et al called it "Kelp-induced goiter" whereas Wolff called it "iodide-goiter," without any evidence that iodide was the cause. Doctor Wolff blamed iodide for the Hokkaido goiter without any scientific data and further, he stated that this iodide goiter was probably caused by the W-C Effect, a double assumption.
Fourth degree excess
"Very high levels of iodide which saturate the active transport of this anion." We have previously demonstrated from a review of the literature, that saturation occurs at 50 mg iodide per day in human adults (4) and thyroid uptake of iodide reached a maximum of 600 ug/day. That level was maintained when higher amounts of iodide were ingested. Essentially the thyroid iodide transport system will pick up increasing amounts of iodide as peripheral iodide levels increase, but up to a point. When saturation is reached, however, thyroid hormone levels were maintained within normal limits.
Let us recapitulate by defining the W-C Effect. When normal rats are injected with a single intraperitoneal dose of potassium iodide, in amounts 5 times or more greater than the total amounts of iodide measured in the thyroid gland of those rats, there is a complete blockage of organic binding of iodine, and by logical deduction, a complete blockage of thyroid hormone synthesis. This blockage persists as long as serum levels of inorganic iodide are maintained above 19 ug percent. However, under chronic conditions, when attempts are made to prolong the inhibition of organic binding of iodine in those rats by maintaining high serum iodide levels, this inhibition persisted for 26 to 40 hours. After this period, the rat thyroid resumed its normal organification of iodine, in spite of the elevated serum iodide levels. Nevertheless, that did not prevent Doctor Wolff from implying that his third degree iodide excess with resultant W-C Effect, which he could not reproduce even in rats on a long term basis, probably occurs in humans.
The W-C Effect, combined with medical stupidity may have caused more human misery and death than both world wars combined by preventing meaningful clinical investigations of optimal levels of iodine on physical and mental health. Today, the optimal requirement of iodine for whole body sufficiency is still unknown. We have attempted to calculate this amount based on a review of the literature and it turns out to be 100 times the RDA. (4)
The use of optimal amounts of iodine in the prevention of cancer of the female reproductive organs was proposed by Stadel, from the National Institutes of Health in 1976, 27 years ago. (12) So far, no such study has been published. There seems to be a moratorium on iodine research in effective amounts. Doctor B. Eskin has attempted to reproduce in human subjects his excellent results on iodine and breast cancer observed in female rats. (13-15) He proposed clinical studies in human subjects using iodine in amounts based on body weight equivalent to those observed to be effective in the rats. He was told this could not be done because of the W-C Effect. (16)
The W-C Effect combined with medical stupidity has caused enough damage. It is time to stop crying Wolff and shake off the Wolff-Chaikoff Effect as a bad dream we need to wake up from.
Based on the publications of Koutras et al. (3) and Fischer et al., (4) we have compiled the serum inorganic iodide levels observed at steady state following increasing amounts of iodide ingested daily.
When this data is plated on an X-Y axis, regression analysis showed a correlation coefficient of 0-999. The slope of 0.023 indicated that at the equilibrium of the daily amount of iodide ingested is present in one liter of serum. An approximate level of serum of II expressed as PPB can be compiled by dividing the daily amount by 40.
To achieve the serum levels of 20 - 35 ug percent, or 200 - 350 ug/L, the daily intake of iodide/iodine would be 200 - 350 ug/L x 40L = 8,000 - 14,000 ug/day or 8 - 14 mg/day. The mainland Japanese consume that amount every day, (5) and they have one of the lowest incidences of hypothyroidism. (5) In 1923, Marine (6) published the results of their study. They administered an average of 9 mg iodide/day to 2,790 adolescent girls to prevent goiter. After 2-1/2 years on the program, Marine did not report hypothyroidism occurring in any of these subjects.
We have given up to 50 mg iodine/iodide per day for up to one year to normal subjects without any ill effect. Serum T4 levels did decrease but remained within the normal range. Serum TSH decreased in those with elevated levels, but not in subjects with TSH below 2.5 mIV/L.
We are offering $10,000 to any physician or other health care professional who can demonstrate the Wolff-Chaikoff Effect in human subjects with normal thyroid function.