A Perspective on High Dose Iodine Supplementation – Part IX – Breaking Iodine News – Plus a discussion of Abrahm’s Perspective on the Wolff-Chaikoff Effect

Breaking News on the Iodine Controversy

Update on the daily iodine intake in Japan

Since writing part VIII of this series, two documents have been brought to my attention that I feel have tremendous significance in relation to two of the major controversies being discussed in this series.  The first document is a recently published letter to the editor entitled “The average of dietary iodine intake due to the ingestion of seaweeds is 1.2 mg/day in Japan” by Nagataki (1).  As the title suggests, it supports my conclusion published in part V of this series, based on a review of the literature available to me at that time, that Abraham’s claim concerning the Japanese average daily intake of dietary iodine, primarily from seaweed ingestion, is incorrect.  As you may recall, Abraham has claimed that the average intake of iodine in Japan is approximately 13.8 mg per day, mainly from seaweed.  In contrast, my review of the literature suggested that the average Japanese intake ranges from 1-5 mg per day.  However, Nagataki (1) in his recently published paper suggests that the average intake may even be less than this.

In addressing this issue, Nagataki (1) first points out the important but often ignored fact that iodine content can often vary greatly depending on the species of seaweed:

“Iodine content of seaweeds differ greatly according to species; Laminaria (Konbu) contains 0.3% of iodine by dry weight; Undaria (Wakame) 0.02-0.03%, and Porphyra (Nori) <0.01%.”

With these differences in mind, iodine intake was calculated using the following criteria:

“Konbu was selected to calculate the average dietary iodine intake.  The Family Income and Expenditure Survey by the Statistics Bureau, Ministry of Internal Affairs and Communications included 8749 target households in 2006 and the survey included items pertaining to specific consumption, such as Konbu.  The other method was to calculate iodine intake from the total consumption of Konbu in Japan using data obtained from the Japan Konbu Association.” 

Using the first methodology based on household evaluation, the following results were noted:

“The average annual consumption of Konbu per household (two or more persons per household, average of 3.16 persons per household) in Japan is 450 g by dry weight, that is, 1.17 mg of iodine per day per person.  Consumption of Konbu per household has decreased gradually by 30% in the last 20 years; from 641 g in 1986 to 450 g in 2006.”

Using the second methodology based on total consumption of Konbu in Japan, the following results were noted:

“Total consumption of Konbu in Japan is 20,000 tons per year by dry weight.  Since the population of Japan is 130 million, the iodine intake by the ingestion of Kombu is 1.26 mg/d per person.”

Given the similarity of the results from these two different methodologies, Nagataki (1) concluded:

“The results of methods numerically derived from independent two sources are remarkably similar and it may be concluded that the average of daily iodine intake through Konbu is about 1.2 mg in Japan.”

Of course, it can rightly be stated that these findings do not necessarily indicate total average daily intake from all sources.  In response to this concern, the author states:

“Of course, iodine intake from Konbu is not the total iodine intake, but the answer to the question ‘What is the iodine intake in Japan’ may be that excessive iodine intake in Japan is due to the ingestion of seaweeds especially Konbu and iodine intake by the seaweeds averaged 1.2 mg/d in 2006.”

Interestingly, what may be the most significant aspect of the above quote in relation to Abraham’s claims is that, contrary to Abraham’s beliefs, experts in Japan do feel that iodine intake from seaweed can be excessive.  In support of this claim that Konbu intake in Japan is often excessive, Nagataki (1) offers the following:

“Adverse effects of Konbu ingestion were reported as costal goiter in one area of Hokkaido where the average daily intake of iodine from Konbu was 20 mg/d.  Ingestion of 10 mg of iodine for 1 week in normal Japanese increased the response of thyrotrophin in the thyrotrophin releasing hormone test.  When 30 mg of iodine was given daily to normal Japanese for 4 weeks, serum free thyroxine concentrations decreased and thyrotrophin levels increased significantly, although within normal ranges, and the size of thyroids measured by echogram increased significantly.  These abnormalities disappeared within 2 weeks after stopping iodide administration.”

As I hope you will agree, the Nagataki paper (1) provides current and highly compelling information that further supports my conclusion from part V of this series that Abraham’s contention that Japanese populations are ingesting an average of 13.8 mg of iodine per day with no thyroid related side effects whatsoever at this or higher doses is incorrect.

Case report on possible adverse effects of milligram dosing of supplemental iodine

On the back page of this newsletter you will find a case report which was submitted to me by Barbara Harvey, MD and is being reprinted in this forum with her permission.  While no definitive cause/effect conclusions concerning the impact of iodine supplementation can be made based on this case report, certainly suspicion is aroused.

Does published research exist that supports the possibility that the doses of iodine discussed in this case report could induce formation of a goiter without elevated levels of thyroid antibodies, as was also noted in this case report?  The paper by Konno et al (2), which was discussed in part V of this series, certainly suggests that this cause/effect relationship can occur.  In evaluating hypothyroid patients who were negative for thyroid autoantibodies (TAA), the author points out the following concerning kelp intake:

“The majority of TAA-negative hypothyroid subjects reported almost daily kelp intake.”

Did these subjects also demonstrate evidence of goiter?  Konno et al (2) state:

“In TAA-negative hypothyroid subjects, thyroid volume was significantly larger than normal controls in the subjects where this was measured.  Palpable goiter was observed in 31% of TAA-negative hypothyroid subjects in the previous study.”

The authors also state the following on this relationship:

“In addition, a recent report shows that prolonged intake of iodine increased the thyroid volume in normal subjects.  Thus, some TAA-negative subjects could have palpable goiter induced by excessive iodine…”

What might be the mechanism underlying goiter formation in patients with excessive iodine intake but TAA negative?  Konno et al (2) state:

“The mechanism of the development of hypothyroidism in the absence of TAA may be unmasking of some preexisting subclinical abnormality by excess iodine intake.”

The authors also suggest the following possible mechanism:

“Alternatively, a histological study has shown that more than half of those with reversible hypothyroidism have adenomatous goiter, which is also known to be associated with disturbances of the thyroidal iodine metabolism.  This pathological change may be an underlying disease of some TAA-negative hypothyroidism in the present study, but this awaits further histological study of the thyroids of these subjects.”

Of course, while I realize that this case report is highly disturbing, and while I realize that the Konno et al (2) study provides ample evidence of the legitimate possibility of direct cause and effect, I do feel we need to avoid any “knee-jerk” reactions and, instead, deliberate carefully on what exactly is a proper response.  As correctly noted by Dr. Harvey in my conversation with her, knowing it is possible that supplemental iodine caused the goiter mentioned in the case report in no way proves that it actually did.  For, while there is suggestion of cause and effect, Dr. Harvey notes that she has treated hundreds of other patients with similar doses of the same form of iodine with not even a hint of the signs and symptoms seen in this case report.  Therefore, how should we respond to a case report that is so dramatic and research that is so suggestive?

While I realize this question could be answered in numerous ways, I would like to offer some responses that seem true and ethical for me.  While I expect that these responses may not ring true for some of you, hopefully you can accept them in the spirit they are offered, which is a desire to help you, my valued clientele, with your efforts to provide the most efficacious and cost efficient treatment possible with the lowest possible risk.

What is the worst possible case scenario? – As I have mentioned often in this series, the thyroid, due to eons of high variability in the levels of iodine intake in humans, possesses an extraordinary ability to compensate for these variations, largely through adjustments in sodium/iodide symporter (NIS) mediated transport.  However, as I have also demonstrated, in some individuals, due to genetic and/or environmentally induced defects in NIS function, excessive transport of iodine into the thyroid can occur.  Via this possible mechanism or others such as those suggested by Konno et al (2) an overwhelming body of published research suggests that adverse effects of milligram doses of supplemental iodine can be of an order of magnitude greater than that for virtually any other micronutrient.  While I realize that Abraham and his colleagues present a very convincing anecdotal argument that the doses of supplemental iodine they recommend are risk free for everyone, based on what I have seen thus far, both from reports form you and my investigation of the literature, this claim is simply not true.  In fact, as suggested in the case report I am presenting to you, it is possible that someone, at some time, will have a major adverse effect.  Granted, as suggested by Konno et al (2), in many of the TAA-negative cases underlying illness may act as an important co-factor along with iodine.  However, in my mind, knowing that iodine is acting as a trigger rather than an absolute cause in no way minimizes the impact on the patient nor reduces our need to do everything we can to avoid such an occurrence.

Of course, as I suggested in the previous installment of this series, everything on earth has the potential to elicit a negative effect in someone at some dose.  Because of this we need to ask another question.  At doses typically consumed, what are the odds of an adverse effect occurring and what is the nature of the worst possible adverse effect?  With most nutrients we typically dispense, at doses typically recommended, risk is low in terms of frequency and when an adverse effect does occur the degree is usually minor and limited in impact in terms of overall health and quality of life.  Supplemental iodine appears to be a notable exception.

Many practitioners such as Dr. Harvey have accurately noted a history of treating hundreds and sometimes thousands of patients with milligram doses of supplemental iodine without incident.  However, even if the odds are 10,000 to1, there still is a possibility that a case history such as the one presented can occur.  Furthermore, even if the odds are 1,000,000 to 1, if an adverse event happens to you and your patient of the magnitude suggested in the enclosed case report, do the odds really matter?

Don’t throw the baby out with the bathwater – Of course, with the above in mind, as I suggested in the last newsletter, our historical tendency has been to initiate efforts to halt all use of a particular supplemental nutrient whenever any significant adverse event is reported, no matter how rare.  Even if it is conclusively determined that supplemental iodine is the cause or a trigger in the enclosed case report, I feel we must resist responding in such a manner.  In contrast, acknowledging that the worst case scenario is much worse than for other supplemental nutrients we usually recommend, I feel we should continue to recommend milligram doses of supplemental iodine but only after a much more in depth patient evaluation than what we typically employ to determine need for most supplemental nutrients.

What are the medico legal risks? – While I am not an attorney and cannot offer expert legal opinion, I would like to offer some thoughts on this issue.  First, what I have offered above does not take into account some of the current litigious realities in our society.  Therefore, given these realities, I feel some sort of statement on this issue is necessary.  As I hope I have demonstrated to you in this series, doses of supplemental iodine up to approximately 10 mg per day have been demonstrated to be efficacious and relatively safe in several studies.  Furthermore, epidemiologic data from Japan suggests that daily intake of iodine up to amounts of approximately 10 mg per day is safe for the majority of the population.  In contrast, no published research that I have seen supports the largely anecdotal claims made by Abraham and his colleagues concerning the safety of the iodine doses they typically recommend.  Therefore, in my opinion, it would be difficult to scientifically defend, in a situation requiring expert testimony, a stance which maintains doses of supplemental iodine above 10 mg per day did not cause a significant thyroid-related adverse effect.


Now I would like to begin my discussion of the intended main topic for this installment of the iodine series, Abraham’s published position on the Wolff-Chaikoff effect.  Before examining his stance in detail, I want to highlight again why I feel it is important to place so much emphasis on this aspect of Abraham’s writings.

As I have mentioned, in addition to his anecdotal reports, Abraham uses two primary research-based suppositions to support his contention that supplemental iodine is almost completely exempt from the dose/response laws I discussed in the last newsletter and therefore totally safe for everyone at doses thousands of times higher than the RDA.  The first was his mistaken stance that the Japanese have suffered no ill-effects from long term ingestion of seaweed containing significant amounts of iodine.  The second, that I would like to explore in detail now, is that the Wolff-Chaikoff effect does not really exist and therefore functions only as a tool used by “medical iodophobes” to suppress clinical use of milligram levels of supplemental iodine.  If published research suggests that this supposition is also incorrect, I feel it must be concluded that Abraham’s claim of safety concerning the doses of iodine he and his colleagues recommend has no scientific basis, based on published research.  Granted, based on the anecdotal reports presented by you, Abraham, and his colleagues, there is a strong suggestion of safety that must be acknowledged.  However, as I have repeatedly suggested, given the worst possible case scenario that has often been noted in the scientific literature in relation to ingesting milligram amounts of iodine, I feel we must err on the side of caution until Abraham’s claims of safety are conclusively proven.

While Abraham presents thoughts on the Wolff-Chaikoff effect in virtually all of his papers that I have read and reviewed in this series, his most extensive discussion on the subject occurred in “The Wolff-Chaikoff Effect: Crying Wolf?” (3)  If there ever were any doubts concerning Abraham’s utter distain for this effect, he certainly removes them right away in the first paragraph of this paper:

“Shortly after the Axis powers capitulated and World War II came to an end, UC-Berkeley dropped a bombshell in 1948, which became known as the Wolff-Chaikoff (W-C) effect.  Where the swords of many nations failed, the pens of two men succeeded.  The W-C effect resulted in the removal of iodine from the food supply, and most likely caused a lot of misery and death in the US due to its negative impact on iodine consumption by the population and on the use of inorganic, non-radioactive iodine in medical practice.”

Is Abraham justified in comparing the impact of the W-C effect to that of World War II?  It seems a bit excessive to me.  However, I really do not know for sure and do not know of a way to determine the validity of this claim.  What I feel I can do, though, is, as I have done in previous installments of this series, examine the references that Abraham (3) uses to support his claims about the W-C effect.  In conducting this examination, I will consider two questions:

  • Did Abraham portray the references accurately?
  • Are the references compelling enough to negate the numerous studies I have presented that affirm the existence of the W-C effect?    

According to Abraham (3), what exactly did Dr. Wolff conclude in defining the effect?

“The W-C effect is supposedly the inhibitory effect of peripheral inorganic iodide (PII) levels equal to or greater than 0.2 mg/L (10-6M) on the organification of iodide by the thyroid gland of rats, resulting supposedly in hypothyroidism and goiter.”

In contrast, Abraham (3) feels that Dr. Wolff misinterpreted his own research:

“These rats never became hypothyroid and thyroid hormones were not measured in their plasma.”

In reality, according to Abraham, what Wolff witnessed in his experiments is the natural and proper response to iodine administration, not a pathologic and detrimental occurrence, as evidenced by the fact that, as stated above, the rats never became hypothyroid:

“Let us recapitulate by defining the W-C effect.  When normal rats are injected with a single intraperitoneal dose of potassium iodide mixed with radioiodide tracer, in amounts five times or more greater than the total amounts of iodide measured in the thyroid gland of those rats, the organic binding of radioiodide by the thyroid becomes undetectable as long as serum levels of inorganic iodide are maintained above 19 µg percent (10-6M).  As we previously discussed, radioiodide uptake by the thyroid gland should be zero when stable (non-radioactive) iodide sufficiency of the thyroid gland is achieved.  Therefore, the so-called blockage of organification of radioiodide by the thyroid gland when serum inorganic iodide reached 10-6M is really the amount of serum inorganic iodide needed for thyroid sufficiency.  There is no blockage of organification of stable iodide by the thyroid gland.”

Nevertheless, according to Abraham (3), Dr. Wolff’s findings were extrapolated to humans:

“Nevertheless, the W-C effect, which did not even occur in the rats, was extrapolated to humans.”

According to Abraham (3), what is the correct interpretation of Dr. Wolff’s experiments on rats:

“The correct interpretation of the results obtained in rats from the W-C experiments is: Iodide sufficiency of the thyroid gland was achieved when serum inorganic iodide levels reached 10-6M, as we previously discussed.  These law-abiding rats refused to become hypothyroid and instead followed their normal physiological response to iodide load.  They were unjustly accused of escaping from the W-C effect.  Labeling these innocent rats as fugitives from the W-C effect was a great injustice against these rodents.”

What references were used to support this claim?  Previous papers written by Abraham, one of which I will discuss shortly.  What was the clinical impact of the discovery of the W-C effect?  According to Abraham (3):

“To the disgrace and stupidity of the medical profession, US physicians swallowed the W-C forgery uncritically, which resulted in a moratorium on the clinical use of inorganic, non-radioactive iodine in effective amounts.  However, this moratorium did not include toxic organic iodine-containing drugs and radioiodide.  The iodophobic mentality prevented further research on the requirement for inorganic, non-radioactive iodine by the human body, which turns out to be 100-400 times the very recently established RDA.  Prior to World War II and the W-C publication, US physicians used Lugol solution safely, effectively and extensively in both hypo- and hyperthyroidism.”

Again, previous papers written by Abraham are used to reference these claims.  One of those papers is “The safe and effective implementation of orthoiodosupplementation in medical practice” (4)  In this paper Abraham does present papers written by other authors to support his contention that the W-C effect is not only fictitious but also the driving force behind a conspiracy to convince American physicians that the findings noted in rats could be extrapolated to humans.  The following quote refers to a publication by Stanley from 1949, which was one of the first to suggest that Wolff’s findings on rats apply to humans:

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

Abraham (4), in the above quote, does provide a reference for the claim made by Wolff and Chaikoff, which I will be discussing.  Abraham continues with his thoughts on Stanley:

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

Stanley concluded, ‘Thus, the observations of Wolff and Chaikoff in the rat were extended to man.'”

Abraham (4) goes on to suggest that Wolff himself doubted the applicability of his findings to humans, as evidenced by this quote from a 1969 publication by Wolff, which I will also discuss shortly:

“However, in a review published in 1969, Wolff stated, ‘The rarity of iodide goiter in the face of the extensive exposure of a great many patients to iodide has not been satisfactorily explained.”

Nevertheless, Abraham (4) feels that an explanation does exist.  What happened in the rat experiments is a normal natural, non-pathologic occurrence and the negative connotation given to these findings is fabrication:

“Without preconceived ideas, it is easily explained-inorganic, non radioactive iodine/iodide is safe.”

Abraham (4) then goes on to describe research that supports his contention:

“Several researchers erroneously concluded that the rapid decrease in serum thyroxine (T4) following oral ingestion of inorganic iodine/iodide in thyrotoxic patients was due to the Wolff-Chaikoff Effect, that is sustained inhibition of T4 synthesis.  However, Wartofsky, et al in 1970, evaluated the effect of Lugol solution, administered at five drops (30 mg iodine/iodide) three times a day in five thyrotoxic patients.  Following a well-designed protocol, they concluded that ‘the rapid decrease in T4 secretion induced by iodine is not the result of an acute sustained inhibition of T4 synthesis (The Wolff-Chaikoff Effect), but rather results from an abrupt decrease in the fractional rate of thyroid T4 release.’  Therefore, in hyperthyroidism, iodine/iodide in Lugol at a daily dose of 90 mg induced a physiological trend toward normalization of thyroid function, a beneficial effect.”

I will discuss in detail the Wartofsky et al paper mentioned in the above quote in the next issue, in order to determine if Abraham’s interpretation of the paper reflects what was actually stated.

As I mentioned above, Wolff issued a publication in 1969 on the issue of iodine and thyroid function.  As noted by Abraham (3), this paper is important to acknowledge because, being published in a major medical journal, it undoubtedly had a major impact on clinicians in this country in terms of administration of iodine to 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.  This article was obviously addressed to clinicians, and coming from the National Institute of Health gave it credibility.  Since it was published in a medical journal, physicians assumed that the W-C effect had been demonstrated in human subjects, as insinuated by Wolff in his review.”

According to Abraham (3), Wolff describes in his review four degrees of iodide excess.  In his text Abraham (3) describes each of these degrees of excess presenting statements refuting their validity.  However, instead of just presenting Abraham’s discussion of these four degrees, I would now like to take a different approach to Abraham’s claims about the W-C effect.  As I mentioned above, my main goal in this discussion is to determine as best as possible whether Abraham has sufficiently supported his position with quality referencing.  In turn, as I also mentioned, two key points need to be considered.  First, did Abraham portray the references accurately?  As you may recall, Abraham did not portray his reference accurately when he determined that the average iodine intake in Japan is 13.8 mg per day.  Second, assuming the references have been portrayed accurately, do they serve as convincing proof, given that so many other papers have taken a stance on the W-C effect that is radically different from that maintained by Abraham?  Therefore, I would like to now present a review of not only the 1969 paper by Wolff just mentioned but all of the major references used by Abraham, including those highlighted above.      

An examination of Abraham’s references – Were they quoted accurately and do they adequately support Abraham’s claims?

As I suggested in the last installment, I felt that Dr. Wolff was a dedicated researcher doing his best to make discoveries to improve the human condition.  Of course, based on what we know now, he may have been overly protective in his suggestions of the amount of iodine intake that poses a threat to human health.  However, making erroneous conclusions about his research does not make him a bad, unethical person.  As you read above, though, Abraham does feel that Wolff was engaging in malevolent, ethically questionable behavior by deliberately conspiring to bring routine use of milligram doses of supplemental iodine to a halt.  Do Wolff’s writings suggest a researcher doing his best even though subsequent research has proved him wrong or do they suggest deliberate intent to deceive?  To hopefully answer this question I would now like to examine Wolff’s highly influential 1969 publication entitled “Iodide goiter and the pharmacologic effects of excess iodide.” (5).

To begin, I would like to present a quote that makes it clear what, according to Wolff (5) is the optimal amount of iodide intake per day:

“Since the normal human thyroid gland delivers about 65 µg. of organic iodine (T4 and T3) to the circulation per day, and since the iodide clearance of the thyroid is half that of the kidneys, a rough estimate of the daily iodide requirement for man would be about 200 µg. of iodine per day.”

What amount does Wolff consider to be clearly excessive and what might be the consequences of excessive ingestion?  This question is answered in the first paragraph of the abstract:

“Chronic ingestion of iodide or iodide-generating compounds in amounts ten or more times the daily requirements for hormone biosynthesis leads to iodide goiter in certain subjects.  Predisposing factors are uncertain but may involve a damaged thyroid parenchyma; this must, however, be minimal since full recovery of normal thyroid function occurs upon iodide withdrawal in nearly all cases.”

Before continuing, I would like to dissect the above paragraph to see if evidence exists to suggest gross lies and/or deliberate efforts to misinform.  True, based on what we know now, stating that any level of iodine intake above 2 mg per day (Ten times the daily requirement noted by the author) represents a clear and present danger is probably too conservative.  In contrast, stating that certain people are predisposed to adversely react to these doses of iodide seems quite true based not only on the dose/response principles discussed last month but the ideas presented in the Konno et al (2) paper discussed earlier in this monograph.  Furthermore, in my opinion, if Wolff (5) truly wanted to discourage all use of milligram doses of supplemental iodine, he could have made a statement much more dire and frightening than “…full recovery of normal thyroid function occurs upon iodide withdrawal in nearly all cases.”

Next, I would like to discuss in detail Wolff’s (5) four degrees of iodide excess mentioned above, starting with the first degree:

“We can arbitrarily define four degrees of iodide excess:

(1)   Relatively low levels which lead to temporary increases in the absolute iodine uptake by the thyroid gland and the formation of organic iodine until each time as the thyroid is required to reduce iodide clearances, etc.  Positive iodine balances may be prolonged and lead to considerable increases in hormone stores.”

Abraham’s (3) rebuttal to refute the validity of Wolff”s (5) statements on first degree excess revolve around a study by Koutras et al (6).  What follows is Abraham’s (3) rebuttal:

“In 1964, five years before Wolff published his review, Koutras et al from Scotland published a well-designed study…They administered potassium iodide to normal subjects for 12 weeks in daily amounts of 100 µg, 200 µg, and 800 µg.  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 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.”

Does Abraham’s (3) rebuttal have validity?  To answer this question I would like to examine both the Wolff paper (5) and the Koutras et al paper (6).  First, I would like to address the last sentence of the above quote.  While it is a small point, its accuracy does, to me, make a statement about credibility.  In fact, the statement is incorrect.  In fact, the Koutras et al (6) paper is listed on page 120 of the Wolff paper (5) as reference #147.

In considering the text of the Koutras et al (6) paper, do the authors maintain that their findings refute the existence of the W-C effect as suggested by Abraham (3)?  As you will see from the following quote, which contains not only the sentence quoted above by Abraham (3) but much more, the authors in no way make an absolute statement:

“It appears, therefore, that when the plasma inorganic iodine (PII) is chronically raised there is less complete utilization of iodide, i.e., the thyroid traps more iodide than it converts to thyroid hormone.  The mechanism underlying this decreased iodide utilization is still uncertain.  Wolff and Chaikoff have shown in rats that, following marked PII rise, the thyroid gland still concentrates iodide but cannot incorporate it completely into organic compounds.  Essentially similar results have recently been obtained in vitro by Braverman and Ingbar.  In thyrotoxic patients treated with iodides and patients with iodide-induced goiter, iodide may be discharged from the thyroid with perchlorate or thiocyanate.  Although this suggests that organic binding of iodine is the factor limiting iodide utilization, in these circumstances large and unphysiological doses of iodide were taken.  There is no evidence that the same mechanism is also responsible for the decreased iodide utilization which accompanies small increases in the PII level.”

What are the key points made in the above quote in relation to Abraham’s (3) claims about the W-C effect?  First, in contrast to Abraham’s interpretation of the paper, it appears to me that the authors acknowledge the validity of the findings of Wolff and Chaikoff.  Second, and most importantly, though, the authors seem to suggest that the effect is dose dependent and, given the low doses of supplemental iodide used in this study (No more than 800 µg daily), the mechanism suggested by Wolff and Chaikoff does not apply.  However, the above quote also suggests that at “…large and unphysiological doses of iodide…” it is possible that the W-C effect can occur.  Finally, please keep in mind that, as stated above, Wolff (5) maintains that the adverse impact of supplemental iodine on the thyroid begins at 2 mg per day.  Therefore, Wolff (5) and Koutras et al (6) seem to be in agreement concerning the lack of ability for up to 800 µg per day to adversely affect thyroid function or create the W-C effect.  Thus, it appears to me that, in actuality, the Koutras et al (6) paper cannot be used as a reference to support a claim that the W-C effect does not exist.

Now I would like to move on to Wolff’s (5) statements on second degree excess:

“(2) A larger amount which can inhibit iodine release from the thyrotoxic human thyroid gland or from thyroids in which iodine release has been accelerated by thyroid-stimulating hormone (TSH).”

Abraham’s (3) rebuttal to this statement is the following:

“Second Degree Excess: ‘A larger amount which can inhibit iodine release from the thyrotoxic human thyroid gland.’  What is wrong with that?  Before the introduction of the toxic goitrogens, the thiocarbamide drugs, the Lugol solution was used extensively during the early and mid 1900s in medical practice for the treatment of hyperthyroidism and with good results.  With daily intake ranging from 6 mg to 180 mg iodine, a success rate as high as 90% was achieved, saving patients’ thyroids from radioiodide and the toxic goitrogens.”

The only reference provided in the above quote is one of Abraham’s own papers (4).  My only reply to this rationale why the W-C effect does not exist would be to say that Wolff is in agreement with the above quote.  Wolfe (5) never maintains that iodine is ineffective clinically.  His central point is that high doses of iodine will cause thyroid-related side effects in some individuals.  Further proof of this is the quote from the Wolff (5) paper that was used by Abraham (4) to suggest that Wolff questioned the validity of his own theory:

“The rarity of iodide goiter in the face of the extensive exposure of a great many patients to iodide has not been satisfactorily explained.”

To me, this statement does not suggest that Wolff is completely rejecting his theory about the W-C effect.  Rather, it affirms the theme that occurs throughout the paper.  What is this theme?  There is no evidence that iodine excess adversely affects thyroid function in everyone.  Rather, it has been noted in a few, susceptible individuals.

Furthermore, I see no evidence in this paper that, as Abraham (3) suggests, that Wolff (5) is conspiring to eliminate all use of milligram dosing of supplemental iodine.  In contrast, he seems to be making a suggestion that we should be aware of the fact that a few people may react negatively.  True, Wolff (5) does feel that, theoretically, given the high levels of iodine exposure, more people should have negative reactions.  However, in actuality, comparatively few reactions occur, a fact which the author cannot readily explain.  To me, these statements suggest a researcher who is doing his best to report findings and make reasonable and prudent suggestions based on these findings.  As I mentioned, I see no evidence of a conspiracy to eliminate the clinical use of iodine supplementation from the practice of health care in the United States.

What is Wolff’s (5) third degree of iodine excess?  The author states:

“A slightly larger intake which leads to inhibition of organic iodine formation and which probably causes iodine goiter.  This is the so-called Wolff-Chaikoff effect.”

As was suggested in Wolff’s (5) abstract quoted above, this amount is approximately 2 mg per day or more.  The following is Abraham’s (3) rebuttal to this statement:

“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.’  Dr. 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.’  Without preconceived ideas, it is easily explained – inorganic, non-radioactive iodine is safe.  ‘The demonstration of the Wolff-Chaikoff effect in man remains presumptive.’  The demonstration of the W-C effect in any animal species remains presumptive.

Does Wolff (5) contradict himself?  In my opinion, no.  Why?  In my reading of the paper I felt that the author was, as I mentioned, quite consistent in pointing out that the W-C effect only occurs in a small group of patients.  Furthermore, I thought he was quite consistent in his humble admission that he did not know why this was so.  However, just because the W-C effect only occurs in a small group of patients does not prove that the effect does not exist at all, as Abraham (3) suggests in the above quote.  Concerning the second statement attributed to Wolff (5) in the above quote, what Abraham (3) presented is a partial sentence.  What follows is the whole sentence:

“Since only one biopsy specimen of an iodide goiter has been analyzed for the 127I moieties, the demonstration of the Wolff-Chaikoff effect in man remains presumptive.”

This sentence concluded a paragraph where Wolff (5) was discussing other thyroid research in humans which employed “…acute iodide loads in man…”  The way I read the paragraph was that Wolff was humbly admitting, as every good researcher should, that even though he feels the results of his experiments deserve our attention, they do not provide conclusive proof since other research has been conflicting.  However, this admission of uncertainty certainly does not prove that Wolff (5) is issuing a confession of error and unethical intent, as Abraham (3) is suggesting.

In the section on third degree excess, Abraham (3) continues his commentary by stating the following:

“Concerning iodide goiter, 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 thyroid enlargement since Japanese subjects from Tokyo without goiter excreted similar levels of iodide in their urine.  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 Suzuki, et al, Konno, et al, 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.  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.”

As you can see, in this quote Abraham (3) provides fairly elaborate referencing to refute Wolff’s (5) statements on third degree iodide excess.  Do these studies, in reality, support his claims that the W-C effect does not exist?  In part X of this series, I will explore this question as well as continue my exploration of all of Abraham’s key references for his highly controversial stance on the W-C effect.

Moss Nutrition Report #222 – 08/01/2008 – PDF Version


  1. Nagataki S. The average of dietary iodine intake due to the ingestion of seaweeds is 1.2 mg/day in Japan. Thyroid. 2008;18(6):667-668.
  2. Konno N et al. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab. 1994;78(2):393-397.
  3. Abraham GE. The Wolff-Chaikoff Effect: Crying Wolf? The Original Internist. 2005;12(3):112-118.
  4. Abraham GE. The safe and effective implementation of orthoiodosupplementation in medical practice. The Original Internist. 2004;11:17-36.
  5. Wolff J. Iodide goiter and the  pharmacologic effects of excess iodide. Am J Med. 1969;47(1):101-124.
  6. Koutras DA et al. Effect of small iodine supplements on thyroid function in normal individuals. J Clin Endocrinol 1964;24:857-862.