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Theodore Zava responds.

I welcome the opportunity to respond to the letter by Drs. Brownstein, Flechas, and Hakala regarding my publication "Evaluation of the Iodine Loading Test: Urine Iodine Excretion Kinetics after Consumption of 50 mg Iodine/Iodide." (1) My comments below refer to some concerns raised in their letter.

1. The letter notes that as long as one understands the difference between the iodine spot test without a loading dose and the 24-hour iodine loading test, there will be no confusion between "whole-body iodine sufficiency" and "iodine sufficiency."

I agree that a well-informed individual will see the difference between the two iodine testing methods and their results, but in my experience this is seldom the case. Many health professionals, as well as commentators in forums, blogs, and newsletters, refer to the iodine loading test as an indicator of iodine sufficiency without mentioning "whole-body." As I explained in my article, this has created confusion over who is at risk of iodine deficiency and iodine-deficiency disorders. Equating failure of an iodine loading test with "iodine deficiency" instead of "whole-body iodine deficiency" is not correct and may lead to unnecessary or excessive iodine supplementation. (1)

2. The letter questions why I did not contact any of the laboratories that offer the loading test to ask how long iodine supplementation should be discontinued before taking the test.

The iodine loading test methodology, validation, and patient testing procedures are published on the Optimox website ( As I referenced in my article, the publication introducing the iodine loading test, the testing procedure, and the laboratories offering it includes instructions to "Have (the) patient stop ingesting iodine 24 to 48 hours before the test if post-supplementation." (2) However, even 48 hours is not adequate time to clear previous supplemental iodine. Our study found that even if supplementation is discontinued for 48 hours, there will still be residual iodine excretion in the urine as a result of previous ingestion of 50 mg iodine/iodide. We saw an average of 1480 pg iodine/24-hours (around 3% of a 50 mg dose), with one patient excreting 2693 pg iodine/24-hours (around 5% of a 50 mg dose), during the period between 48 and 72 hours following ingestion of 50 mg iodine/iodide. This significant amount of residual iodine would therefore affect the iodine loading test outcome in patients who discontinued supplementation 48 hours before taking the test. This is why my article noted that supplementation should be stopped several days; that is, more than 48 hours, prior to taking the iodine loading test.

3. The letter mentions that the 90010 iodine loading dose excretion cutoff to determine whole-body iodine sufficiency was chosen arbitrarily. Drs. Brownstein, Flechas, and Hakala claim that by following iodine loading test parameters, patients with the best clinical responses reached 90% or more iodine excretion during the iodine loading test.

In an online article describing the development of the iodine loading test, there is no mention of individuals discontinuing iodine supplementation before retesting to determine when whole-body iodine sufficiency is reached. (3) This very well may be the reason why initial studies showed patients eventually passing the loading test, reaching >90% excretion after iodine supplementation. For this reason my article stressed that the arbitrary 90% excretion level should be reevaluated. I would challenge Drs. Brownstein, Flechas, and Hakala to report the amount of time it takes after supplementing with iodine to show whole-body iodine sufficiency (>90% excretion of a 50 mg dose of iodine/iodide during a 24-hour collection) with all testers discontinuing iodine supplementation multiple days prior to testing.

4. In response to my suggestion that 24-hour fecal testing of iodine levels would help identify other routes of elimination of iodine, the letter states, "Fecal excretion of 2% has been confirmed on a patient taking 100 mg of lodoral daily" and that these data are on file at Hakala Research.

I would challenge Hakala Research to continue this study and test multiple patients' fecal excretion of iodine after a 50 mg dose of iodine/iodide. I believe that there are many factors, most unexplored, that can potentially affect fecal iodine excretion. It cannot, therefore, be assumed that fecal elimination of iodine after a 50 mg dose of iodine/iodide is negligible without studying fecal excretion of iodine in various study populations over a range of collection times. It would be crucial to include data on the time and length of fecal sample collection (spot vs. 24-hour sample). Extending the fecal collection period past 24 hours following a 50 mg iodine/iodide loading dose will determine if fecal iodine levels peak at a later time period. In a study of 6 euthyroid children (ages 18-27 months) receiving a dose of radioactive 1-131, the radioactive peak in feces was seen during the second 24-hour fecal collection. (4) Fecal excretion of iodine in 5 men aged 20 to 28 after supplementation with 2 mg potassium iodide was found to increase during exposure to a "hot moist" environment compared with "comfortable" environment. (5) Also, investigators testing normal subjects without iodine supplementation observed that fecal iodine excretion was higher in women than it is in children. (6)

I hope that these points answer some of the concerns raised and that Drs. Brownstein, Flechas, and Hakala will consider my suggestions to reinforce the validity of the iodine loading test, and ensure that patients are correctly assessed for whole-body iodine sufficiency.


(1.) Zava T. Evaluation of the iodine loading test: urine iodine excretion kinetics after consumption of 50 mg iodine/iodide. Townsend Lett. January 2013.

(2.) The iodine/iodide loading test [Web page]. Optimox Corporation. Test.htm. Accessed August 9,2013.

(3.) Abraham GE. The concept of orthoiodosupplementation and its clinical implications [online document]. Accessed August 9,2013.

(4.) Ingenbleek Y, Beckers C. Evidence for intestinal malabsorption of iodine in protein-calorie malnutrition. Am J Clin Nutr. 1973;26:1323-1330.

(5.) Spector H, Mitchell HH, Hamilton TS. The effect of environmental temperature and potassium iodide supplementation on the excretion of iodine by normal human subjects. Biol Chem. 1945;161:137-143.

(6.) Vought RI, London WT. Iodine intake and excretion in healthy nonhospitalized subjects. Am J Clin Nutr. 1964;15:124-132.

Theodore Zava

Research Associate, ZRT Laboratory
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Title Annotation:Letters to the Editor
Author:Zava, Theodore
Publication:Townsend Letter
Article Type:Letter to the editor
Date:Nov 1, 2013
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