The bioavailability of iodine applied to the skin
by Guy E. Abraham, M.D.
I have decided to write a series of manuscripts on the most commonly asked questions about iodine. These manuscripts will be displayed on our website. This report is the first of this series. I have often been asked: 1) Is the application of iodine to the skin an acceptable way to supplement iodine? 2) Are there any data confirming the validity of the iodine skin patch test to assess body sufficiency for iodine? The interpretation commonly used to assess the results of the iodine skin patch test: The faster the yellow color of iodine disappears from the skin, the more iodine deficient the person tested; and vise versa: if the yellow color lingers, the more sufficient in iodine the person tested.
A review of the published literature is required to answer the above questions. The bioavailability of iodine applied to the skin is well known. Over 100 years ago, application of iodine to the skin was used extensively for iodine supplementation. In 1932, Nyiri and Jannitti (1) from the College of Pharmacy of Rutgers University wrote:
"Iodine is being used extensively as a prophylactic and therapeutic agent by application to the outer integument, (For the reader’s information, that is the skin) and has maintained its place in medicine for many decades. Its use by external application is merely on an empirical basis; very little proof of its efficacy has been obtained by experimental work. The main question as to whether or not iodine passes through the unbroken human and animal skin has not been conclusively answered."
In order to assess the bioavailability of iodine applied to the skin, these investigators used 44 rabbits and 6 dogs, not human subjects.
"Although the question of iodine penetration has been studied extensively especially during the second half of the last century, no satisfactory conclusion has been reached because the techniques of the various experiments were not fully reliable. Considering the increasing biological significance of the outer integument (Klose (30), Unna (31), Vollmer (32), Urbach (33)) and the wide spread medicinal use of iodine on the skin, we made a series of experiments about the fate of iodine applied to the skin; thereby studying the possibility of penetration of free iodine, its fate in the body, its elimination, and its conditions of evaporation for the surface. We carried out the experiments on six dogs and forty-four rabbits."
To summarize the results of their experiments:
1. Free iodine penetrates through the unbroken skin.
2. Approximately 88 per cent of the iodine evaporate from the surface within three days.
3. Colloidal iodine evaporates somewhat more quickly than tincture of iodine; Lugol’s solution is more stable than either of them.
4. The influence of ambient temperature on the evaporation of iodine is significant: within the first minute, the losses of iodine by evaporation are: 10-15% at 9° c; 18-25% at 24° c; and 35% at 37° c.
5. The remaining iodine on the skin following evaporation of 88% of the total iodine, approximately 12 per cent, is at the disposal of the body, and penetrates through the skin. The bioavailability of the remaining 12% of the skin iodine is very gradual.
6. The fate of iodine in all above experiments is the same whether iodine is applied to the skin in the form of an alcoholic solution or in colloidal suspension. (For the reader’s information, the alcoholic solution is tincture of iodine and the colloidal suspension is a saturated aqueous solution of diatomic iodine, I2 ).
The authors concluded (1):
"Our quantitative determinations prove that iodine which penetrates through the skin is removed only slowly from within this area into the body, thus forming an iodine depot in the skin for several days. In this prolonged retention of iodine within the skin, we see a favorable condition for a possible local prophylactic and therapeutic action."
The above conclusions apply to rabbits and dogs, but not to human subjects. The best study of the bioavailability of iodine applied to the skin in normal human subjects was reported by Miller et al in 1989 (2). The purpose of Miller’s study was to assess the effectiveness of skin application of iodine in blocking radioiodide uptake by the thyroid gland. The subjects used in this study were 24 adult male volunteers aged from 21 to 51 years. These subjects were divided into 4 groups of 6 subjects each. One groups served as control and did not receive stable iodine. The other subjects in the remaining 3 groups received respectively 130 mgm KI orally equivalent to approximately 100 mg iodide; 80 mg iodine (tincture) on the skin; and 160 mg iodine on the skin. All 24 subjects ingested 131I labeled NaI and radioiodide thyroid uptake was measured at time 2 hr, 6 hr, and 24 hr post- ingestion of radioactive iodide and stable iodine. Serum inorganic iodide levels were measured at time zero, 2 hr, 6 hr and 24 hr post intervention. 24 hr radioiodide uptake by the thyroid gland as percent of dose administered was used to assess the effectiveness of iodine in blocking radioiodide uptake by the thyroid. The 24 hr percent radioiodide uptake by the thyroid gland were: control: 10.9 ± 2.9 (SD) oral KI: 0.34 ± 0.26; skin 80 mg iodine = 7 ± 5.5%; and skin 160 mg iodine = 2.0 ± 2.5%. Prior to administration of stable iodine the mean serum iodide in the 3 intervention groups were: 0.024 mg/L; 0.033 mg/L; and 0.02 mg/L. The mean of the 3 mean values is 0.026 mg/L.
Under steady state conditions, the computed daily intake of iodine based on serum iodide is equal to the product of serum iodide times 43.5 L/day, which is the renal clearance of iodide (3). The estimated average daily intake of iodine by this group of men is: 0.026 mg/L × 43.5 L/day = 1.13 mg/day. This daily intake may be due to the iodization of bread in the 1960’s, 1970’s and in some states in the 1980’s. The estimated daily intake of iodine during that time in the U.S.A. was 1 mg (4). This computed daily intake in Miller’s subjects is in agreement with the mean percent radioiodide uptake by the thyroid gland in this group of subjects with a mean of 10.9. By interpolation on Fig. 2 of Reference 5, 10.9% uptake corresponds to an average intake of approximately 1.5 mg iodine (See Fig. 1).
The two questions mentioned previously can now be answered:
I. Is the cutaneous route of iodine supplementation practical and effective?
II. Does the skin iodine patch test give a reliable indication of whole body sufficiency for iodine?
To answer the first question, we will use the data in the six subjects who were exposed to 160 mg iodine via cutaneous application, because the mean serum iodide levels were relatively constant over the 24 hr period: 0.27 mg/L at 2 hr; 0.2 mg/L at 6 hr and 0.24 mg/L at 24 hr post intervention. The mean value of the 3 means is 0.24 mg/L iodide. The average amount of iodine bioavailable in these 6 subjects would be the product of the serum iodide levels by the renal clearance of iodide, that is 43.5 L/day (3). 0.24 mg iodide/L × 43.5 L/day = 10.4 mg. The percent of bioavailable iodine from 160 mg applied to the skin is 10.4 x 100 / 160 = 6.5%. If the data reported by Nyiri and Jannitti (1) in dogs can be extrapolated to humans, that is 12% of the applied iodine was available for utilization by the body, with 88% evaporated; then some 50% of the remaining skin depot of iodine was available during the first 24 hrs following skin exposure to iodine.
One can conclude that skin application of iodine is an effective if not efficient and practical way for supplementation of iodine with an expected bioavailability of 6 to 12% of the total iodine applied to the skin. The serum iodide levels were 10 times higher 2 hr post intervention with oral ingestion of 100 mg iodide than with 160 mg iodine applied to the skin(Fig. 2).
From the published data, the skin iodine patch test is not a reliable method to assess whole body sufficiency for iodine. Many factors play a role in the disappearance of the yellow color of iodine from the surface of the skin. For example, if iodine is reduced to iodide by the skin, the yellow color of iodine will disappear because iodide is white. In order to regenerate iodine on the skin, one needs to apply an oxidant such as hydrogen peroxide, complicating the test further. The evaporation of iodine from the skin increases with increased ambient temperatures and decreased atmospheric pressure due to weather conditions and altitude. For example, the yellow color of iodine will disappear much faster in Denver, Colorado at 5,000 feet above sea level then Los Angeles, California at sea level, irrespective of the amount of bioavailable iodine. The iodine/iodide loading test (4) is much more accurate and it is now available from laboratories.
References
Nyiri, W., Jannitti, M., About the fate of free iodine upon application to the unbroken animal skin. An experimental study. J. Pharmacd. Exp. Ther., 45:85-107, 1932.
Miller, K.L., Coen, P.E., White, W.J., et al, Effectiveness of Skin Absorption of Tincture of I in Blocking Radioiodine from the Human Thyroid Gland. Health Physics, 56:911-914, 1989.
Abraham, G.E.: The concept of orthoiodosupplementation and its clinical implications. The Original Internist, 11:29-38, 2004.
Abraham, G.E., The safe and effective implementation of orthoiodosupplementation in medical practice. The Original Internist, 11:17-36, 2004.
Abraham, G.E., Flechas, J.D., Hakala, J.C., Orthoiodosupplementation: Iodine sufficiency of the whole human body. The Original Internist, 9:30-41, 2002
