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Iodine Research

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                        Iodine and the Body

Blood

ABRAHAM
The historical background of the iodine project.
Abraham GE
The Original Internist, 12(2):57-66, 2005

In order to assess the presence of iodine and iodate (the oxidized forms) in serum following
orthoiodosupplementation, serum iodide levels (the reduced form) were measured by ion-selective
electrode before and after reduction with sodium metabisulfate. The 3 inorganic forms of the
element iodine consumed by human subjects are: the negatively charged reduced iodide; the
negatively charged highly oxidized iodate IO-3; and the neutral oxidized iodine I2. The iodide
selective electrode is influenced only by negatively charged forms of this element that is, iodide I-
and iodate IO-3.  Experiments performed by the author with sodium iodate revealed that the iodate
molecule, because of its larger size than iodide, did not have any appreciable effect on the
electromotive force (EMF) of the electrode, even at concentrations 10,000 times higher than the
amount of iodide influencing significantly the EMF of the selective electrode.

"Pilot studies were performed in order to quantify the amount of the reductant needed for the
reduction of iodine and iodate to iodide. Almost 10 times more reductant was required for the
reduction of iodate to iodide than iodine to iodide. The reduction of iodate resulted in the formation
of iodine first, then iodide. When this procedure was applied to urine samples, no significant
difference was observed between pre- and post-reduction levels, suggesting that only iodide, the
reduced form, was present in urine. However, serial serum samples obtained for 24 hours following
the loading test, showed a significant difference in the serum iodide levels between pre- and
post-reduced samples within the first 2 hours in a female subject, with post reduction levels 5-10%
higher. This suggests the presence of serum iodine early after ingestion of the Lugol tablets. Iodine
obviously is not completely reduced to iodide in the intestinal tract during absorption as mentioned
in medical textbooks. "

"Serum inorganic iodide levels are a good index of the bioavailability of ingested iodine/iodide.
Serum inorganic iodide is cleared rapidly by the kidneys with a daily clearance rate of 43.5.  At
steady state condition, the serum iodide levels expected for patients receiving 50 mg iodine/day
should be approximately: serum iodide (mg/L) = daily intake (mg) / 43.5 Liter = 50 mg / 43.5 = 1.15
mg/L. If patients continue to excrete low levels of iodide after orthoiodosupplementation for 3
months, serum inorganic iodide levels are indicated to assess whether this is due to decreased
absorption or increased demand. Malabsorption of iodine/iodide would result in very low serum
inorganic iodide levels (10-8M) in the presence of low urinary excretion. We have not observed a
case of malabsorption of iodine yet, when iodine supplementation was in the range of 12.5 to 50
mg/day.



DANIEL
The lymphatic and venous pathways for the outflow of thyroxine, iodoprotein and inorganic iodide
from the thyroid gland.
Daniel PM, Plaskett LG, Pratt OE.
J Physiol. 1967 Jan;188(1):25-44.

1. Baboons and cats were given radioactive iodine and, at varying times after the injection, samples
of thyroid and non-thyroid lymph and of thyroid venous and peripheral venous blood were collected.
The radioactive material in these samples was separated by paper chromatography or by differential
precipitation and solvent extraction into three main fractions: inorganic iodide, iodoamino acid iodine
and high molecular-weight material (retained at the origin of chromatograms and not extractable by
butanol or ethanol). The latter was considered to be iodoprotein.

2. Thyroxine was the main component of the radioactive iodoamino acid iodine in thyroid lymph, in
thyroid venous and in peripheral blood. The concentration of thyroxine radioactivity in the thyroid
lymph was several times greater than that in either thyroid venous or peripheral blood plasma, both
before and after giving thyroid stimulating hormone.

3. An unidentified thyronine compound that was frequently found in thyroid lymph and also in blood
samples contained an appreciable proportion of the radioactive iodine. This substance was probably
a metabolite of one of the iodothyronines. In addition, iodotyrosines probably accounted for up to
4% of the radioactivity in the lymph and blood samples but radioactive triiodothyronine could not be
detected with certainty.

4. In some experiments lymph was obtained from the cervical lymph trunk at a considerable distance
from the thyroid gland, in order to avoid operative trauma to the gland. This cervical lymph
contained diluted thyroid lymph but even so it contained more radioactivity in the form of iodoamino
acid and iodoprotein than did peripheral blood or non-thyroid lymph. Cervical lymph and thyroid
lymph both contained less radioactive inorganic iodide than did non-thyroid lymph.

5. The administration of thyroid stimulating hormone caused a prolonged rise in the output of
radioactive iodoamino acid in the thyroid venous blood and, for a limited period, an increase in the
output of radioactive inorganic iodide. At the same time there was an increase in the output of
radioactive material in the thyroid lymph. The main part of the latter was due to a rise in the output
of iodoprotein.

6. The lymphatics and the venous system provide alternative pathways for the outflow of iodine
compounds from the thyroid gland. These pathways differ in relative importance for different iodine
compounds. For iodoprotein the lymphatic pathway is the important one since there is no
appreciable release of this substance into the thyroid venous blood. In the case of inorganic iodide,
where there is no appreciable difference in concentration between thyroid lymph and blood, the
greater flow of blood makes the venous pathway relatively more important than the lymphatic one.
Thyroxine is released into the thyroid lymph in higher concentration than into the blood but the
faster flow of blood makes the venous pathway relatively more important.


Radioactive iodoprotein in thyroid lymph and blood.
Daniel PM, Plaskett LG, Pratt OE.
Biochem J. 1966 Sep;100(3):622-30.

1. Samples of thyroid and non-thyroid lymph and of thyroid and peripheral venous blood were
obtained from primates and cats that had previously been given radioactive iodine. The distribution
of the organic radioiodine between the protein and non-protein fractions in these samples was
determined.

2. The proportion of the organic radioiodine in the form of iodoprotein was assessed by paper
chromatography, acid-ethanol precipitation, hot-butanol washing, column chromatography and
separate estimation of iodotyrosines after enzymic hydrolysis.

3. In thyroid lymph the relative proportion of the organic radioiodine in the form of iodoprotein was
75-98%; in blood it was much lower, probably no more than 6-7%. The absolute concentration of
iodoprotein radioactivity also was considerably greater in thyroid lymph than in blood.

4. Enzymic hydrolysis of the protein of the thyroid lymph yielded a pattern of iodoamino acids that
corresponded closely with that obtained after hydrolysis of protein extracted from the thyroid gland
itself.

5. It can be concluded that the iodoprotein in thyroid lymph consists mainly of thyroglobulin or a
closely related compound.



WINKLER
Effect of iodide on total antioxidant status of human serum.
Winkler R, Griebenow S, Wonisch W.
Cell Biochem Funct. 2000 Jun;18(2):143-6.

Free radicals and subsequent lipid peroxidation have been implicated in the pathogenesis of several
degenerative and chronic diseases which are also treated frequently in spas. There are some data
arising from previous studies which support an antioxidant or scavenging effect of iodide, being the
essential ingredient of a therapeutically used local brine. The aim of the study was to test the
antioxidant capacity of iodide in human serum. For this reason we measured the so-called Total
Antioxidant Status determined by a colorimetric method, which reflects the protection against the
attack of reactive oxygen species, including enzymic and non-enzymic antioxidants. Exogenous
iodide applied as NaI, shows a significantly increased antioxidant capacity in comparison with NaCl at
a concentration of 15 microM, which is quite comparable to the upper range of serum iodide levels
achieved through balneo-therapeutical intervention. This result is in accordance with previous
results from in vitro depolymerization experiments with hyaluronic acid. The antioxidant effect of 15
microM NaI has been found to be approaching the physiologically relevant concentration of ascorbic
acid (50 microM).


Dual method for the determination of peroxidase activity and total peroxides--iodide leads to a
significant increase of peroxidase activity in human sera.
Tatzber F, Griebenow S, Wonisch W, Winkler R.
Anal Biochem. 2003 May 15;316(2):147-53.
[abstract only]

Peroxidases are very important enzymes, e.g., as preventive antioxidants by removing noxious
peroxides from the blood. For this reason we evaluated a colorimetric method which detects the
activity of endogenous peroxidases by their reaction with hydrogen peroxide, using
tetramethylbenzidine as the chromogenic substrate. This assay design can be easily reversed by
change of the variable compound to measure also total peroxides in plasma or serum. An increased
total antioxidant status was reported previously by the addition of iodide to human serum. In this
study iodide activated the endogenous peroxidases significantly in comparison to control sera and
isomolar NaCl as well as horseradish peroxidase. Corresponding to the increased peroxidase
activity a concomitant decrease of total peroxides occurred in the same samples. This exchangeable
assay design is a beneficial opportunity to screen total peroxide levels as well as peroxidase activity
in human sera without time-consuming preparations. The method proved to be simple and is
favorable due to its specificity, reproducibility, and low costs. Moreover, we were able to find an
explanation for the increased total antioxidant status in the presence of iodide, which is presumably
an indirect protective effect via an enhanced activity of enzymatic antioxidants, thereby reducing
endogenous peroxides.