A great misconception is that iodine's sole function in the body
is to act as an essential component of thyroid hormones. The thyroid
gland is not the only organ to concentrate and organify iodine.
Accumulating evidence suggests there are many extrathyroidal benefits
of iodine including maintaining the integrity of the mammary gland,
antioxidant functions, anti-tumor activities, detoxification, immune
system strengthening, and protection against potentially pathogenic
bacteria. Since iodine is essential to every cell in the human body
and has several biological functions beyond maintaining normal thyroid
function, a reevaluation of "iodine sufficiency" is warranted.
Thirty years ago, Americans consumed twice as much iodine as they
do today, but the average daily intake of 240 µg is still
above the reference daily intake (RDI) for iodine (150 µg),
which is nearly one hundred times less than populations consuming
non-Western-style diets.1 Because the whole body, not just the thyroid
gland, needs iodine, most Americans would benefit from consuming
larger quantities of dietary inorganic iodine.
Deficiency of dietary iodine causes a spectrum of disorders including
goiter, hypothyroidism, mental retardation, cretinism, and varying
degrees of other growth and developmental abnormalities.2 The world's
leading cause of preventable brain damage is iodine deficiency.3
The World Health Organization (WHO) speculates that iodine deficiency
disorders affect 740 million people worldwide and that nearly 35%,
about two billion, of the world's population are iodine-deficient.4
In an effort to prevent deficiency-related disorders, the WHO and
other world health policymakers subscribe to similar optimal reference
daily intakes of 100-199 µg iodine per day.4 While this amount
has preventative activity, it may be far from the optimal amount.
In fact, the optimal intake of iodine has never been determined.
While the thyroid is known as the principal user of iodine in the
body, recent biological research has discovered several organs that
actively concentrate iodine including the stomach mucosa, mammary
glands, salivary glands, thymus, choroid plexus, kidney, joints,
arteries, and bones.1,5 The lactating mammary gland and salivary
glands concentrate iodine almost to the same degree as the thyroid
gland does. Growing evidence now suggests iodine provides several
extrathyroidal benefits when consumed in larger quantities.
From 1971 through 1994, data from National Health and Nutrition
Examination Survey (NHANES) have demonstrated a surprising reduction
in the average American dietary iodine intake.6 Even though there
was a decrease in iodine intake, the amount ingested was still considered
sufficient.6 However, iodine deficiency rose tenfold to 8.1% of
men and 15.1% of women throughout this period.6 Caucasian females
between the ages of 40 and 49 years had the highest incidence of
iodine deficiency at 25.5%.6 These results suggest that iodine deficiency
is again becoming significant in the United States.
Even though dietary habits and iodine consumption of Americans have
dramatically changed in the last century, the amount of iodine consumed
by the average American is still considered sufficient by the Food
and Nutrition Board of the Institute of Medicine.1 Extensive use
of iodine in the dairy industry or as a dough conditioner in bread
making is a thing of the past. For many Americans, iodized salt
is the most significant contributor to their daily iodine consumption.
However, over the last 25 years, salt consumption in America has
decreased 65%.1 The consumption of eggs, which contain iodine-rich
yolks, has also been reduced because of cholesterol concerns. Another
study recently reported the significance of iodine lost in sweat,
suggesting previous studies have underestimated the implications
of iodine loss during exercise.7 Unlike the amount of research done
on electrolyte replacement, little has been done on iodine replacement
Insufficient iodine intake and sustained loss have significant implications
to overall health.7 The Japanese consume iodine in milligram quantities
compared to the microgram amounts consumed by Americans.1 Equally
startling is that Japanese women, who have among the highest iodine
intake in the world, have the lowest rate of breast cancer mortality
compared to US women who have the highest.1 Japanese women who adopt
a Western-style diet have higher rates of breast cancer than women
consuming traditional Japanese diets.1 Compared to the US, Japan
has a higher life expectancy and the world's lowest infant mortality
rate.1 While no direct conclusions about the health benefits of
iodine can be drawn from these data, they do suggest that increased
iodine is not only safe, but may also provide additional benefits
not obtained with current Western-style diets.
Iodine exists in nature in several inorganic forms including iodates
(IO3-), iodides (I-), and organic monoatomic iodine (C-I).8 Naturally
occurring molecular iodine (I2) is rarely, if ever, encountered.
Molecular iodine must be synthesized usually by reacting either
sodium or potassium iodide.9 Tincture of iodine, the usual source
of iodine for purposes of supplementation, may be made using either
sodium or potassium iodide according to United States Pharmacopeia
specifications.10 Both sodium and potassium iodide enhance the solubility
of molecular iodine. There are also organic man-made forms of iodine
that are extremely toxic and should not be mistaken for the forms
listed above.11 Inorganic iodine consumed in large amounts is well
tolerated.12 Several grams of iodine may produce acute toxicity,
but this is a rare occurrence.2,13 The greatest amount of natural
iodine is found in our oceans. Foods of marine origin concentrate
iodide and have higher concentrations than terrestrial plants and
In humans, the various ingested forms of iodine are reduced in the
gut and are absorbed as iodide.2 Once in the bloodstream, iodide
is transported throughout the body and eventually removed by the
thyroid gland and the kidney.2 The thyroid gland takes up around
60 µg of iodide from circulation daily to use in the production
of the thyroid hormones triiodothyronine (T3) and thyroxine (T4).
These hormones are synthesized, stored, and released from the thyroid
when needed. After binding to target tissues, the thyroid hormones
regulate a number of physiologic processes, including growth, development,
metabolism, and reproductive function.
In states of iodine deficiency, the thyroid enlarges, which increase
its surface area and its iodine trapping efficiency.6 More severe
cases of iodine deficiency can result in hypothyroidism and decreased
fertility. A recent study of the mammary gland, showed that iodine
contributes to the maintenance of its normal integrity.14 As opposed
to the thyroid gland, which selectively accumulates iodide, the
mammary gland favors iodine, suggesting that different chemical
forms of iodine exhibit different functions in various organs. In
human breast carcinoma tissue, iodine levels are significantly lower
than in surrounding tissue in the breast containing the tumor.15
Fibrocystic breast disease (FBD) is characterized by microcysts,
fibrosis, epithelial hyperplasia, and painful lumpy breasts in reproductive-aged
In a review of three clinical trials, which determined the response
of patients with FBD to different forms of iodine, researchers reported
molecular iodine was superior to protein-bound iodide and sodium
iodide when treating FBD.16 In one study, 74.5% of the women with
FBD treated with 0.08 mg molecular iodine per kilogram showed improvement
with microcysts disappearing within five months.16 Other forms of
iodine were less efficient and included side effects such as iodine
poisoning (iodism) and acne.16 These data substantiate studies showing
iodine, rather than iodide, is the preferred form of iodine to support
breast health. In addition to forming thyroid hormones, iodine in
thyroid and mammary tissue can be incorporated into lipid molecules,
called iodolipids, which regulate cell metabolism and proliferation
and possibly have an anti-proliferative role in breast tissue.14,17
Anti-Tumor Effects of Iodine
The antioxidant properties of inorganic iodine were first revealed
in kelp, when it was shown to neutralize hydrogen peroxide and prevent
hydroxyl radical formation. The researchers also noted that kelp
absorbed increased amounts of iodine when placed under oxidative
stress.18 Since then, an ancestral antioxidant function has been
proposed for life forms from primitive marine algae to vertebrates.14
In cells, iodide can act as an electron donor in the presence of
hydrogen peroxide and peroxidase enzymes to prevent free radical
formation.14 Iodine atoms iodinate amino acids, lipids, and other
membrane or nuclear components, making them less reactive to free
oxygen radicals.14 In mammals, dietary iodides have shown antioxidant
activity in the eyes, an ability to defend brain cells from lipid
peroxidation19, and an increased antioxidant status of human serum.20
Iodine has also been shown to induce apoptosis in cancer cells both
in vivo and in vitro.1,14,21 The administration of iodine-rich kelp
was found to significantly delay the occurrence of chemically induced
tumors in animals.22 The direct uptake of inorganic iodine by DMBA-induced
breast tumor tissue in animals significantly suppressed tumor growth.23
Human breast cancer and genetically modified lung cancer cell lines
have been shown to undergo apoptosis in the presence of inorganic
iodine.21 Iodine was also shown to limit the growth of iodine-accumulating
tumor xenografts compared with non-iodine-accumulating tumors in
animals.21 Studies suggest that high iodine intake is associated
with lower occurrence of breast cancer, while lower intake is associated
with higher occurrence of breast cancer.1 The incidence of breast
cancer is three times greater in people with goiters resulting from
iodine deficiency.1 Epidemiological studies have reported increased
prevalence of gastric cancer in iodine-deficient Italian populations.
With increased dietary consumption of iodine-rich foods, these Italian
populations have shown decreased incidences of gastric cancer. Researchers
speculate this effect is due to the iodide-concentrating ability
of the stomach, which uses iodide's antioxidant qualities to protect
the cells from damage caused by lipid peroxidation.19
of Inorganic Iodine
Additional benefits of consuming iodine in milligram amounts are
currently being studied. Among these benefits is detoxification.
In one study to determine the optimal dose of iodine, women supplemented
with 12.5 mg elemental iodine daily showed increased urine levels
of mercury, lead, and cadmium after just one day.11 Although the
exact mechanism by which iodine increases immune function is not
known, it has long been used therapeutically in various pathologies
involving the immune system. Studies have reported that adequate
iodine intake is necessary for maintaining normal cell-mediated
immunity,24 suppressing certain autoimmune diseases,25 and possibly
preventing the development of gastric cancer induced by abnormal
growth of Helicobacter pylori.26 The long-term consumption of high-iodide
eggs resulted in increased lipid metabolism and thyroid function
in animals.25 Long-term consumption suppressed age-induced lipid
peroxide accumulation in the brain, reduced serum cholesterol, and
elevated tissue lipoprotein lipase activity, which accompanied a
moderate hypotriacylglycerolemic effect.27 Aging animals fed high-iodide
eggs also exhibited higher thermogenic and serum T3 responses to
cold, suggesting they were better suited to maintain normal thyroid
function than control animals.27 In a small study of 12 patients
with type 1 diabetes mellitus given between 50-100 mg of iodine
per day, a decrease in the total amount of medications used to control
the diabetes was seen in all patients, and remarkably, six patients
were able to stop taking diabetes medication altogether.12
Defining the Optimal
Whole-body iodine sufficiency may require consumption in milligram
doses. The current RDI for iodine is 150 µg per day. Although
this amount is sufficient in preventing mental retardation, hypothyroidism,
goiter, and cretinism in the majority of the population, it does
not account for whole-body iodine usage. The RDI was last examined
by the Food and Nutrition Board in 2002 and has not changed since
1980.2 While the RDI gives 1.1 mg per day as an upper limit of iodine
intake, it considers only the body's thyroidal needs and not its
extrathyroidal needs. An iodine-deficient person can tolerate between
12.5-50 mg per day without reported adverse side effects, allowing
enough iodine in the body to sufficiently cover all needed areas.12,28
Japanese populations living in the coastal regions consume copious
amounts of iodine, averaging 13.8 mg daily due to the large quantity
of seaweed in their diets.1 These people are among the healthiest
in the world. The RDI of 150 µg per day does not provide the
body with sufficient iodine to create normal cell-mediated immunity
or to protect from gastric cancer and fibrocystic breast disease.1,24,25
The mechanisms for these extrathyroidal roles of iodine are not
well defined, but it is clear that iodine is needed in parts of
the body other then the thyroid. For a generally healthy person
living in any area, whether he or she has low or high levels of
iodine intake, an amount of 12.5 mg up to 50 mg of inorganic iodine/iodide
per day may support full body health.8 These larger amounts could
enhance immune function and in women, contribute to the integrity
of normal mammary glands.14 Although iodine is well tolerated, not
everyone should take higher doses. Those who shouldn't take higher
doses include children under 18 and people with thyroid disease,
as the risk of subclinical hypothyroidism and autoimmune thyoiditis
is greater in this population.29,30 It is imperative that anyone
thinking of beginning iodine milligram dose supplementation be checked
for underlying thyroid disease to evaluate for subclinical hyperthyroidism.
Americans consume only half the amount of iodine they did 30 years
ago and nearly 100 times less than the Japanese. The number of Americans
who are iodine deficient has risen tenfold in a 20-year span.6 With
food manufacturers reducing the amounts of iodine in milk and breads,
and the number of Americans consuming fewer eggs and table salt,
many Americans are not consuming sufficient amounts of iodine. The
recommended daily intake 150 µg. This amount is far too low
for many Americans. Even though this recommended intake reduces
the prevalence of hypothyroidism related to iodine deficiency, it
does not take into account whole-body health. Daily iodine intake
in the milligram dosage may provide immune system benefit and antioxidant
protection. Increased inorganic iodine/iodide has been shown to
be safe in healthy adults whether iodine-deficient or not.12,30,31
The benefits of increased iodine intake may include improvements
in fibrocystic breast disease, a decrease in gastric and breast
cancer risk, and a reduction in the amount of medication needed
to control diabetes mellitus. The antioxidant and antiproliferative
effects of iodine on the body may benefit healthy individuals.
1. Miller WD. Extrathyroidal benefits of iodine. J
Am Physicians Surgeons. 2006;11:106-10.
2. Food and Nutrition Board, Institute of Medicine. Iodine. Dietary
reference intakes for vitamin A, vitamin K, boron, chromium, copper,
iodine, iron, manganese, molybdenum, nickel, silicon, vanadium,
and zinc. Washington, D.C.: National Academy
3. Higdon J, Drake VJ. Micronutrient Information Center, Iodine.
Linus Pauling Institute. 2007.
4. Andersson M, Takkouche B, Egli I, et al. Current global iodine
status and progress over the last decade towards the elimination
of iodine deficiency. Bulletin of the World
Health Organization. 2005;83:518-25.
5. Spitzweg C, Dutton CM, Castro MR, et al. Expression of the sodium
iodide symporter in human kidney. Kidney
6. Lee K, Bradley R, Dwyer J, Lee S. Too much versus too little:
the implications of current iodine intake in the United States.
Nutrition Reviews. 1999;57:177-81.
7. Smyth PPA, Duntas LH. Iodine uptake and loss – can frequent
strenuous exercise induce iodine deficiency? Horm
Metab Res. 2005;37:555-8.
8. Abraham GE. The concept of orthoiodosupplementation and its clinical
implications. The Original Internist.
9. Hammond CR. The elements. In: Lide DR (ed). Handbook
of Chemistry and Physics. 78th Edition. Boca Raton, New York:
CRC Press; 1997, 4-15.
10. Iodine. Official Monographs. United States Pharmacopeia 31.
Baltimore: Port City Press; 2007, 2414-2415.
11. Abraham GE. The historical background of the iodine project.
The Original Internist. 2005;12:57-66.
12. Flechas JD. Orthoiodosupplementation in a primary care practice.
The Original Internist. 2005;12:89-96.
13. Inchem website. Available at: http://www.inchem.org/documents/jecfa/jecmono/v024jell.htm/.
Accessed October 17, 2007. (http://www.inchem.org/documents/jecfa/jecmono/v024je11.htm)
14. Aceves C, Anguiano B, Delgado G. Is iodine a gatekeeper of the
integrity of the mammary gland? J Mammary
Gland Neoplasia. 2005;10:189-96.
15. Kilbane MT, Ajjan RA, Weetman AP, et al. Tissue iodine content
and serum-mediated 125I uptake blocking activity in breast cancer.
J Clin Endocrinol Metab. 2000;85:1245-50.
16. Ghent WR, Eskin BA, Low DA, Hill LP. Iodine replacement in fibrocystic
disease of the breast. Can J Surg.
17. Venturi S. Is there a role for iodine in breast diseases? The
18. Kupper FC, Schweigert N, Gall E, et al. Iodine uptake in Laminariales
involves extracellular, haloperoxidase-mediated oxidation of iodine.
19. Venturi S, Venturi M. Iodide, thyroid and stomach carcinogenesis:
Evolutionary story of a primitive antioxidant? Eur
J Endocrinology. 1999;140:371-2.
20. Winkler R, Griebenow S, Wonisch W. Effect of iodide on total
antioxidant status of human serum. Cell
Biochem Funct. 2000;18:143-6.
21. Zhang L, Sharma S, Zhu XL, Kogai T, Hershman JM, Brent GA, Dubinett
SM, Huang M. Nonradioactive iodide effectively induces apoptosis
in genetically modified lung cancer cells. Cancer
22. Teas J, Harbison M, Gelman R. Dietary seaweed (Laminaria) and
mammary carcinogenesis in rats. Cancer
23. Funahashi H, Imai T, Tanaka Y, et al. Suppressive effect of
iodine on DMBA-induced breast tumor growth in the rat. J
Surg Oncol. 1996;61:209-13.
24. Marani L, Venturi S. Iodine and delayed immunity. Minerva
25. Schuppert F, Taniguchi S, Schroder S, et al. In vivo and in
vitro evidence for iodide regulation of major histocompatibility
complex class I and class II expression in graves' disease. J
Clin Endocrinol Metab. 1996;81:3622-8.
26. Ma F, Zhao W, Kudo M, Aoki K, Misumi J. Inhibition of vacuolation
toxin activity of heliobacter pylori by iodine, nitrite and potentiation
by sodium chloride, sterigmatocystin and fluoride. Toxicol
In Vitro. 2002;16:531-7.
27. Katamine S, Hoshino N, Totsuka K, Suzuki M. Effects of the long-term
(17-19 months) feeding of high-iodine eggs on lipid metabolism and
thyroid function in rats. J Nutr Sci Vitaminol.
28. Brownstein D. Clinical Experience with Inorganic, Non-radioactive
Iodine/Iodide. The Oridinal Internist.
29. Yoon SJ, Choi SR, Kim DM, et al. The effect of iodine restriction
on thyroid function in patients with hypothyroidism due to Hashimoto's
Thyroiditis. Yonsei Med J. 2003;44:227-35.
30. Markou KB, Paraskevopoulou P, Karaiskos KS, et al. Hyperthyrotropinemia
during iodide administration in normal children and children born
with neonatal transient hypothyroidism. J
Clin Endocrinol Metab. 2003;88:617-21.
31. Abraham GE, Flechas JD, Hakala JC. Optimum levels of iodine
for greatest mental and physical health. The
Original Internist. 2002;9:5-20.
Copyright © ProThera, Inc.
All rights reserved. No part of this publication may be reproduced,
stored, or transmiitted in any form by any means, including electronic,
mechanical, photocopying, or otherwise, without prior written permission
of the copyright owner.