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Iodine Research
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Orthosupplementation
IODINE TOXICITY
PENNINGTON
A review of iodine toxicity reports.
Pennington JA.
J Am Diet Assoc. 1990 Nov;90(11):1571-81.
"This article summarizes case reports, population studies, and experimental studies from the literature concerning adverse effects
of exposure to iodine from the mid-1880s to 1988. Exposure to excessive iodine through foods, dietary supplements, topical
medications, and/or iodinated contrast media has resulted in thyroiditis, goiter, hypothyroidism, hyperthyroidism, sensitivity
reactions, or acute responses for some individuals. Reports of maternal iodine exposure during pregnancy or lactation affecting
newborn or nursing infants are cited. Susceptibility to excess iodine is discussed as well as the relationship between dose and
response. It is concluded that some individuals can tolerate very high levels of iodine with no apparent side effects and that iodine
intakes less than or equal to 1.000 mg/day are probably safe for the majority of the population, but may cause adverse effects in
some individuals. Determination of maximum tolerable levels of iodine intake will require human experimental studies at levels
between 0.150 and 1.000 mg/day for normal subjects, subjects with autonomous thyroid tissue, and iodine-sensitive subjects."
DIETARY REFERENCE INTAKES
Iodine. Chapter 8 in Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron,
Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
Food and Nutrition Board, Institute of Medicine
The National Academies Press. 2000
"Summary. Iodine is an essential component of the thyroid hormones that are involved in the regulation of various enzymes and
metabolic processes. Thyroid iodine accumulation and turnover were used to set the Estimated Average Requirement. The
Recommended Dietary Allowance (RDA) for adult men and women is 150 μg/day. The median intake of iodine from food in the
United States is approximately 240 to 300 μg/day for men and 190 to 210 μg/day for women. The Tolerable Upper Intake Level
(UL) for adults is 1,100 μg/day (1.1 mg/day), a value based on serum thyrotropin concentration in response to varying levels of
ingested iodine." (p. 258)
"Function. Iodine is an essential component of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3), comprising 65 and
59 percent of their respective weights. Thyroid hormones, and therefore iodine, are essential for mammalian life. They regulate
many key biochemical reactions, especially protein synthesis and enzymatic activity. Major target organs are the developing brain,
muscle, heart, pituitary, and kidney.
Observations in several areas have suggested possible additional roles for iodine. Iodine may have beneficial roles in mammary
dysplasia and fibrocystic breast disease (Eskin, 1977; Ghent et al., 1993). In vitro studies show that iodine can work with
myeloperoxidase from white cells to inactivate bacteria (Klebanoff, 1967). Other brief reports have suggested that inadequate
iodine nutrition impairs immune response and may be associated with an increased incidence of gastric cancer (Venturi et al.,
1993). While these other possibilities deserve further investigation, the overwhelming importance of nutritional iodine is as a
component of the thyroid hormones." (pp. 258-9)
"Bioavailability. Under normal conditions, the absorption of dietary iodine is greater than 90 percent (Albert and Keating, 1949;
Nath et al., 1992; Vought and London, 1967). The fate of organic compounds of iodine in the intestine is different from that of
iodine. When thyroxine is orally administered, the bioavailability is approximately 75 percent (Hays, 1991)." (p. 267)
"Tolerable Upper Intake Levels. The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to
pose no risk of adverse health effects in almost all individuals. Although members of the general population should be advised not
to routinely exceed the UL, intake above the UL may be appropriate for investigation within well-controlled clinical trials. Clinical
trials of doses above the UL should not be discouraged, as long as subjects participating in these trials have signed informed
consent documents regarding possible toxicity and as long as these trials employ appropriate safety monitoring of trial subjects. In
addition, the UL is not meant to apply to individuals who are receiving iodine under medical supervision." (p. 278)
"Adverse Events. Summary. Challenged thyroid function shown by TSH concentrations elevated over baseline is the first effect
observed in iodine excess. While an elevated TSH concentration may not be a clinically significant adverse effect, it is an
indicator for increased risk of developing clinical hypothyroidism. Therefore, an elevated TSH concentration above baseline was
selected as the critical adverse effect on which to base a UL." (p. 280)
"Uncertainty Assessment. There is little uncertainty regarding the range of iodine intakes that are likely to induce elevated TSH
concentration over baseline. A LOAEL of 1,700 μg/day and a NOAEL of 1,000 to 1,200 μg/day are estimated for adult humans.
This results in an uncertainty factor (UF) of 1.5 to derive a NOAEL from a LOAEL. A higher uncertainty factor was not considered
because of the mild, reversible nature of elevated TSH over baseline." (p. 281)
"Special Considerations. Autoimmune thyroid disease (AITD) is common in the U.S. population and particularly in older adult
women. Individuals with AITD who are treated for iodine deficiency or nodular goiter (Carnell and Valente, 1998; Foley, 1992;
Massoudi et al., 1995) may have increased sensitivity to adverse effects of iodine intake. Some young adults with simple goiter and
iodine deficiency who were supplemented with 200 μg/day of iodine developed either mild transient hyperthyroidism or
hypothyroidism, positive antibodies, and reversible histological changes of lymphocytic thyroiditis (Kahaly et al., 1997). The
sensitivities of these distinct subgroups do not fall within the range of sensitivities expected for the healthy population.
Studies have correlated an increase in the incidence of AITD with a population’s higher intake of iodine (Foley, 1992). Additional
data provide some correlation between the incidence of circulating antithyroid antibodies (a marker for AITD) and dietary iodine
intake (Schuppert et al., 2000). At this time there is not sufficient data to determine a UL for this subpopulation. Therefore, a UL
could not be set for individuals with AITD." (p. 283)
ASTDR
Toxicological Profile for Iodine
Agency for Toxic Substances and Disease Registry (ATSDR)
"The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the
hazardous substance described here. Each peer-reviewed profile identifies and reviews the key literature that describes a hazardous
substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies.
The complete list of topics covered (chapter titles) is shown at the left and in more detail further down this page. "
IODINE TOXICITY
PENNINGTON
A review of iodine toxicity reports.
Pennington JA.
J Am Diet Assoc. 1990 Nov;90(11):1571-81.
"This article summarizes case reports, population studies, and experimental studies from the literature concerning adverse effects
of exposure to iodine from the mid-1880s to 1988. Exposure to excessive iodine through foods, dietary supplements, topical
medications, and/or iodinated contrast media has resulted in thyroiditis, goiter, hypothyroidism, hyperthyroidism, sensitivity
reactions, or acute responses for some individuals. Reports of maternal iodine exposure during pregnancy or lactation affecting
newborn or nursing infants are cited. Susceptibility to excess iodine is discussed as well as the relationship between dose and
response. It is concluded that some individuals can tolerate very high levels of iodine with no apparent side effects and that iodine
intakes less than or equal to 1.000 mg/day are probably safe for the majority of the population, but may cause adverse effects in
some individuals. Determination of maximum tolerable levels of iodine intake will require human experimental studies at levels
between 0.150 and 1.000 mg/day for normal subjects, subjects with autonomous thyroid tissue, and iodine-sensitive subjects."
DIETARY REFERENCE INTAKES
Iodine. Chapter 8 in Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron,
Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
Food and Nutrition Board, Institute of Medicine
The National Academies Press. 2000
"Summary. Iodine is an essential component of the thyroid hormones that are involved in the regulation of various enzymes and
metabolic processes. Thyroid iodine accumulation and turnover were used to set the Estimated Average Requirement. The
Recommended Dietary Allowance (RDA) for adult men and women is 150 μg/day. The median intake of iodine from food in the
United States is approximately 240 to 300 μg/day for men and 190 to 210 μg/day for women. The Tolerable Upper Intake Level
(UL) for adults is 1,100 μg/day (1.1 mg/day), a value based on serum thyrotropin concentration in response to varying levels of
ingested iodine." (p. 258)
"Function. Iodine is an essential component of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3), comprising 65 and
59 percent of their respective weights. Thyroid hormones, and therefore iodine, are essential for mammalian life. They regulate
many key biochemical reactions, especially protein synthesis and enzymatic activity. Major target organs are the developing brain,
muscle, heart, pituitary, and kidney.
Observations in several areas have suggested possible additional roles for iodine. Iodine may have beneficial roles in mammary
dysplasia and fibrocystic breast disease (Eskin, 1977; Ghent et al., 1993). In vitro studies show that iodine can work with
myeloperoxidase from white cells to inactivate bacteria (Klebanoff, 1967). Other brief reports have suggested that inadequate
iodine nutrition impairs immune response and may be associated with an increased incidence of gastric cancer (Venturi et al.,
1993). While these other possibilities deserve further investigation, the overwhelming importance of nutritional iodine is as a
component of the thyroid hormones." (pp. 258-9)
"Bioavailability. Under normal conditions, the absorption of dietary iodine is greater than 90 percent (Albert and Keating, 1949;
Nath et al., 1992; Vought and London, 1967). The fate of organic compounds of iodine in the intestine is different from that of
iodine. When thyroxine is orally administered, the bioavailability is approximately 75 percent (Hays, 1991)." (p. 267)
"Tolerable Upper Intake Levels. The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to
pose no risk of adverse health effects in almost all individuals. Although members of the general population should be advised not
to routinely exceed the UL, intake above the UL may be appropriate for investigation within well-controlled clinical trials. Clinical
trials of doses above the UL should not be discouraged, as long as subjects participating in these trials have signed informed
consent documents regarding possible toxicity and as long as these trials employ appropriate safety monitoring of trial subjects. In
addition, the UL is not meant to apply to individuals who are receiving iodine under medical supervision." (p. 278)
"Adverse Events. Summary. Challenged thyroid function shown by TSH concentrations elevated over baseline is the first effect
observed in iodine excess. While an elevated TSH concentration may not be a clinically significant adverse effect, it is an
indicator for increased risk of developing clinical hypothyroidism. Therefore, an elevated TSH concentration above baseline was
selected as the critical adverse effect on which to base a UL." (p. 280)
"Uncertainty Assessment. There is little uncertainty regarding the range of iodine intakes that are likely to induce elevated TSH
concentration over baseline. A LOAEL of 1,700 μg/day and a NOAEL of 1,000 to 1,200 μg/day are estimated for adult humans.
This results in an uncertainty factor (UF) of 1.5 to derive a NOAEL from a LOAEL. A higher uncertainty factor was not considered
because of the mild, reversible nature of elevated TSH over baseline." (p. 281)
"Special Considerations. Autoimmune thyroid disease (AITD) is common in the U.S. population and particularly in older adult
women. Individuals with AITD who are treated for iodine deficiency or nodular goiter (Carnell and Valente, 1998; Foley, 1992;
Massoudi et al., 1995) may have increased sensitivity to adverse effects of iodine intake. Some young adults with simple goiter and
iodine deficiency who were supplemented with 200 μg/day of iodine developed either mild transient hyperthyroidism or
hypothyroidism, positive antibodies, and reversible histological changes of lymphocytic thyroiditis (Kahaly et al., 1997). The
sensitivities of these distinct subgroups do not fall within the range of sensitivities expected for the healthy population.
Studies have correlated an increase in the incidence of AITD with a population’s higher intake of iodine (Foley, 1992). Additional
data provide some correlation between the incidence of circulating antithyroid antibodies (a marker for AITD) and dietary iodine
intake (Schuppert et al., 2000). At this time there is not sufficient data to determine a UL for this subpopulation. Therefore, a UL
could not be set for individuals with AITD." (p. 283)
ASTDR
Toxicological Profile for Iodine
Agency for Toxic Substances and Disease Registry (ATSDR)
"The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the
hazardous substance described here. Each peer-reviewed profile identifies and reviews the key literature that describes a hazardous
substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies.
The complete list of topics covered (chapter titles) is shown at the left and in more detail further down this page. "