Transcript Iodine to the Rescue

Iodine to the
Rescue
Jay H Mead MD FASCP
Iodine
• Discovered by Frenchman;
Bernard Courtois in 1804
• The name originates from
the greek word “iodes”
which means violet.
Iodine deficiency is
Pandemic
• 70%…of the world’s population is
estimated to be iodine deficient
Nutrition Research, vol 24, Issue 12
Pp1005-1010, S. Elahi, Z. Syed, S Nagra
“Iodine
Why You Need It, Why You Can’t Live Without
It.” David Brownstein MD, 2nd edition, 2006
• Recent Study…Of 3000 patients
(USA) tested
• 95% were found to be
deficient.
Iodine’s Widespread Use
• From 1900-1960’s nearly every
physician in the United States used
Iodine (Lugol’s solution) supplements
in their practice for both hypothyroid
and hyperthyroid conditions… all with
excellent results.
There was an era where it was
spoken about as a “cure-all”
because it helped so many things!
However, today it is irrationally
avoided (iodophobia) as a clinical
therapy due to a great deal of
medical misinformation (Abraham GE, The
historical background of the iodine project. The Original
Internist, 12(2):57-66)
RDA in US=150ug
• Average cat weighs 9-11 pounds
• “To meet the daily requirements of
iodine and thyroid hormone levels in
cat blood serum in group II, we suggest
that the iodine requirement proposed
by Kraft which equals to 100-150 µg
iodine/cat/day is quite adequate.”
Kuosad A. Influence of iodine contents in cat food on its consumption, urinary iodine excretion
and concentration of thyroid hormones in cat blood serum. Medycyna Weterynaryjna,
2005;61(8):900-903
RDA in US=150ug
• Mainline Japanese population
consume 13.8mg of iodine/day
• 92 x 150ug = 13,800ug=13.8mg
In 1932…
South Carolina
• Before being known as the Palmetto State, South
Carolina was known as, and had emblazoned on their
license plates, the Iodine State.
• South Carolina has been referred to as "The Iodine
State" because of the large percentages of iodine found
in the vegetation growing in the state.
• In the 1920s SC grown fruits and vegetables were
thought to have had enormously greater quantities of
iodine than produce from other states. Thus, SC became
known as the "Wonderful Iodine State." The call letters of
WIS radio and now WIS-TV stem from "Wonderful Iodine
State."
Iodine was considered so
ESSENTIAL …
♦That it was added to Bread as a
supplement (until twenty years ago)
♦Now the toxin: Bromine is added instead
– Which interferes with iodine uptakes and
ultimately depletes the body of iodine
Origin of IODOPHOBIA
• 1948- Scientific experiment on rats was
published (Drs Wolff and Chaikoff) which
erroneously concluded that serum iodine levels
of 0.2mg/l inhibited iodine uptake by the thyroid
gland. The correct interpretation should have
been that this dose make the rats euthyroid.
Thyroid hormones were not measured in the
study. Bad science!!
• This was later mistakenly translated to humans
and included in all medical textbooks, including
endocrinology and nutrition textbooks
(Abraham GE, The historical background of the iodine project. The
Original Internist, 12(2):57-66)
Guy E. Abraham MD
• “medical iodophobia has reached pandemic
proportions. It is highly contagious and has
wreaked havoc on the practice of medicine
and on the US population. More misery
and death in the US may have resulted
from (Medicine’s unwarranted fear of iodine)
than from both World Wars combined.”
Former professor of OB/GYN and Endocrinology
UCLA School of Medicine
Change in Dietary Intake
• Between 1917 and 1924 salt was
successfully iodized for the prevention of
goiter and cretinism. Note: a minimum of
0.05 mg/day (50mcg/day) is needed for
prevention. There were marketing efforts
to discourage the use of Lugol’s solution
and forms of iodine supplementation in
favor of the iodized salt.
Change in Dietary Intake
• Prior to the iodization program, the public
relied heavily on apothecaries for iodine
needs. The recommended daily dose of
Lugol’s solution was 0.1-0.3ml or 12.537.5mg of elemental iodine.
• It is estimated that salt provides 0.75mg of
iodide of which 10% is bioavailable. This
is less than 1% of the daily recommended
Lugol’s solution.
Change in Dietary Intake
• Another major factor was the introduction of
thyroid hormones in the 1930’s
• “Diagnosis and Treatment of Diseases of the
Thyroid” Amy Rowland editor, 1932, summarized
the trend: “The treatment of hypothyridism of any
type consists merely in the substitution of thyroid
extract for the deficient secretion. Any form of
prepared gland or the active principle, thyroxin,
may be used.”
Change in Dietary Intake:
Coincidence?
• In the 1960s bread dough contained
potassium iodate as a dough
conditioner, which added 150mcg of
iodide per slice. Beginning in the
1970s this was replaced by Bromine
(iodine antagonist and goitrogenic
substance)
Change in Dietary Intake:
Coincidence?
• In 1940 the typical American
diet contained 500-800
mcg/day of iodine. By 1995
intake was reduced to 135
mcg/day.
FOOD
Salt (iodized)
Cod
Shrimp
Fish sticks
Tuna, in oil
Milk (cow’s)
Egg, boiled
Navy beans
Potato c peel
Turkey breast
Seaweed
SERVING
1 gram
3 ounces
3 ounces
2 fish sticks
3 ounces
1 cup (8 oz)
1 large
½ cup
1 medium
3 ounces
¼ ounce, dried
Iodine (mcg)
77
99
35
35
17
56
12
32
60
34
>4,500
Iodine Physiology
• Essential Trace Element: The only
one required for hormone synthesis.
– Iodine containing hormones are essential
for:
• Embryogenesis
• Differentiation
• Cognitive development
• Growth
• Metabolism
• Core temperature maintenance
Iodine Physiology
• Is detected in every organ and tissue in
the body
– Especially high levels are found in
the
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Thyroid
Liver
Lung
Heart
Adrenals
– And highest concentrations in fat and muscle tissue
– Sweat glands
– Stomach tissue
Functions of Iodine
Prevent Cancers (especially breast, ovaries,
uterus, prostate and thyroid gland):
Japanese women have one of the
lowest breast cancer rates in the
world, ingest an average of 13.8
mg of iodine daily from seaweed
without any adverse
consequences.
Toshihiko Kawamura and Tomotaka Sobue. Comparison of Breast Cancer Mortality in Five Countries:
France, Italy, Japan, the UK and the USA from the WHO Mortality Database (1960-2000).
Japanese Jounrnal of Clinical Oncology. 2005; 35(12):758-759.
Summary of established conditions
responsive to orthoiodosupplementation
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Fibrocystic breasts
Polycystic Ovarian Syndrome
Hypothyroid
Hyperthyroid
Cognitive dysfunction (Brain fog)
Diabetes
Arrhythmias (supra-ventricular, e.g. atrial
fib.)
• Breast Cancer prevention
Flechas JD. Orthoiodosupplementation in a Primary Care Practice. The Original Internist, 2005; 12(2):89-96
Breast Cancer
• Breast Cancer and Thyroid Disease
–
Finley JW and Bogardus GM. Q Rev Surg Obstet Gynecol. 1960 Jul-Sep;17:139-47;
30(2):209-20
(N=79)
Seventy nine women with breast cancer were assessed for
thyroid disease. All were euthyroid: 37(47%) Goiters, 5(6%)
History of thyroid disease.
“It seems reasonable to suggest further studies of
population groups with high and low breast
cancer incidence and studies centered around the
effects of iodine lack, TSH levels, and propionic
acid analogues on breast cancer and other
endocrine and growth phenomena.”
Breast Cancer and FCD evidence
• Iodine and Mammary Cancer
– Eskin BA. Adv Exp Med Biol. 1977; 91:293-304
Review article of rat studies:
♦ Iodine deficiency leads to dysplastic changes
♦ Iodine deficiency exacerbates carcinogenesis
related to DMBA exposure
♦ Iodine deficiency directly correlates with
pathology v hypothyroidism by perchlorate
challenge
♦ Partial reversal with iodine deficiency correction
Breast Cancer and FCD evidence
• Effects of Iodide-Deficiency on Rat Mammary
Gland
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Strum JM. Virchows Archiv. B. 1979; 30(2):209-20
3 Study Groups (N=64)
Iodide deprived
Iodide deprived plus SQ daily estradiol
Normal diet plus SQ daily estradiol
Controls injected with NS
Findings:
Iodide deficiency leads to atrophy and necrosis,
dysphasia and atypia. Adding E2 causes cell
proliferation with alveoli formation (hyperplasia).
Continue stimulation leads to cyst formation.
Breast Cancer and FCD evidence
• Effects of Iodide-Deficiency on
Rat Mammary Gland
– Strum JM. Virchows Archiv. B. 1979; 30(2):209-20
“The cellular alterations reported here
during iodide deficiency and after estradiol
stimulation, demonstrate the importance
of iodide in maintaining the normal
structure and function of the rat mammary
gland.”
Breast Cancer and FCD evidence
Rising Levels of estrogen Receptor in Breast Cancer
Over 2 Decades
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Pujol P, et al. CANCER Sept 1994; 74(5):1601-6
Receptor Levels 1973: 14 fmol/mg
Receptor Levels 1993: 58 fmol/mg
Conclusion: “The measured level of ER in primary
breast cancers has increased during the last 2
decades. It is unlikely that technical
improvements or changes in tumor size, age, or
nodal status fully explain this increase. The rising
level of ER may reflect a change in breast cancer
biology and hormonal events that influence breast
cancer genesis and growth.”
Breast Cancer and FCD evidence
• A Direct Relationship between Thyroid
Enlargement and Breast Cancer.
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Smyth PPA, et al. J Clin Endocrin and Med Dec 2007; 81(3):937-41
Control group: 12.5ml mean volume
Breast Cancer group: 21.1ml mean volume
Benign Breast Dz group: 14.5ml mean volume
Conclusion: “Although there is no evidence that
thyroid enlargement represents a risk factor for
breast cancer, the results emphasize the
importance of raising the consciousness of the
coincidence of both disorders.”
Breast Cancer and Thyroid
Autoantibodies
• Thyroid function in patients with breast
cancer.
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Rasmusson B, et al. Euro J Cancer Lin Oncol. May 1987; 23(5):553-6
N=58
Age matched control group: 3 out of 58 (5%)
Breast Cancer group (euthyroid): 29 out of 58 (50%) showed
TSAb, TgAb or MAb is various combinations (P<0.05)
“In conclusion, we found an increased frequency of
thyroid autoantibodies in euthyroid patients with
breast cancer compared with healthy controls
suggesting a possible relation between this
disease and autoimmune thyroid disease.”
Breast Cancer and Thyroid
Autoantibodies
• Favorable predictive value of thyroid autoimmunity
in high aggressive breast cancer
–
Fore E, et al. J Endocrinol Invest. 2007; 30):734-738
N=47
Forty seven women with highly aggressive BC where followed
for five years. TAb (TPO) and ER status were evaluated
regarding prognosis.
“Patients with ER+ and TAb+ have a better
prognosis and the absence of a significant
relationship between these two parameters
suggests an independent prognostic role in high
malignancy degree BC women.”
Breast Cancer and iodine symporter
(NIS)
• Functional expression of sodium iodide symporter
(NIS) in human breast cancer tissue
–
Upadhyay G, et al. Breast Cancer Research and Treatment.. 2003; 77:157-65
N=12
Twelve women with infiltrating ductal carcinoma between age
33-58 were evaluated for NIS activity.
“The unequivocal demonstration of NIS expression,
its functionality and retention of iodine by
organification further provides supportive
evidence for use of radioiodine as an additional
treatment modality of human breast carcinoma.”
Is this crazy or what!!
Breast Cancer and Iodine Therapy
• Is Iodine a Gatekeeper of the Integrity of the Mammary Gland?
Aceves C, et al. J Mammary Gland Biolology and Neoplasia. Apr 2005; 10(2):189-96
AN EXCELLENT REVIEW ARTICLE
“Iodine, in addition to its incorporation into thyroid
hormones, is bound into antiproliferative
iodolipids in the thyroid called iodolactones,
which may also play a role in the proliferative
control of mammary gland. We propose that an I2
supplement should be considered as an adjuvant
in breast cancer therapy.”
Iodine is an antioxidant!!
Why Lugols (formulation) is
effective.
• Dr Abrahams notes that the research
shows that the thyroid gland prefers Iodide
• The other organs (breasts etc.) prefer
elemental Iodine.
*both forms are present in equal parts in
Lugols solution
IODINE AND BRAIN DEVELOPMENT
IODINE AND BRAIN DEVELOPMENT
• Role of thyroid hormone during early brain
development. Escobar G, et al. Euro J Endocrinol 2004;151:U25-U37
A Excellent Review Article
“As mild-moderate iodine deficiency is still the most
widespread cause of maternal hypothyroxinemia in
Western societies, the birth of many children with
learning disabilities may already be preventable by
advising women to take iodine supplements as soon
as pregnancy starts, or earlier if possible.”
IODINE AND BRAIN DEVELOPMENT
CIA INFANT MORTALITY REPORT
(deaths/1,000 live births)
• USA: 6.37 (180/221)
• JAPAN: 2.80 (219/221)
• SWEDEN: 2.46 (220/221)
• SINGAPORE: 2.30 (221/221)
• ANGOLA: 184.44 (1/221), YIKES!
12 February, 2008
https://www.cia.gov/library/publications/the-world-factbook/rankorder/2091rank.html
IODINE AND BRAIN DEVELOPMENT
• Original Communication: Mild iodine deficiency is
associated with elevated hearing thresholds in
children in Benin. Van den Briel T, et al. Euro J Clin Nutr. 2001;55:763-68
Random Control Study (N=197). Study group was given 540mg as Iodized
oil, then introduced to iodized salt.
“The findings in this study provide further justification
of the large salt iodization programmes being
untaken worldwide. Although the causes of hearing
impairment in relation to iodine deficiency are not
fully understood, our results suggest that access to
iodine affects hearing as well as mental
performance. Public health officials should continue
to promote adequate iodine intake through salt
iodization programs and other means.”
IODINE AND BRAIN DEVELOPMENT
• Improved iodine status is associated with
improved mental performance of
schoolchildren in Benin. Van den Briel T, et al. Euro J Clin
Nutr. 2000;72:1179-85
Prospective study 7-11 y/o comparing urine iodine improved
group (N=128) to iodine unimproved group (N=68) after a single
PO dose of 540mg iodized oil and introducing iodized salt.
“Conclusions: An improvement in iodine
status, rather than iodine status itself
determined mental performance in this
population which was initially iodine
deficient. These finding suggest a “catch-up”
effect in terms of mental performance.”
IODINE AND BRAIN DEVELOPMENT
• UNICEF: “Iodine deficiency disorders (IDD)”
Nov 2007 http://www.childinfo.org/areas/idd/
There has been dramatic progress over the
past decade in the global campaign to
eliminate iodine deficiency, the world's
leading cause of preventable mental
retardation and impaired psychomotor
development in young children. In its most
extreme form, iodine deficiency causes
cretinism. It also significantly raises the risks
of stillbirth and miscarriage for pregnant
women.
IODINE AND BRAIN DEVELOPMENT
“All degrees of iodine deficiency (mild: iodine
intake of 50-99 µg/day, moderate: 20-49 µg/day,
and severe: <20 µg/day) affect thyroid function
of the mother and the neonate as well as the
mental development of the child.”
“Iodine deficiency results in a global loss of 10-15
IQ points at a population level and constitutes
the world's greatest single cause of preventable
brain damage and mental retardation.”
Postgrad Med J 2001;77:217-220 ( April )
AMIODARONE
Toxicity
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Corneal microdeposits:100%
Anorexia/nausea:80%
Skin: Photosensitivty/discoloration: 55-75%
Neurological sxs: 48%
Elevated LFTs: 25%
Thyroid dysfunction: 14-18%
Lung dysfunction: 10-13% (9% fatality rate)
Martino E, et al. The effects of amiodarone on the thyroid. Endocr Rev. 2001 Apro;22(2):240-54
AMIODARONE
Toxicity
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Benzofuranic derivative structurally resembling T4
37% by weight iodine
10% deiodinated daily
Maintenance dosage from 200-600mg/day
Approximately 7-21mg/day
The mainland Japanese ingest on average 13.8mg/day
Martino E, et al. The effects of amiodarone on the thyroid. Endocr Rev. 2001 Apro;22(2):240-54
AMIODARONE
Liver Toxicity
• Inhibits the 5’-deiodinase, which converts T4
to T3.
• Inhibits thyroid hormone entry into
peripheral tissues.
• Leads to increased T4 and rT3
• TSH levels are usually normal or may
increase transiently upon initiation of the
drug
Martino E, et al. The Effects of Amiodarone on the Thyroid. Endorine Reviews, 2001;22(2):240-54
AMIODARONE
Toxicity
• Most often prescribed antiarrhythmic: 24.% of all
antiarrhythmic scripts 1998
• 33-74% of prescriptions in Europe, North and South
America
• 0.3% of prescriptions in Japan and Philippines
Note the symmetry: The Japanese consume 100 times
more iodine in their diet and are prescribed
amiodarone 100 times less often
Connolly SJ. Evidence-Based Analysis of Amiodarone Efficacy and Safety. Circulaton 1999;100:2025-2034
AMIODARONE
Why it works at all.
• Amiodarone is a sustained release form
of inorganic non-radioactive iodine.
• Inorganic non-radioactive iodine is the
treatment of choice in those clinical
conditions treated with amiodarone.
Abraham GE. The History of Iodine in Medicine Part 1: From Discovery to Essentiality. The Original Interniest,
2006;13:29-36.
Allergic Reactions
Executive Summary
• Anaphylactoid reactions to RCM
(Radiocontrast Material) should not be
considered evidence of KI allergy.
• Allergic contact dermatitis from iodinecontaining antibacterial preparations should
not be considered evidence of IgE antibody
mediated KI allergy or sensitivity.
Academy Position Statement: The Risk of Severe Allergic Reactions from the Use of Potassium Iodide for Radiation
Emergencies. American Academy of Allergy Asthma and Immunonology. February 24, 2004.
Allergic Reactions
Executive Summary (cont’d)
• IgE antibody mediated allergy to
seafood should not be considered
evidence of KI allergy or sensitivity.
• Physicians should ensure that persons
are not allergic to inactive
ingredients/components of the KI
formulation prescribed.
Academy Position Statement: The Risk of Severe Allergic Reactions from the Use of Potassium Iodide
for Radiation Emergencies. American Academy of Allergy Asthma and Immunonology. February
24, 2004.
Allergic Reactions
OBSERVATIONS ON IODIDE SENSITIVITY
Peacock LB and Davison HM. Ann Allergy. 1957 Mar-Apr;15(2):158-164
• Retrospective study of 502 asthmatics.
• 81 reactions to KI reported (16.1%); 68
discontinued therapy (13.5%); 13
continued at a lower dose (2.6%).
• Dose ranges (gms): Single 0.53 to 1.87;
Daily 1.6 to 5.6. Note: KI
supplementation is typically 0.012.5 to
0.050 gm/day
Allergic Reactions
OBSERVATIONS ON IODIDE SENSITIVITY
Peacock LB and Davison HM. Ann Allergy. 1957 Mar-Apr;15(2):158-164
• Rash (papular) 42 (51%), Nausea 10 (12%),
Metallic taste 7 (8.6%), Salivary gland edema
7 (8.6%), Goiter 5 (6%), Nasal sxs 5 (6%),
Increased asthma 3 (4%)
• Hoarseness, diarrhea, throat edema and sore
throat: 2 ea (2%)
• Insomnia, thinning hair, bladder/kidney sxs,
headache, chills fever, vomiting,
nervousness, aching jaw, herpes and
burning in mouth and nose: 1 ea (1%) .
Allergic Reactions
OBSERVATIONS ON IODIDE
SENSITIVITY
Peacock LB and Davison HM. Ann Allergy. 1957 Mar-Apr;15(2):158-164
No Anaphylactic Reactions
Reported!
Iodine allergies to routine dosages are
essentially a Myth!
THYROID REPLACEMENT
“Approximately 600,000 elderly
individuals have iatrogenic
hyperthyroidism from thyroid
hormone overdose, putting them at
risk for atrial fibrillation and
osteoporosis.”
Cooper DS, Ridqway EC. Thought on prevention of thyroid disease in the United States.
Thyroid 2002 Oct;12(10):925-9
Iodine Testing
• Tincture of Iodine/skin test; Not precisebut lay-person can perform at home.
– Paint tincture on a 2 inch spot on arm-if it disappears in less than
eight hours…You are severely deficient in iodine. If it disappears
in 24 hours you also need iodine…if it stays on your arm and
begins to slowly fade in color after a full 24 hours, you have
reached iodine sufficiency.
• Urine Iodine Loading
– Collect baseline “spot urine. Then take 50 mg of iodine and
collect all urine in next 24 hour period. If you secrete out 90% or
more iodine you have iodine sufficiency. If the percentage is less
than 90% you are iodine deficient
Forms of Iodine—inorganic,
organic
• Liquid (Lugol’s solution, SSKI)
–Tastes bad, can upset your
stomach and will stain
clothing
• Coated Tablets
Therapeutic Protocol after testing
for iodine deficiency
50 mg/day PO for ninety days
12.5 mg/day PO maintenance
Lugols solution
• 10% iodine(I2), 10% potassium iodide (KI) in
80% distilled water with a total iodine content
of 130mg/ml
• was OTC Until AUGUST/2007, when the DEA
began regulation of Lugol’s and any other
iodine solutions containing greater than 2.2%
iodine.
• Also known as IKI (Iodine Potassium Iodide),
Strong solution and Aqueous Iodine Solution
BP.
Therapeutic Protocol after testing
for iodine deficiency
CAUTION DETOXIFICATION
(spilling Bromine, chlorine and Hg)
Feeling funky, e.g.
Headaches
Malaise
Loss of appetite
Sleep Difficulty
*Reduce dose for two weeks and retry.
IODINE IS DEPLETED BY:
• FLUORIDE
• CHLORINE
• BROMINE
• THYROID HORMONE
• PESTICIDES
Summary of possible conditions
responsive to orthoiodosupplementation
• Hypertension
• Cardiovascular Disease
• Glaucoma
• Liver Dysfunction
Laboratory Response to
Orthoiodosupplementation
• TSH generally goes down. TSH may go up
and likely represents the bodies attempt to
make more sodium iodine symporters (iodine
channels), aka, NIS
• Free T4 usually goes down
• Free T3 usually goes down
• Majority of patients lose fat and gain muscle
mass
Flechas JD. Orthoiodosupplementation in a Primary Care Practice. The Original Internist, 2005; 12(2):89-96
Thyroidectomy
• Even patients with no thyroid
gland benefited from iodine
therapy:
THYROID HORMONE REPLACEMENT
• Depletes the body’s stores of iodine
– Shown by fluorescent scan
• Increased risk of cancer with long-term
use
• Recommend all thyroid medications be
used in conjunction with iodine!