Iodine to the Rescue (PowerPoint)

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					Iodine to the

  Jay H Mead MD FASCP
• Discovered by Frenchman;
  Bernard Courtois in 1804
• The name originates from
  the greek word ―iodes‖
  which means violet.
  Iodine deficiency is
• 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
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
 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,
  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
    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
                   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 12.5-
  37.5mg 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:

• 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
   Change in Dietary Intake:

• In 1940 the typical American
  diet contained 500-800
  mcg/day of iodine. By 1995
  intake was reduced to 135
FOOD             SERVING          Iodine (mcg)
Salt (iodized)   1 gram           77
Cod              3 ounces         99
Shrimp           3 ounces         35
Fish sticks      2 fish sticks    35
Tuna, in oil     3 ounces         17
Milk (cow’s)     1 cup (8 oz)     56
Egg, boiled      1 large          12
Navy beans       ½ cup            32
Potato c peel    1 medium         60
Turkey breast    3 ounces         34
Seaweed          ¼ ounce, dried   >4,500
     Iodine Physiology
• Essential Trace Element: The only
  one required for hormone synthesis.
  – Iodine containing hormones are essential
     • 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
    •   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
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
• Fibrocystic breasts
• Polycystic Ovarian Syndrome
• Hypothyroid
• Hyperthyroid
• Cognitive dysfunction (Brain fog)
• Diabetes
• Arrhythmias (supra-ventricular, e.g. atrial
• 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;

      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
 ♦ Partial reversal with iodine deficiency correction
Breast Cancer and FCD evidence
• Effects of Iodide-Deficiency on Rat Mammary
  –   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
    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
Breast Cancer and FCD evidence
Rising Levels of estrogen Receptor in Breast Cancer
  Over 2 Decades
   –   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.
  –   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
• Thyroid function in patients with breast
  –   Rasmusson B, et al. Euro J Cancer Lin Oncol. May 1987; 23(5):553-6

  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
• Favorable predictive value of thyroid autoimmunity
  in high aggressive breast cancer
   –   Fore E, et al. J Endocrinol Invest. 2007; 30):734-738

   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
• 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

  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
• 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

• 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.”

 CIA INFANT MORTALITY REPORT                                                          12 February, 2008

        (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!
• 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.”
• 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.”
• UNICEF: “Iodine deficiency disorders (IDD)”
  Nov 2007

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

―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 )
•   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
•   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
                               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
Martino E, et al. The Effects of Amiodarone on the Thyroid. Endorine Reviews, 2001;22(2):240-54
• Most often prescribed antiarrhythmic: 24.% of all
  antiarrhythmic scripts 1998
• 33-74% of prescriptions in Europe, North and South
• 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
                        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,
     Allergic Reactions
                              Executive Summary
• Anaphylactoid reactions to RCM
  (Radiocontrast Material) should not be
  considered evidence of KI allergy.
• Allergic contact dermatitis from iodine-
  containing 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
     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
        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
 Peacock LB and Davison HM. Ann Allergy. 1957 Mar-Apr;15(2):158-164

No Anaphylactic Reactions
Iodine allergies to routine dosages are
            essentially a Myth!
 “Approximately 600,000 elderly
   individuals have iatrogenic
  hyperthyroidism from thyroid
hormone overdose, putting them at
   risk for atrial fibrillation and
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 precise-
  but 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,
• Liquid (Lugol’s solution, SSKI)
  –Tastes bad, can upset your
    stomach and will stain
• 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%
• Also known as IKI (Iodine Potassium Iodide),
  Strong solution and Aqueous Iodine Solution
  Therapeutic Protocol after testing
         for iodine deficiency
     (spilling Bromine, chlorine and Hg)
                 Feeling funky, e.g.
                  Loss of appetite
                  Sleep Difficulty
*Reduce dose for two weeks and retry.
    Summary of possible conditions
responsive to orthoiodosupplementation

• Hypertension
• Cardiovascular Disease
• Glaucoma
• Liver Dysfunction
               Laboratory Response to
• 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
Flechas JD. Orthoiodosupplementation in a Primary Care Practice. The Original Internist, 2005; 12(2):89-96
• Even patients with no thyroid
  gland benefited from iodine

• Depletes the body’s stores of iodine
   – Shown by fluorescent scan
• Increased risk of cancer with long-term
• Recommend all thyroid medications be
  used in conjunction with iodine!