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 12.5- 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: 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 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 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 • 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 • 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 – 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 – 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 Autoantibodies • Thyroid function in patients with breast cancer. – 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 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! 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 • 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 • 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 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 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 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, 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!