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1 Functional Diagnostic Medicine Training Program Module 7 * FMDT 561D The Biochemical Effects of Iodine (Review of Nutrient Element Status Testing) Limits of Liability & Disclaimer of Warranty We have designed this book to provide information in regard to the subject matter covered. It is made available with the understanding that the authors are not liable for the misconceptions or misuse of information provided. The purpose of this book is to educate. It is not meant to be a comprehensive source for the topic covered, and is not intended as a substitute for medical diagnosis or treatment, or intended as a substitute for medical counseling. Information contained in this book should not be construed as a claim or representation that any treatment, process or interpretation mentioned constitutes a cure, palliative, or ameliorative. The information covered is intended to supplement the practitioner s knowledge of their patient. It should be considered as adjunctive and support to other diagnostic medical procedures. This material contains elements protected under International and Federal Copyright laws and treaties. Any unauthorized reprint or use of this material is prohibited. Functional Medicine University; /Insider s Guide Module 7: FDMT 561D: The Biochemical Effects of Iodine (Review of Nutrient Element Status Testing) Copyright 2010 Functional Medicine University, All Rights Reserved

2 Contents Functional Medicine University s Introduction 2 Elements of the Body 3 The Effect of Iron Deficiency on Iodine and Thyroid Function 3 Major Roles of Essential Elements in Biological Systems 4 Nutrient & Toxicant Interaction 4 Bioavailability of Elements 5 Choosing the Best Specimen for Element Testing 5 Blood 5 Hair 6 Urine 6 Iodine 7 Iodine toxicity 8 Assessing Iodine Status 8 Iodine Deficiency: Thyroid Function Tests 10 Indirect Iodine Measurements 10 Iodine Excess: Thyroid Function Tests 11 Effects of Iodine Nutritional Status on Thyroid Function Tests 12 Clinical Protocols for Lowering Bromide and Fluoride in the Body 12 The Reactivity Trend of the Halogens (Group 7 of the Periodic Table) 13 Repletion of Iodine 13 Summary 13 References 14 1

3 Mega doses of iodine have been recommended by several health care practitioners in the recent past to treat various conditions. Dr. Alan R. Gaby, who writes the literature review and commentary section of the Townsend Letter has stated the following; the use of mega doses of nutrients is an important component of nutritional medicine. Many nutrients can be administered safely and effectively in large doses. However, certain trace minerals are dangerous and can even be fatal when given in very large amounts; these include selenium, copper, zinc and iodine. 1 There are various combinations of factors that can lead to elemental deficiency in general. To illustrate this, let s take a look at factors that should be considered in a patient who is iron deficient. The following is a list of factors contributing to iron deficiency. (This information will be obtained from a comprehensive patient history, physical exam and diagnostic labs testing.) Processed Foods & Soil Depletion High Cereals (foods that bind iron) Low Beans & Meats (foods that supply iron) Enteropathy Hypochlorhydria Dysbiosis GI Inflammation Hemorrhage Menstruation Hookworm, Trichuris, Ascaris Injury, Trauma Pregnancy Rapid Growth 2

4 The Effect of Iron Deficiency on Iodine and Thyroid Function Iron deficiency has been shown to impair response to iodine supplementation in the iodine deficient population. 2 Iron deficiency itself can affect thyroid function even in the absence of iodine deficiency. Studies in human have shown that moderate-to- severe iron deficiency significantly lowers both T3 and T4 (although T3 to a greater extent) and reduces TSH responsiveness. This is thought to be due to impaired thyroid peroxidase activity. 2 Elements of the Body Macro elements are present in total-body content of tens or hundreds of grams Phosphorus Magnesium Calcium Sodium Potassium Chloride (Sodium, potassium, and chloride are classified as electrolytes because of their roles in maintaining ionic equilibria in physiological systems.) Thirteen trace elements are currently known to be nutritionally essential for human health. (micrograms per gram of tissue): Iron, copper, zinc, iodine, selenium, boron, cobalt, chromium, molybdenum, manganese, vanadium, silicon, and nickel. A defining characteristic of a trace element is that a very small amount is necessary for proper function of the whole organism. 3 Accurate laboratory testing to assess body status pre & post supplementation can ensure repletion by demonstration of normal test results; along with clinical observations and a nutritional assessment questionnaire, to monitor patient improvement. 3 Clinical laboratory testing clarifies questions of excessive use of nutrient elements and significant exposure for toxic elements, whereas functional markers can demonstrate metabolic poisoning. 3

5 Major Roles of Essential Elements In Biological Systems 3 Electron acceptors in oxidative/reductive homeodynamics Enzyme cofactors Crystalline structures (bone) Ionic migrations necessary for nerve signal transmission or cell regulatory responses Nutrient & Toxicant Interaction 3 Element deficiency is common and tends to occur in multiples. Poor diet, poor digestion, and malabsorption Element-deficient state can cause an up regulation of transport proteins in the GI tract, which can cause greater absorption of toxic elements (element deficiency can increase toxic element exposure) e.g. Iron deficiency increases the absorption of lead and cadmium. Excessive zinc decreases copper absorption. Copper deficiency increases iron deficiency anemia. Selenium mitigates the toxic effects of mercury and arsenic. 4

6 Bioavailability of Elements 3 Elements contained in food undergo several changes in chemical bonding. The digestive process must be in good working order. Digestive factors that can decrease element absorption include inadequate (or dilute) stomach acid, low alkaline pancreatic output, or low pancreatic digestive enzymes. Dietary supplements of elements (as elemental salts) are available in many forms. Complexed or chelated forms are usually recommended -Lactate, gluconate, citrate, picolinate or amino acid (especially aspartate) salts (You should recall that salt is an ionic compound, consisting of a cation and anion. In water, the salt dissociates into ions.) Choosing the Best Specimen for Element Testing 3 Blood Hair Urine Chelation Challenge (provocation) Testing Urinary Porphyrin Profiling There is no single best specimen for simultaneous, optimal status assessment of essential elements and toxic heavy metals. For each element, there are merits and limitations of the specimens commonly tested. The best specimen for detecting essential element deficiency depends on the element. Comparing results from multiple types of specimens can provide a more complete picture of elemental status. Enhanced sensitivity may be obtained by measuring 24 hours excretion following oral or IV challenge with nutrient elements or with chelating agents that mobilize toxic elements. Blood Whole blood or RBC specimens are valuable when assessing nutrient status. Whole blood is commonly used for baseline, non-challenged toxic element status. Since each essential element functions synergistically with other elements and nutrients, multi-element profiles coupled with functional biomarkers can provide the best insight into abnormalities in mobilization, utilization and excretion. 5

7 It may be difficult to demonstrate chronic exposure to toxic metals in samples of hair, blood, and urine despite clinically significant body burdens because they tend to accumulate in specific tissues Bone Liver Kidneys If the main routes of elimination are compromised, testing of body fluids may show falsely normal values. In these situations, testing that shows metabolic impact of toxic elements is helpful (urinary porphyrin profiles). Hair Hair specimens can be useful in routine screening for toxic metal exposure. Keratin, which is rich in sulfur and contains cysteine residues, is the major component of hair. (You should recall that DMSA has two electron rich sulfur atoms which attract metals) When elements, circulating in the blood, reach the hair follicle, they bind with high affinity to keratin. Hair concentrates toxic metals at least 10-fold above concentrations found in blood. Hair can be used as a chronological recorder of toxic metal exposure. Analysis of hair for status assessment of some nutrient elements can also be helpful. Hair analysis has been controversial with regard to element analysis, however, there appears to be strong potential for clinical use. Urine Urine elements can vary with recent dietary intake. Over 90% of most chelating agents are cleared by the kidneys in a few hours. Thus, a six to eight hour urine specimen collection is not only more convenient, but also may be superior for assessment of toxic element excretion following a chelation challenge when results are expressed in micrograms per milligram of creatinine. 6

8 Iodine Adequacy Assessment: urinary iodine, TSH, TT4, TT3, FT4, FT3, RT3, Thyroglobulin Optimal forms: Potassium iodide, molecular iodine (iodine I 2 ), (iodide I - - the reduced form of iodine) Clinical indications of deficiency: Goiter, hypothyroidism, hyperthyroidism, fibrocystic breast disease Food sources: Seaweed, shellfish, marine fish, iodized salt Iodine Function, Absorption and Metabolism The normal adult human body contains about mg of iodine, of which 70-80% is concentrated in the thyroid gland. In the presence of a goiter and a low iodine intake, the amount of iodine in the gland can be as little as 1 mg. Iodine occurs in the tissues mainly as organically bound iodine: inorganic iodide is present in very low concentrations. 4 Iodine is an essential element required for normal function of the thyroid gland, immune system, and the integrity of the thyroid and breast tissue. Suboptimal total body iodine status is associated with insufficient intake of the essential element and excessive intake of the highly antagonistic halides: bromide and fluoride. Specific tissues in the body require adequate iodine and the reduced form of the element iodide for normal metabolism and optimal health. Adequate iodine uptake and organification of iodine by the thyroid gland is required for the production, storage, and release of thyroid hormones. Triiodothyronine (T3) regulates metabolism in several tissues by affecting energy production and neuronal and sexual development. Iodine is ingested in several different forms. Before absorption, iodine is reduced to iodide in the gut. Then, absorption of iodide takes place rapidly, manly from the upper small intestine and stomach, after which it is taken up immediately by the thyroid gland. 4 [It s interesting to note that iodide is found in the gastric juices via the sodium iodide symporter found in the gastric mucosa. The hypotheses of iodide in the gastric juice include: antimicrobial effects, recirculation of iodide, and anti-oxidative effects of iodide. Gastric cancer, as well as thyroid disease, is more prevalent in areas of iodine deficiency. 2 ] 7

9 Iodine insufficiency is associated with subclinical thyroid deficiency, weight gain, loss of energy, goiter and impaired mental function. Iodine is also concentrated in breast tissue, where it elicits anti-proliferative effects and protection against fibrocystic breast disease and cancer. Iodine and organic iodine compounds are also concentrated and secreted by the gastric mucosa, salivary glands and the cervix. Iodine deficiency is a problem worldwide mainly due to soil depletion. Iodine deficiencies are a leading cause of preventable mental retardation world-wide. Iodine toxicity 3 Although up to 1000 ug of iodine daily is considered safe, therapeutic dosages of iodine are not agreed upon, making iodine testing very important. Excessive intake of iodine reduces organic binding of iodine, resulting in hypothyroidism, goiter, thyroiditis, and thyroid nodules. Assessing Iodine Status 1. Direct Iodine Measurements: Approximately 10 to 20 ug of iodine are lost daily in the feces, and 100 to 150 ug as urinary iodine in iodine-sufficient populations. The table below is based on median urinary iodine levels. [Note that measurement of urinary iodine is not appropriate in dietary conditions in which goitrogens prevent the uptake of iodine into the thyroid, and subsequent synthesis of thyroid hormones. Urinary iodine does not reflect thyroid function, so in such conditions, urinary iodine excretion may be normal. 4 ] 8

10 Twenty-four hour Urine Iodine testing is preferred for its reliability. Normal iodine 24-hour urine collections are ug/d (test available through Doctor s Data). Multiple test samples with relatively constant intake of iodine for at least six months may be required to obtain an accurate steady state value Iodine Plasma/Serum Values only measure circulating thyroid hormones Normal values ug/l Iodine/Iodide status is greatly influenced by dietary intake, but also by exposure to goitrogens that inhibit the absorption and binding of iodine. Goitrogenic substances include chlorine (tap water, pools/hot tubs, cleaning products), fluoride (water toothpaste, mouth wash, some medications) and bromide (pools/hot tubs, baked goods, soft drinks, pesticides, medications). 3. Functional Iodine Tests Iodine patch (skin) test 2% iodine solution (must be color based; not clear iodine solution) is painted on the skin. Observe the time interval for fading of the color. Rapid fading indicates a need for iodine. There are no accepted norms for the time of fading, and the observation is complicated by darker skin tones. Most Functional Medicine practitioners use the 24 hour mark (ex: color should stay on the skin for 24 hrs). Early fading is a sign of deficiency. 4. Urinary Iodine Load Test (Not Recommended By FMU). Oral loading dose of iodine/iodide is ingested (usually 50 mg). A 24 hr urine collection is required in which Iodine & displaced bromide and fluoride are measured. Results for each element are reported as ug/gm creatinine and ug/24 hrs. Iodine status is assessed by evaluation of the percentage of the ingested dose excreted. Low iodine excretion is suggestive of greater bodily retention and need. [Note: This test is not recommended by FMU due to the fact that validity of the test depends on the undocumented and erroneous assumption that the average person can absorb at least 90% of a 50 mg dose. 1 ] 9

11 Indirect Iodine Measurements: Serum Thyroglobulin Iodine deficiency can cause the thyroid cells to proliferate, which causes enhanced turnover by the thyroid cells leading to an increase in serum thyroglobulin. When habitual intakes of iodine are low, an inverse association between levels of thyroglobulin in the serum and iodine intakes is observed. 4 Using serum thyroglobulin as an indirect functional marker of iodine status must be interpreted according to the status of function of the thyroid gland. The influence of thyroid status and iodine intake on serum thyroglobulin is as follows: Eufunction (normal thyroid output) hypothyroid hyperthyroid Iodine Intake Deficiency Adequate Excess Deficiency Adequate Excess Deficiency Adequate Excess Serum Tg Concentration Increased Normal Normal or increased Decreased Decreased Decreased Increased Increased Increased (Keep in mind that excessive iodine intake can also inhibit thyroid function. Serum thyroglobulin levels are also used as a marker for recurrence thyroid cancer.) Iodine Deficiency: Thyroid Function Tests Adaptive mechanisms are as follows: Increased serum TSH Increased iodine trapping of the thyroid Preferential synthesis of the thyroid of T3 Increased peripheral conversion to T3 Increased thyroid volume 10

12 In general, increasing iodine deficiency will result in increasing serum TSH and freet4, and a decreasing free T3. Caution: Some studies have shown a lower TSH in iodine deficient patients than those with normal iodine status. The study points out that the lower serum TSH was due to nodularity of the thyroid gland and thyroid autonomy. 2 (These will be discussed in detail in a future lesson in this module. For now think about what happens to the thyroid gland in the iodine deficient state. Iodine deficiency causes hyperplasia of the thyroid gland. If the person is under oxidative stress (over abundance of free radicals), mutagenesis of the thyroid cells can take place, which can lead to hot or cold nodules on the thyroid gland. A mutation can occur on the TSH receptor causing the thyroid gland to function without TSH. This is called thyroid autonomy.) Physical examination of the thyroid and diagnostic ultrasound of the thyroid gland can rule out thyroid nodules. Keep in mind that thyroid functions tests are not absolute for iodine status; however they can serve as a guide if they are viewed with the patient history, physical exam, and other diagnostic tests. Iodine Excess: Thyroid Function Tests Acute iodine excess can cause: Decrease in iodine transport Decreased intrathyroidal organification Decreased release of thyroid hormones from the gland The effect of 15 days of 80 mg oral iodine on thyroid function: Increased serum TSH T4 slightly decreased T3 slightly decreased Note: There may be increased incidences of goiter, hyperthyroidism and hypothyroidism with chronic iodine excess. 2 The antiarrhymic medication, cordarone (aka: amiodarone), contains a significant amount of iodine and will inhibit the conversion of T4 to T3. This drug has been known to cause overt hyperthyroidism, Graves disease and hypothyroidism in people with pre-existing thyroid autoimmune disease. 11

13 Effects of Iodine Nutritional Status on Thyroid Function Tests 2 TSH Free T4 Free T3 Other Iodine deficiency Increased Decreased Increased Decreased rt3, increased TG Acute iodine excess Increased Decreased Decreased Acute iodine excess in nodular thyroid gland Decreased Increased Increased Possible development of thyrotoxicosis Chronic iodine excess* May appear normal May appear normal May appear Normal Cordarone Increased Increased Decreased Increased rt3 *Chronic iodine excess may show normal thyroid functions tests due to the resumption of organification of iodide and resumption of the release of thyroid hormone. 2 Clinical Protocols for Lowering Bromide and Fluoride in the Body. 1. Stop ingesting bromide & fluoride containing foods and medicines. Bromide and fluoride complete with iodide at the sodium-iodide symporter. Excessive intake can displace iodide and compromise thyroid hormone production. Bromide is found in baked goods, soft drinks, pesticides, brominated chemicals, spas and pools, and some medication Fluoride is found in fluoridated water, beverages, toothpaste, mouthwashes and some medication 2. If your patient is iodine deficient, prescribe iodine/iodide accordingly. It has been suggested that fluoride does not impair the capacity of the thyroid gland to synthesis hormones due to the fact that fluoride inhibits the iodide concentrating mechanism of the thyroid, but it does not accumulate in the gland. 6 If iodide status is adequate, fluoride levels should not impair production of hromones. 6 Bromide completes with chloride in the extracellular space, therefore prescribing unrefined salt intake and adequate hydration should assist with its removal. Bromide can also be found intracellularly, which is said not to be removed by unrefined salt intake. Unrefined salt can also help remove fluoride by the same mechanism. Iodine/Iodide taken in physiologic doses, it can help to competitively inhibit the binding of bromine & fluoride. 12

14 The Reactivity Trend of the Halogens (Group 7 of the Periodic Table) As one goes down the periodic table in group 7, the reactivity of the elements decreases. That is, the halogens become less reactive down the group. Chemically, a more reactive halogen will displace a less reactive halogen. Fluoride is more reactive than chloride. Chloride is more reactive than bromide. Bromide is more reactive than iodide. Repletion of Iodine FMU s position statement on iodine repletion: The U.S. Food and Nutritional Board Tolerance Upper Intake Level for iodine intake of adults greater than 19 years and pregnant and lactating women is 1100 micrograms per day (1.1 mg). 4 Some authorities have recommended not to exceed 600 micrograms per day (.6mg), due to the predictability of thyroid toxicity. Thyroid function should be monitored during aggressive dosing. Always retest urine. Forms: a mixture of iodine and iodide is recommended Lugol s: mixture of iodine and potassium iodide (topical or oral) Iodoral (iodine or I 2 ) 12 mg/ tablet Prolamine Iodine (standard process) 3mg iodine /tablet potassium iodine and potassium iodide Therapeutic dose range is 6-50 mg/d Lugol s solution: 1 drop = 2.5 mg I2 & 4 mg I Lugol s tablets: 1 tablet 5 mg I2 & 7.5 mg I Summary There has been much discussion about the indications and contraindications of prescribing iodine/iodide. What is clear is the fact that excess iodine intake is toxic, therefore assessing the need of iodine repletion is critical. The most practical indicator of iodine status is measurement of urinary excretion in a 24 hour urine specimen taken several times to obtain a steady state value. 13

15 References: Functional Medicine University s 1. Mega dose Iodine: An Idea Whose Time Has Gone, Alan R. Gaby, MD, Townsend Letter, December, Comprehensive Handbook of Iodine, Nutritional, Biochemical, Pathological, and Therapeutic Aspects, 2009, Victor R. Preedy, Gerard N.Burrow, Ronald Ross Watson 3. Laboratory Evaluations for Integrative and Functional Medicine, 2 nd ed., Richard S. Lord, J. Alexander Bralley 4. Toxicological Profile for Iodine; Agency for Toxic Substances and Disease Registry, 5. Principles of Nutritional Assessment, 2 nd ed., Rosalind S. Gibson 6. Iodine Supplementation Markedly Increases Urinary Excretion of Fluoride and Bromide Letters to the Editor, Townsend Letter, May