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Drug Nutrient Depletion by Dr. Meletis


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Drug Nutrient Depletion by Dr. Meletis

  1. 1. Dr. Chris D. Meletis Executive Director Institute for Healthy Aging copyright Dr. Meletis 2011
  2. 2. <ul><li>The information shared in this presentation is educational only. Consulting with ones personal physician and pharmacist is essential prior to changing medications or adding supplements to current medications taken. </li></ul><ul><li>The information shared here is not intended as either diagnosis or treatment. </li></ul>copyright Dr. Meletis 2011
  3. 3. <ul><li>Drug side effects are the fourth leading cause of death in the United States. </li></ul><ul><li>According to an article published in the Journal of the American Medical Association, approximately 106,000 Americans die and 2,000,000 suffer from severe reactions every year from drugs prescribed in hospitals. </li></ul><ul><li>Lazarou J., Pomerantz, B., Corey, P., Incidence of Adverse Drug Reactions in Hospitalized Patients, A Meta-analysis of Prospective Studies, JAMA, April 15, 1998, 279(15): 1200-1205. </li></ul>copyright Dr. Meletis 2011
  4. 4. copyright Dr. Meletis 2011
  5. 5. <ul><li>A study published in 2005 showed that many Americans were not meeting the U.S. Recommended Dietary Allowances for a number of nutrients: 73 percent of people were not getting enough zinc in their diets, 65 percent were deficient in calcium intake, 62 percent were low in magnesium, 56 percent in vitamin A and 54 percent in vitamin B6. </li></ul><ul><li>A new concern in health care is that, on top of already marginal nutrient intake for some people, nutrient depletion is worsened by some of the common medications taken by many Americans. </li></ul>copyright Dr. Meletis 2011
  6. 6. <ul><li>Medication-induced nutrient depletion can occur though </li></ul><ul><li>several mechanisms: </li></ul><ul><li>Interfere with the Absorption </li></ul><ul><li>Increased Excretion </li></ul><ul><li>Altered Metabolism </li></ul>copyright Dr. Meletis 2011
  7. 7. <ul><li>Stating the Obvious: </li></ul><ul><li>Stomach acid medications, including proton pump inhibitors like Prilosec, H2 blockers such as Zantac , and general antacids, all block the production of stomach acid. </li></ul><ul><li>Short term, the long-term suppression of stomach acid leads to reduced absorption of many nutrients, including calcium, magnesium, zinc, iron, vitamins B12 and C, and beta carotene. </li></ul>copyright Dr. Meletis 2011
  8. 8. <ul><li>Omeprazole (brand names: Losec, Prilosec , Zegerid, ocid, Lomac, Omepral, Omez) </li></ul><ul><li>Lansoprazole (brand names: Prevacid , Zoton, Monolitum, Inhibitol, Levant, Lupizole) </li></ul><ul><li>Dexlansoprazole (brand name: Kapidex, Dexilant) </li></ul><ul><li>Esomeprazole (brand names: Nexium , Esotrex) </li></ul><ul><li>Pantoprazole (brand names: Protonix , Somac, Pantoloc, Pantozol, Zurcal, Zentro, Pan, Controloc) </li></ul><ul><li>Rabeprazole (brand names: Zechin, Rabecid,Nzole-D,(NEHAL PHARMA Pvt. Ltd.), AcipHex , Pariet, Rabeloc. </li></ul>copyright Dr. Meletis 2011
  9. 9. <ul><li>In March, the FDA published a safety announcement on the risk of magnesium deficiency in anyone taking proton pump inhibitors for more than a year. </li></ul><ul><li>And while some people may be protected by taking a daily magnesium supplement, studies suggest that about 25 percent of people who take PPIs are unable to normalize their blood magnesium level with a supplement -- they have to stop the drug in order to return their blood magnesium levels to normal. </li></ul><ul><li>Long-term reduction in calcium absorption from PPIs also can affect your bone health and increase your risk of osteoporosis. </li></ul><ul><li>Magnesium deficiency can contribute to anxiety, restless leg syndrome, insomnia and muscle spasm, life-threatening arrhythmias. </li></ul>copyright Dr. Meletis 2011
  10. 10. <ul><li>Gastric Acid Reducing/AntiulcerAgents/Nutrient Depletion: </li></ul><ul><li>Beta-carotene </li></ul><ul><li>Boron </li></ul><ul><li>Calcium </li></ul><ul><li>Chromium </li></ul><ul><li>Copper </li></ul><ul><li>Folic acid </li></ul><ul><li>Iron </li></ul><ul><li>Phosphorus </li></ul><ul><li>Selenium </li></ul><ul><li>Thiamin </li></ul><ul><li>Vitamin B12 </li></ul><ul><li>Vitamin C </li></ul><ul><li>Vitamin D </li></ul><ul><li>Vitamin E </li></ul><ul><li>Vitamin K </li></ul>copyright Dr. Meletis 2011
  11. 11. <ul><li>(NSAIDS)/Nutrient Depletion: </li></ul><ul><li>Folic Acid </li></ul><ul><li>Iron </li></ul><ul><li>Melatonin </li></ul><ul><li>Vitamin C/ascorbic acid </li></ul><ul><li>Vitamin K </li></ul><ul><li>Zinc </li></ul>copyright Dr. Meletis 2011
  12. 12. copyright Dr. Meletis 2011
  13. 13. Nutrition and heart failure: impact of drug therapies and management strategies. Nutr Clin Pract. 2009 Feb-Mar;24(1):60-75. Abstract Nutrition impairment commonly occurs in patients with heart failure and affects disease progression. Vitamin and mineral deficiencies are associated with early mortality, particularly in patients classified as cachectic. Guideline-based therapies approved for heart failure, such as loop diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, aldosterone antagonists, and beta-adrenergic blockers, can lead to electrolyte abnormalities and predispose to some vitamin and micronutrient deficits. copyright Dr. Meletis 2011
  14. 14. <ul><li>Clinical trial evidence in support of supplementary vitamin and mineral therapies for heart failure patients is limited with the exception of documented calcium and possibly vitamin D, thiamine, and coenzyme Q10 deficiencies. </li></ul>copyright Dr. Meletis 2011
  15. 15. <ul><li>Diuretics, cause multiple nutrient losses in the urine. </li></ul><ul><li>All diuretics cause urinary loss of potassium, magnesium and vitamin B1 (thiamine), which can cause or aggravate heart disease . </li></ul><ul><li>Certain diuretics also cause loss of calcium, vitamin B6, folic acid and vitamin C. </li></ul>copyright Dr. Meletis 2011
  16. 16. <ul><li>Diuretics/Nutrient Depletion: </li></ul><ul><li>Calcium </li></ul><ul><li>Coenzyme Q10 (CoQ10) </li></ul><ul><li>Copper </li></ul><ul><li>Folate </li></ul><ul><li>Magnesium </li></ul><ul><li>Melatonin </li></ul><ul><li>Pyridoxine </li></ul><ul><li>Potassium </li></ul><ul><li>Riboflavin </li></ul><ul><li>Sodium </li></ul><ul><li>Thiamine </li></ul><ul><li>Vitamin C </li></ul><ul><li>Zinc </li></ul>copyright Dr. Meletis 2011
  17. 17. <ul><li>Coenzyme Q10 (CoQ10): </li></ul><ul><li>Diuretics may reduce CoQ10 concentrations. </li></ul><ul><li>Specific diuretics mentioned in anecdotal reports include benzthiazide, chlorthiazide, hydrochlorothiazide, indapamide, methyclothiazide, metolazone, and polythiazide. </li></ul>copyright Dr. Meletis 2011
  18. 18. <ul><li>Limited human data suggests that diuretics may increase excretion of folic acid. Reduced red blood cell folate levels, possibly contributing to increased homocysteine levels, a risk factor for cardiovascular disease, were found in one group of people taking diuretics for six months or longer. </li></ul><ul><li>Based on in vivo evidence , triamterene (potassium sparing diuretic) inhibits the intestinal absorption of folic acid in a dose-dependent manner. </li></ul>copyright Dr. Meletis 2011
  19. 19. <ul><li>Research: </li></ul><ul><li>17 hypertensive patients receiving long-term diuretic therapy vs . 17 hypertensive patients not taking diuretics </li></ul><ul><li>Mean homocysteine concentration for patients taking diuretics (17.87 +/- 1.72 micromol/L) vs. (10.31 +/- 0.99 micromol/L). </li></ul><ul><li>Mean RBC folate concentration for patients taking diuretics </li></ul><ul><li>(281.01 +/- 17.56 ng/mL) vs. lower (430.85 +/- 28.58 ng/mL). </li></ul><ul><li>CONCLUSIONS: </li></ul><ul><li>Chronic diuretic use is associated with a significant increase in serum homocysteine concentration, a significant decrease in RBC folate concentration , and no significant change in concentrations of vitamins B6 and B12. </li></ul>copyright Dr. Meletis 2011
  20. 20. <ul><li>Coenzyme Q10 (CoQ10) : </li></ul><ul><li>Based on human evidence, HMG-CoA reductase inhibitors (e.g. lovastatin) lead to a decreased concentration of CoQ10 on human studies , CoQ10 concentrations decreased in patients treated with pravastatin and lovastatin or pravastatin and simvastatin. </li></ul><ul><li>Drug Saf. 2006;29(8):703-12. </li></ul><ul><li>Eur Neurol. 2007;57(4):232-5. Epub 2007 Mar 26. </li></ul><ul><li>Mol Aspects Med. 1997;18 Suppl:S137-44. </li></ul><ul><li>J Atheroscler Thromb. 2005;12(2):111-9. </li></ul><ul><li>Atherosclerosis. 2005 Mar;179(1):201-6. Epub 2004 Dec 29. </li></ul><ul><li>Clin Pharmacol Ther. 2005 Jul;78(1):60-8. </li></ul><ul><li>Drug Saf. 2006;29(8):703-12. </li></ul><ul><li>Arzneimittelforschung. 1999 Apr;49(4):324-9. </li></ul>copyright Dr. Meletis 2011
  21. 21. <ul><li>Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. </li></ul><ul><li>CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage. </li></ul>copyright Dr. Meletis 2011
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  23. 23. copyright Dr. Meletis 2011
  24. 24. <ul><li>Thiamine: Loop diuretics , particularly furosemide (Lasix®), also another drug Bumex; have been associated with decreased thiamine levels in the body by increasing urinary excretion (and possibly by decreasing absorption and increasing metabolism). </li></ul><ul><li>Animal evidence suggests that the increase in urinary excretion of thiamine may be associated with furosemide, acetazolamide, chlorothiazide, amiloride, and mannitol. </li></ul><ul><li>Can J Clin Pharmacol. 2003 Winter;10(4):184-8. Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. </li></ul>copyright Dr. Meletis 2011
  25. 25. <ul><li>Symptoms of beriberi include severe lethargy and fatigue, together with </li></ul><ul><li>complications affecting the cardiovascular, nervous, muscular, and </li></ul><ul><li>gastrointestinal systems. </li></ul><ul><li>Dry beriberi </li></ul><ul><li>Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis . It is characterized by: </li></ul><ul><li>Difficulty walking </li></ul><ul><li>Tingling or loss of feeling (sensation) in hands and feet </li></ul><ul><li>Loss of muscle function or paralysis of the lower legs </li></ul><ul><li>Mental confusion/speech difficulties </li></ul><ul><li>Pain </li></ul><ul><li>Involuntary eye movements (nystagmus) </li></ul><ul><li>Vomiting </li></ul>copyright Dr. Meletis 2011
  26. 26. copyright Dr. Meletis 2011
  27. 27. <ul><li>Wet beriberi affects the heart and it causes a combination of heart failure and weakening of the capillary walls. </li></ul><ul><li>Peripheral edema </li></ul><ul><li>Awakening at night short of breath </li></ul><ul><li>Increased heart rate </li></ul><ul><li>Shortness of breath with activity </li></ul><ul><li>Swelling of the lower legs </li></ul>copyright Dr. Meletis 2011
  28. 28. <ul><li>Zinc : </li></ul><ul><li>Based on human evidence, loop and thiazide diuretics may increase urinary </li></ul><ul><li>zinc excretion </li></ul><ul><li>Abstract </li></ul><ul><li>Mean hair zinc was found to be significantly lower in 20 mild hypertensive patients treated with thiazides for 6-36 months than in 19 mild hypertensive patients who had not been given diuretics for at least six months before study. </li></ul><ul><li>Chronic diuretic treatment can result in zinc deficiency through enhanced urinary excretion of zinc. </li></ul>copyright Dr. Meletis 2011
  29. 29. <ul><li>Serotonin: </li></ul><ul><li>Based on human evidence, losartan (Cozaar) may cause a decrease in serotonin levels. </li></ul><ul><li>Asian Cardiovasc Thorac Ann 2001;9:302-307 </li></ul>copyright Dr. Meletis 2011
  30. 30. copyright Dr. Meletis 2011
  31. 31. copyright Dr. Meletis 2011
  32. 32. copyright Dr. Meletis 2011
  33. 33. <ul><li>Zinc: </li></ul><ul><li>According to human study, captopril and enalapril may increase urinary zinc excretion. </li></ul><ul><li>J Am Coll Nutr. 1998 Feb;17(1):75-8. </li></ul><ul><li>Metabolism. 1990 Jul;39(7):665-7. </li></ul>copyright Dr. Meletis 2011
  34. 34. copyright Dr. Meletis 2011
  35. 35. GLA at Work—For The Good of the Body High blood pressure (Hypertension) In one study, men with borderline high blood pressure who took 6g of blackcurrant oil had a reduction in diastolic blood pressure compared to those who took placebo. Another study examined people with intermittent claudication, pain in the legs while walking that is caused by blockages in the blood vessels. Those who took GLA combined with EPA had a reduction in systolic blood pressure compared to those who took placebo. copyright Dr. Meletis 2011
  36. 36. <ul><li>Happy Pills? </li></ul>copyright Dr. Meletis 2011
  37. 37. <ul><li>Based on human study, melatonin changes after antidepressant use may be due to pharmacological action of these drugs on melatonin secretion. </li></ul><ul><li>After treatment with selective serotonin reuptake inhibitors (SSRIs), levels of 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, increased. In human trial, fluoxetine (Prozac) reduced melatonin levels. </li></ul>copyright Dr. Meletis 2011
  38. 38. <ul><li>A six-week case-controlled study with repeated overnight blood sampling was conducted. Ten patients fulfilling the criteria for major depressive disorder, seasonal type, with a 29-item Hamilton Depression Rating Scale (HDRS) score of at least 20 were compared with ten age- and sex-matched healthy controls in a clinical laboratory. The effects of fluoxetine (20 mg/day) on the HDRS and melatonin concentration were measured. </li></ul><ul><li>RESULTS: Fluoxetine significantly reduced melatonin levels in both groups. There was no significant difference in melatonin secretion between the groups. </li></ul><ul><li>CONCLUSIONS: The effect of fluoxetine differs from tricyclics and fluvoxamine (Luvox), both of which increase melatonin. </li></ul>copyright Dr. Meletis 2011
  39. 39. <ul><li>Treating various sleep disorders (such as insomnia, jet lag, and others) </li></ul><ul><li>Preventing or treating Alzheimer's disease </li></ul><ul><li>Treating fibromyalgia </li></ul><ul><li>Treating chronic fatigue syndrome </li></ul><ul><li>Preventing cluster or migraine headaches </li></ul><ul><li>Treating cancer (when used in combination with standard cancer treatment). </li></ul>copyright Dr. Meletis 2011
  40. 40. <ul><li>Amitriptyline (Elavil, Endep and many others) </li></ul><ul><li>Amoxapine (Asendin) </li></ul><ul><li>Clomipramine (Anafranil) </li></ul><ul><li>Desipramine (Norpramin, Pertofrane) </li></ul><ul><li>Doxepin (Adapin, Sinequan) </li></ul><ul><li>Imipramine (Tofranil) </li></ul><ul><li>Nortriptyline (Pamelor, Aventyl) </li></ul><ul><li>Protriptyline (Vivactil) </li></ul><ul><li>Trimipramine (Surmontil) </li></ul>copyright Dr. Meletis 2011
  41. 41. <ul><li>Sodium : </li></ul><ul><li>According to a review, hyponatraemia may be a possible reaction to treatment with selected serotonin reuptake inhibitors (SSRIs) and measurement of serum electrolytes may be recommended, particularly in patients over the age of 65. </li></ul>copyright Dr. Meletis 2011
  42. 42. <ul><li>Over 18 million Diabetes </li></ul><ul><li>60 million Pre-Diabetics </li></ul>copyright Dr. Meletis 2011
  43. 43. <ul><li>Metformin (Glucophage), common diabetic medication. </li></ul><ul><li>Contributes Deficiency of: Vitamin B12, folic acid and coenzyme Q10. </li></ul><ul><li>Up to 30 percent of people taking metformin will develop B12 deficiency, whose symptoms include anemia and neuropathy. </li></ul>copyright Dr. Meletis 2011
  44. 44. <ul><li>Coenzyme Q10: </li></ul><ul><li>Some oral diabetic medications such as chlorpropamide, glimepiride, glipizide, glyburide (Micronase, Diabeta, Glynase Prestab), tolazamide, tolbutamide, and acetohexamide, may reduce the levels of coenzyme Q10 (CoQ10). </li></ul><ul><li>Based on secondary sources, biguanides may reduce CoQ10 concentrations. </li></ul>copyright Dr. Meletis 2011
  45. 45. <ul><li>Folate: </li></ul><ul><li>Based on human study, reduced folate levels may occur in some people treated with metformin. </li></ul><ul><li>Diabete Metab. 1976 Dec;2(4):187-90. </li></ul>copyright Dr. Meletis 2011
  46. 47. copyright Dr. Meletis 2011
  47. 48. <ul><li>Hyperhomocysteinemia, deep vein thrombosis and </li></ul><ul><li>vitamin B12 deficiency in a metformin-treated diabetic patient. </li></ul><ul><li>Vitamin B12 deficiency may be induced by long-term use of metformin, which may in turn lead to hyperhomocysteinemia. </li></ul><ul><li>Hyperhomocysteinemia may increase the risk of vascular thrombosis in diabetic patients, when metformin is used and a homozygous methylenetetrahydrofolate reductase (MTHFR) . </li></ul><ul><li>Our findings highly suggested the role of metformin in causing vitamin B12 deficiency, which may serve as an additional risk factor for venous thrombosis in diabetic patients. Our report also highlights the need to check vitamin B12 levels during metformin treatment. </li></ul>copyright Dr. Meletis 2011
  48. 49. <ul><li>Chromium: </li></ul><ul><li>Based on human evidence, corticosteroids may increase urinary chromium excretion ; and therefore, lead to chromium deficiency or corticosteroid-induced hyperglycemia. </li></ul><ul><li>Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabet Med. 1999 Feb;16(2):164-7. </li></ul>copyright Dr. Meletis 2011
  49. 50. <ul><li>Glutathione: </li></ul><ul><li>Based on animal evidence, glutathione may be reduced by acetaminophen in a dose-dependent manner. </li></ul><ul><li>A review discussing acetaminophen-related toxicity explains that the hepatic glutathione stores are depleted to combine with acetaminophen’s toxic metabolite. According to the review, for such toxicity, N-acetylcysteine (NAC) may be recommended and effective if given within the first 15 hours of overdose. </li></ul><ul><li>Physiol Res. 2010;59(2):225-32. Epub 2009 Jun 19. </li></ul><ul><li>Curr Gastroenterol Rep. 1999 Feb-Mar;1(1):42-9. </li></ul>copyright Dr. Meletis 2011
  50. 51. <ul><li>Melatonin: </li></ul><ul><li>Based on evidence from studies performed in humans and animals, diazepam and temazepam may alter synthesis or release of melatonin. </li></ul>copyright Dr. Meletis 2011
  51. 52. <ul><li>RESULTS: </li></ul><ul><li>Diazepam clearly affected pineal melatonin biosynthesis and plasma melatonin levels. Diazepam reduced the pineal melatonin content (by a factor of 2) and the activity of N-acetyltransferase (NAT) (by a factor of 3.5) , as well as plasma melatonin levels (by a factor of 1.5). </li></ul><ul><li>Psychopharmacology (Berl). 2001 Apr;154(4):403-7. </li></ul><ul><li>Chem Pharm Bull (Tokyo). 1991 Oct;39(10):2674-6. </li></ul>copyright Dr. Meletis 2011
  52. 53. <ul><li>DHEA </li></ul><ul><li>Folate </li></ul><ul><li>Magnesium </li></ul><ul><li>Melatonin </li></ul><ul><li>Riboflavin </li></ul><ul><li>Selenium </li></ul><ul><li>Thiamin </li></ul><ul><li>Vitamin A </li></ul><ul><li>Vitamin B5 (pantothenic acid) </li></ul><ul><li>Vitamin B6/pyridoxine </li></ul><ul><li>Vitamin B12 </li></ul><ul><li>Vitamin C/ascorbic acid </li></ul><ul><li>Zinc </li></ul>copyright Dr. Meletis 2011
  53. 54. <ul><li>DHEA: </li></ul><ul><li>Human studies: Ortho Novum® 1/35 and Ovcon® 35 decreased serum concentration of DHEA sulfate (DHEAS). </li></ul><ul><li>Based on human evidence, estrogen-containing oral contraceptives have also resulted in decreased DHEAS. </li></ul><ul><li>Contraception. 1984 Apr;29(4):319-24. </li></ul><ul><li>Am J Obstet Gynecol. 2005 Jun;192(6):2055-9. </li></ul>copyright Dr. Meletis 2011
  54. 55. <ul><li>Based on human evidence, oral contraceptives (birth control pills) may impair folate metabolism producing depletion . BUT the effect is unlikely to cause anemia or megaloblastic changes . </li></ul><ul><li>There have been cases of megaloblastic anemia in humans, however, with long term use of oral contraceptives. Progesterone based therapy may decrease folate levels, as witnessed in animal study involving chick embryos. </li></ul>copyright Dr. Meletis 2011
  55. 56. <ul><li>Oral contraceptive hormones, folate metabolism, and the cervical epithelium. </li></ul><ul><li>Am J Clin Nutr. 1975 Apr;28(4):346-53. </li></ul><ul><li>About 20 percent of women taking contraceptive hormones manifest mild megaloblastic changes on Papanicolaou smears of the cervicovaginal epithelium which disappear after folic acid therapy. </li></ul>copyright Dr. Meletis 2011
  56. 57. <ul><li>A 34-year-old woman developed megaloblastic anemia and peripheral polyneuropathy following the use of oral contraceptives for 4 years. Low levels of folic acid and vitamin B12 were found. Both the complete recovery after therapy with the vitamins, and the absence of other causes of vitamin B12 and folate deficiency, suggest that the vitamin deficiencies were caused by the oral contraceptives and resulted in the rare combination of megaloblastic anemia and polyneuropathy. The poor response to vitamin B12 alone, and the development of anemia and polyneuropathy 4 months after cessation of vitamin B12 therapy suggest that folate deficiency was the primary problem. </li></ul>copyright Dr. Meletis 2011
  57. 58. <ul><li>The use of contraceptive pills has been shown to decrease the physiologic levels of six nutrients--riboflavin, pyridoxine, folacin, vitamin B12, ascorbic acid and zinc--and to increase the levels of four others--vitamin C, iron, copper and vitamin A. </li></ul>copyright Dr. Meletis 2011
  58. 59. <ul><li>Am J Obstet Gynecol. 1979 Sep 1;135(1):129-34. </li></ul><ul><li>The group using oral contraceptive agents (OCA) had significantly lower serum levels of vitamin B12 vitamin as compared to those of the control group. </li></ul><ul><li>The OC group had a significantly lower total serum vitamin B12 binding capacity, a lower total transcobalamin 1 level, and a higher transcobalamin 3 level. The fall of serum vitamin B12 in OC users appears to be due to changes in vitamin B12 binders of serum and does not represent vitamin B12 deficiency, giving no justification for vitamin B12 supplementation in users of OCs. </li></ul>copyright Dr. Meletis 2011
  59. 60. <ul><li>Based on human evidence, selenium levels may be decreased in patients taking oral contraceptives. </li></ul>copyright Dr. Meletis 2011
  60. 61. <ul><li>Contraception. 2009 Jul;80(1):40-3. Epub 2009 Apr 5. </li></ul><ul><li>CONCLUSIONS: These findings may be important because selenium is currently believed to offer protective benefits against carcinogenesis. It has been thought that the decrease in serum zinc could be reflected in a reduction of tissue zinc status due to changes in zinc absorption, excretion or tissue turnover. If these changes occur, the dietary zinc requirement would be greater in women using OCP. </li></ul>copyright Dr. Meletis 2011
  61. 62. copyright Dr. Meletis 2011
  62. 63. copyright Dr. Meletis 2011
  63. 64. Supporting Full Body Basal Metabolic Rate copyright Dr. Meletis 2011
  64. 65. Thyroid Gland copyright Dr. Meletis 2011
  65. 66. <ul><ul><li>T3 is three to five times more active than T4  </li></ul></ul>Reverse T3 Free T3 Free T4 copyright Dr. Meletis 2011
  66. 67. Assessment of Production, Transport, Sensitivity, and Excretion of Thyroid Hormones <ul><li>Factors that contribute to proper production of thyroid hormones </li></ul><ul><ul><li>Nutrients: iodine, tyrosine, zinc, vitamins: E, B2, B3, B6, C </li></ul></ul><ul><ul><li>Antioxidants </li></ul></ul><ul><li>Factors that inhibit proper production of thyroid hormones </li></ul><ul><ul><li>Stress </li></ul></ul><ul><ul><li>Infection, trauma, radiation, medications </li></ul></ul><ul><ul><li>Fluoride (antagonist to iodine) </li></ul></ul><ul><ul><li>Toxins: pesticides, Hg, Cd, Pb </li></ul></ul><ul><ul><li>Autoimmune disease: Celiac </li></ul></ul><ul><li>Factors that increase conversion of T4 to T3 </li></ul><ul><ul><li>Selenium </li></ul></ul><ul><ul><li>Zinc </li></ul></ul><ul><li>Factors that improve cellular sensitivity to thyroid hormones </li></ul><ul><ul><li>Vitamin A </li></ul></ul><ul><ul><li>Exercise </li></ul></ul><ul><ul><li>Zinc </li></ul></ul><ul><li>Factors that increase conversion of T4 to RT3 </li></ul><ul><ul><li>Stress </li></ul></ul><ul><ul><li>Trauma </li></ul></ul><ul><ul><li>Low-calorie diet </li></ul></ul><ul><ul><li>Inflammation (cytokines, etc.) </li></ul></ul><ul><ul><li>Toxins </li></ul></ul><ul><ul><li>Infections </li></ul></ul><ul><ul><li>Liver/kidney dysfunction </li></ul></ul><ul><ul><li>Certain medications </li></ul></ul>T3 RT3 T3 and RT3 compete for binding sites Nucleus/ Mitochondria T4 copyright Dr. Meletis 2011 Cell
  67. 68. “ Treat Upstream”
  68. 69. <ul><li>Calcium: </li></ul><ul><li>Based on human evidence, thyroid hormones may increase urinary loss of calcium. </li></ul><ul><li>Levothyroxine may adsorb (stick) to calcium in an acidic environment, which may block its absorption. </li></ul><ul><li>JAMA. 1991 May 22-29;265(20):2688-91 . </li></ul>copyright Dr. Meletis 2011
  69. 70. <ul><li>Cimetidine (Tagamet®) and Ranitidine (Zantac®) may reduce the activity of 5'-Deiodinase. </li></ul><ul><li>What about Pepcid? </li></ul><ul><li>Histamine H2 receptor antagonists have been reported to increase the conversion of T4 into reverse T3 by inhibiting the 5'-Deiodinase enzyme that catalyzes the conversion of T4 into T3. </li></ul><ul><li>Perret, G., et al. Pharmacology. 32:101-108, 1986. </li></ul>copyright Dr. Meletis 2011
  70. 71. <ul><li>Iron : </li></ul><ul><li>Iron may decrease the absorption and efficacy of levothyroxine (Levoxyl®, Synthroid®) by forming insoluble complexes in the gastrointestinal tract. </li></ul>copyright Dr. Meletis 2011
  71. 72. copyright Dr. Meletis 2011
  72. 73. copyright Dr. Meletis 2011
  73. 74. <ul><li>T3 is more active than T4. </li></ul><ul><ul><li>Though T4 and T3 are both active as thyroid hormones; T3 is three to five times as active as T4.  </li></ul></ul><ul><li>T2 and rT3 are not “positively” active. </li></ul>copyright Dr. Meletis 2011
  74. 75. Liothyronine (T3, R= H) is 3 to 5 times as active as thyroxine (T4, R=I). The extra iodine atom present in T4 causes steric hindrance in binding to the thyroid receptor.  This steric hindrance is responsible for the lower activity of T4 . copyright Dr. Meletis 2011
  75. 76. For the Sake of Thirst ? copyright Dr. Meletis 2011
  76. 77. copyright Dr. Meletis 2011
  77. 78. <ul><li>Other Ingredients: Water, Sucrose Syrup, Glucose-Fructose Syrup, Citric Acid, Natural Orange Flavor with Other Natural Flavors, Salt, Sodium Citrate, Monopotassium Phosphate, Yellow No. 6, Ester Gum, Brominated Vegetable Oil . </li></ul>copyright Dr. Meletis 2011
  78. 79. copyright Dr. Meletis 2011
  79. 80. <ul><li>Tiotropium bromide (Spiriva)  Contains Bromide </li></ul>Battle Royal Iodine vs. Tag Team of Bromide, Fluoride, Chloride and Perchlorate Flovent Flonase Paxil C 19 H 20 FNO 3   Prozac C 17 H 18 F 3 NO   copyright Dr. Meletis 2011
  80. 81. <ul><li>Atrovent® (Ipratropium bromide ) Nasal Spray </li></ul><ul><li>Pyridostigmine Bromide (nerve gas protection) </li></ul><ul><li>Vecuronium Bromide (Pre-surgical Muscle Relaxant) </li></ul><ul><li>Malenchenko AF et al., The Content and Distribution of Iodine, Chlorine and Bromide in the Normal and Pathologically Changed Thyroid Tissue, Med Radiol 1984 . </li></ul>copyright Dr. Meletis 2011
  81. 82. <ul><li>Cimetidine (Tagamet®) and Ranitidine (Zantac®) may reduce the activity of 5'-Deiodinase. </li></ul><ul><li>Histamine H2 receptor antagonists have been reported to increase the conversion of T4 into reverse T3 by inhibiting the 5'-Deiodinase enzyme that catalyzes the conversion of T4 into T3. </li></ul><ul><li>Perret, G., et al. Effect of a short-term oral administration of cimetidine and ranitidine on the basal and thyrotropin-releasing hormone-stimulated serum concentrations of prolactin, thyrotropin and thyroid hormones in healthy volunteers. A double-blind cross-over study. Pharmacology. 32:101-108, 1986. </li></ul>copyright Dr. Meletis 2011
  82. 83. copyright Dr. Meletis 2011
  83. 84. <ul><li>We are MAGNIFICIENTLY comprised of 75 trillion cells. </li></ul><ul><li>When altering the biochemistry of the human frame, it is NEVER just one pathway that is ultimately impacted. </li></ul><ul><li>In order to have a sufficient physiological response , a rippling in the biochemical pond ensues. </li></ul>copyright Dr. Meletis 2011