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Herbal toxins grand rounds feb 2014

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  • 1. Nobody but Almighty God and I can know what I have been through these past few days. I have been familiar with death in the years since I received my M.D. from Tulane University School of Medicine with the rest of my class of 1911.
  • 2. Covington County has been my home. I have practiced here for years. Any doctor who has practiced more than a quarter of a century has seen his share of death.
  • 3. But to realize that six human beings, all of them my patients, one of them my best friend, are dead because they took medicine that I prescribed for them innocently, and to realize that that medicine which I had used for years in such cases suddenly had become a deadly poison in its newest and most modern form, as recommended by a great and reputable pharmaceutical firm in Tennessee: well, that realization has given me such days and nights of mental and spiritual agony as I did not believe a human being could undergo and survive. I have
  • 4. But to realize that six human beings, all of them my patients, one of them my best friend, are dead because they took medicine that I prescribed for them innocently, and to realize that that medicine which I had used for years in such cases suddenly had become a deadly poison in its newest and most modern form, as recommended by a great and reputable pharmaceutical firm in Tennessee:
  • 5. well, that realization has given me such days and nights of mental and spiritual agony as I did not believe a human being could undergo and survive. I have known hours when death for me would be a welcome relief from this agony.
  • 6. 1937
  • 7. 1937 Sulfanilamide, used to treat streptococcal infections Salesmen for the S.E. Massengill Co. report demand for a liquid formulation
  • 8. Chief chemist and pharmacist, Harold Cole Watkins discovered he could dissolve sulfonamide in diethylene glycol.
  • 9. Chief chemist and pharmacist, Harold Cole Watkins discovered he could dissolve sulfonamide in diethylene glycol. Watkins tested the solution for flavor, appearance, and fragrance and found it satisfactory
  • 10. Chief chemist and pharmacist, Harold Cole Watkins discovered he could dissolve sulfonamide in diethylene glycol. Watkins tested the solution for flavor, appearance, and fragrance and found it satisfactory by September 1937, Massengill had distributed 268 gallons of the liquid, called Elixir Sulfanilamide, across the country
  • 11. 1937
  • 12. 1937 June Sales person reports demand
  • 13. 1937 June July Aug Sales person reports demand Sept 268 gallons shipped nationally
  • 14. 1937 June July Aug Sales person reports demand Oct 11 Sept Oct 268 gallons shipped nationally American Medical Association received reports from Tulsa, OK, that an unfamiliar sulfanilamide compound was responsible for 6 deaths
  • 15. 1937 June July Aug Sales person reports demand Oct 11 Oct 14 Sept Oct 268 gallons shipped nationally American Medical Association received reports from Tulsa, OK, that an unfamiliar sulfanilamide compound was responsible for 6 deaths NY physician alerts the FDA An inspector in the Kansas City Station confirms 9 deaths
  • 16. 1937 June July Aug Sales person reports demand Oct 11 Sept Oct 268 gallons shipped nationally American Medical Association received reports from Tulsa, OK, that an unfamiliar sulfanilamide compound was responsible for 6 deaths Oct 14 NY physician alerts the FDA An inspector in the Kansas City Station confirms 9 deaths Oct 17 AMA, FDA Inspectors and the chemists at Messingil all concur, the elixir contains diethylene glycol.
  • 17. diethylene glycol is two ethylene glycol molecule bound by an ether bond HO CH2 CH2 O CH2 CH2 OH
  • 18. diethylene glycol is two ethylene glycol molecule bound by an ether bond HO CH2 CH2 O CH2 CH2 OH
  • 19. diethylene glycol is two ethylene glycol molecule bound by an ether bond HO CH2 CH2 O CH2 CH2 OH
  • 20. diethylene glycol is two ethylene glycol molecule bound by an ether bond HO CH2 CH2 O CH2 CH2 OH
  • 21. diethylene glycol is two ethylene glycol molecule bound by an ether bond HO CH2 CH2 O CH2 CH2 OH
  • 22. diethylene glycol is two ethylene glycol molecule bound by an ether bond HO CH2 CH2 O CH2 CH2 OH
  • 23. diethylene glycol is two ethylene glycol molecule bound by an ether bond HO CH2 CH2 O CH2 CH2 OH
  • 24. diethylene glycol is two ethylene glycol molecule bound by an ether bond HO CH2 CH2 O CH2 CH2 OH
  • 25. In order to recover all of the medicine, the entire field force of the FDA, 239 inspectors and chemists were told to stop their current projects and focus on sulfonilamide
  • 26. One physician postponed his wedding to help an FDA chemist search for a 3-year-old boy whose family had moved into mountain country after obtaining a prescription.
  • 27. Another inspector was investigating a pharmacy and was told that only 6 ounces had been dispensed. That patient had suffered no ill effects. But when the inspector examined shipping receipts, he found 12 ounces had been dispensed. After some questioning and poking through the local gossip he learned that two others had bought the elixir. Both died.
  • 28. The first time I ever had occasion to call in a doctor for Joan and she was given Elixir of Sulfanilamide. All that is left to us is the caring for her little grave. letter to FDR
  • 29. The first time I ever had occasion to call in a doctor for Joan and she was given Elixir of Sulfanilamide. All that is left to us is the caring for her little grave. Even the memory of her is mixed with sorrow for we can see her little body tossing to and fro and hear that little voice screaming with pain and it seems as though it would drive me insane. letter to FDR
  • 30. The first time I ever had occasion to call in a doctor for Joan and she was given Elixir of Sulfanilamide. All that is left to us is the caring for her little grave. Even the memory of her is mixed with sorrow for we can see her little body tossing to and fro and hear that little voice screaming with pain and it seems as though it would drive me insane. It is my plea that you will take steps to prevent such sales of drugs that will take little lives and leave such suffering behind and such a bleak outlook on the future as I have tonight. letter to FDR
  • 31. In 1937 the law did not prohibit the sale of dangerous, untested, or poisonous drugs.
  • 32. In 1937 the law did not prohibit the sale of dangerous, untested, or poisonous drugs. 25 seizures were made under federal law. The charge was misbranding. "Elixir," FDA said, implied the product was an alcoholic solution.
  • 33. In 1937 the law did not prohibit the sale of dangerous, untested, or poisonous drugs. 25 seizures were made under federal law. The charge was misbranding. "Elixir," FDA said, implied the product was an alcoholic solution. If the product had been called a "solution" no charge of violating the law could have been made. FDA would have had no legal authority to seize the drug
  • 34. Final score
  • 35. Final score 268 gallons shipped 267 gallons confiscated
  • 36. Final score 268 gallons shipped 267 gallons confiscated 1 gallon consumed
  • 37. Final score 268 gallons shipped 267 gallons confiscated 1 gallon consumed 105 dead, inclu d ing 34 children
  • 38. 1937 June July Aug Sales person reports demand Sept Oct 268 gallons shipped nationally National Tragedy
  • 39. 1937 June July Aug Sales person reports demand 1938 Jan Feb Mar Sept Oct Nov 268 gallons shipped nationally National Tragedy Apr May Dec
  • 40. 1937 June July Aug Sales person reports demand 1938 Jan Feb Mar Sept Oct Nov Dec 268 gallons shipped nationally National Tragedy Apr May June Passed the house June 1 Passed the Senate June 2 Signed into law June 25 Food, Drug, and Cosmetic Act The law required manufacturers to submit evidence of a drug's safety before it could go on the market.
  • 41. Drugs have to be safe (1938) to be approved for sale in the United States
  • 42. Frances O. Kelsey receiving the President's Award for Distinguished Federal Civilian Service
  • 43. Frances O. Kelsey receiving the President's Award for Distinguished Federal Civilian Service The Drug Amendment of 1962 was approved unanimously after Dr. Kelsey, an FDA officer, refused approval of Thalidomide.
  • 44. Frances O. Kelsey receiving the President's Award for Distinguished Federal Civilian Service The Drug Amendment of 1962 The amendment added a requirement for effectiveness was approved unanimously for drug approval. after Dr. Kelsey, an FDA officer, refused approval of Thalidomide.
  • 45. Drugs have to be safe (1938) and effective (1962) to be approved for sale in the United States
  • 46. Drugs have to be safe (1938) and effective (1962) to be approved for sale in the United States
  • 47. October 1994 Dietary Supplement Health and Education Act (DSHEA)
  • 48. October 1994 Dietary Supplement Health and Education Act (DSHEA)
  • 49. October 1994 Dietary Supplement Health and Education Act (DSHEA) Food Drug
  • 50. October 1994 Dietary Supplement Health and Education Act (DSHEA) Food Supplement Drug
  • 51. October 1994 Dietary Supplement Health and Education Act (DSHEA) Food Supplement Drug
  • 52. before DSHEA • Before 1994, herbal products were considered food additives • Manufacturers required to show proof of safety before sales
  • 53. under DSHEA • Dietary supplements are presumed to be safe • No FDA approval for marketing claim • No FDA requirement for purity or manufacturing standards • No FDA review of claims of efficacy
  • 54. Drugs have to be safe (1938) and effective (1962) to be approved for sale in the United States
  • 55. Drugs have to be safe (1938) and effective (1962) to be approved for sale in the United States Supplements do not have to be safe or effective to be approved for sale in the United States (1994)
  • 56. Drugs have to be safe (1938) and effective (1962) to be approved for sale in the United States Supplements do not have to be safe or effective to be approved for sale in the United States (1994) This deregulation has worked just like Milton Friedman and Ralph Nader suspected
  • 57. Drugs have to be safe (1938) and effective (1962) to be approved for sale in the United States Supplements do not have to be safe or effective to be approved for sale in the United States (1994) This deregulation has worked just like Milton Friedman and Ralph Nader suspected Salses (millions) $30,000 26000 $22,500 $15,000 $7,500 $0 700 1994 2010
  • 58. NIH $30,860,913,000
  • 59. NIH $30,860,913,000 National Center of Complementary and Alternative Medicine (NCCAM) $128,057,000
  • 60. NIH $30,860,913,000 NCI $5,072,183,000 National Center of Complementary and Alternative Medicine (NCCAM) $128,057,000
  • 61. NIH $30,860,913,000 NCI $5,072,183,000 National Center of Complementary and Alternative Medicine (NCCAM) $128,057,000 Office of Cancer Complementary and Alternative Medicine (OCCAM) $105,341,737
  • 62. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Untoward side-effects
  • 63. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Untoward side-effects
  • 64. 2 out of 5 adults
  • 65. 1 out of 9 children
  • 66. Grubbs V, Plantinga LC, et al. AJKD 2013; 61(5):739-47. supplement use Hispanics African Americans 31% Caucasians 36% 43% 64% 69% Use Don’t Use 57%
  • 67. Grubbs V, Plantinga LC, et al. AJKD 2013; 61(5):739-47. supplement use less than high school high school college 36% 46% 40% 54% 65% Use Don’t Use 60%
  • 68. Grubbs V, Plantinga LC, et al. AJKD 2013; 61(5):739-47. supplement use 50% Poverty Index ratio 1-3 Poverty Index ratio >3 35% Poverty Index ratio <1 31% 50% 65% Use 69% Don’t Use
  • 69. Grubbs V, Plantinga LC, et al. AJKD 2013; 61(5):739-47. • • people that use supplements are not casual users they are committed, overwhelmingly they take them everyday 70% 10% <7 18% 7-20 21+
  • 70. Grubbs V, Plantinga LC, et al. AJKD 2013; 61(5):739-47. people that use supplements are not casual users they are committed, they take them for years ye ar s 30% >3 ye ar s 3 hs m on t 12 6- on t m 6 20% 1- 22% hs 27% < • •
  • 71. Grubbs V, Plantinga LC, et al. AJKD 2013; 61(5):739-47. • • • supplement use in CKD the worse the CKD the more supplements same phenomenon in cancer 48.9% 50.2% No CKD CKD 1, 2 65.1% CKD 3, 4
  • 72. Ashar BH, Rice TN, Sisson SD. Arch Intern Med. 2007;167(9):966-9. physician knowledge No FDA approval No requirement for efficacy 35% 37% 63% 40% 65% Clueless No FDA quality assurance Clued 60%
  • 73. Harris Interactive Pole 1,010 phone interviews. October 2002 patient knowledge Evidence of efficacy FDA approval Labels list side effects & risks 32% 41% 59% 45% 55% 68% Required Not Required
  • 74. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Contamination • Adulteration • Untoward side-effects
  • 75. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Contamination • Adulteration • Untoward side-effects
  • 76. silicate stones • they are dog and sheep kidney stones • about 1% of all stones evaluated in dogs are more than 70% silicate • fewer than 50 cases have ever been reported in humans
  • 77. • 38 yr old presents with episodic left flank pain and urinary gravel-like sediment • after an initial work-up was unremarkable she recovered two small stones from her urine Stones were 100% silicate
  • 78. • • • • • Vitamin C • • • FlexProtex calcium glutamine natural gelatin chinese herbal “neck formula” Digestive Advantage Uncaria tomentosa Stones were 100% silicate
  • 79. • all the supplements were less than 2% silica • yet over two years she had ingested over 35 kg of silica and developed stones Stones were 100% silicate
  • 80. Flank pain
  • 81. Flank pain Told to stop the pills She stops the pills Pain goes away She resumes the pills Pain returns
  • 82. St John’s Wart • Induces intestinal P- glycoprotein MDRP1 • moves drug from the blood to the intestinal lumen • Induces hepatic cytochrome P-450 • 3A4 • Cyp2E1 • Cyp2C19 decreases bioavailability
  • 83. reduced bioavailability • • • • • • Calcineurin inhibitors protease inhibitors NNRTI lipid lowering agents thyroid hormone oral contraceptives • • • • • digoxin theophylline warfarin SSRI Tyrosine kinase inhibitors
  • 84. Drug levels St John’s Wort Grapefruit Juice increased P450 means drug levels fall decreased P450 means drug levels rise
  • 85. Potassium Content Noni Juice Orange Juice Tomato juice Pineapple juice
  • 86. Potassium Content Noni Juice Orange Juice Tomato juice Pineapple juice 58 mEq/L
  • 87. Potassium Content Noni Juice 56 mEq/L Orange Juice Tomato juice Pineapple juice 58 mEq/L
  • 88. Potassium Content Noni Juice 56 Orange Juice 51 Tomato juice 58 Pineapple juice mEq/L mEq/L mEq/L
  • 89. Potassium Content Noni Juice 56 Orange Juice 51 Tomato juice 58 Pineapple juice 34 mEq/L mEq/L mEq/L mEq/L
  • 90. Potassium Content Noni Juice 56 Orange Juice 51 Tomato juice 58 Pineapple juice 34 mEq/L mEq/L mEq/L mEq/L
  • 91. Potassium Content Noni Juice 56 mEq/L Orange Juice 51 Tomato juice 58 Pineapple juice 34 mEq/L mEq/L mEq/L • • • • dandelion alfalfa nettle horsetail
  • 92. Potassium Content Noni Juice 56 mEq/L inhibit Na-K-ATP • milkweedJuice 51 Orange • lily of the valley mEq/L • hawthorne berries Tomato juice • siberian ginseng 58 mEq/L Pineapple juice 34 mEq/L • • • • dandelion alfalfa nettle horsetail
  • 93. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Untoward side-effects
  • 94. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Untoward side-effects
  • 95. Under DSHEA the FDA bears the burden of showing that a supplement is unsafe or mislabeled before it can restrict or ban the product’s use.
  • 96. ephedra is a naturally occurring stimulant, alpha adrenergic found in the herb Ma Huang It was marketed as a weight loss agent under many names, the most famous being Metabolife 356
  • 97. ld ivately he ll r nal, the p its sales wi Internatio stuff, says fe Metaboli oduces the An d at places h that pr -a figure t ckbuster company 1 billion this year- s such blo a $ approach in the same league Viagra. 3/99 life sweek 10/ and New Metabo as Prozac aceuticals phar m
  • 98. It had predictable cardiovascular side effects, psychosis and radiolucent kidney stones by 1996 15 deaths and >400 adverse reactions
  • 99. It had predictable cardiovascular side effects, psychosis and radiolucent kidney stones by 1996 15 deaths and >400 adverse reactions
  • 100. In 1996 The FDA began proceedings to ban ephedra
  • 101. In 1998 and 1999, Ellis and Metabolife sent letters to the FDA "...never received a notice from a consumer that any serious adverse health event has occurred because of the ingestion."
  • 102. In 1998 and 1999, Ellis and Metabolife sent letters to the FDA "...never received a notice from a consumer that any serious adverse health event has occurred because of the ingestion." The truth was they received 14,000
  • 103. In 1998 and 1999, Ellis and Metabolife sent letters to the FDA "...never received a notice from a consumer that any serious adverse health event has occurred because of the ingestion." Six months federal penitentiary
  • 104. February 2003
  • 105. d by nne s ba wa 004 ra il 2 hed Ep Apr A in e FD th February 2003
  • 106. banning ephedra did nothing to ban similar alpha agonists
  • 107. banning ephedra did nothing to ban similar alpha agonists
  • 108. • bitter orange • seville orange • citrus aurantium banning ephedra did nothing to ban similar alpha agonists
  • 109. • bitter orange • seville orange • citrus aurantium banning ephedra did nothing to ban similar alpha agonists
  • 110. OH Ephedra N
  • 111. OH N Ephedra OH HO N Synephrine
  • 112. banning ephedra did nothing to ban similar alpha agonists
  • 113. • blue cohosh • sympathomimetic alkaloids • an ephedra derivative banning ephedra did nothing to ban similar alpha agonists
  • 114. • blue cohosh • sympathomimetic alkaloids • an ephedra derivative banning ephedra did nothing to ban similar alpha agonists
  • 115. OH Ephedra N
  • 116. DMAA N OH Ephedra N
  • 117. 1948: Eli Lilly introduces 1,3 dimethylamylamine as a nasal inhaler for rhinitis.
  • 118. • Physiology studies of the compound in the 1940s and 1950s • sympathomimetic physiological effects that mimic the action of epinephrine • increases in blood pressure • increased heart rate • increased blood sugar levels
  • 119. Council of Pharmacy and Chemistry of the American Medical Association described the toxicity of DMAA to be: ephedrine DMAA amphetamine DMAA exerted a pressor effect 3.5 times that of epinephrine. J Pharmacol Exp Ther 1946; 88(1):10-3 In 1983 Eli Lilly voluntarily removed it from the market sighting safety concerns
  • 120. 2006
  • 121. • Under the DSHEA of 1994 in order for a supplement to be an ingredient it must be naturally naturally occurring and in use prior to 1994. • DMAA was clearly used prior to 1994 • Naturally occurring is a bit slippery
  • 122. In 1996 Ping et al. isolated DMAA from geranium oil
  • 123. Published in the Journal of the Guizhou Institute of Technology The journal is now defunct
  • 124. Published in the Journal of the Guizhou Institute of Technology The journal is now defunct
  • 125. • Others have failed to find DMAA in geraniums • Prasad et al. 2008 • Jalali-Heravi et al. 2006 • Peterson et al. 2006 • Babu and Kaul 2005 • Vernin et al. 2004 • Rajeswara Rao et al. 2002 • Jain et al. 2001
  • 126. • Others have failed to find DMAA in geraniums • Prasad et al. 2008 • Jalali-Heravi et al. 2006 • Peterson et al. 2006 • Babu and Kaul 2005 • Vernin et al. 2004 • Rajeswara Rao et al. 2002 • Jain et al. 2001
  • 127. • Others have failed to find DMAA in geraniums • Prasad et al. 2008 • Jalali-Heravi et al. 2006 • Peterson et al. 2006 • Babu and Kaul 2005 • Vernin et al. 2004 • Rajeswara Rao et al. 2002 • Jain et al. 2001
  • 128. 105.5 Renal failure Severe metabolic acidosis rhabdomyolysis hyperkalemia 105.0 75 73
  • 129. Department of defense report found 40 soldiers affected by DMAA 4 fatalities 5 heat injury/rhabdo 4 seizures syncope 4 tachycardia or palpitations 4 hypertensive crisis or cerebrovascular events 3 parasthesia 2 hepatic failure 2 renal failure
  • 130. Department of defense report found 40 soldiers affected by DMAA 4 fatalities 4 hypertensive crisis or cerebrovascular events rom ed f n anparasthesiaes as b 3 sari w AA syncope mmis 4 seizures DM e co 2 hepatic failure bas or 4 tachycardia 5 heat injury/rhabdo palpitations 2 renal failure
  • 131. 1944: Eli Lilly patents and begins selling DMAA as a nasal decongestant. Trade name Florthane
  • 132. 1944: Eli Lilly patents and begins selling DMAA as a nasal decongestant. Trade name Florthane 1983: Eli Lilly removes DMAA from the market due to safety concerns
  • 133. 1944: Eli Lilly patents and begins selling DMAA as a nasal decongestant. Trade name Florthane 1983: Eli Lilly removes DMAA from the market due to safety concerns 1994: DSHEA signed into law
  • 134. 1944: Eli Lilly patents and begins selling DMAA as a nasal decongestant. Trade name Florthane 1983: Eli Lilly removes DMAA from the market due to safety concerns 1994: DSHEA signed into law 1996: Sloppy, flawed and unreproducible research finds DMAA in geraniums
  • 135. 1944: Eli Lilly patents and begins selling DMAA as a nasal decongestant. Trade name Florthane 1983: Eli Lilly removes DMAA from the market due to safety concerns 1994: DSHEA signed into law 1996: Sloppy, flawed and unreproducible research finds DMAA in geraniums 2006: DMAA is reintroduced without FDA approval by combining the DSHEA with geranium data
  • 136. 1944: Eli Lilly patents and begins selling DMAA as a nasal decongestant. Trade name Florthane 1983: Eli Lilly removes DMAA from the market due to safety concerns 1994: DSHEA signed into law 1996: Sloppy, flawed and unreproducible research finds DMAA in geraniums 2006: DMAA is reintroduced without FDA approval by combining the DSHEA with geranium data 2012: FDA challenges use of DMAA sighting safety concerns from 42 adverse events. 11 companies are sent warning letters. 10 complied, but USPlabs challenged the order in court.
  • 137. 1944: Eli Lilly patents and begins selling DMAA as a nasal decongestant. Trade name Florthane 1983: Eli Lilly removes DMAA from the market due to safety concerns 1994: DSHEA signed into law 1996: Sloppy, flawed and unreproducible research finds DMAA in geraniums 2006: DMAA is reintroduced without FDA approval by combining the DSHEA with geranium data 2012: FDA challenges use of DMAA sighting safety concerns from 42 adverse events. 11 companies are sent warning letters. 10 complied, but USPlabs challenged the order in court.
  • 138. 1.   http://www.fda.gov.
  • 139. This product is not intended to diagnose, treat, cure or prevent disease
  • 140. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Untoward side-effects
  • 141. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Untoward side-effects
  • 142. • adulteration: intensional addition of unlabeled ingredients • contamination: accidental addition of unlabeled ingredients
  • 143. The U.S. FDA laboratory isolated two anabolic steroids: • dimethazine • methasterone (Class III controlled substance) To date, 29 illnesses have been confirmed, but federal health officials say that number could rise.
  • 144. The U.S. FDA laboratory isolated two anabolic steroids: • dimethazine • methasterone (Class III controlled substance) To date, 29 illnesses have been confirmed, but federal health officials say that number could rise.
  • 145. The U.S. FDA laboratory isolated two anabolic steroids: • dimethazine • methasterone (Class III controlled substance) To date, 29 illnesses have been confirmed, but federal health officials say that number could rise.
  • 146. Laing Q, J Pharm Biomed Anal. 2006; 40:305-11 Gratz SR, J Pharm Biomed Anal. 2004; 36:525-33 From 35 to 50% of herbal erectile dysfunction treatments contain PDE-5 inhibitors
  • 147. Zotrex was a male sexual enhancement supplement manufactured by Nova pharmaceutical in Utah. The primary active ingredient was Ophioglossum polyphyllous
  • 148. Zotrex was a male sexual enhancement supplement manufactured by Nova pharmaceutical in Utah. The primary active ingredient was Ophioglossum polyphyllous
  • 149. Zotrex was a male sexual enhancement supplement manufactured by Nova pharmaceutical in Utah. The primary active ingredient was Ophioglossum polyphyllous sulfoaildenafil
  • 150. Zotrex was a male sexual enhancement supplement manufactured by Nova pharmaceutical in Utah. The primary active ingredient was Ophioglossum polyphyllous sulfoaildenafil Nova sold over 14 million pills of suloaildenafil under various names, including:
  • 151. Zotrex was a male sexual enhancement supplement manufactured by Nova pharmaceutical in Utah. The primary active ingredient was Ophioglossum polyphyllous sulfoaildenafil Nova sold over 14 million pills of suloaildenafil under various names, including: OMG
  • 152. Zotrex was a male sexual enhancement supplement manufactured by Nova pharmaceutical in Utah. The primary active ingredient was Ophioglossum polyphyllous sulfoaildenafil Nova sold over 14 million pills of suloaildenafil under various names, including: OMG-45
  • 153. Zotrex was a male sexual enhancement supplement manufactured by Nova pharmaceutical in Utah. The primary active ingredient was Ophioglossum polyphyllous sulfoaildenafil Nova sold over 14 million pills of suloaildenafil under various names, including: Maxyte
  • 154. Zotrex was a male sexual enhancement supplement manufactured by Nova pharmaceutical in Utah. The primary active ingredient was Ophioglossum polyphyllous sulfoaildenafil Nova sold over 14 million pills of suloaildenafil under various names, including: Maxyte Modified form of sildenafil, modifying existing drugs is a sinister method to evade FDA detection.
  • 155. herbal weight loss medications Vaysse J. Food Additives Contaminants Part A: Chemical Analysis, Control, Exposure & Risk Assessment 2010; 27: 903-16.
  • 156. herbal weight loss medications Medical impact of obesity Vaysse J. Food Additives Contaminants Part A: Chemical Analysis, Control, Exposure & Risk Assessment 2010; 27: 903-16.
  • 157. herbal weight loss medications Medical impact of obesity Social impact of obesity Vaysse J. Food Additives Contaminants Part A: Chemical Analysis, Control, Exposure & Risk Assessment 2010; 27: 903-16.
  • 158. herbal weight loss medications Medical impact of obesity Social impact of obesity Few medications Vaysse J. Food Additives Contaminants Part A: Chemical Analysis, Control, Exposure & Risk Assessment 2010; 27: 903-16.
  • 159. herbal weight loss medications Medical impact of obesity Social impact of obesity Few medications Medication safety concerns Vaysse J. Food Additives Contaminants Part A: Chemical Analysis, Control, Exposure & Risk Assessment 2010; 27: 903-16.
  • 160. 2D diffusion ordered spectroscopy 1H-nuclear magnetic resonance spectroscopy
  • 161. 20 13 5 1 0 u Sib e min tra h olp n phe n alei th yne s rine ph 1 ca eine ff
  • 162. 20 13 Cathartic Carcinogenic 5 1 0 u Sib e min tra h olp n phe n alei th yne s rine ph 1 eine ff ca Dunnick JK, Hailey JR. Phenolphthalein exposure causes multiple carcinogenic effects in experimental model systems. Cancer Res. 1996;56(21):4922-6.
  • 163. Among the 20 formulations analysed, 2 were strictly herbal (formulations 17 and 18), and 4 had a composition corresponding to declared ingredients on the packaging or the leaflet (formulations 6, 16, 19, 20). The others were all adulterated. Herbal 2 declared 4 adulterated 14
  • 164. sibutramine
  • 165. sibutramine
  • 166. randomized, double blind 10 mg silbutramine or placebo age 55+ BMI 25-27 must have a history of CV disease both DM + CV risk factor
  • 167. • Nonfatal MI • Cardiac arrest • Nonfatal CVA • CV death
  • 168. 40 mg/pill 30 20 10 0 23 13 1 31 16 20 5 4 2 3 4 5 7 13 12 11 8 9 10 15 14 Sample number 11 14 13 15 14
  • 169. 40 mg/pill 30 20 10 0 23 13 1 31 16 20 5 4 2 3 4 5 7 13 12 11 8 9 10 15 14 Sample number 11 14 13 15 14
  • 170. adulteration licorice glycyrrhiza glabra 50x sweeter than sucrose often it is an undeclared ingredient, sweetener 11-beta steroid dehydrogenase
  • 171. aldo Cortisol 7-30 ng/dL 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration
  • 172. aldo Cortisol 7-30 ng/dL 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration
  • 173. Inside the principle cell aldo MR 7-30 ng/dL Mineralcorticoid receptor MR Cortisol 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration
  • 174. Inside the principle cell MR 7-30 ng/dL aldo Mineralcorticoid receptor MR Cortisol 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration
  • 175. Inside the principle cell MR Na-K ATPase ENac K+ channel H+-ATPase 7-30 ng/dL aldo Mineralcorticoid receptor MR Cortisol 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration
  • 176. Inside the principle cell Mineralcorticoid receptor MR Cortisol 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration
  • 177. Inside the principle cell Mineralcorticoid receptor MR Cortisol 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration
  • 178. Inside the principle cell Na-K ATPase ENac K+ channel H+-ATPase Mineralcorticoid receptor MR Cortisol 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration
  • 179. Inside the principle cell Na-K ATPase ENac K+ channel H+-ATPase Mineralcorticoid receptor MR Cortisol 5-20 mcg/dL Cortisol circulates at 1,000 times the aldosterone concentration but does not have any mineralocorticoid activity. Why?
  • 180. • 11ß-hydroxysteroid dehydrogenase converts cortisol to cortisone • Prevents cortisol from MR Cortisol having mineralocorticoid effect
  • 181. • 11ß-hydroxysteroid dehydrogenase converts cortisol to cortisone • Prevents cortisol from MR Cortisol having mineralocorticoid effect 11ß-hydroxysteroid dehydrogenase
  • 182. • 11ß-hydroxysteroid dehydrogenase converts cortisol to cortisone • Prevents cortisol from MR Cortisone Cortisol 11ß-hydroxysteroid dehydrogenase having mineralocorticoid effect
  • 183. 11ß-hydroxysteroid cortisol cortisone dehydrogenase • 11ß-hydroxysteroid dehydrogenase converts cortisol to cortisone • Prevents cortisol from MR Cortisone Cortisol 11ß-hydroxysteroid dehydrogenase having mineralocorticoid effect
  • 184. • Glycyrrhiza glabra is 11ß-hydroxysteroid dehydrogenase inhibitor MR Cortisol • Allows cortisol to have mineralocorticoid activity
  • 185. • Glycyrrhiza glabra is 11ß-hydroxysteroid dehydrogenase inhibitor MR Cortisol • Allows cortisol to have mineralocorticoid activity 11ß-hydroxysteroid dehydrogenase
  • 186. • Glycyrrhiza glabra is 11ß-hydroxysteroid dehydrogenase inhibitor MR Cortisol • Allows cortisol to have mineralocorticoid activity 11ß-hydroxysteroid
  • 187. Na-K ATPase ENac K+ channel H+-ATPase MR Cortisol 146 106 8 78 3.0 33 0.4 165/96 • hypertension • hypokalemia • metabolic alkalosis • Glycyrrhiza glabra is 11ß-hydroxysteroid dehydrogenase inhibitor • Allows cortisol to have mineralocorticoid activity 11ß-hydroxysteroid
  • 188. Consumer Health Information www.fda.gov/consumer Black Licorice: Trick or Treat? A s it turns out, you really can overdose on candy— or, more precisely, black licorice. Days before the biggest candy eating holiday of the year, the Food and Drug Administration (FDA) encourages moderation if you enjoy snacking on the old fashioned favorite. So, if you’re getting your stash ready for Halloween, here’s some advice from FDA: If you’re 40 or older, eating 2 ounces of black licorice a day for at least two weeks could land you in the hospital with an irregular heart rhythm or arrhythmia. FDA experts say black licorice contains the compound glycyrrhizin, which is the sweetening compound derived from licorice root. Glycyrrhizin can cause potassium levels in the body to fall. When that happens, some people experience abnormal heart rhythms, as well as high blood has a long history of use as a folk or traditional remedy (www.nlm.nih.gov/medlineplus/druginfo/natural/881. html) in both Eastern and Western medicine. It has been used as a treatment for heartburn, stomach ulcers, bronchitis, sore throat, cough and some infections caused by viruses, such as hepatitis; however, NIH says there are insufficient data available to determine if licorice is effective in treating any medical condition. Licorice is also used as a flavoring in food. Many “licorice” or “licorice flavor” products manufactured in the United States do not contain any lic- some medications, herbs and dietary supplements. Consult a health care professional if you have questions about possible interactions with a drug or
  • 189. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Untoward side-effects
  • 190. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Untoward side-effects
  • 191. contamination sloppy production practices can result in lead and cadmium contamination
  • 192. contamination sloppy production practices can result in lead and cadmium contamination Ayurvedic medications Heavy metals are mixed with herbs for therapeutic effect
  • 193. Ayurvedic medications • used by the majority of India’s 1.1 billion people • Two varieties • Herbal only • Rasa Shastra deliberately combining herbs with metals (Hg, Pb, Fe, Zn), minerals, and gems.
  • 194. Saper RB, Phillips RS, Sehgal A, et al. Lead, Mercury, and Arsenic in US- and IndianManufactured Ayurvedic Medicines Sold via the Internet. JAMA. 2008;300(8):915-923.
  • 195. • randomly selected 230 ayurvedaic products that were top search results and available for sale over the Internet • examined the samples by x-ray fluorescence
  • 196. Of 230 products randomly selected for purchase, we received and analyzed 193 (84%) made by 37 different manufacturers. Reasons for failure to fill our orders included the following: 21 products were no longer available or out of stock; 1 supplier refused to fill our order of 14 products after recognizing that we were authors of a previous study of Ayurvedic medicines.
  • 197. Of 230 products randomly selected for purchase, we received and analyzed 193 (84%) made by 37 different manufacturers. Reasons for failure to fill our orders included the following: 21 products were no longer available or out of stock; 1 supplier refused to fill our order of 14 products after recognizing that we were authors of a previous study of Ayurvedic medicines.
  • 198. Of 230 products randomly selected for purchase, we received and analyzed 193 (84%) made by 37 different manufacturers. Reasons for failure to fill our orders included the following: 21 products were no longer available or out of stock; 1 supplier refused to fill our order of 14 products after recognizing that we were authors of a previous study of Ayurvedic medicines.
  • 199. Of 230 products randomly selected for purchase, we received and analyzed 193 (84%) made by 37 different manufacturers. Reasons for failure to fill our orders included the following: 21 products were no longer available or out of stock; 1 supplier refused to fill our order of 14 products after recognizing that we were authors of a previous study of Ayurvedic medicines.
  • 200. Of 230 products randomly selected for purchase, we received and analyzed 193 (84%) made by 37 different manufacturers. Reasons for failure to fill our orders included the following: 21 products were no longer available or out of stock; 1 supplier refused to fill our order of 14 products after recognizing that we were authors of a previous study of Ayurvedic medicines.
  • 201. entire cohort Metals 40 None 153
  • 202. US Website or Distributor Metals 38 None 137
  • 203. Member of AHPA American Herbal Products Association Metals 3 None 43
  • 204. Member of ADMA Ayurvedic Drug Manufacturers Association Metals 5 None 20
  • 205. Claims GMP or metal testing American Herbal Products Association Metals 30 None 121
  • 206. Rasa shastra medicine Metals 13 None 19
  • 207. Non Rasa shastra medicine Metals 27 None 131
  • 208. Safe 0.1 1.0 10 100 1,000 10,000 100,000
  • 209. Safe 10 100 1,000 10,000 100,000 Safe 1.0 10 100 1,000
  • 210. • NHANES • examined use of herbal supplements found to have excess lead in previous studies: • • • • • Ayuvedic medicine Traditional Chinese medicine St John Wort Ginko Ginseng • 455 with exposure • 12,352 with exposure • • • • • • Echinacea Kava* Velerian* Black kohosh* Bee polen* Nettle*
  • 211. • NHANES • examined use of herbal supplements found to have excess lead in previous studies: • • • • • Ayuvedic medicine Traditional Chinese medicine St John Wort Ginko Ginseng • 455 with exposure • 12,352 with exposure • • • • • • Echinacea Kava* Velerian* Black kohosh* Bee polen* Nettle*
  • 212. percent change in blood lead levels (BLL)
  • 213. percent change in blood lead levels (BLL)
  • 214. percent change in blood lead levels (BLL)
  • 215. percent change in blood lead levels (BLL)
  • 216. percent change in blood lead levels (BLL)
  • 217. Ernst E. Risks of herbal medicinal products. Pharmacoepidemiol Drug Saf. 2004;13(11):767–771. Chu NF, Liou SH, Wu TN, et al. Risk factors for high blood lead levels among the general population in Taiwan. Eur J Epidemiol. 1998;14:775–781. Chien LC,Yeh CY, et al. Effect of the mother’s consumption of traditional Chinese herbs on estimated infant daily intake of lead from breast milk. Sci Total Environ. 2006;354 (2–3): 120–6. • Similar results in Taiwan among users of Traditional Chinese Medicine • In China, higher lead levels were found in the breast milk of users of Chinese herbs
  • 218. CDC action threshold for BLL in children
  • 219. CDC action threshold for BLL in children 60 mcg/dL 45 30 60 40 15 30 25 10 0 s 60’ 19 1970 1975 1985 1991 5 2011
  • 220. • the kidney is on the front line for damage from heavy metals tubular toxicity lead ✔︎ cadmium ✔︎ uranium ✔︎ arsenic ✔︎ mercury ✔︎ nephrotic syndrome ✔︎
  • 221. • The renal tubules contain divalent cationic transporters: • Zn2+ Fe 2+ Mg 2+ Cu2+ • Limited ability to discriminate among divalent cations so the tubules avidly reabsorb • Cd2+ Pb2+ Pt2+ Ni2+ Hg2+
  • 222. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Unexpected side-effects
  • 223. herbal dangers • Who? What? Why? • interaction and accumulation • FDA inability to restrict unsafe drugs • Adulteration • Contamination • Unexpected side-effects
  • 224. • January 1992, 40 year old woman who complained of fatigue presented with a Cr 5. A kidney biopsy showed interstitial fibrosis and normal glomeruli. • From May 1990-March 1991 she enrolled in a slimming clinic and taken herbal medications • by March she was on chronic dialysis
  • 225. • April 1992, 46 year old woman referred for an incidental finding of a Cr of 3.8. Renal biopsy showed tubular atrophy and interstitial fibrosis. • 4 months later her Cr was 7.7. • From May 1990 to November 1991 she was enrolled in the same slimming clinic and took the same herbal regimen.
  • 226. following these two cases the investigators did an analysis of woman starting dialysis prior to the age 50. 9 3 1 1 1989 1990 1991 1992 first 6 months
  • 227. following these two cases the investigators did an analysis of woman starting dialysis prior to the age 50. Nine had followed the same slimming regimen from the same clinic. 9 3 1 1 1989 1990 1991 1992 first 6 months
  • 228. following these two cases the investigators did an analysis of woman starting dialysis prior to the age 50. Nine had followed the same slimming regimen from the same clinic. 9 Eight had renal biopsies that showed interstitial nephritis 3 1 1 1989 1990 1991 1992 first 6 months
  • 229. prior to the age 50. Nine had followed the same slimming regimen from the same clinic. Eight had renal biopsies that showed interstitial nephritis 9 In mid 1990 they introduced powdered extracts of Stephania tetrandra and Magnolia 3 officinalis 1 1 1989 1990 1991 1992 first 6 months
  • 230. • Stephania tetrandra belongs to the same Feng-ji family as Aristolochia Fang-ji • the Chinese characters for both plants are the same except for prefixing: • • Guang for Aristolochia Han for Stephania
  • 231. Aristolochia
  • 232. Aristolochia A Wrist Loki
  • 233. Vanhaelen MR,Vanhaelen-FastrePB, Jean-Louis Vanherweghem. 1994. The Lancet 343, (8890) (Jan 15): 174
  • 234. Vanhaelen MR,Vanhaelen-FastrePB, Jean-Louis Vanherweghem. 1994. The Lancet 343, (8890) (Jan 15): 174 Analysis of 12 different samples of Stephania tetrandra delivered to Belgium from 1990 to 1992 showed only two contained Stephania, eleven contained Aristolochia
  • 235. Vanhaelen MR,Vanhaelen-FastrePB, Jean-Louis Vanherweghem. 1994. The Lancet 343, (8890) (Jan 15): 174 Analysis of 12 different samples of Stephania tetrandra delivered to Belgium from 1990 to 1992 showed only two contained Stephania, eleven contained Aristolochia
  • 236. • Ultimately 100 women were found with varying degrees of renal failure • 70 were on dialysis or pre-terminal phase of CKD • 30 had stable creatinine less than 3 mg/dL • Estimates of exposure by looking at import records point to 1,500-2,000 people
  • 237. • Later the women developed urogenital cancer • transitional cell carcinoma of the bladder in a 28 year old 12 months after her kidney transplant • 42 year old woman developed papillary transitional cell carcinoma • 49 year old woman developed multifocal transitional cell carcinoma of the ureter after transplant
  • 238. Cosyns JP, Jadoul M, Squifflet JP, Wese FX,Van ypersele de strihou C. Urothelial lesions in Chinese-herb nephropathy. Am J Kidney Dis. 1999;33(6):1011-7. Nortier JL, Martinez MC, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med. 2000;342(23):1686-92. • women on dialysis were offered prophylactic bilateral nephrectomy and ureterectomies • this was highly effective Cancer 4 None 6 Cancer 18 None 21
  • 239. Aristocholic Acid O COOH O NO2 H2N O N N HO O N N N N OH deoxyadenosine HO O OH N NH2 N deoxyguanosine NH2
  • 240. Aristocholic Acid O Aristolactam nitrenium ion O O COOH N O NO2 O metabolic activation H2N O N N HO O N N N N OH deoxyadenosine HO O OH N NH2 N deoxyguanosine NH2
  • 241. Aristocholic Acid O Aristolactam nitrenium ion COOH O NO2 N A Ad du c tF or m at io n metabolic activation D H2N O N N O OH deoxyadenosine HO O N N O N N O N O HO N N OH NH2 deoxyguanosine NH2
  • 242. DNA Adducts are aristocholic acid’s fingerprints
  • 243. DNA Adducts are aristocholic acid’s fingerprints Moreover, Schmeiser et al. were able to detect DNA adducts formed by metabolites of aristolochic acid (aristolactams) in samples of kidneys removed from five patients with Chinese-herb nephropathy. These adducts are specific markers of exposure to aristolochic acids and are directly involved in tumorigenesis. Nortier JL, et al. N Engl J Med. 2000; 342.
  • 244. These DNA adducts cause adenine to thymine transversion mutations in the tumor suppressor gene TP53
  • 245. These DNA adducts cause adenine to thymine transversion mutations in the tumor suppressor gene TP53 “It is now clear that p53 inactivation is essential for the formation of nearly all cancers...TP53 is more frequently mutated in human tumors than any other gene in the genome...” Bert Vogelstein and Carol Prives
  • 246. The FDA found Aristolochia in numerous herbal supplements in the U.S.
  • 247. Radix aristolochiae Jade Meridian Circulation: East Earth Herb Inc The FDA found Aristolochia in numerous herbal Qualiherb ChinesesupplementsQualiHerb (Division of Finemost) Herbal Formulas in the U.S. Dianthus Formulas Ba Zheng San Clematis & Carthamus Formula 21280 QualiHerb (Division of Finemost) Virginia Snake Root, Cut Aristolochia serpentaria Penn Herb Co. Green Kingdom Akebia Extract Ava Health Green Kingdom Stephania Extract Ava Health Neo Concept Aller Relief BMK International, Inc. Mu Tong Clematis armandi Botanicum.com Fang Ji Stephania Botanicum.com Stephania tetrandra, roots, whole Ethnobotanical
  • 248. Balkan nephropathy, a disease of middle-aged Romanian farmers
  • 249. • chronic interstitial nephritis • affects people in the Danube River basin • ages 30-60 with a latency of 15 years • familial but not inherited pattern of distribution
  • 250. Etiologies of ESRD
  • 251. Etiologies of ESRD 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% Diabetes Hypertension Glomeruloneph Cystic kidney 2008 2006 2004 2002 2000 1998 1996 1994 1992 1990 1988 1986 1984 1982 1980 0%
  • 252. Etiologies of ESRD 100% 90% 80% 70% Balkan nephropathy is responsible for 70% of ESRD in some endemic areas 40% 30% 20% 70% 2000 50% 1986 60% 10% Diabetes Hypertension Glomeruloneph Cystic kidney 2008 2006 2004 2002 1998 1996 1994 1992 1990 1988 1984 1982 1980 0%
  • 253. “An important complicating feature is an apparently increased incidence in the development of transitional cell tumors of the renal pelvis, ureter, and bladder. These malignancies may be multiple and bilateral.”
  • 254. The pathway of exposure to humans remained a mystery. So Grollman spoke with dialysis patients. "I was sure they had been taking herbal medicines," Grollman says. "And then we interviewed them through a translator and that made clear they hadn't." When shown pictures of the plant, the patients identified it as Wolf's Paw, a common weed. Grollman says he later walked around the farms outside the city and found the plant on the outer fringes of the fields. When they tramped the plowed rows, they found it entwined among the wheat stalks. Mead JC. The Scientist Nov 1, 2007.
  • 255. Taiwan
  • 256. highest incidence of dialysis in the world 430 per million
  • 257. Yang MH, Chen KK,Yen CC, et al. Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan. Urology. 2002;59(5):681-7.
  • 258. Yang MH, Chen KK,Yen CC, et al. Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan. Urology. 2002;59(5):681-7. • Taiwan had a high rate of urothelial cancer, especially upper tract disease which ordinarily is unusual • this was thought to be due to arsenic poisoning, blackfoot disease • epidemiological studies showed high rates in areas not endemic for arsenic • High rates of women, young people and elevated creatinine
  • 259. Yang CS, Lin CH, Chang SH, Hsu HC. Am J Kid Dis Feb 2000 vol 35;2: 313-8 • Following the publication of the Belgian slimming clinic other cities began reporting series of Chinese herb nephropathy • Taiwan published an early case series of 12 people with the syndrome
  • 260. • Cohort of 200,000 • Prescription data from the National Health Insurance • 39.3% of the Taiwanese population treated Chinese herbal medicine with aristocholic acid January 1997 and November 2003 • Cumulative dose exceeded 100g per person
  • 261. • Cohort of 200,000 • Prescription data from the National Health Insurance ned ban 39.3% of the Taiwanesewas • hia population treated oloc medicineer 2003 ist herbal emb with aristocholic r Chinese 1997 and November 2003 A acid Januaryov in N • Cumulative dose exceeded 100g per person
  • 262. this represents nearly 1,200 people avoiding dialysis a year
  • 263. • • • • • Jean-Louis Vanherweghem Michel F. Depierreux Michel Jadoul Renee Vanhaelen-Fastre Maurice Vanhaelen • • • Discovered the nephropathy • Inspired the solution to Balkan nephropathy • Key to the discovery of the cause of Taiwanese ESRD Tracked down the cause Decided to offer prophylactic nephrectomy
  • 264. The Taiwan experience shows us the way. Government action to restrict dangerous herbals can influence public health.
  • 265. Blendon RJ, Benson JM, Botta MD, Weldon KJ. Users' Views of Dietary Supplements. JAMA Intern Med. 2013;173(1):74-76. 2011: 584 dietary supplement users over the age 18 Stop 25% only 25.4% would stop using a supplement if public health authorities stated it was ineffective None 75%
  • 266. Blendon RJ, Benson JM, Botta MD, Weldon KJ. Users' Views of Dietary Supplements. JAMA Intern Med. 2013;173(1):74-76. 2011: 584 dietary supplement users over the age 18 discussed 36% None 64% only 25.4% would stop using a supplement if public health authorities stated it was ineffective only 35.9% had told their doctor about their use of supplements
  • 267. 2 out of 5 adults
  • 268. 1 out of 9 children
  • 269. In America we expect all foods, medicines, supplements, vitamins, and health foods to be safe and uncontaminated. We give these medicines to our children. They have to be safe and pure.
  • 270. Senators John McCain (R-AZ) and Byron Dorgan (R-ND)
  • 271. 2010: Dietary Supplement Safety Act Replaced the existing new dietary ingredient provisions of the Food, Drug and Cosmetic Act (FDCA) with a list of accepted dietary ingredients to be created by the FDA Created potential civil liability for retailers that fail to obtain certification from their suppliers that the products they sell have met all upstream regulatory requirements Required companies to report all adverse events to FDA. 
  • 272. Orin Hatch (R-UT) Chief author of DSHEA
  • 273. Orin Hatch (R-UT) Chief author of DSHEA
  • 274. Orin Hatch (R-UT) Chief author of DSHEA Tom Harkin (D-IA) Co-author of DSHEA Recieved money from Herbalife
  • 275. Orin Hatch (R-UT) Chief author of DSHEA McCain droppped support for his own bill after talking with Hatch
  • 276. thank-you
  • 277. • http://jama.jamanetwork.com/article.aspx?articleid=187430#REF-JED80023-12 • http://argunalbayrak.files.wordpress.com/2010/06/ chicago_cemetary_1989_bw.jpg • cemetary pic • http://www.shorpy.com/node/10051?size=_original • steam boat http://commons.wikimedia.org/wiki/ • • FDR • http://www.thenation.com/sites/default/files/fdr_ap.jpg School girls http://www.stjohns-es.org/page.cfm? p=1792&nmonth=any&nyear=any&ncat=6%2C2&pageStart=121 NIH Budget http://officeofbudget.od.nih.gov/pdfs/FY12/Approp.%20History%20by%20IC)2012.pdf File:Tulane_U_Gibson_Hall_from_Audubon_Park_New_Orleans_1900.jpg • tulane • bottle • https://www.etsy.com/listing/98628805/foley-co-4-apothecary-bottlechicago-usa?ref=related-1, and i bought the bottle • http://commons.wikimedia.org/wiki/ File:StateLibQld_1_140295_Portrait_of_a_wedding_party,_1930-1940.jpg • wedding • http://www.defense.gov/DODCMSShare/NewsStoryPhoto/2011-05/ hrs_110503-D-9999G-001.JPG • badge • http://sydney.edu.au/senate/images/pharmacy/a417001.jpg • pharmacy (http://sydney.edu.au/senate/ students_early1_gallery_pharmacy.shtml) • http://www.huffingtonpost.co.uk/2012/04/18/queen-mother-lady-colincampbell-french-cook-_n_1433853.html#s881105 • lady writing, queen mother • Image credit: <a href='http://www.123rf.com/photo_10500918_herbs-withalternative-medicine-herbal-supplements-and-pills.html'>elenathewise / 123RF Stock Photo</a> OCCAM budget from annual report on complementary and alternative medicine 2011 1940 eli lilly http://www.friendsofwillis.hampshire.org.uk/elylilly.jpg geraniums http://www.coldclimategardening.com/2009/06/16/garden-bloggers-bloom-dayjune-2009/ Muscle guys http://farm5.staticflickr.com/4124/5064711595_b968ac2589_o.jpg http://farm4.staticflickr.com/3093/2651904068_ccaa17a5f8_o.jpg picture of meat http://youronestophalalshop.com/meat.html picture of chicken http://www.fresh-poultry.com/poultry-menu/ Picture of eggs http://www.imcpl.org/kids/blog/?p=8917 Dialysis patient http://upload.wikimedia.org/wikipedia/commons/c/c2/ Patient_receiving_dialysis_03.jpg