Dietary Supplements: Enough Already! Top Ten Things to Know Rhonda M. Cooper‐DeHoff, Pharm D, MS, FACC, FAHA University of Florida Associate Professor of Pharmacy and Medicine Presenter Disclosure Statement No conflicts or commercial relationships to disclose Learning Objectives After this lecture you will be able to: Understand current usage and expenditure patterns for dietary supplements Recall US regulations surrounding dietary supplements Recognize how dietary supplements may affect efficacy of and interact with prescription drugs Promote patient safety by counseling patients on issues pertaining to dietary supplement use Audience Response I take (have taken) herbal / dietary supplements Audience Response I recommend (have recommended) herbal/ dietary supplements to my patients #1 Definition and Cost of Complimentary and Alternative Medicine (CAM) Categories of CAM (NIH) •Group of diverse medical and healthcare systems, Definition practices and products that are not generally considered part of conventional medicine. Alternative Biologically Manipulative Mind‐body Energy Medical Based and Body‐ Techniques Medicine Based Systems Vitamins Approaches & Spiritual Biofield Acupunct. Minerals Massage Natural therapy Magnetic Chinese Products Meditative field Medicine •Plants (gingko) Chiropract medicine Relaxation Reiki Ayurveda Diets 1998 Expenditure on CAM Manipulative and Biologically Mind‐body Alternative Body‐Based Energy Medicine Based Techniques Medical Systems Approaches 1.5% of $34 total HCE Billion but 11% of OOP OOP NCAM 2007 survey, published in 2009 Expenditure on CAM Manipulative and Biologically Mind‐body Alternative Body‐Based Energy Medicine Based Techniques Medical Systems Approaches Vitamins & Minerals $32 Billion > 33% of OOP total OOP Natural Products ($10 B Herbals) Rx Expense •Plants (gingko) NCAM has awarded more than $250 Million over the last decade NCAM 2007 survey, published in 2009 #2 Who is taking Dietary Supplements and Why Who’s Taking Supplements? 4 in 10 US (38%) used a DS in last 2 years adults Female, Richer, more educated Users tend to American Indian / Caucasian be Ages 18‐70 1 in 3 US take both Rx and dietary Adults (72 M) supplements Why People Take Dietary Supplements 2011 Harvard School of Public Health Survey 41% 41% 36% 28% To To feel To boost To reduce improve better immune risk of overall system heart energy disease levels Telling their Health Care Provider 2006 AARP Survey 35% in 2011 Harvard Survey CAM – Complimentary and Alternative Medicines #3 What are they taking and why do we care? The 20 Top‐Selling Herbal Supplements in the US for 2012 (Food, Drug, Mass Market Channel) St. John’s wort (Hypericum perforatum) Interactions Herb‐Drug Interactions Pharmacodynamic Pharmacokinetic Augments or antagonizes the activity Absorption, Distribution, of the drug Metabolism, or Elimination Induction of metabolism Warfarin + Ginkgo Bleeding Inhibition of metabolism Concentration Gardiner P, Am Fam Physician. 2008 Jan 1;77(1):73-8 Time St. John’s Wort‐CYP3A4 and P‐gp (Hyperforin) (Hypericin) CV DRUGS Drug Effect Pathway Cyclosporin A 46% ↓ AUC CYP3A, P‐gp Digoxin 25% ↓ AUC P‐gp Simvastatin 48% ↓ AUC CYP3A Tacrolimus 35% ↓ AUC CYP3A Drug Effect Pathway Warfarin 28% ↓ AUC CYP2C9 Irinotecan 24% ↓ ACU CYP3A Verapamil 78%↓ AUC CYP3A Indinavir 57% ↓ AUC CYP3A Amitriptyline 22% ↓ AUC CYP3A Midazolam 20% ↓ AUC CYP3A Fexofendadine 10% ↓ AUC P‐gp Alprazolam 53% ↓ AUC CYP3A Norethindrone 14% ↑oral CL CYP3A Poly Herbs 70 yo african american man seen on house call by NP and consultant pharmacist PMH: hypertension, CHF, osteoarthritis hip, neuropathy, depression, anxiety, BPH, gastritis CC: light headedness and worsening hip pain, feeling depressed Exam: orthostatic hypotension, elevated pulse Meds: EC ASA, methadone, enalapril, furosemide, pantoprazole, doxazosin, travoprost eye drops, sertraline Prevention Magazine Herbal Medications can help conditions, improve overall QOL St John Wart, Bilberry, Zing (gingko biloba, ginseng etc), Hawthorne extract, CoQ10, Cata‐clear (bilberry, vitamins), Colon‐Helper (aloe, gentian, goldenseal, etc), Valerian, Saw Palmetto Cappuzzo K. Consultant Pharmacist 2006;11:911-915 Audience Response Which of the following are potential drug‐herb interactions in this patient? A) St John Wart – Methadone (decreased activity) B) St John Wart – SSRI (serotonin syndrome) C) Ginkgo Biloba – ASA (platelet inhibition) D) All of the above At end of visit patient asked about whether he could take Viagra to reduce stress on his heart…….. He had heard about it on the news……… Herb Containing Stimulants INGREDIENT USE Adverse CV Effect Bitter Orange Weight Loss, Nasal Cong. Hypertension Cola Nut (1-3.5% caff) Mental or physical fatigue Arrhythmia, ↑ HR, palpit. Country Mallow (0.8-1.2% Weight loss, ↑ energy, Arrhythmia, ↑ BP, tachy ephedrine) impotence, asthma Ephedra Appetite sup ↑ HR, ↑BP Green Tea (2-4% caff) Cognition, diuretic, Arrhythmia, ↑ HR, palpit. cholesterol Guarana (2.5% caff) Weight loss, athletic perf, ↑ HR, CNS stimulant fatigue Khat (bath salts) Depression, fatigue, obesity SOB, circ stimulant Yerba mate (0.2-2% caff) Appetite sup, mental stim. Arrhythmia, ↑ HR, palpit. Ann Pharmacotherapy 2004;38:812-6 Statins 61 yo man w/ hx of hypercholesterolemia x 11 yrs, tx with multiple different statins (all at 10mg dose) which was unsuccessful due to muscle intolerance (w/in 1 week). Normal CK, moderate LFT bumps. Patient drank 3 cups of green tea everyday “to reinforce his health”. Prodrug Active Metabolite Werba et al. Annals of Int Med 2008;149:286-288 Audience Response The likely underlying mechanism for the green tea –simvastatin interaction is A) CYP3A4 induction B) CYP3A4 inhibition C) Unknown mechanism #4 We need to know more about DS! Case Presentation DSB is a 42 yo police officer. He weighs 260 lbs, BP 143/92, TC 200, LDL 130mg/dl, glucose 105 mg/dl He takes a weight loss supplement (imported from Brazil) and loses 10 lbs Label: vitamin E, centella, senna, cascara, other “natural ingredients” He undergoes routine, random drug screen He loses his job “Natural Ingredient”: AMPHETAMINE NEJM 2009;361:1523-1525 Audience Response How comfortable do you feel with your knowledge of CAM? A) Very comfortable B) Somewhat comfortable C) Not at all comfortable How much do we know? # of subjects Self-assessed knowledge of herbal toxicities and herb–drug interactions among physicians • 16 question MC quiz regarding toxic effects and drug interactions of herbals • Mean score was only slightly higher than would have occurred from random guessing Suchard JR et. al., Eur J Emerg Med. 2004 Aug;11(4):193-7. Pharmacists scored < 50% in a yes or no quiz on herbal medicines Chang et. al. Ann Pharmacother. 2000 Jun;34(6):710-5 Red Yeast Rice ‐ Content Becker D J et al. Ann Intern Med 2009;150:830-839 Halbert SC et al. Am J Cardiol 2010;105:198-204 Citrinin (byproduct of fermenting process) is a mycotoxin (nephrotoxic) #5 DS Regulation / Oversight Dietary Supplement Oversight •Dietary Supplement Health and Education Act •Statute of US federal legislation (Orin Hatch R‐Utah April DSHEA 1993) •Went through senate and house in less than a year and signed by Clinton in Oct 1994 •DS are regulated on the food side of FDA (not drug side) FDA •Serving Size, not Dose • Supplement vs Food USP •Nongovernmental, NFP organization (United States •USP sets standards for Rx and OTC drugs (required) Pharmacopeia) • 2001 USP launched verification program for DS (voluntary) Companies Participating in the USP Programs Products . Verifies what’s on the label is in the bottle . No harmful contaminants . DS will break down and release ingredients in the body . DS has been made under GMP #6 Where does the FDA fit in? What is the FDA Doing? Reumofan Plus & WOW August 2012 Pulled due to discovery of dexamethasone, diclofenac and methocarbamol Sexual Enhancement Products FDA puts out warnings on many products –all contain Sildenafil ViaXtreme Black Ant Weight Loss Industry Expenditure HCA – What is that?? FDA puts out warnings on many products –all contain Sibutramine (withdrawn from market in 2010) Advanced Slim 5 6.6 mg Lorcaserin (Belviq) (10mg in standard tablet) Jimpness Beauty Fat Loss Capsule MAXILOSS FDA Recalled Supplements FDA Allowed Claims “Healthful diets with adequate folate may Health reduce a woman’s risk of having a child with a brain or spinal cord birth defect” DISCLAIMER "This statement“fortified, has not beenhigh, evaluatedrich in, excellent by the sourceFDA. NutrientThis product isof, not good intended source to of, diagnose, and high treat, potency” cure, or prevent any disease." Structure “calcium builds strong bones” Function Men’s Health Magazine (March 2012) #7 Medical Literature Impact of Study Results Impact of • 75% said “minimally influenced government‐ by government statements contradicting efficacy claims of sponsored DS manufacturers” studies on • 25% said “would cease use of a efficacy of DS if public health authorities DS: stated it was ineffective” Professional Societies The widespread, indiscriminate use of dietary supplements presents substantial risks to public health and pharmacists have an opportunity and a professional responsibility to reduce those risks State of complementary and alternative medicine in CV, lung and blood research fosters and encourages collaboration among scientists Integrating complementary medicine into CV medicine – puts emerging area of CAM into focus and enables physicians to provide better patient care #8 Energy Drinks –Cause for Concern?!