Herbs Every Pediatrician Should Know

1. Herbs Every Pediatrician Should Know Kathi J Kemper, MD, MPH Director, Center for Integrative Medicine Professor of Pediatrics and Public Health Sciences Wake Forest University Health Sciences

2. Disclaimer • I have the following financial relationships with the manufacturer(s) of any commercial product(s) and/or provider of commercial services discussed in this CME activity:         American Academy of Pediatrics, “Mental Health, Naturally “ Author. Royalties anticipated. • The presentation will include no description of any proprietary items for screening, diagnosis, or treatments. • I do not intend to discuss an unapproved or investigative use of a commercial product in my presentation.

3. Objectives By the end of this presentation, participants will be able to: • Describe the role of herbal medicine in the overall scheme of health care • Identify at least one herbal product they already use • Confidently and effectively ask patients about their use of herbal products • Use evidence-based resources to advise patients about the safe and effective use of herbal products and report adverse events

4. Integrative Approach – herbs’ role? • Lifestyle – Environment, Exercise/Sleep, Nutrition, Mind-Body • Supplements, including herbs; vitamins, minerals, amino acids, hormones, medications • Massage, PT, chiropractic, osteopathic, surgical and other biomechanical approaches • Biofield therapies

5. Role of herbs; ask all • NOT a replacement for fundamentals • May be a useful adjunct if used wisely • Patients may be using; ask! • What is this patient ALREADY taking???? Ephedra? Laxative herbs? Diuretic herbs? Stimulant herbs?

6. Asking patients • By show of hands, how many people in this room use an herbal product 4 + days weekly to achieve a health goal?

7. Common, unconscious • When you ask, give examples! • For example, coffee, tea, commonly used products for age/gender/condition • For children - echinacea, goldenseal, elderberry • For men - saw palmetto • For women - cranberry, vitex, black cohosh • For elderly - ginkgo • Unique cultural/ethnic traditions - garlic, chamomile

8. Be Safe! • Ask all patients and document the product, ingredients and manufacturer in medical record • Herb-drug interactions can occur • ‘94 DSHEA means little consumer protection; marked variability in purity and potency • Use caution during pregnancy, lactation and infancy, and with other biochemical remedies • Opportunity costs - using herbs when another approach would be more cost-effective and safer M Cirigliano, JAMA, 1998;280:1565-6

9. Herbs and Medication - differences • Processing • Purity • Potency • Politics/ regulation • PR – perceptions, marketing • Power of advertising; impact on peer review

10. 1994 DSHEA on food supplements 1. Supplements can be marketed without testing efficacy. 2. Safety need not be proved before marketing. Burden is on FDA to prove product is unsafe. (Ephedra was banned in 2004 after YEARS after reports of deaths) 3. Standards not required for manufacture. 4. Structure/function product claims allowed. 5. Label claims do not require extensive evidence. 6. FDA approval not needed for marketing claims. More recent requirements for GMP FTC has cracked down on marketing more in last 5 years. Report adverse effects to FDA MedWatch test.fda.gov/medwatch/

11. http://www.fda.gov/downloads/Safety/MedWatch/HowToReport/DownloadForms/ucm082725.pdfhttp://www.fda.gov/downloads/Safety/MedWatch/HowToReport/DownloadForms/ucm082725.pdf

12. Toxicity • Herbs themselves; direct (eg allergies or rashes from echinacea) • Natural variability • Wrong or diluted product • Wrong dose (Excessive ephedra) • Manufactured NOT customary (kava) • Heavy metals (Ayurveda, Mexican, Asian - melamine, anyone?) • Drugs; intentional “spiking”

13. Safety Summary • Herbs are not necessarily safe just because they’re natural • Herbs work biochemically • FDA regulation needed to assure purity/potency

14. IF YOU BUY HERBS, • Manufacturer has base in Germany, France or Canada • Label: • Scientific (Latin species) name of plant • standardized extract • expiration date, lot # • source (leaves, root, flower, etc.) • Local manufacturer whose plant you have visited? • CAN YOU RECOGNIZE IT?

15. Skin • You have just spent a little too much time in the sun, getting your vitamin D and enjoying the pools and beach • Skin is red, not blistered • What herbal product can you use to help relieve the pain and promote healing?

16. Aloe vera - History and Common uses • used by Egyptians (Cleopatra’s beauty secret?), Greeks, Chinese, Ayurveda, S. Africa, S. America • Used for: • burns and skin irritations • ulcers, canker sores • laxative

17. Aloe - active ingredients • glucomannan - emollient polysaccharide • carboxypeptidase - bradykininase, reduces pain • magnesium lactate; zinc, calcium, glucose, cholesterol, triglycerides • salicylic acid and other anti-prostaglandin/ anti-thromboxane compounds • acemannan - immune stimulator • aloin or barbaloin- strong laxative; uterine contractions?

18. Aloe - scientific evidence of effectiveness • minor burns and wound healing, comparable to Silvadene; good antibacterial properties • acemannan stimulates killer T cells and fights viral replication, including HIV; increases WBC in HIV infected persons; no studies on aloe affecting AIDS clinical course • preliminary studies suggest potential use in duodenal ulcer, canker sores • barbaloin, aloin are potent cathartics

19. Aloe - bottom line • good for home treatment of minor wounds including burns, scrapes, etc. • possibly useful for canker sores • very safe for external use

20. Nervines You have just had a rough day at the office. You come home and try to decide which herbal product might help you relax. Assuming you aren’t allergic to any, which of the following “herbal remedies” is safest? A. Beer B. Whiskey C. Chamomile/lemon balm tea D. Kava kava

21. Chamomile • Mild anti-inflammatory • Mild sedative (stress, insomnia) • Mildly relaxes intestinal spasms (colic) • Yes, Peter Rabbit’s mother was on to something (1 Tablespoon to be taken before bedtime - rabbit dose)

22. Chamomile - Biochemistry/ Active Ingredients • chamazulene • alpha-bisapolol • apigenin • flavonoids and other antioxidants

23. Chamomile - Scientific Evidence • apigenin binds GABA receptors - like many sedatives • RCT of essential oil fragrance in young adults: signif. calming • Case series:10/12 hospitalized patients drinking c. tea slept • Helps rats sleep Shinomiya K. Biol Pharm Bull, 2005 • Good for stressed cows, too Reis LS. J Vet Sci, 2006

24. Other herbal sedatives • Valerian (sleep aid), hops, lemon balm, passionflower (anxiety), skullcap • All recommended by German commission E to treat restlessness • Low risk • Often found in combination products • NOT processed kava kava - potent liver toxicity

25. Valerian - Smelly soporific • Galen used to treat seizures • 1700’s - sedative, anti-spasmodic • WW1 - treat shell shocked soldiers; anti-anxiety • 120 chemical constituents; potency varies by species and wanes over time • GABA receptors; positive effects in mice and men • Helpful for sleep, anxiety

26. Valerian - Scientific Evidence: anxiety and sleep • RCT of 40 anxious adults; 100 mg TID X 21 d, signif improved sx compared with placebo • DB X-over study of 128 insomniac adults, 400 mg qhs ->signif improvement in sleep onset compared with placebo • Comparison study of 450 mg qhs: shorter sleep onset and no hangover • Young adults: 450 mgs qhs shorter sleep onset and better quality of sleep than placebo

27. Valerian - Toxicity/Side Effects • Very safe even in those who’ve taken huge intentional ODs • Mild side effects - headaches, restlessness • No apparent addictive or dependent qualities; no interaction with EtOH

28. Stress, part 2 • You like caffeine, but want to avoid the jitteriness and irritability. What else might you drink? • WHY?

29. Green tea • Theanine (amino acid) • Counteracts negative effects of caffeine without making you sleepy Kimura K. Biol Psychiatry, 2007

30. Immune Function • You are seeing a patient for a health supervision visit (check-up). She is starting to develop cold symptoms, and has taken vitamin C and zinc lozenges, and plans to make some chicken soup. • She washes her hands, sleeps well and covers her cough. • What herbal remedies does evidence suggest MIGHT be helpful (safe for most people) to boost immune function?

31. Immune boosters? • Echinacea - maybe (I do) • Elderberry (brand tested has been Sambucol) - maybe (I do) • Ginseng (brand tested has been Cold-FX) - maybe (I do) • Astragalus - maybe (I don’t)

32. Echinacea- Botany • Activity varies by species, part used, harvest timing, preparation, storage • MANY different constituents

33. Echinacea - Scientific Evidence: Immune System • Polysaccharides increase # WBCs released from bone marrow; activate phagocytosis; enhance production of TNF, interferon, interleukeins 1 and 6 • Inulin stimulates alternative complement pathway

34. Echinacea - Scientific Evidence • E. purpurea extracts taken daily in high doses • reduce the number of cold and flu symptoms in adults • reduce the number of colds acquired by adults • No benefits on cure kids; may help prevention • Safety - some allergies (skin rashes) Linde K. Cochrane Database Rev, 2006 Weber W. J Alt Comp Med, 2005 Taylor JA. JAMA, 2003

35. Elderberry (Sambucol) • used in folk medicine to treat influenza, colds and sinusitis • has antiviral activity against influenza and herpes simplex • RCT of adults with < 48 hours influenza symptoms given 15 mL QID, significantly reduced length of symptoms Zakay-Rones Z. J Int Med Res, 2004 Barak V. Isr Med Assoc J, 2002 Vlachojannis JE, Phytother Res. 2010

36. Ginseng • 5 Canadian studies including > 700 adults of Cold-FX, suggest it can help PREVENT and reduce duration (by nearly 6 days) of viral respiratory infections in adults • 1 study shows it is feasible to give to children Seida JK. Evid Based Complement AlternatMed. 2009 Vohra S. Pediatrics, 2008

37. Case: Migraines • 17 year old with recurrent migraines. She keeps a headache diary, avoids triggers, gets enough sleep; she has started B2 supplements, 5-HTP supplements, fish oil; is thinking about massage and acupuncture. She does not want to take drugs. • Which herbal supplements might be helpful? • Ginger for nausea • Feverfew - for prevention • Butterbur (UPA-free) • All of the above

38. Ginger (Zingiber officinale) • related to turmeric and cardamom • contains: shogoal, gingerols (sesquiterpenes), bisabolene, zingiberene, zingiberol • RCT: + effects on nausea and vomiting with chemo, motion sickness, pregnancy, post-op • Safe- rare allergies, upset stomach • Dose: 500 - 1000 mg/QID or tea ad lib White B. Am Family Phys, 2007

39. Feverfew: Tanacetum parthenium • Purity and potency vary markedly between products; British > American products in general; higher with spring harvest; look for at least 0.2% parthenolide content • 3+ RCT show 25-50 mg daily help prevent migraines • Safety: 10% mouth sores; rebound if stopped Tepper SJ. Curr Pain Headache Rep, 2008

40. Feverfew - Scientific Evidence: Migraines • Parthenolide reduces platelet activation • P. prevents release of arachidonic acid and serotonin, reducing prostaglandin-mediated inflammation • P. reduces damage to microvessel walls • 3 RCT in humans show that 2-3 fresh leaves (25-50 mgs BID of dried leaves) effectively prevent migraine, and rebound HA when leaves stopped • NOT effective in treating HA acutely

41. Butterbur (Petadolex) • 2 RCTs before 2006; 293 adults; 150 mg daily showed benefits, but not 100 mg daily • 2008 German RCT in children showed positive prophylactic effect (brand used in most studies is Petadolex) • Must be UPA-free! Oelkers-Ax R, Eur J Pain, 2008 Sadler, Pediatrics in Review, 2007 Oelkers-Ax R. Eur J Pain, 2008 Agosti R. Phytomedicine, 2006 Pothman R. Headache, 2005

42. Depression case 15 year old landscaper with recurrent depression; gets plenty of exercise; poor sleep; junk food junky, unwilling to change; just broke up with girlfriend; lost his job Is St. John’s wort a good idea? (Note: if he asks you, he’s probably already using it. Ask about which brands he’s tried and what he’s already read on the internet)

43. St Johns Wort • Depression – possibly effective 300 mg three times daily http://nccam.nih.gov/health/stjohnswort/ • Sunburn • Interferes with many other medicines • Which brands contain what they say they do? • http://www.consumerlab.com/results/sjw.asp

44. Resources • Free • NIH NCCAM • *NIH MedLine Plus • WFUBMC - BestHealth • Subscription, but worth it • Natural Medicines Comprehensive Database • Natural Standard • ConsumerLab.com

45. Suggested Practice Changes • Try drinking green tea to see how it affects you • Try an aloe product on your next sunburn or canker sore. • Try using echinacea, ginseng, or elderberry for your next cold • Ask at least 50% of patients in the next week about their use of herbs • Advise your patients who use herbal products to avoid herbal products from developing countries • Ask your assistant to print out the FDA MedWatch form. • Subscribe to an herbal information resource for 1 year to see how useful it is in your practice. • Join the AAP SOCIM (tsalus@aap.org or www.aap.org/sections/chim/

46. Extra Info Slides

47. Product variability - ginseng • 25 commercial products analyzed • All products contained species listed on label • Ginsenoside concentrations varied 15 and 36 fold in capsules and liquids, respectively • Eleutheroside concentrations varied 43- and 200- fold in caps and liquids respectively Harkey, et al. Am J Clin Nutr, 2001

48. Heavy metals in folk remedies • Lead (12 cases in US in 2002-2003 from Ayurvedic herbs from India) • Mercury in TCM • Arsenic and Mercury in Chinese herbal balls • AVOID HERBAL PRODUCTS FROM DEVELOPING COUNTRIES MMWR, 2004 Occup Environ Med, 1998

49. Also for Depression • Saffron • Studies from Iran suggest it is as effective as antidepressant medications with fewer side effects • Expensive to get the real thing • No insurance coverage

50. Curcumin (Turmeric) • Anti-inflammatory (inhibits LOX and COX-2) • Antioxidant; free radical scavenging • 19 ongoing clinical trials for chemoprevention of cancer; may reduce multi-drug resistance and protect normal cells • Increases antibacterial effects of commonly used antibiotics • Neuroprotective effects (Alzheimer’s prevention?) • Absorbed better with oil and black pepper • Safety: causes biliary contractions (avoid if stone history); inhibits platelet aggregation