1. Herb-Drug Interactions “Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs”

2. Numbers of Herb-Drug Interactions Reported by Various Sources Source # of herbs described # of herbs w/interactions Botanical Safety Handbook 54011 Herb Contraindications and Drug Interactions 20779* British Herbal Compendium 8417 ESCOP Monographs on the Medicinal Use of Plant Drugs 6015 The Complete German Commission E Monographs 30835 Herbal Medicines-A Guide for Health-Care Professionals 10742 WHO Monographs on Selected Medicinal Plants 2814 Herbal Medicines-A Guide for Health-Care Professionals 141---† Mechanisms of Drug Interactions NA55‡ HealthNotes Clinical Essentials 15148

3. Types of Herb-Drug Interactions Type of Interaction # of Herbs Modifies intestinal absorption of medicines Impairment by hydrocolloidal fiber 23 Selective precipitation of drug by tannins 38 Selective precipitation of drug by iodine 12 Enhancement of drug by pungent herbs 4 Potentiates cardiotonic medicines Herbal cardiotonics 11 Stimulant laxatives 17 Enhancers of urinary potassium excretion 8 Potentiates sedative or tranquilizing 21 medications Modifies blood sugar in insulin-dependent diabetes Hypoglycemic herbs 72 Hyperglycemic herbs 9 Modifies effects of prothrombopenic anticoagulants Potentiation by coumarin-containing plants 7 Potentiation by platelet aggregation inhibitors 11 Antagonism by plants high in vitamin K 18 Incompatible w/medications for gastrointestinal tract Stimulants for secretion of stomach acid 37

4. Potential Severity of Herb- Drug Interactions Severity of Interaction # (and %) of Interactions Beneficial effects or reduction of drug side effects 18 (17.0) Innocuous effects28 (26.4) Production of disease or enhancement of side effects 18 (17.0) Threat to life through interaction with dangerous drugs 42 (39.6) Total106 (100 %)

5. Potentially Serious Herb-Drug Interactions Type of Interaction # of Herbs Affects absorption of drugs 17 Enhances potassium loss if given with diuretics 5 Interacts with monoamine oxidase inhibitors 11 Interacts with cardiac glycosides 12 Enhances effects of barbiturates 10 Alters effects of blood sugar medications 9 Interacts with anticoagulant medications 9

6. Herb-Drug Interactions “Evidence that it Occurs” (2,000 Study) No. and % of Type of studyinteractions Animal trials 28 19.5 Speculative 27 18.9 Empirical 26 18.2 Human case reports 15 10.5 Human clinical trials 11 25.2 Human studies 36 7.7 TOTAL 143

7. Herb-Drug Interactions (Some Examples) Bleeding when warfarin is combined with ginkgo or garlic Mild serotonin syndrome when S.J.W. is taken with serotonin re-uptake inhibitors Decreased bioavailability digoxin and cyclosporin when S.J.W. is consumed Induction of mania in depressed patients with neoleptic drugs; are taken with betel nut (Areca sp.) Increased risk of hypertension when tricyclic antidepressants are combined with yohimbine High soluble fiber plants such as psyllium decreases drug absorptions

8. Herb-Drug Interactions “10 herbs you can trust” Bilberry (Vaccinium sp.) for night blindness, simple diarrhea, glaucoma and cataracts Echinaceae for colds, flu and respiratory infections Feverfew (Tonacetum sp.) to prevent migraines Ginger (Zingiber sp.) for motion sickness, indigestion Ginkgo to improve memory – avoid with blood thinners Hawthorne (Cratagus sp.) reduce high blood pressure, treat congestive heart failure Milk Thistle (Silybum sp.) to treat liver disease Saw palmetto (Serenae) to increase urine flow Saint John’s Wort (Hypercium sp.) for mild depression Valerian (Valeriana sp.) for insomnia and restlessness * American Botanical Council and based on the German Commission E. monographs.

9. Herb-Drug Interactions “The Dirty Dozen” Category 1: “Definitely hazardous” a.Aristolochic acid (Aristolochia sp.) 1993: 30 cases of kidney failure among Belgian women using powered Chinese herbs (weight control) which was adulturated with Aristolochia sp. 2002: 237 of nephropathy is Asia and Europe after prolonged use of Chinese herbs for increased athletic performance. Product was contaminated with aristolochic acid. (aristolochic acid is metabolically activated to carcinogen compounds by cytochrome P450) b.Germander (Teucrium sp.) 1990’s in France: 26 cases of hepatic toxicity after 9 weeks use of germander for weight and cholesterol reduction. - jaundice disappears within 8 weeks discontinued use but returned “promptly” after re-use started - the furano diterpenoids in germander causes reduction in glutathione (reversed with cystine) * Alternative Medicine Alert Vol. 7: 2004 and Consumer Reports May 4, 2004

10. Herb-Drug Interactions “The Dirty Dozen” Category 2: “Potentially hazardous with prolonged internal use a.Comfrey (Symphytum sp.) – contains pyrrolizidine alkaloids which are hepatotoxins. Concentration is 100x higher in roots than aerial parts. Primary use: as a tea, but has been used long-term (safely) in the form of powdered root for external treatment of insect bites, sprains, inflammations and bruises. b.Chaparrel (Larrea sp.) – long-term use as a external anti- inflammatory but if used internally can cause non-fatal kidney/liver damage. Since 1969, when it was reported to cause remission of melanoma, the use of chaparrel in tea has been widespread yet few adverse case reports except where other herbs have been used. c.Kava (Piper sp.) – popular use as a relaxant but in 2002 FDA issued a warning about its association with liver toxicity. In 2003, Kava was banned in Germany. It’s toxicity has not been established so care in its use should be standard procedure. d.Androstenedione – a non-herb supplement derived from animal adrenal glands and gonads. It is used in conjunction with some herbs as a testosterone precursor to enhance muscle development. Currently banned by most amateur / athletic organizations. Short-term use has little or no side effects but evidence of increased cancer rates with long- term usage.

11. Herb-Drug Interactions “The Dirty Dozen” Category 3: Hazardous with acute excessive dosage” a.Pennyroyal oil (Hedeoma sp.) excessive use of the volatile oil to treat colds should be avoided such at high level as it is a hepatoxic/nephrotoxic compound. In the 1980’s reports of women taking toxic levels of pennyroyal oil to induce abortion but not effective. b.Yohimbine (Pausinystalia sp.) has been marketed for 80 years to treat impotence. Potential toxicity: hypertension, anxiety, dizziness but rarely death. c.Lobelia (Lobelia sp.) widely used in American herbalism as a expectorant. Potential toxicity: nausea, vomiting, arrhythmias and rarely death; often used with other herbals as a muscle relaxant (external) or internally to treat respiratory problems. d.Bitter orange (Citrus sp.) – the Seville orange popular in some areas of South America for insomnia, anxiety and epilepsy. Also, becoming popular as a anti-obesity agent. Since the amines present apparently increase lipolysis and fat oxidation in mammalian fat cells. Concern is with occurrence of arrithymias in obese people use bitter orange formulations