EBM of Herbal Medicine & Phytopharmaca (safety and efficacy)

Jarir At Thobari Department of Pharmacology Faculty of Medicine GMU

COMPLEMENTARY & ALTERNATIVE MEDICINE

A group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine.

While some scientific evidence exists regarding some CAM therapies, for most there are key questions that are yet to be answered through welldesigned scientific studies. - NCCAM Are they safe? Do they work?

COMPLEMENTARY & ALTERNATIVE MEDICINE

Complementary medicine - used together with conventional medicine. Aromatherapy to help lessen a patient's discomfort following surgery

Alternative medicine - used in place of conventional medicine. A special diet to treat cancer instead of undergoing surgery, radiation, or chemotherapy recommended by a conventional doctor.

5 MAIN TYPES OF CAM

Alternative medical systems
Homeopathy, Naturopathy

Mind-body interventions
hypnosis, imagery, support groups

Biologically-based treatments
Herbal, dietary treatment,

Manipulative and body-based methods

chiropractic, acupressure, osteopathy

Energy therapies
magnets, therapeutic touch

THE USE OF HERBS

81% US adults take 1+ med/week

7 of 10 US adults regularly take vitamin, mineral, herb or supplement Rates and numbers of meds increase with age

THE USE OF HERBS

14% percent of the population takes at least 1 herbal/supplement each week* 16% of prescription drug users also use 1+herbal/supplement $17.8 BILLION on dietary supplements $4.2 Billion for Herbal products**
*JAMA Jan 16, 2002 **NEJM Dec 19, 2002

YET - only 38% told their doctor

WHY DO PEOPLE TAKE HERBS?

Health/good for you 16% Arthritis 7% Memory Improvement 6% Energy 5% Immune Booster 5% Joints 4%
JAMA Jan 16, 2002

Supplement diet 4% Sleep aid 3% Prostate 3% Dont know/no reason 2% All other reasons 45%

WHY DO PEOPLE TAKE HERBS?

60% of US physicians recommended CAM at least once
47% of physicians reported using alternative therapies themselves

PROBLEMS OF HERBAL
Many drugs came from plants. So, why shouldnt there be potential for efficacy of herbs?
Herbs have pharmacological properties including side effects & interactions Suggestive evidence exists on efficacy

PROBLEMS OF HERBAL
WHO 65%-80% of the world's population use traditional medicine as their primary form of health care. dominant in developing countries, increasing in developed countries safety and efficacy are an important issue for the health professions. Potential adverse drug reactions (ADRs).

PROBLEMS: REGULATORY ISSUE

1906 Food and Drug Act - Accurate labeling, purity required 1962 Kefauver-Harris Amendment - Safe & Effective required 1994 Dietary Supplement Health and Education Act
FDA lost authority over Herbs, Vitamins unless proven to be unsafe Became Nutritionals

PROBLEMS: REGULATORY ISSUE

Unmonitored, uncontrolled, non-uniform products No standards of bioequivalence between brands, or between lots Ingredients not required to be completely listed Producers do not need to prove safety or efficacy Adulteration has commonly been described

PROBLEMS WITH HERBAL MEDICINE

Many touted for prevention hard to evaluate
Placebo effect is strong Quality of science varies Much of the research is not in English

PROBLEMS WITH HERBAL MEDICINE

It is widely perceived that "natural" products are safe, the evidence suggests that CAM use is not without risk. Of 90 patients with rheumatoid arthritis,
82% had tried more than one form of alternative medicine or therapy, including dietary modification 31% of these patients had experienced at least one adverse effect

CLASSIFICATION ADE
Intrinsic effects Intrinsic effects are those of the herb itself and are characterized, as for pharmaceuticals type A (predictable, dose dependent) type B (unpredictable, idiosyncratic) reactions overdose or accidental poisoning and interactions with pharmaceuticals.

CLASSIFICATION ADE
Extrinsic effects
manufacture or extemporaneous compounding. Good Manufacturing Practice Misidentification
Contamination Incorret dosage/preparation

Lack of standardization
Substitution Adulteration

Inappropriate labelling/adv

MISIDENTIFICATION
It is difficult to track and identify adverse effects of herbal ingredients, as the plants can be named in four different ways
the common English name, the transliterated name, the Latinized pharmaceutical name, the scientific name

Plant material can be misidentified at the time of the manufacturer's bulk purchase or when wild plants are picked

STANDARDIZATION
Therapeutic/toxic components
ripeness, geographic area where the plant is grown, and storage conditions.

Batch-to-batch reproducibility of plant material should be assessed in the production of marketed products product variation Ginsenoside (glycosylated steroid) 50 commercial brands of ginseng sold in 11 countries.
44 product 1.9% to 9% 6 no ginsenoside one of these six contained large amounts of ephedrine (for which athlete was accused of doping)

CONTAMINATION
Growth, storage, crude plant material can become contaminated by pesticide residues, microorganisms, aflatoxins, radioactive substances and heavy metal (lead, cadmium, mercury, arsenic and thallium) 6%-60%

SUBSTITUTION
A report of nine cases of rapidly progressive interstitial nephritis in young women taking a Belgian slimming treatment Aristolochia fangchi, containing the nephrotoxic component aristolochic acid Eighty cases have now been identified and more than half of these patients developed terminal renal failure

ADULTERATION
Product contains/mix with chemical drugs
Unethical herbal compund Mefenamic acid and diazepam acute interstitial nephritis, reversible renal failure, loss of blood pressure control and peptic ulceration a Chinese herbalist was prosecuted for adding a steroid cream to a herbal preparation, which produced severe facial erythema in a patient

PREPARATION AND LABELLING

The processing of crude plant material carried out by a manufacturer, practitioner or the patient is a major determinant of the pharmacological activity of the finished product. The alkaloid composition and plant's toxicity Products claim a certain unproven effect

GINGER ROOT
Traditional use: stimulant, diuretic, antiemetic, dyspepsia, prevention of motion sickness Evidence: RCTs
> placebo in postop nausea, similar to metoclopramide > placebo in seasickness

Safety:
low toxicity; no side effects; platelet changes; not recommended during pregnancy

HORSE CHESTNUT SEED EXCTRACT

Traditional use: arthritis/rheumatism; congestion (leaves) Evidence: Numerous RCTs, systematic review
superior to placebo, reduced edema, leg circumference; better compliance than compression hose; improved pain, fatigue, itching, leg tension (observational)

Safety:
No Contraindications; mild and rare adverse effect (occais. pruritis, nausea, GI c/o); no restrictions in pregnancy; whole seed is toxic.

VALERIAN ROOT
Traditional use: sedatives, insomnia, Restlessness, sleeping disorders based on nervous conditions Evidence: RCTs
Improvement in sleep latency, quality REM maintained Releases GABA in brain; weak affinity for benzodiaz. receptors

Safety:
No known side effects, interactions, contraindications, non addictive

BLACK COHOSH
May relieve menopausal symptoms (mood, flushes, sleep) No evidence of other protection benefits of estrogen Safe
no drug-herb interactions Possible interaction with tamoxifen

FEVERFEW
Prevention of migraines Cochrane review, 2003:
3 of 4 trial suggest beneficial effect; 1 showed no difference vs.. placebo Conclusion: Suggestive, but efficacy not established beyond a doubt

Avoid:
In pregnancy, W/antiplatelet agents

ECHINACEA
Wide variability in products, adulteration Positive and negative results have been reported:
Poor evidence for prevention of URIs, flu Possible mild decrease in length/severity

Appears generally safe Avoid in HIV, immunocompromised pts, longer then 810 weeks

GARLIC
Evidences:
Insufficient data on clinical CV outcomes (claudication and MI) Possible small, positive, short-term effects on lipids Inconsistent reductions in blood pressure Promising but inconclusive on antithrombotic activity. Use < 3 to 5 years not associated with decreased risks of breast, lung, gastric, colon, or rectal cancer.

Cautions:
Problems with standardization Watch in combination with anti-platelet agents

GINSENG
Use: For fortification; fatigue; improve capacity for work, concentration; colds and flu; diabetes; immune support; herpes; general well being; stress; male sexual function; sports performance COCHRANE (2003): efficacy is not established for any outcomes Concerns:
Adulteration is common Expensive Anti-platelet properties Insomnia, diarrhea, vaginal bleeding, SJ syndr

TURMERIC
Anti-inflammatory Dyspepsia Billiary dyskinesia Gallstone prevention Osteoarthritis HIV Peptic ulcers Rheumatid arthritis Uveitis Cancer prevention Hyperlipidemia Evidence grade B1 Evidence grade B1 Evidence grade B2

Evidence grade B2
Evidence grade B2 Evidence grade B2 Evidence grade C Evidence grade C Evidence grade C Evidence grade D

Evidence grade D

LEVEL OF EVIDENCE

NO EVIDENCE YET
Cochrane Review :
No firm evidence of efficacy for any medicinal herbs for Hepatitis C infection Some herbs may work in Chronic Hep B, but evidence is too weak to recommend any

HERBS-DRUGS INTERACTION
Garlic Ginger Ginko Ginseng Feverfew Clove oil

Aspirin Warfarin

PRACTICE POINTS
Ask every patient about herbs and supplements Address
natural doe not mean safe If it sounds too good to be true, it probably is

Avoid preparations with >1 herb Avoid switching brands frequently Buy packaged products with
name/address of manufacturer, batch/lot number common and scientific name, standardization when possible dosing guidelines, side effects

RESOURCES

American Botanical Council: http://www.herbalgram.org NIH National Center for Complementary and Alternative Medicine: http://nccam.nih.gov/ Sloan Kettering Cancer Cntr Information About Herbs www.mskcc.org/aboutherbs MEDLINEplus http://medlineplus.gov/ then search Herbs Office of Dietary Supplements (NIH) http://ods.od.nih.gov/ iHerb www.iherb.com/health.html , then use The Natural Pharmacy and Commission E Monographs ClinicalTrials.gov http://clinicaltrials.gov/ then type in Herbs FDA Safety and Adverse Reporting Program http://www.fda.gov/medwatch For warnings on dietary supplement see also http://www.cfsan.fda.gov/%7Edms/ds-warn.html

Herbs & Natural Supplements An Evidence-based Guide Second Edition