Jarir At ThobariJarir At ThobariDepartment of PharmacologyDepartment of Pharmacology
Faculty of Medicine GMUFaculty of Medicine GMU
EBM of Herbal Medicine & Phytopharmaca
(safety and efficacy)
COMPLEMENTARY &ALTERNATIVE MEDICINE
• “While some scientific evidence exists regarding some CAM therapies, for most there are key questions that are yet to be answered through well-designed scientific studies.” - NCCAM
• “A group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine.”
Are they safe? Do they work?
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.
Complementary medicine - used together with conventional medicine. Aromatherapy to help lessen a patient's discomfort following surgery
COMPLEMENTARY &ALTERNATIVE MEDICINE
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
• 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
THE USE OF HERBS
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%
Supplement diet 4%Sleep aid 3%Prostate 3%
Don’t know/no reason 2%
All other reasons 45%
JAMA Jan 16, 2002
• 60% of US physicians recommended CAM at least once
• 47% of physicians reported using alternative therapies themselves
WHY DO PEOPLE TAKE HERBS?
PROBLEMS OF HERBAL
Herbs have pharmacological properties
including side effects & interactionsSuggestive evidence
exists on efficacy
Many ‘drugs’ came from plants. So, why shouldn’t there be
potential for efficacy of herbs?
• 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 OF HERBAL
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’
• 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: REGULATORY ISSUE
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
PROBLEMS WITH HERBAL MEDICINE
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 Lack of standardization
SubstitutionContamination
AdulterationIncorret dosage/preparation
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
URI’s, flu– Possible mild decrease in
length/severity
• Appears generally safe• Avoid in HIV, immuno-
compromised pts, longer then 8-10 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
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
Anti-inflammatory
Dyspepsia
Billiary dyskinesia
Gallstone prevention
Osteoarthritis
HIV
Peptic ulcers
Rheumatid arthritis
Uveitis
Cancer prevention
Hyperlipidemia
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
• Aspirin• Warfarin
• Garlic• Ginger• Ginko• Ginseng• Feverfew• Clove oil
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
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