Regulation of herbal supplements:Â
- Herbal products considered dietary supplements, not regulated as medicines
- not required to meet standards for drugs in Federal Food, Drug, and Cosmetic Act
- must meet standards in 1994 Dietary Supplement and Health Education Act (DSHEA)
- MF is responsible for truthfulness of claims on label and evidence of support
- MF can claim product affects structure and function of body
- MF cannot claim effectiveness for prevention or treatment of a specific disease (but other people can)
- must have disclaimer that FDA did not evaluate agent
- does not require submission of evidence to FDA
- does not require pre-marking safety testing
- no requirement that MF must record, investigate, or report adverse effects
- MF responsible for controlling quality and safety, but FDA has burden of proof
- no assurance of Good Manufacturing Practice
- no prior approval of efficacy and safety by FDA
- hard to investigate adverse effects because of lack of MF information
- other countries:Â
- Germany: registered as medicines based on information in monograms
- European Commission: proposing simplified procedure for registration
Quality of herbal supplements:Â
- many contain adulterants and contaminants: prescription, OTC drugs, heavy metals
- difficulty: herbs are complex mixtures
- variation in composition
- discrepancies between label and actual content
- US Pharmacopeial Convention: voluntary label of “US Pharmacopeia” and “National Formulary” means product complies with standards of quality under DSHEA
Safety of herbal supplements:Â
- serious health risks
- drug interactions
- compromise, delay, replace effective conventional treatment
- Western use does not reflect traditional use
- apparenty safe herbs can be hazardous under special circumstances or when combined with traditional drugs (1/6 prescription drug users used at least one herbal prep)
Efficacy of herbal supplements:Â
- not many randomized, controlled, trials (herbs are too distinctive)
- differences in source, processing, final composition, genetic variability, variable growing conditions, differences in harvesting procedures, extract processing
- some are mixtures, cannot account for relative contributions
- intermediate endpoints are reported instead of hard ones
- few trials consider herbal med combined with conventional drug
- publication bias: positive results reported more often than negative results, only 10% of serious adverse effects are reported to FDA
– National Standards Grading: A- strong positive evidence from more than 2 random studies, B- good positive evidence from 1-2 random studies, C- unclear evidence, D- fair negative evidence, F- strong negative evidence, lack of evidence
– Jadad Score Calculation: measure quality of design/reporting of RCTs: double blind?, randomization?
Anxiety: Kava: strong – hepatotoxicity, Lavender
Hepatitis: milk thistle – drug interactions w/CYP450
Proestrogen, proprogesterone: chasteberry, bloodroot
Hypoglycemia: aloe vera, ginseng, Hyperglycemia: arginine, Cause bleeding: garlic
| herb | advocated for | study outcome | side effects | contraindications |
| Ginkgo biloba | dementia (Alzheimer’s), peripheral vascular disease (claudication), neurosensory problems (tinnitus), memory | Alzheimer’s, dementia, claudication | headache, nausea, GI symptoms, diarrhea, allergic skin rxns | bleeding when combined with NSAIDs, rofecoxib, warfarin |
| Hawthorn (Crataegus) | mild heart failure | need more data | GI symptoms, palpitations, chest pain | digitalis glycosides |
| Saw palmetto, sabal fruit | benign prostatic hyperplasia | ↓DHT, ↑testosterone, antiestrogen, reduces cell proliferation, no effect on postate volume | ||
| St. John’s wort | depression, anxiety, nervous unrest | short term treatment of mild depression | GI symptoms, confusion | induces CYP450 activity,Â
SSRI → serotonin syndrome |
| Ephedra | weight loss | CV, CNS stimulant | strokes, cardiac arrhythmia, sequres, psychosis, MI, death | enhanced toxicity when combined with caffeine |
- 20% take prescription drugs
- 16% taking prescription drugs also taking herbal or supplement prep
- $30 billion spent on CAM in U.S. annually
- More CAM visits than primary care visits (700M)
- 100 million Americans utilize CAM
- 66% of HMOs offer CAM services
- $7 billion spent on CAM information services
- >40% of Americans utilize unconventional therapies annually; 70% have tried alternative medicine during their lives.[iv],[v],[vi]
- 60% of physicians recommend CAM therapies regularly; CAM referrals are on the rise.[i],[ii],[iii]Â Â
- Alternative practitioners are increasing in number
- Medical and lay publications regularly report on CAM therapies.
- U.S. federal fundinsg for CAM scientific research is >$100 million/year through the Office of Dietary Supplements (ODS) and the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH). Â
- An increasing number of third-party payers cover alternative therapies as expanded benefits. Â
- Most commonly covered are acupuncturists, chiropractors, & naturopaths; recent reimbursement increases for relaxation practitioners, imagery experts, commercial diet specialists, energy healers, & biofeedback expertsÂ
- ⅔ of HMOs offer ≥1 type of alternative care; many provider systems offer access to chiropractors and acupuncturists on-site.
- 11% of hospitals offer CAM therapies in-house to patients.
- Patient pressures: 60% of Americans believe HMOs should cover alternative care
- Legislative/legal pressures: State legislatures are mandating insurance coverage for alternative treatments through “every category of provider” laws. Â
- Forty-four states offer licenses for alternative practitioners.Â
History Of Herbal Medicine
Conventional Pharmaceuticals Derived from Plants
- Atropine  Atropa belladonna
- Digoxin  Digitalis purpurea
- Colchicine  Colchicum autumnale
- Codeine  Papaver somniferum
- Taxol  Taxus brevifolia
- Pseudoephedrine  Ephedra sinica
- Salicylin  Salix purpurea
- Vincristine  Catharanthus roseus
Complementary and Alternative Medicine
A group of diverse medical and healthcare systems, practices, and products not presently considered to be part of conventional medicine
Biological Based Practices
- Herbal medicine, Botanical medicine, Phytotherapy
- Vitamins and Minerals
- Non-herbal, non-vitamin supplements
- Amino acids, NADH, glutathione
- Glucosamine sulfate, fish oil
- Lactobacillus
- Functional Foods
Dietary Supplement Health and Education Act
- DSHEA passed by Congress in 1994
- Dietary supplements include herbs, vitamins, minerals, metabolites, or extracts
- Companies not required to prove efficacy or safety before marketing
- Burden of proving inefficacy or lack of safety fell to FDA
DSHEA
- Label can make “health” claims, but not “disease” claims
- Regulation akin to food, not drugs
- Lead to a deregulation of supplement industry
Variation of Ginseng Preparations
Prevalence of Ayurvedic Products Purchased over the Internet that Contain Pb, Hg, and/or As
Americans’ Views on Dietary Supplements
- 35% believed supplements were regulated by the govt; 12% not sure
- 81% favored pre-market testing of products for safety by the FDA
- 72% would continue use even if a govt scientific study was negative
(Blendon R et al, Arch Intern Med 2001)
Epidemiology:Â Â U.S. Trends In Herbal Medicine Use
% U.S. Adults Using Herbal Rx in Past 12 Months (Eisenberg 1990, 1998, Barnes 2004)Â
Frequently Asked Questions
How are herbal supplements regulated in the U.S.?
In the U.S., herbal supplements are regulated as dietary supplements under the Dietary Supplement Health and Education Act (DSHEA) of 1994. They are not regulated as medicines and do not need to meet the same safety and efficacy standards as drugs. Manufacturers are responsible for ensuring the truthfulness of their claims and must include disclaimers that the FDA has not evaluated the products. Unlike conventional drugs, there is no requirement for pre-market safety testing or submission of evidence to the FDA.
What are the common quality issues with herbal supplements?
Herbal supplements often face quality issues due to adulterants and contaminants, such as prescription drugs, over-the-counter drugs, and heavy metals. The complexity of herbs, variations in composition, and discrepancies between label claims and actual content further complicate quality control. The U.S. Pharmacopeial Convention offers a voluntary labeling system to indicate compliance with quality standards.
Are there safety concerns associated with taking herbal supplements?
Yes, there are significant safety concerns with herbal supplements. They can cause serious health risks, including adverse drug interactions and delayed conventional treatment. Some herbs, although seemingly safe, can be hazardous, especially when combined with prescription drugs. For example, Ginkgo biloba can cause bleeding if used with NSAIDs or warfarin, and St. John's wort can induce serotonin syndrome when taken with SSRIs.
Do herbal supplements have proven efficacy?
The efficacy of herbal supplements is not well-established due to limited randomized, controlled trials. Factors such as source variability, processing differences, and genetic variability contribute to inconsistent outcomes. Most studies report intermediate endpoints rather than definitive outcomes, and publication bias often skews the perception of effectiveness. While some herbs show promise, the evidence is generally inconclusive.
Which herbal supplements have known drug interactions?
Several herbal supplements are known to interact with conventional drugs. For instance, St. John's wort can interfere with antidepressants, potentially leading to serotonin syndrome. Ginkgo biloba may increase bleeding risk when taken with blood thinners like warfarin. Milk thistle can affect liver enzymes, altering the metabolism of drugs processed by the liver. It's crucial to consult a healthcare provider before combining herbal supplements with prescription medications.
How does the regulation of herbal supplements in the U.S. compare to other countries?
In the U.S., herbal supplements are regulated as dietary supplements, not as medicines. In contrast, countries like Germany register herbal products as medicines, which requires more rigorous standards and evidence of efficacy. The European Commission is also proposing a simplified procedure for the registration of herbal supplements, suggesting a more structured regulatory approach than in the U.S.
What are some examples of pharmaceuticals derived from plants?
Many conventional pharmaceuticals have origins in plants. Examples include Atropine from Atropa belladonna, Digoxin from Digitalis purpurea, and Codeine from Papaver somniferum. These plant-derived compounds have been studied extensively and developed into drugs with known efficacy and safety profiles, unlike many herbal supplements that lack rigorous testing.
Why is there a growing interest in complementary and alternative medicine (CAM) in the U.S.?
Interest in CAM is rising due to increasing patient demand and legislative support. Many Americans seek alternative therapies, with over 40% using them annually. CAM services are becoming more integrated into healthcare systems, with HMOs offering coverage and hospitals providing in-house CAM therapies. Federal funding for CAM research also supports this growth, reflecting a broader acceptance and integration into mainstream healthcare.