Regulation of herbal supplements: 

  • 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: 
    • Germany: registered as medicines based on information in monograms
    • European Commission: proposing simplified procedure for registration

Quality of herbal supplements: 

  • 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: 

  • 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: 

  • 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, 

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]  
  • 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).  
  • An increasing number of third-party payers cover alternative therapies as expanded benefits.  
  • Most commonly covered are acupuncturists, chiropractors, & naturopaths; recent reimbursement increases for relaxation practitioners, imagery experts, commercial diet specialists, energy healers, & biofeedback experts 
  • 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.  
  • Forty-four states offer licenses for alternative practitioners. 

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:  U.S. Trends In Herbal Medicine Use

 

% U.S. Adults Using Herbal Rx in Past 12 Months (Eisenberg 1990,  1998, Barnes 2004)