An Analysis of the Relative Safety of Ephedra

  1. An Analysis of the Relative Safety of Ephedra

    An Analysis of the Relative Safety of Ephedra
    By Doug Kalman MS, Jose Antonio, Ph.D., FACSM, and Richard
    B. Kreider, PhD,

    In an early Internet release, the Annals of Internal
    Medicine posted an upcoming brief communication concerning
    the dietary supplement ephedra (1).

    This study raised media frenzy concerning the regulatory
    status of ephedra.

    The authors utilized the Toxic Exposure Surveillance System
    (TESS) report of 2001 and compared it with ephedra sales
    data provided to them by SPINS, a market analysis firm.

    In addition, the authors also utilized a magazine report to
    approximate the total sales of ephedra within the United
    States for the year 2000 (2).

    There are several methodological and fundamental flaws with
    the design and conclusions made by Bent et al.

    The TESS raw data indicates that 55.5% of all Poison Control
    Center reports related to Ma Huang (ephedra) alone or in
    combination with another herb (multi-botanical) were in
    people under the age of 19.

    Additionally, 27.9% of all of the exposures were in children
    less than 6 years of age (3).

    This information is vital as in 7,927 exposures; the Poison
    Control Centers deemed 14% (1,178) to be an adverse

    In clinical research the guidelines set forth by the
    International Committee on Harmonization (ICH) defines an
    adverse reaction/event (AE) 'any untoward medical occurrence
    in a patient or clinical investigation subject administered
    a pharmaceutical product and which does not necessarily have
    to have a causal relationship with this treatment' (4).

    The TESS system defines an adverse reaction (AR) as 'an
    adverse event occurring with normal, prescribed, labeled or
    recommended use of the product, as opposed to overdose,
    misuse or abuse'.

    The TESS system also captures AR's that are 'unwanted
    effects due to an allergic, hypersensitive, or idiosyncratic
    response to the active or inactive ingredients, or

    Thus, the definitions and establishment of clear causality
    or relationship is not clear within the TESS system and when
    contrasted with normal research guidelines for defining and
    AE/AR appear to be questionable.

    The Center for Drug Evaluation and Research (CDER) policy on
    AR/AE's is that accumulated case reports (AER's) cannot be
    used to calculate incidence or estimates of drug risk (5).

    This misguided calculation is exactly what the authors
    attempted to do.

    The 2001 TESS report details that the vast amount of
    exposures were unintentional (85.2%).

    In the ephedra analysis, 46.7% of the exposures were of the
    unintentional variety (using TESS definitions and data from
    table 22B).

    It cannot be downplayed that the TESS report only captured
    data on 12 known herbs, Drs. Bent et al mistakenly state
    that ephedra accounts for 64% of all herbal related adverse
    reactions, however, there are hundred of herbals sold on the
    U.S. market, not 12, thus their conclusion is overstated.

    The sales data that Drs. Bent et al utilized in an attempt
    to correlate the TESS data with sales is incomplete. The
    SPINS database does not capture data by zip code nor does it
    capture the true mass market (i.e., Walmart, Costco, GNC
    Corporate stores), thus any data generated by the SPINS
    agency is only a small snapshot of what is truly happening
    in the sales of ephedra or ephedra-related products.

    The Nutrition Business Journal estimates that in 2000,
    ephedra and ephedra related products generated
    $1,050,000,000 (6).

    Utilizing the NBJ market analysis, the best estimate is that
    26,250,000 servings (or individual capsules/tablets) of
    ephedra or ephedra related products were sold in 2000.

    The sales figures are based upon retail mass market, mail
    order, practitioners, Internet sales and natural food/health
    chain channels (6).

    In the Bent report, it is stated that an assumption was
    made that ephedra related sales were one-half of all non-
    retail herb sales and this accounted for 0.82% of herbal
    product sales.

    The confliction in detail does not make sense. It appears
    that the SPINS data is inaccurate when comparing it to the
    more comprehensive NBJ data.

    Thus, this section of the Bent paper appears to be out of
    context and unreliable.

    While we as scientists and health care providers need to
    know the evidence (direct, not computed) concerning the
    safety of ephedra or ephedra related products, we must not
    fail to use the published peer-reviewed clinical studies as
    the basis for an understanding.

    While the clinical trials are limited in subject size as
    compared to Phase III drug studies, they do give us a basis
    for understanding the potential for serious adverse events
    and what population is best suited for potential use of
    these products.

    It is clear that people under the age of 19 should not take
    this herb; there simply have been no studies in that age
    group (on the herbal ephedrine).

    The TESS data states 55.5% of all exposures were from people
    19 or younger.

    The comparison of ephedra versus other herbs inherently
    inaccurate as the TESS data only captured 12 total named

    Given the TESS data for ephedra reporting an adverse
    reaction rate of 14% (TESS conclusion) and a mortality rate
    of 0.000757% (comparison of 6 deaths versus 7,927
    exposures), one would expect a better comparison to be made
    using this data.

    For example with relation to kava, there was one death in
    336 exposures (0.002976%), thus we can also conclude that
    kava is 3.9 times as likely to cause death as ephedra.

    It should also be noted that the adverse reaction frequency
    was similar for Gingko biloba (13.7% vs 14%) as ephedra
    and the AR for kava was much higher (17.5%).

    Perhaps, a less negative conclusion would not serve the
    purpose of the study.

    The manipulative presentation of the data shared by Bent et
    al viewed alongside the fact that the authors have and still
    testify for plaintiff law firms on behalf of anti-ephedra
    litigation, leads to speculation that this study's intent
    was to establish their published paper as evidence that
    ephedra is dangerous.

    An informed professional audience must wonder where the
    truth actually lays. Whose future and benefit does this
    paper serve?

    Douglas S. Kalman MS, RD, FACN
    Miami Research Associates
    6280 Sunset Drive
    Suite 600
    Miami, FL. 33143

    Disclosure: Mr. Kalman has testified in cases related to
    ephedra on behalf of Cytodyne Technologies, Inc.

    Jose Antonio, Ph.D., FACSM
    Adjunct Professor
    Exercise Science & Health Promotion
    Florida Atlantic University
    777 Glades Road
    P. O. Box 3091
    Boca Raton, FL 33431-0991

    Richard B. Kreider, PhD, EPC, FACSM, FASEP
    Professor & Chair
    Exercise & Sport Nutrition Laboratory
    Center for Exercise, Nutrition, and Preventive Health
    Department of Health, Human Performance & Recreation
    Baylor University
    PO Box 97313
    Waco, TX 76798-7313

    Disclosure: Dr. Kreider has served as an expert in
    litigation for Metabolife.


    1) Bent S, Tiedt TN, Odden MC, Shiplak MG. The relative
    safety of ephedra compared with other herbal products. Ann
    Intern Med 2003;138:000-000.
    Accessed online February 5, 2003

    2) Richman A, Witkowski JP. 7th Annual Herb Sales Survey.
    Whole Foods Magazine. 2001:23-30.

    3) Litovitz TL, Klein-Schwartz W, Rodgers GC, Cobaugh DJ,
    Youniss J, Omslauer JC, May ME, Woolf AD, Benson BE. 2001
    Annual report of the American Association of Poison Control
    Centers Toxic Exposure Surveillance System. Amer J Emerg Med

    4) Cohen A, Posner J. A Guide to Clinical Drug Research. 2nd
    edition Kluwer Academic Publishers 2002. Pp XI, 34,-35, 154.

    5) and
    Accessed February 18, 2003.

    6) NBJ's Supplement Business Report 2002. Penton Media, Inc.
    Pp 5-171-2,
    Figure 5-5, Figure 5-7. Available:

  2. damn man, kinda long, but very, very nice...karma
    Read This Book!!: Anabolic Steroids and the Athlete by William N. Taylor M.D.

  3. doesnt surprise attempt is made to give an accurate picture...just one that "they" want to dicredit and effective supp...

  4. those are some of the best minds and most respected in the exercise science fields. nice post bro

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