AMERICAN HERBALISTS: Proposed Rule for Ephedra Supplements

[Guest guest]

AMERICAN HERBALISTS:

Proposed Rule for Ephedra Supplements

 

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Docket No. 095N--0304

BEFORE THE UNITED STATES OF AMERICA DEPARTMENT OF HEALTH AND HUMAN

SERVICES FOOD AND DRUG ADMINISTRATION

http://www.americanherbalistsguild.com/

 

THE AMERICAN HERBALISTS GUILD ON THE PROPOSED RULE FOR

DIETARY SUPPLEMENTS CONTAINING EPHEDRA ALKALOIDS

UPON THE REOPENING OF THE COMMENT PERIOD

 

American Herbalists Guild

1931 Gaddis Road

Canton, GA 30115

770.751.6021

ahgof-

 

 

Submitted April 7, 2003

1. PREAMBLE

 

1. The American Herbalists Guild (AHG) is a non-profit organization

that

represents professional practitioners of herbal medicine in the USA.

 

2 AHG professional members are elected by rigorous peer review and

have

extensive training and clinical experience in herbal medicine.

Members

include licensed practitioners such as Naturopathic physicians and

Acupuncturists, as well as lay members - there being no license for

herbalists in the USA at this time.

 

AHG members are by definition experienced not only with medicinal

plants, or herbal " medicines " as such, but also with the practice of

using botanicals therapeutically i.e. herbal medicine (practice)

using

herbal medicines (remedies).

 

 

 

3. AHG professional members operate entirely within the current

legal

and regulatory framework governing the availability of and access to

botanical medicines.

 

However the AHG also believes that the current regulatory framework

in

the USA, embodied in DSHEA 1994, fails to embody a coherent

description

of traditional herbal medicines.

 

By subsuming botanicals within its over inclusive definition

of " dietary

supplements " , the Act confounds crude medicinal herbs as used in

herbal

medicine with manipulated commercial products, concentrates,

components

or combination products which have no established record of safety

in

traditional use, nor indication for derived from empirical

traditional

practice.

 

The AHG views the current problematic status of Ephedra and Ephedra

alkaloid containing supplements to be an inevitable result of the

underlying problems of definition embedded within DSHEA.

 

 

 

4. The AHG understands that comments are requested on matters of

interpretation of the current regulations regarding the available

data

on Ephedra products, their safety, indicated usage, and labeling,

not

upon the regulations themselves.

 

However the issues surrounding Ephedra safety as currently framed,

including the recent RAND report, derive from the current regulatory

context and cannot be commented upon without some contextualization.

 

 

 

5. Restriction of public access to the crude herb Ephedra sinica,

and

extracts thereof, could, under the current legislative framework,

also

prevent AHG professionals, Licensed Acupuncturists, Naturopathic

physicians and other healthcare professionals from access to the

herb

unless specific exemptions are made.

 

 

 

6. The AHG therefore welcomes the re-opening of the comment period

on

the proposals in the Federal Register regarding Ephedra (Docket No

95N-0304) and the opportunity to present the viewpoint of

professional

herbalists in the USA regarding Ephedra sinica and the dietary

supplements containing Ephedra alkaloids.

 

2. SUMMARY OF THE AMERICAN HERBALIST GUILD GENERAL POSITION ON

EPHEDRA

SINICA

 

 

 

1. Ephedra sinica (Ma Huang) is a traditional herbal medicine that

has

an established history of safe clinical usage in East Asian and

Western

herbal medicine.

 

 

 

2. " Ephedra " properly refers to the dried aerial parts of the

medicinal

species,

or crude extracts thereof,

not to its isolated alkaloidal constituents.

 

 

 

3. There is no credible review to date which analyzes safety data

(whether experimental, clinical or derived from pharmacosurveillance

sources), including the RAND and CANTOX reports, that takes

systematic

account of the terminological confusion

 

between the crude herb, isolated ephedrine,

 

and Ephedra/ephedrine plus caffeine combination products.

 

 

 

Rather, all these literary sources compound the problem.

 

 

 

4. Traditional usage of Ephedra sinica (Ma Huang) regularly involves

combination with other herbs,

 

but never stimulants.

 

 

 

5. Ephedra sinica is safe when used for traditional indications at

the

established therapeutic doses.

 

 

 

6. The established therapeutic dose range of Ephedra sinica in

herbal

medicine delivers 60 -90 mg total alkaloid per day (adults).

 

There is broad agreement between traditional Chinese formulae,

western

herbal doses, and recommended doses of OTC preparations in terms of

total daily alkaloid intake.

 

 

 

7. Doses of ephedra alkaloids in excess of the therapeutic dose

range,

whether delivered via crude herb,

concentrated extracts or isolated alkaloids,

do have the potential to induce adverse effects.

 

 

 

8. " Weight loss " and " athletic performance " are not traditional

indications for the use of Ephedra -

 

traditional indications are centered around the use of the herb for

febrile and catarrhal respiratory conditions.

 

Arguably, from a clinical natural medicine perspective,

 

obesity is more likely to be a contraindication rather than an

indication for use of Ephedra.

 

 

 

9. The lobby of sections of the natural products industry for the

weight

loss indication of Ephedra cannot readily be dissociated from their

interest

in the ($6.8billion) market for ephedra weight loss products while

the

lobby against " Ephedra "

is often ill informed and politically motivated.

 

 

 

10.The scope and magnitude of Ephedra safety and the problem of

herbal

adverse effects in general should be seen in the larger context of

the

outstanding safety record

of herbal medicines compared to that of licensed pharmaceuticals.

 

3. THE AMERICAN HERBALIST GUILD GENERAL POSITION ON EPHEDRA

 

 

 

The general position of the AHG on Ephedra is summarized in the

following points.

 

 

 

[Note: The capitalized " Ephedra " is used to designate crude herb of

medicinal species of the Ephedra taxon as defined below].

 

 

 

1. Ephedra sinica (Ma Huang) is a traditional herbal medicine that

has

an established history of safe clinical usage in East Asian and

Western

herbal medicine.

 

 

 

Currently recognized medicinal species of the genus are E. sinica

Stapf., E. equisetina Bunge., E. intermedia Shenk and CA Meyer., (f.

Ephedraceae) all of which contain

Ephedra alkaloids and are regarded as medicinally (and commercially)

interchangeable.

 

 

 

Traditional indications for medicinal Ephedra species include

febrile

and congested catarrhal conditions of the upper respiratory tract,

with diaphoretic, diuretic, and cardiotonic actions.

 

 

 

2. " Ephedra " properly refers to the dried aerial parts of the

medicinal

species, or crude extracts thereof,

 

not to its isolated alkaloidal constituents.

 

 

 

2i. There is a persistent terminological confusion in the current

literature, perpetuated by all parties concerned including FDA and

DHHS

and which pervades the current medical literature including the

recent

RAND report.

 

This confusion implies the crude herb is interchangeable with

ephedrine,

the alkaloid,

or even with commercial dietary supplements

containing isolated Ephedra alkaloids

 

in combination with other agents, such as caffeine.

 

 

 

2ii. The distinction is not academic, but axiomatic. Ephedra sinica

crude herb and crude herb extracts have different pharmacological

and

medicinal characteristics than the purified isolated alkaloids in

isolation.

 

 

 

· Ephedra contains catechin tannins such as (-)epicatechin (EC) and

(-)

epigallocatechin (EGC), catechin and gallocatechin.

 

These polyphenolics, much studied as constituents of green tea, have

antioxidant effects,

hypolipidemic effects,

cause NO mediated vasodilation,

have antithrombotic, anti-inflammatory, antidiabetic, and

antiproliferative and chemoprotective effects.

 

 

 

· Ephedra contains a volatile oil, composed largely of monoterpenes

such

as terpinol and cineole.

 

These are well known as constituents of Eucalyptus and Juniper that

have significant pharmacological actions at bronchial,

respiratory and urinary epithelia.

 

Ephedra also contains various phenolic acids, especially cinammic

acid

and derivatives that are common in the balsams,

 

well known for their respiratory effects.

 

 

 

· The medicinal Ephedraceae contain the characteristic

phenylethylamine

alkaloids, in amounts that vary from >1.0% and which can exceed 2%.

The

predominant alkaloid is (-)-ephedrine, which occurs alongside

(+)-pseudoephedrine and their corresponding nor- and methyl-

derivatives.

 

These alkaloids all are indirect sympathomimetics, each alkaloid

has, in

a small degree, differing pharmacokinetic and pharmacodynamic

properties, e.g. the nor- derivatives appear to be more centrally

stimulating.

 

The pharmacology of their action at the adrenoreceptor subtype level

is

not well understood, in part because the molecular biology of these

receptor-sub types is currently still being unraveled.

 

However, in general the Ephedra alkaloids are relatively non-

specific in

their effects with regard to adrenoreceptor subtypes, and in

mainstream

pharmacotherapy

more receptor-selective adrenergic agonists are generally preferred

to

minimize general adrenergic side effects.

 

 

 

· This overall combination of constituents determines the medicinal

effects of the crude herb.

 

The total alkaloid content may vary by up to 100%, and the profile

of

component alkaloids varies between species,

plant parts and season.

 

Whilst the alkaloids indeed dominate the activity of the plant, its

pharmacodynamics cannot be reduced to the properties of a single

alkaloid alone,

nor can the other constituents be disregarded.

 

..

 

· In parenthesis, it should be noted that in Chinese medical usage,

a

distinction is also made between the stems

of the plant, Ma Huang, and the root, Ma Huang gen.

 

The roots contain dimeric flavonols and macrocyclic alkaloids not

found

in the aerial parts, and in Chinese medicine the root is

antisudorific,

whilst the stem is diaphoretic – essentially opposite actions. The

corollary being, as always with medicinal plants,

that it is necessary to identify the plant part used as medicine.

 

 

 

2iii. The following categories are therefore quite distinct and

rationally need to be considered as such in technical, scientific,

medical and regulatory contexts:

 

 

 

· Isolated Ephedra alkaloids, (the phenylethylamines (-)-ephedrine,

(+)-pseudoephedrine, their nor- and methyl, derivatives their

optical

isomers and salts of these compounds).

 

· Crude herb and extracts of crude herb of medicinal Ephedra taxa

(as

defined above) containing naturally occurring alkaloids and other

compounds without manipulation, concentration, or adulteration such

as

in decoctions or crude herb extracts.

 

 

 

· Extracts of Ephedra that are concentrated, manipulated or

adulterated

such that the naturally occurring proportions and/or quantities of

ephedrine alkaloids are changed.

 

 

 

· Combination " ephedra/ephedrine products " variously including any

of

the above with any other agents, herbal or otherwise for example:

 

Caffeine, caffeine containing herbs (e.g. Guarana, Cola), or

concentrates of caffeine containing herbs;

salicylates,

either in the form of ASA, (aspirin)

or salicylate containing herbs

(e.g. willow bark)

or concentrates of salicylate containing herbs;

synephrine

and accessory nutrients such as chromium picolinate, L-carnitine,

CoQ10

and B vitamins.

 

 

 

· Legitimate traditional herbal medicinal combination formulations

such

as " Minor Blue Dragon " or other standard Ma Huang containing Chinese

formulae.

 

 

 

2iv. Confusion is compounded by regulatory differentiation between

isolated (-)-ephedrine concentrated

from crude herb sources

and laboratory synthesized (+)-ephedrine.

 

The former is a " dietary ingredient "

while the latter is a listed (controlled) chemical compound

 

(also a marker for identifying adulteration).

 

Addition of the former to an Ephedra dietary supplement product

containing Ma Huang

would simply require adding an " ingredient " to the label; addition

of

the latter would constitute

illegal " adulteration " of the dietary supplement.

 

 

 

3. The AHG maintains that there is no credible review to date which

analyzes safety data (whether experimental, clinical or derived from

pharmacosurveillance sources),

including the RAND and CANTOX reports, that takes systematic account

of

the terminological confusion

between the crude herb, isolated ephedrine, and Ephedra/ephedrine

plus

caffeine combination products.

 

Rather, all these literary sources compound the problem.

 

 

 

The RAND report conclusions exemplify both the logical and

terminological confusions.

 

Even the first page of the conclusions (p201) uses ALL of the

following

terms:

" ephedra " , " herbal ephedra " , " ephedra without caffeine containing

herbs " ,

" ephedra with caffeine containing herbs " , " ephedra containing

dietary

supplements with caffeine containing herbs " , " ephedra and herbs with

caffeine " ,

" ephedrine " , " ephedrine plus caffeine " .

 

 

 

The RAND meta-analysis refers to one study (Donikiyan and

colleagues,

unpublished, 2002) that purports to examine " ephedra " alone vs.

placebo;

this study is mentioned also in the conclusions.

 

In fact the preparation used in this study contained 450 micrograms

of

chromium picolinate per dose,

and therefore cannot be considered a crude herb extract vs. placebo

at

all.

 

This failure to identify and disclose all the ingredients of the

product

lacks

scientific rigor and is inevitably misleading.

 

 

 

4. Traditional usage of Ephedra sinica (Ma Huang) regularly involves

combination with other herbs, but never stimulants.

 

 

 

In all extant traditions of herbal medicine, East Asian and Western,

that incorporate Ephedra use, it is almost never used as a single

agent.

 

In medicinal use, it is considered to have stimulating properties,

and

is never combined with herbs

that also have stimulant properties such as caffeine containing

herbs

(Coffea, Paullinia, Cola).

 

In East Asian herbal use, Ephedra is characterized by its warming

and

diaphoretic qualities,

and is therefore combined with herbs that moderate this warming

aspect,

 

or which mitigate its stimulatory tendencies.

 

This specifically excludes combination with stimulant herbs.

 

The common proportion of Ephedra in such formulations is rarely more

than 15% of total herb.

 

Professional herbalists thus consider the traditionally prepared

combination products to have a much greater margin of safety than

ephedrine isolates

or combination caffeine products.

 

 

 

5. Ephedra sinica used for traditional indications at the

established

therapeutic doses is completely safe.

 

 

 

To our knowledge, there is not a single published report in the

medical

or toxicological literature recording serious adverse effects

resulting

from the crude herb

or crude extracts of the medicinal Ephedra species used within the

therapeutic dose

range for traditional medical indications.

 

 

 

This point cannot be overemphasized. Every literature review,

including

RAND, CANTOX or the recent comprehensive review by McKenna and

colleagues cited in RAND,

refers to " ephedra/ephedrine combination products " i.e. combinations

with other stimulants,

or the effects of isolated alkaloids, usually ephedrine (this being

more studied than the others).

 

 

 

The safety record of the crude herb used at therapeutic doses is

exemplary, and at complete variance

with the " bad press " that

has become associated with it.

 

 

 

The process whereby such a " bad press " becomes attached to a

botanical

because of commercial-industrial exploitation of concentrates

or isolated derivatives rather than the crude herb

is familiar to those who are fluent

in the science

and care to follow the literature.

 

Licorice root is a classic example, although lacking in the market

profile enjoyed by Ephedra products its notoriety is nonetheless an

established " fact "

in the medical literature despite a complete absence of adverse

effect

reports concerning

the medicinal herb at therapeutic doses – all reports referring to

concentrated commercial licorice extracts and flavorings in products

such as chewing tobacco.

 

 

 

 

 

6. The established therapeutic dose range of Ephedra sinica in

herbal

medicine delivers 60 -90 mg total alkaloid per day (adults).

 

There is broad agreement between traditional Chinese formulae,

western

herbal doses,

and recommended doses of OTC preparations in terms of total

alkaloid.

 

 

 

OTC use of ephedrine salts in commercial OTC preparations, indicated

for

nasal congestion,

deliver up to 25mg every 4 hours with a suggested maximum of 150mg

alkaloid daily.[1]

 

Meanwhile, PDR recommendations for maximum dose of pseudoephedrine

hydrochloride in nasal

decongestant products (such as e.g. Sudafed™) suggest a daily adult

maximum of 240 mg alkaloid over a twenty-four hour period.

 

 

 

Traditional Chinese standard formulae (such as Minor Blue Dragon, Ma

Huang C Decoction) typically deliver

60-90 mg alkaloid per day,

(assuming that Ephedra alkaloids are present at concentrations of

>1%

w/w in the crude herb). Ma Huang is usually <15% of such formulae.

 

 

 

This broad therapeutic dose range is confirmed by numerous

international

authorities in western herbal medicine.

 

The German Commission E gives the maximum daily dose at 300mg total

Ephedra alkaloid, which is higher than might be expected from this

source, which is normally considered conservative in terms of safety

issues.

 

 

 

 

 

7. Doses of Ephedra alkaloids in excess of the therapeutic dose

range,

whether delivered via crude herb or concentrated extracts, do have

the

potential to induce adverse effects.

 

 

 

From a clinical perspective, the potential for sympathomimetic

agents to

cause autonomic side effects is both plausible and predictable; no

responsible or competent clinician would think otherwise.

 

The potential for interaction with other adrenergic agonists, with

MAO

inhibitors,

and exogenous catecholamines is also very probable.

 

Similarly, contraindication in specific conditions, such as

hypertension

and cardiac dysrhythmia,

is also a corollary of the known pharmacology of these compounds.

 

Herbal medicine is a context based patient-centered discipline and

herbal combinations

are administered on a case-by-case basis recognizing each individual

as

unique.

 

Despite the general safety of traditional combinations of Ephedra

used

at the therapeutic dose range,

professional herbalists monitor for side effects and adjust dosage

accordingly in sensitive individuals

who exhibit symptoms of adverse effects.

 

 

 

 

 

8. " Weight loss " and " athletic performance " are not traditional

indications for the use of Ephedra.

 

Traditional indications are centered on the use of the herb for

febrile

and catarrhal respiratory conditions.

 

Arguably, from a clinical natural medicine perspective, obesity is

more

likely to be a contraindication

 

rather than indication for use of Ephedra.

 

 

 

8 i. Medicinal herbal indications are incrementally established by

empirical clinical use over centuries, sometimes millennia.

 

They are generally not defined by scientific studies, although

modern

scientific research may often confirm or illuminate an already

established traditional indication.

 

 

 

8 ii. Extrapolation from the known pharmacology of herbal

constituents

may suggest non-traditional therapeutic uses of an herb.

 

Commercial promotion of these suggested uses by marketing of dietary

supplements does not constitute validation of these indications.

 

 

 

· Echinacea for example is traditionally indicated for boils and

abscesses, or for snakebites.

As its immunomodulating properties were studied, the use of

echinacea

as a cold and flu remedy became promoted by the supplement industry.

Scientific support of echinacea for colds and flu is in fact quite

weak,

and the majority of herbalists still regard it as a lymphatic system

agent with short term modulating effects on cell mediated immunity.

 

The significant point being that the debate in the medical and

popular

literature about " does echinacea work? " i.e. for " colds and flu " is

simply an artifact of a mistaken presumption by both the

investigating

researchers and journalists that the market driven " indications "

suggested by the US natural products industry are the traditional

indications of the herb.

 

There are no published studies on echinacea for topical bites, but

its

ability to deal with serious necrotoxic venomous spider and

snakebites

is well established among modern herbalists.

 

 

 

In other words, although onset of a cold or flu may be a plausible

indication for echinacea based on its immuno-modulatory

pharmacology,

it does not mean that " echinacea for colds " is an appropriate

indication

for the herb.

 

 

 

8 iii. Not only is the overwhelming majority of adverse effect data

(See

3 above) based upon combination products

but all the trials used

to support the weight loss indication meta-analysis in the RAND

report

were similarly based upon combination products,

the majority being ephedrine

in combination with caffeine and other stimulants.

 

Not one study single study was based upon the use of crude herb.

 

 

 

8 iv. Nonetheless, due to the thermogenic and lipolytic

characteristics

of the Ephedra sympathomimetic amines, coupled with some central

anorectic effects,

the demonstration of a moderate effect on weight loss is to be

expected

given the known pharmacology of these alkaloids.

 

 

 

8 v. Thermogenic agents typified by the Ephedra alkaloids are not

approved for weight loss,

either as OTC or prescription drugs.

 

However, these alkaloids are approved for use in respiratory OTC and

prescription products.

 

Sensible medical use as currently approved appears to corroborate

traditional indications.

 

 

 

8 vi. While ephedrine alkaloid containing products may promote

modest

weight loss, and while we recognize that even modest weight loss can

represent a significant health benefit,

AHG professional herbalists do not consider this a sensible approach

to

a long-term, sustainable weight loss program.

 

Sustained weight loss would either require dietary and lifestyle

modifications,

or chronic consumption of ephedrine alkaloid

containing weight loss products, the latter which is contraindicated

by

traditional use standards.

 

 

 

8 vii. Because obese populations are predisposed (by definition) to

higher risk of cardiovascular disease,

we consider such populations to be

at increased risk for potential ephedrine alkaloid side effects.

 

The use of such agents is also associated with other undesirable

side

effects,

including the tachyphylaxis (habituation or induced tolerance) that

results from prolonged exposure, as well as undesirable

psychological

symptoms.

 

 

 

8 viii. Obesity is a serious public health problem affecting

significant

numbers of the population in the USA,

 

with direct impact on morbidity and mortality statistics.

 

The problem of obesity has a multifactorial cultural, psychological,

dietary, lifestyle and pharmacogenetic etiology.

 

" Popping fat burner stimulants " is seen by the AHG and most natural

healthcare professionals more as part of the problem,

 

not part of the solution.

 

Arguably, from a clinical perspective, obesity is more likely to be

a

contraindication

rather than indication for use of Ephedra.

 

 

 

8 ix. With regard to " athletic performance enhancement " , not only is

there no significant scientific support for this non traditional use

of

Ephedra,

but the International Olympic Committee and most international

sporting

authorities define Ephedra alkaloids as prohibited stimulants.

 

Athletes are disqualified even if these compounds were ingested

unknowingly as OTC decongestant ingredients.

 

Stimulant abuse in sports has been associated with numerous tragic

serious adverse events related to drug abuse, usually sudden cardiac

death.

Promotion of " Ephedra performance products " in this market is

unjustifiable on numerous counts and should be prohibited.

 

 

 

 

 

9. The lobby of sections of the natural products industry for the

weight

loss indication of Ephedra

 

cannot readily be dissociated from their interest in the

($6.8billion)

market for ephedra weight loss products while the

 

lobby against " Ephedra " is often ill informed and politically

motivated.

 

 

 

 

Industry organizations such as AHPA present a well-informed

perspective

on the issues of Ephedra.

 

The problems of ephedra product regulation are created by the

current

market for weight loss dietary supplements and the legislation that

enables it.

 

The AHG believes that clinical perspectives of herb professionals

and

those of natural product manufacturers should be closely aligned,

for example in the development of and implementation of appropriate

product characterization and appropriate claims review.

 

Many AHG professional members depend on the ability of AHPA member

companies to supply high quality, reliable, and safe crude herb

extract.

 

The AHG maintains that increased liaison and communication between

the

natural products industry,

clinical practitioners,

and regulatory authorities on matters relating to botanical

medicines is

desirable.

 

 

 

The AHG is particularly critical of those sections of the medical

community, consumer watch dogs, various organizations and

individuals

including politicians, who call for sweeping restrictions

on " Ephedra "

(often along with attacks on all dietary supplements and botanicals),

yet who demonstrate a lack of familiarity with either the technical,

pharmacological,

medical or public health and regulatory issues involved.

 

The AHG considers this lobby to often have parochial agendas,

ranging

from political opportunism

to conservative opposition to CAM (complementary and alternative

medicine)

and its tools, including botanicals.

 

 

 

 

 

10. The scope and magnitude of Ephedra safety and the problem of

herbal

adverse effects in general should be seen in the larger context of

the

outstanding safety record of herbal medicines compared to licensed

pharmaceuticals.

 

 

 

The AHG maintains that the magnitude of the threat to public safety

posed by the sum of all available botanical medicines is of minor

significance compared to the number of serious adverse events,

including

deaths,

among the US population due to non error related medication causes,

estimated by various authorities

to be at a figure of well over 100,000 deaths per anum.

(Brown SD and Landry FJ. South Med J 2001;94(4):370-373; Lazarou J,

et

al. JAMA 1998;279(15):1200-1205)

 

 

 

The magnitude and scope of the Ephedra product safety problem, and

of

botanicals in general,

 

needs to be contextualised within the larger picture of the

extra-ordinarily good safety record of herbal medicines

compared to

pharmaceutical drugs approved by the FDA.

 

 

 

4. DOCKET 95N-0304: SPECIFIC COMMENTS OF THE AMERICAN HERBALIST

GUILD

 

 

 

The DHHS has requested specific comments " on the new evidence of

public

health risk associated with Ephedra " and " on whether the currently

available evidence and medical literature present a `significant or

unreasonable risk of illness or injury' from dietary supplements

containing Ephedra " and upon a " strong new warning label on any

Ephedra

products that continue to be marketed "

 

 

 

Thus the specific comments of the AHG, derived from the foregoing

general position on Ephedra are as follows:

 

 

 

1. The AHG contends that there is in fact no " new evidence " of

public

health risk associated with medicinal Ephedra species crude herb or

extracts used at therapeutic doses for traditional indications.

 

 

 

The RAND report meta-analysis does not include a single study of

Ephedra

crude

herb vs. placebo for weight loss or athletic performance since there

is

none.

 

Similarly the adverse event data from the various sources in the

RAND

document (Medwatch, Metabolife files, clinical trial statistics) do

not

constitute " new evidence " about Ephedra, but merely reanalyze

existing

data, the quality of which has been critically reviewed previously,

and

none of which relates to the crude herb.

 

Furthermore the RAND report persistently perpetuates the confusion

of

terminology relating to " ephedra " and the various products

containing

ephedra alkaloids, and to combinations with caffeine or other

agents.

 

 

 

The AHG urges that a consistent terminology be adopted by the FDA

and

those medical and scientific authorities and investigators involved

in

the area, whereby inconsistent use of the term " ephedra " is replaced

either by the term

" ephedrine alkaloid containing products "

as opposed to " Ephedra sinica " or crude extracts thereof, to

distinguish the various manipulated dietary supplement products from

the

crude medicinal herb.

 

Specific alkaloids should be referred to by their chemical name.

 

Rationally, data deriving from investigations on different products

should be identified as relating to the product concerned, should

identify and quantify all the ingredients, and should not assume

interchangeability with different preparations.

 

 

 

2. The AHG does not concur that weight loss or athletic performance

enhancement are valid or traditional indications for Ephedra sinica.

 

However the AHG considers there are inevitable risks associated with

using ephedrine alkaloid containing products alone

or in combination with other stimulants,

in certain populations or individuals for such purported

indications.

 

 

 

Quantifying " significant or unreasonable risk of illness or injury "

requires contextualization, including details of the exact nature of

the

preparation, the dose and duration of administration, the indication

for

which it is taken, the specifics of the individual case, and whether

or

not the administration is supervised or monitored by a healthcare

practitioner. The level of risk will thus depend to a degree on the

" appropriateness " of use.

 

 

 

The AHG considers that the public availability of Ephedra/ephedra

alkaloid plus caffeine type combination products, and their

promotion

for weight loss and athletic enhancement constitutes inappropriate

use

which can reasonably and plausibly be predicted to generate a

significant incidence of adverse effects,

including a proportion of serious adverse effects in at-risk

individuals,

which is not the case with appropriate use of Ephedra sinica or

crude

extracts used for traditional indications at therapeutic doses.

 

 

 

3. The AHG concurs that a (strong) " new warning label " is desirable

for

any publicly available product that contains Ephedra sinica,

including

the crude herb.

 

 

 

Such warning labels would not be necessary for crude herb product

distributed to healthcare professionals, including AHG professional

members.

 

In this regard, the AHG is not making extensive verbiage

recommendations

for public warning labels or about how " strong " they should be.

 

However, logically, the medical warnings and contraindications

should

correspond to those currently applied to OTC medications containing

ephedra alkaloids,

 

the maximum dose of total alkaloid should correspond to the OTC

established limits,

and the labels would ideally include a clear statement that ephedra

alkaloids cannot be recommended for weight loss.

 

 

 

4. The AHG urges the FDA to consider in future the separation of

herbs

and botanicals

into an additional regulatory category such as " traditional herbal

medicine " .

 

 

 

The current legislative definition of dietary supplement under DSHEA

1994 " is defined as:

 

1. A product other than tobacco intended to supplement the diet that

bears or contains one or more of the following dietary ingredients:

 

* a vitamin; * a mineral; * an herb or other botanical; * an amino

acid;

* a dietary substance for use by man to supplement the diet by

increasing the total dietary intake; or * a concentrate, metabolite,

constituent, extract, or combination of the above listed dietary

ingredients. " (our emphasis).

 

 

 

The AHG urges the FDA to consider in future the separation of herbs

and

botanicals into a separate category such as " traditional herbal

medicine " .

 

This would create a more appropriate and sophisticated regulatory

armamentarium for distinguishing between say, ephedrine alkaloids

and

Ephedra sinica, and hence a more rational, effective and incisive

means

of protecting public safety.

 

 

 

Such a scheme for botanical medicines is supported by the World

Health

Organization.

 

Moreover, such systems have been in place throughout Europe for

decades

and currently there is a unified European Union traditional

medicines

proposal under development.

 

We believe such a system is the most appropriate manner for the sale

and

use of herbs as medicines and represents the most rational approach

by

which to maximize the potential of their benefit to human health and

to

insure public safety.

 

This system has been adopted by numerous countries, including

Canada,

Australia, the UK and other EEC members. While there are some minor

national differences of interpretation, the essence of the matter is

that crude medicinal herb and crude herb extracts with traditional

indications

are made available because of established safety record

in traditional indications unless modern investigation and review

deems

otherwise.

 

 

 

Crude herb extracts which are concentrated (logically those

concentrated

beyond 1:1) and extracts whose composition has been manipulated, or

adulterated in any way cannot legitimately claim safety on the basis

of

established use nor claim traditional indications for their use.

 

These products are phytopharmaceuticals distinct from crude herb,

and

cannot reasonably be considered exempt from regulatory requirements

to

demonstrate safety or efficacy by virtue of their relationship to

crude

herb.

 

 

 

 

---

-----------

 

 

[1] HHS OTC monograph 21 CFR Ch 1 para 341.76 " Labeling of

bronchodilator products " 4.1.99 edition.

 

 

 

[2] There are perhaps a very few arguable exceptions to this

generalization such as the European research into Ginkgo flavonoids

that

developed the western herbal use of Ginkgo leaf as opposed to the

traditional Ginkgo seed of TCM.

_________________

 

 

JoAnn Guest

mrsjo-

DietaryTi-

http://www.geocities.com/mrsjoguest