[Fwd: FYI Aristolochia & FDA]

[Guest guest]

OK, there's a lot of scary stuff in here that can be taken out of context

to whip up hysteria. I have boldfaced the relevant passages to our

profession, though. In a nutshell, about a dozen chinese herbs that

may sometimes be confused with aristolochic acid containing plants are

subject to immediate seizure without examination. The will not be

released without a certificate of analysis proving absence of AA.

The most interesting part of this ruling is that the FDA is keenly aware

of the very complex issues involved in this situation regarding naming

of herbs in chinese and latin. In addition, they refrain from using

the hyperbolic term chinese herb nephropathy and refer specifically to

the detailed mechanisms of AA induced nephropathy, carefully distinguishing

between sudden overdose and long term cumulative toxicity.

While I submitted comment to the FDA calling for each of these things

on behalf of Chinese Herbal Medicine, I have no indication that we were

actually heard. Nevertheless, the end result satisfies all

the criteria of Chinese Herbal Medicine Consensus Statement on this subject.

I think once again the FDA has surprisingly shown itself to be a moderating

force rather than a supplement gestapo.IA #54-10 - 7/6/00, IMPORT ALERT #54-10, "DETENTION

WITHOUT PHYSICAL

EXAMINATION

OF BULK OR FINISHED DIETARY SUPPLEMENTS AND OTHER PRODUCTS THAT

MAY

CONTAIN

ARISTOLOCHIC ACID"

TYPE OF ALERT: Detention Without Physical Examination (DWPE)

(Note: This import alert represents the Agency's current

guidance to FDA field personnel regarding the manufacturer(s)

and/or products(s) at issue. It does not create or confer any

rights for or on any person, and does not operate to bind FDA

or the public).

PRODUCT: Dietary Supplements or

Drugs, Bulk or Finished, Other Bulk or

Finished Products Labeled as Containing Aristolochia spp.,

Stephania spp., Clematis spp., Cocculus spp., Akebia spp.,

Asarum spp., Bragantia spp., Diploclisia spp., Menispernum

spp., or Sinomenium spp.

PRODUCT

CODE:

54F31 Aristolochia (Fang chi)

54F26 Stephania (Fang ji)

54F73 Akebia

54F74 Clematis

54F75 Cocculus

54F99 Herbals & Botanicals (not Teas), N.E.C.

66V99 Miscellaneous patent medicines, etc.

PROBLEM: Poisonous and Unapproved

drug

PAF: FAD

- Food Additive

APP - Approvals

HAZ - Hazardous Conditions

PAC FOR

COLLECTION: 09006A

56008H

COUNTRY: All countries (ZZ)

MANUFACTURER/

SHIPPER FEI#: All

IMPORTER'S

ID#: N/A

CHARGE: "The product is subject

to refusal of admission pursuant to

Section 801(a)(3) in that it appears to be a dietary

supplement or contain a dietary ingredient (aristolochic acid

or Aristolochi ssp.) that presents a significant or

unreasonable risk of illness or injury under the conditions of

use set out in the labeling or, if none are set out in the

labeling, under customary conditions of use [Adulteration,

Section 402(f)(1)(A)."

and/or

"The product is subject to refusal of admission pursuant to

Section 801(a)(3) in that it appears to contain or bear a

poisonous or deleterious substance (aristolochic acid or

Aristolochia spp.) which may render it injurious to health

[Adulteration, Section 402(a)(1)]."

and/or

"The product is subject to refusal of admission pursuant to

Section 801(a)(3) in that it appears to contain or bear a

poisonous or deleterious substance (aristolochic acid or

Aristolochi ssp.) which renders it adulterated under section

402(a)(1) under conditions of use recommended in or suggested

in the labeling [Adulteration, Section 402(f)(1)(D)."

and/or

"The product is subject to refusal of admission pursuant to

Section 801(a)(3) in that its labeling appears to be false or

misleading [Misbranded, 403(a)(1)]; it appears to be offered

for sale under the name of another food (Stephania spp.,

Clematis spp., Cocculus spp., Akebia spp., Asarum spp.,

Bragantia spp., Diploclisia spp., Menispernum spp., or

Sinomenium spp. [Misbranded, 403(b)]; and it appears to be

fabricated from one or more ingredients but fails to declare

the ingredient Aristolochia spp. by its common or usual name

[Misbranded, 403(i)(2)]."

and/or

"The article is subject to refusal of admission pursuant to

801(a)(3) in that it appears to be a new drug within the

meaning of Section 201(p) without an approved new drug

application [unapproved new drug, Section 505(a)]."

and/or

"The article is subject to refusal of admission pursuant to

801(a)(3) in that it appears to be a misbranded drug in that

it lacks adequate directions for its intended use [Misbranded

drug, Section 502(f)(1)]."

OASIS CHARGE

CODE:

POISONOUS

FALSE

WRONG IDEN

LIST INGRE

UNAPPROVED

DIRECTIONS

UNSFDIETLB

UNSFDIETUS

RECOMMENDING

OFFICE: CFSAN, Office of

Nutritional Products, Labeling, and Dietary

Supplements, Division of Compliance and Enforcement (HFS-810)

REASON FOR

ALERT: The botanical

Aristolochia spp. and other plants in the

Aristolochiaceae family are widely used as ingredients in

traditional Chinese herbal medicines and other traditional

medicines. These products may often be labeled for drug use

(e.g., claims that they are intended for use in the diagnosis,

cure, mitigation, treatment, or prevention of diseases),

although there are no approved new drug applications (NDAs) or

current investigational new drug applications (INDs) on file.

Some products containing botanicals in this family may also be

labeled as dietary supplements or may not be labeled in

accordance with the requirements for any specific FDA-

regulated product. However, FDA is not aware of any uses for

botanicals in this family except as drugs or dietary

supplements.

Plants in the Aristolochiaceae family contain aristolochic

acid, which is a substance known to result in serious adverse

health effects when taken orally by humans or animals.

Several outbreaks of renal failure in recent years have been

attributed to the use of Chinese herbal medicines that were

later shown to contain aristolochic acid. In each instance,

the source of aristolochic acid was determined to be an

Aristolochia spp. plant that was used in the product for one

of two reasons: (1) the plant ingredient that was listed on

the label was mis-identified; or (2) the identity of the plant

ingredient or product was confused with an aristolchia-

containing ingredient or product because the traditional

Chinese names were misinterpreted or similar.

The outbreaks of aristolochic acid-associated renal failure

have been reported in several countries, including Belgium,

France, Spain, Japan, Australia, and the United Kingdom.

Moreover, recent chemical analyses of currently marketed

Chinese herbal medicines and dietary supplements by British

and Canadian health authorities identified products that

contained aristolochic acid. However, the labels of the

aristolochic acid-positive products did not indicate that they

contained an ingredient known to contain aristolochic acid.

This indicates that there is a potential for dietary

supplements and some traditional herbal medicines to

inadvertently be formulated using aristolochic-acid containing

ingredients. FDA is aware that these and similar products are

being sold in the United States.

The data currently available indicates that Aristolochia spp.

plants are most likely substituted for the plants Stephania

spp., Clematis spp., Cocculus spp., Akebia spp., Asarum spp.,

Bragantia spp., Diploclisia spp., Menispernum spp., and

Sinomenium spp. Therefore, products that are labeled as

containing Stephania spp., Clematis spp., Cocculus spp.,

Akebia spp., Asarum spp., Bragantia spp., Diploclisia spp.,

Menispernum spp., or Sinomenium spp. may contain Aristolochia

spp. in place of part or all of the intended plant. One

reason this appears to happen is that the Chinese names for

the different plants are similar. For example, in the 1993

Belgian outbreak, the root of Stephania tetrandra (known as

"fang ji") was adulterated with the root of Aristolochia

fangchi (known as "guang fang ji"). In the two 1999 British

cases, the stem of Aristolochia manshuriensis (known as "guang

mu tong") was substituted for the stem of Clematis armandii

(known as "chuan mu tong") or the stem of one of the species

of Akebia (known as "mu tong").

Aristolochic acid is a potent carcinogen and nephrotoxin. Its

nephrotoxic potential has been shown in animals and has been

demonstrated in humans in both case reports and in at least

one human clinical study. Products that contain a large

amount of aristolochic acid have been documented to result in

the rapid onset of acute toxicity symptoms. However, a

product containing a small amount of aristolochic acid could

be used for years with no apparent adverse effects until

serious, irreversible effects, such as renal damage, has

occurred. In sum, products containing aristolochic acid cause

renal damage and can cause or contribute to renal failure.

There are analytical methods available to examine suspect raw

material and finished product for the presence of aristolochic

acid. Products that contain Aristolochia spp. or those that

contain ingredients that have been shown to be at risk of

being substituted with Aristolochia spp. should be evaluated

in order to establish that the product is free of aristolochic

acid.

GUIDANCE: Districts may detain without

physical examination bulk or

finished dietary supplements or drugs, or bulk or finished

products of other commodity types that are identified as being

composed, in whole or in part, of any Aristolochia spp. (see

Attachment A) or other herbs that may be substituted for it

(i.e., Stephania spp., Clematis spp., Cocculus spp., Akebia

spp., Asarum spp., Bragantia spp., Diploclisia spp.,

Menispernum spp., or Sinomenium spp. (see Attachment B)).

Products identified using the traditional Chinese Herbal

Medicine names of "fang ji,guang fang ji,guang mu tong,"

"chuan mu tong," or "mu tong," or other names noted in

Attachment C, may also be detained without physical

examination.

If product labeling includes claims for the diagnosis, cure,

mitigation, treatment, or prevention of disease, use the new

drug charge and the misbranding drug charge. If the product

labeling does not include disease claims but the district has

determined through other means (e.g., conversation with the

importer, letter from the importer, etc.) that the product is

intended for disease use, then use the drug misbranding

charge. In this instance please contact the Deputy Chief

Counsel For Litigation, (301) 827-1138, to further discuss the

circumstances and evidence of the importation and whether or

not a new drug charge would also be appropriate. In addition,

the appropriate food charges (see below) should be included.

If the product does not appear to be a drug, only food

adulteration charges should be used. If the products appear

to be finished products labeled as dietary supplements,

charges under section 402(a)(1), section 402(f)(1)(A), and

section 402(f)(1)(D) should be used. If the product is a bulk

dietary ingredient (e.g., root, powder, extract) charges under

section 402(a)(1) and section 402(f)(1)(A) should be used.

A food misbranding charge may also be used in addition to the

adulteration charges if the product is found to contain

aristolochic acid upon private laboratory analysis and the

label fails to declare that the product contains Aristolochia

spp.

A product labeled as a dietary supplement may be released when

a firm is able to provide analytical evidence that it is free

of aristolochic acid. Only certificates of analysis or other

evidentiary documents that rely on liquid chromatograpy-mass

spectrometry analytical determination of aristolochic acid

content should be accepted as a basis to release detained

product.

For questions or issues concerning science, science policy,

sample collection, analysis, preparation, or analytical

methodology, contact the Division of Field Science at (301)

443-3320 or 3007.

For questions or issues concerning declared ingredient names,

please email inquiry to Dr. Robert Moore, Office of

Nutritional Products, Labeling and Dietary Supplements, at

rmoore2 or fax inquiry to (202) 260-8957.

PRIORITIZATION

GUIDANCE: I

FOI: No

purging is required

KEYWORDS: Aristolochic acid, toxin, carcinogen,

nephrotoxin, herbs,

herbals, drugs

PREPARED BY: Ted Poplawski, DIOP, (301) 443-6553

DATE LOADED

INTO FIARS: July 6,

2000

Attachment A

for Import Alert #54-10 - 7/6/00

Botanicals Known or Suspected to Contain Aristolochic Acid

Botanical Name*

Common or Other Names

Aristolochia spp.

Aristolochia

Guan mu tong

Guang mu tong

Aristolochia acuminata Lam.

None

Aristolochia argentina Griseb.

None

Aristolochia baetica Linn.

None

Aristolochia bracteata Retz.

Ukulwe

Aristolochia cinnabarina C.Y. Cheng & J.L. Wu

None

Aristolochia clematitis L.

Birthwort

Aristolochia contorta Bunge

Ma dou ling

Tian xian teng

Aristolochia cymbifera Mart. & Zucc.

Mil homens

Aristolochia debilis Siebold & Zucc.

Ma dou ling

Tian xian teng

Qing mu xiang

Aristolochia elegans Mast.

None

Aristolochia esperanzae Kuntze

None

Aristolochia fangchi Y.C. Wu ex L.D. Chow Guang fang

ji

& Hwang

Fang ji

Mokuboi (Japanese)

Kwangbanggi (Korean)

Fang chi

Aristolochia fimbriata Cham

None

Aristolochia heterophylla Hemsl.

Yellowmouth Dutchman'sb

pipe

Aristolochia indica L.

Indian birthwort

Aristolochia kaempferi Willd.

None

Aristolochia kankauensis Sasaki

None

Aristolochia kwangsiensis Chun & How ex Liang

None

Aristolochia longa Linn.

Birthwort

Long birthwort

Aristolochia manschuriensis Kom.

Manchurian birthwort

Manchurian Dutchman's pipe

Guang mu tong

Kan-Mokutsu (Japanese)

Mokuboi (Japanese)

Kwangbanggi (Korean)

Aristolochia maurorum Linn.

None

Aristolochia maxima Jacq.

None

Aristolochia rotunda Linn.

None

Aristolochia serpentaria L.

Virginia snakeroot

Serpentaria

Aristolochia sipho L'Herit.

None

Aristolochia tagala Champ.

Oval leaf Dutchman's pipe

Aristolochia watsoni Wooton & Standley

None

Aristolochia westlandi Hemsl.

None

Asarum canadense Linn.

Wild ginger

Indian ginger

Bragantia wallichi R.Br.

None

*The Latin binomial name may appear without the author's name.

Attachment B

to Import Alert# 54-10 - 7/6/00

Botanicals which may be adulterated with Aristolochic Acid

Botanical Name*

Common or Other Names

Akebia spp.

Akebia

Mu tong

Ku mu tong

Zi mutong

Bai mu tong

Mokutsu (Japanese)

Mokt'ong (Korean)

Akebia quinata (Houtt.) Decne.

Chocolate vine

Fiveleaf akebia

Mu tong

Yu zhi zi

Akebia trifoliata (Thunb.) Koidz).

Mu tong

Three leaf akebia

Yu zhi zi

Clematis spp.

Clematis

Mufangji

Clematidis

Ireisen (Japanese)

Wojoksum (Korean)

Clematis armandii Franch.

Armand's clematis

Chuan mu tong (stem)

Xiao mu tong

Armand's virgin bower

Clematis chinensis Osbeck.

Chinese clematis

Wei ling xian (root)

Clematis hexapetala Pall.

None

Clematis montana Buch.-Ham. Ex DC.

None

Clematis uncinata Champ. Ex Benth.

None

Cocculus spp.

Cocculus

Cocculus carolinus DC.

None

Cocculus hirsutus Diels

None

Cocculus indicus Royle

Indian cockle

(synonym: Anamirta paniculata Colebr.)

Cocculus laurifolius DC.

None

Cocculus leaebe DC.

None

Cocculus madagascariensis Diels

None

(synonym: Cocculus diversifolius

DC.)

Cocculus orbiculatus DC.

None

(synonym: Cissampelos pareira Linn.)

Cocculus pendulus Diels

None

(synonym: Cebatha pendula (J.R. & C.

Forst.) Kuntze)

(synonym: Epibaterium pendulus Forst. f.)

(synonym: Cocculus Epibaterium DC.)

Cocculus palmatus Hook.

Colombo

(synonym: Jateorhiza Miersii Oliver)

Cocculus thunbergii DC.

None

Cocculus trilobus DC.

None

Diploclisia chinensis Merrill

Xiangfangchi

Menispernum dauricum

None

Sinomenium acutum (Thunb) Rehd et Wils

Ovientvine

Xunfengteng

Dafengteng

Daqingmuxinag

Zhuigusan

Da ye qingshener

Mufangji

Hanfangji

Tuteng

Zhuigufeng

Sinomenium acutum (Thunb) Rehd Wils et Wils Maofangji

var cinereum (Diels) Rehd et Wils

Stephania spp.

Stephania

Stephania tetrandra S. Moore

Fen fang ji, fang ji

Fang ji (root)

Han fang ji

Kanboi (Japanese)

Hanbanggi (Korean)

*The Latin binomial name may appear without the author's name.

Attachment C

to Import Alert# 54-10 - 7/6/00

Mu Tong and Fang Ji are declared ingredients in the following products:

Ba Zheng Wan

Chun Yang Zheng Ji Wan

Da Huang Qing Wei Wan

Dang Gui Si Ni Wan

Dao Chi Wan

Dieda Wan

Fu Ke Fen Quing Wan

Guan Xin Su He Wan

Ji Sheng Ju He Wan

Kat Kit Wan

Long Dan Xie Gan Wan

Quell Fire

Shi Xiang Fan Shen Wan

Xin Yi Wan

 

 

[Guest guest]

Well, it could have been worse I guess. Remind me again why

Wei Ling Xian (I prescribed it twice today, uncharactoristically) is on

the list.

 

We can only hope that Plum Blossom and other herb lines will respond with

" legal patents " for the patents that were listed below. Kai Kit

is another favorite I would miss if it were truly taken away.

The Chinese companies have often gotten around import restrictions before

to the detriment of non-Chinese speaking consumers and

practitioners.

Hopefully David Kessler will get off our backs for a while.

 

Doug

 

 

Ba Zheng Wan

Chun Yang Zheng Ji Wan

Da Huang Qing Wei Wan

Dang Gui Si Ni Wan

Dao Chi Wan

Dieda Wan

Fu Ke Fen Quing Wan

Guan Xin Su He Wan

Ji Sheng Ju He Wan

Kat Kit Wan

Long Dan Xie Gan Wan

Quell Fire

Shi Xiang Fan Shen Wan

Xin Yi Wan

 

 

L.Ac.

safe, compassionate care

acupuncture, herbs, Chinese Internal Medicine

Santa Monica, California

 

[Guest guest]

Hello,all.Here is a new question.HAS ANYBODY WORKED WITH THE CONDITION OF EYE

FLOATERS? I have a patient with this condition,usually the condition is

caused by Liv.Yin Xu. The patient has no other signs of the condition.He has

Liv.Qi Yu and some Sp.Qi Xu in a mild form. Has anybody successfully treated

patients with similar circunstances? Thank you for reply.

[Guest guest]

 

 

I just want to take a moment to tell you that I think you are one of the heroes of the TCM scene. A lot of us love to talk about our field, and you certainly do this with knowledge and wisdom. However, there aren't many of us that are willing to engage the outside world in the way you do. You truly go above and beyond all expectations for a what a practitioner should be willing to do for their profession.

 

Mark Reese

[Guest guest]

In a message dated 7/25/00 2:50:31 AM, herb-t writes:

 

<< While I submitted comment to the FDA calling for each of these things on

behalf

of Chinese Herbal Medicine, I have no indication that we were actually heard.

Nevertheless, the end result satisfies all the criteria of the Chinese Herb

Academy Consensus Statement on this subject. I think once again the FDA has

surprisingly shown itself to be a moderating force rather than a supplement

gestapo. >>

 

I dont think aristolochic acid is the bogeyman it is made out to be, any more

than most constituents taken out of context in large doses and in a non

traditional way.

DAVe

[Guest guest]

, acuman1@a... wrote:

 

>

> I dont think aristolochic acid is the bogeyman it is made out to

be, any more than most constituents taken out of context in large

doses traditional way.

> DAVe

 

The issue does not appear to be large doses out of traditional

context,

but rather small doses given cumulatively. And the issue always

involved identification problems or lay prescribing. Since

aristolochia species were not used longterm in TCM, the issue of

cumulative nephrotoxicity never surfaced. But I am convinced it is a

real issue, for which there are hardly adequate safeguards for the

public. I also think statements like this are exactly the

unreasonable, uncompromising posture that will prompt an FDA

backlash.

They could have easily just banned about 20 commonly used herbs, but

they did not.

 

Yes, we must remain vigilant, but the public is safer today and I can

still get the herbs I actually use. Some of you may be riled that we

lost a couple of herbs today (the aristolochiae are essentially

banned), but I wonder how of you made regular use of guang fang ji or

guang mu tong. I have never prescribed either on purpose in 13

years.

But then I use very few toxic herbs (no poisonous insects and only

heavily processed ban xia, fu zi and nan xing). Strong poisons are

essentially drugs; they are always inferior herbs and they never

promote healing, just relieve symptoms. I would almost just assume

my

patients take drugs short term to control severe symptoms when

necessary.

 

[Guest guest]

I also have never used guang fang ji or guang mu tong KNOWINGLY.. . .and I

agree with I don't have much use for the poisonous insects, and use

heavily processed toxic herbs.

 

 

 

>

> Yes, we must remain vigilant, but the public is safer today and I can

> still get the herbs I actually use. Some of you may be riled that we

> lost a couple of herbs today (the aristolochiae are essentially

> banned), but I wonder how of you made regular use of guang fang ji or

> guang mu tong. I have never prescribed either on purpose in 13

> years.

> But then I use very few toxic herbs (no poisonous insects and only

> heavily processed ban xia, fu zi and nan xing). Strong poisons are

> essentially drugs; they are always inferior herbs and they never

> promote healing, just relieve symptoms. I would almost just assume

> my

> patients take drugs short term to control severe symptoms when

> necessary.

>

 

>

>

>

>

>

> Chinese Herbal Medicine, a voluntary organization of licensed healthcare

> practitioners, matriculated students and postgraduate academics specializing

> in Chinese Herbal Medicine, provides a variety of professional services,

> including board approved online continuing education.

>

>

>

>

[Guest guest]

In a message dated 7/25/00 9:49:13 PM, herb-t writes:

 

<< The issue does not appear to be large doses out of traditional

context,

but rather small doses given cumulatively. And the issue always

involved identification problems or lay prescribing. >>

 

I have talked with herbalists from Belgium, and they used raw herbs and herbs

600 times the dose normally used (on a body weight ratio, of course) on cats,

dogs, and mice. It hurt mice, so they said it was bad if used for long

periiods. The whole thing was a sham. Trouble is that I have a whole booklet

of info on it to disprove the whole thing and it is in French, so I need an

interpreter, and dont' have one.

There was no misidentification, butthey thought that could be the reason. The

reason why the liver problems and cancer happened had only ot do with the

drugs and diet programs they were given, and a similar program without the

drugs in another town had no problems (same herbs no drugs). The media wasn't

interested. Here inthe US, some of the media is.

Volunteers?

David Molony

[Guest guest]

on 7/26/00 9:06 AM, acuman1 at acuman1 wrote:

 

>

> In a message dated 7/25/00 9:49:13 PM, herb-t writes:

>

> << The issue does not appear to be large doses out of traditional

> context,

> but rather small doses given cumulatively. And the issue always

> involved identification problems or lay prescribing. >>

>

> I have talked with herbalists from Belgium, and they used raw herbs and herbs

> 600 times the dose normally used (on a body weight ratio, of course) on cats,

> dogs, and mice. It hurt mice, so they said it was bad if used for long

> periiods. The whole thing was a sham. Trouble is that I have a whole booklet

> of info on it to disprove the whole thing and it is in French, so I need an

> interpreter, and dont' have one.

> There was no misidentification, butthey thought that could be the reason. The

> reason why the liver problems and cancer happened had only ot do with the

> drugs and diet programs they were given, and a similar program without the

> drugs in another town had no problems (same herbs no drugs). The media wasn't

> interested. Here inthe US, some of the media is.

> Volunteers?

> David Molony

>

>

>

> Chinese Herbal Medicine, a voluntary organization of licensed healthcare

> practitioners, matriculated students and postgraduate academics specializing

> in Chinese Herbal Medicine, provides a variety of professional services,

> including board approved online continuing education.

>

>

>

>

David,

Send me a copy and I (or my wife, who is more fluent) will work on

translating it.

 

 

6667 Fisk Ave.

San Diego, Ca. 92122