Ä [52]  IN*TOUCH DRUGS (1:375/48) ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TALK.POLITICS.DRUGS Ä
 Msg  : #2671 [101]                                                             
 From : Nikolaos Daniel Willmore            1:2613/335      Tue 11 Jan 94 20:24 
 To   : All                                                                     
 Subj : Pt 1/6: Here's what created the public outcry against the FDA!          
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
From: ndw1@bonjour.cc.columbia.edu (Nikolaos Daniel Willmore)
Organization: Columbia University

This summer, the FDA presented to congress, as recorded in the Federal
Register, new regulations concerning nutritional supplements (amino acids,
vitamins, and herbs). This has resulted in the largest public outcry the
Clinton administration has seen on any topic. Here is the full text of
what the FDA proposed, from the Federal Register. The bills S.784 and
H.R.1709, coming before congress very soon, would limit FUTURE FDA
attempts to limit access to supplements. NOW is the time to write those
letters!

Vol. 58 No. 116 Friday, June 18, 1993  p 33690 (Proposed Rule)
DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Ch. I

[Docket No. 93N-0178]

RIN 0905-AD90

Regulation of Dietary Supplements

AGENCY: Food and Drug Administration, HHS.

ACTION: Advance notice of proposed rulemaking.

SUMMARY: The Food and Drug Administration (FDA) is reviewing
the manner in which it regulates dietary supplements, including
products containing vitamins, minerals, amino acids, herbs,
and other similar nutritional substances. FDA is requesting
public comment on approaches, consistent with the requirements
of the Federal Food, Drug, and Cosmetic Act (the act), for assuring
the safety of such products offered as dietary supplements.
FDA is announcing the agency's intention to bring amino acid-
containing dietary supplement products into compliance with
the law and requests manufacturers of these products to submit
any additional information that may be available on the safety
and use of individual amino acids or combinations of amino acids
as ingredients in dietary supplements. FDA is also announcing
the availability of a report entitled ``Task Force on Dietary
Supplements Final Report'' and requests comment on the recommendations
made in this report. This action is being taken in response
to the Dietary Supplement Act of 1992 (the DS act), recent developments
and events in the marketplace, and the report of an outside
expert body on the safety of amino acid supplements.

DATES: Written comments by August 17, 1993.

ADDRESSES: Submit written requests for single copies of ``Task
Force on Dietary Supplements Final Report,'' to the National
Technical Information Service (NTIS), U.S. Department of Commerce,
5285 Port Royal Rd., Springfield, VA 22161. Send two self-addressed
adhesive labels to assist that office in processing your requests.
Submit written comments to the Dockets Management Branch (HFA-
305), Food and Drug Administration, rm. 1-23, 12420 Parklawn
Dr., Rockville, MD 20857. Requests and comments should be identified
with the docket number found in brackets in the heading of this
document. The ``Task Force on Dietary Supplements Final Report,''
and comments received in response to this document are available
for public examination in the Dockets Management Branch between
9 a.m. and 4 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT: Judith S. Kraus, Center for
Food Safety and Applied Nutrition (HFS-456), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-205-5233.

SUPPLEMENTARY INFORMATION:


I. Background


A. Description of Dietary Supplements

   Dietary supplements constitute a large and diverse class
of products consumed in capsule, tablet, liquid, or powder form
by a substantial portion of the American public. These supplements
encompass a wide array of products that include vitamins, essential
minerals, protein, amino acids, herbs, animal and plant extracts
(e.g., garlic extracts and inert glandulars), fats and lipid
substances (e.g., fish oils, sterols, and essential fatty acids),
dietary fibers, and chemical compounds that may have biological
activity but that are generally not recognized as nutrients
under the traditional definition of that term (e.g., bioflavonoids,
enzymes, nucleic acids, para-aminobenzoic acid, and rutin).
   Many of the ingredients in dietary supplements are concentrated
substances that occur naturally in plant and animal products
that have a history of safe use as food. When these substances
are prepared for incorporation into dietary supplements in tablet,
capsule, or bulk powder form, significant differences from their
conventional food forms may result. For example, a substance
may be added to a supplement at a much higher concentration
than naturally found in foods, making it easy to ingest the
target substance in an amount that greatly exceeds the intake
that is likely or possible from food in conventional food form.
What is safe at low levels in foods may not necessarily be safe
at higher levels or in more concentrated forms. The chemical
form of the substance in dietary supplements may also differ
from that commonly consumed in foods in conventional food form.
   Supplement products are frequently sold in containers that
look like, and that have label information resembling, drugs
(e.g., expiration dates, lot numbers, cotton fillers, tamper
proof caps). Product information leaflets bearing claims are
often available on store shelves and at the point of purchase.
Products or particular ingredients in products may also be promoted
by sales person at health food and specialty nutrition stores.

B. Recent Developments Suggesting Need for a Review

   Significant changes in the dietary supplement market and
in consumers' use of supplements have occurred in recent years.
Public interest in the potential effect of vitamins (e.g., vitamin
E and other antioxidant vitamins) in lowering the risk of chronic
disease, a wider marketing and promotion of amino acids (e.g.,
for body building), and a general growth in the herbal market
have contributed to this changing market. Consumers have reported
the use of dietary supplements for various reasons: Cultural
and ethnic practices, perceived health and nutritive effects
including emotional and psychological needs, and perceived insurance
against dietary insufficiency (Refs. 1 and 2). There is wide
variation in the use of these products according to age, lifestyles,
socioeconomic status, and geographic location.
   Dietary supplements are now readily obtainable at grocery
stores, drug stores, health food stores, and specialty nutrition
stores, as well as by mail order. These products are also widely
advertised in health promotion or body building magazines. A
recent survey of dietary supplement advertisements showed that
12 health and body building magazines contain advertisements
for 311 dietary supplement products from 89 different companies
(Ref. 4).
   At the same time that dietary supplement use is growing,
there have been at least two recent significant outbreaks of
public health problems associated with dietary supplements.
In 1989, at least 1,500 cases of eosinophilia myalgia syndrome
(EMS), including 38 deaths, were associated with the use of
L-tryptophan-containing dietary supplements. Within the last
year, there also have been a number of reports of serious illnesses
associated with certain herbal and other botanical supplements.
These developments have raised significant public health concerns.
   Another significant factor that has compelled FDA to review
current regulatory policies is enactment by Congress of the
DS Act (Pub. L. 102-571). This legislation imposed a 1-year
moratorium on FDA implementation of the Nutrition Labeling and
Education Act of 1990 (the 1990 amendments (Pub. L. 101-535))
with respect to dietary supplements not in conventional food
form, called for studies by the General Accounting Office and
the Office of Technology Assessment of FDA's regulatory program
for dietary supplements, and ordered FDA to complete a new round
of rulemaking by the end of 1993 implementing the 1990 amendments
for dietary supplements.
   In addition to rulemaking, FDA is developing a strategy to
evaluate solutions to achieve its public health goals in keeping
with the intent of the DS Act that contemplates a review of
FDA's policies and actions with respect to dietary supplements.

C. FDA's Public Health Mission

   FDA's public health mission includes assisting Americans
in capitalizing on the scientific advances over the last 30
years that have expanded the understanding of the relationship
between health and diet and of the role that diet can play in
improving the health of Americans. FDA encourages positive changes
in dietary habits and recognizes that access by consumers to
adequate nutrition and health information is an important part
of this process. The agency is committed to ensuring, consistent
with applicable law, that consumers have access to information
on nutrition and health. This goal was given particular prominence
and importance by the passage of the 1990 amendments.
   To fulfill its public health mission with regard to dietary
supplements FDA must also ensure that these products are safe,
and that claims made for their use are scientifically supported,
truthful, not misleading, and otherwise in accord with applicable
legal standards. Indeed, ensuring safety and proper labeling
is FDA's most basic and traditional responsibility and will
remain the agency's first priority with respect to dietary supplements.

D. Recent FDA Activities to Address the Issues

   FDA is addressing the safety and labeling issues regarding
dietary supplements. An agency task force on dietary supplements
has produced a report that sets out its conclusions and recommendations.
In addition, the agency has received a report on the availability
of data to evaluate the safety of amino acids, which was prepared
under an agency contract with the Life Sciences Research Office,
Federation of American Societies of Experimental Biology (LSRO/FASEB).
The conclusions and recommendations of both of these reports
are discussed in detail in this document.
   In response to the 1990 amendments and the DS act, FDA has
prepared proposed regulations on nutrition labeling, nutrient
content claims, and health claims for dietary supplements. These
documents appear elsewhere in this issue of the Federal Register.
In addition to these projects, FDA has established a dialogue
with industry, public health, and consumer group representatives
through a series of meetings on safety and labeling issues for
dietary supplements.

E. Task Force on Dietary Supplements

   In May 1991, following the EMS outbreak associated with consumption
of L-tryptophan-containing dietary supplements, the Commissioner
of Food and Drugs (the Commissioner) established an internal
FDA task force to review the agency's regulatory program for
dietary supplements and to recommend improvements. Known as
the Dietary Supplement Task Force (the Task Force), it was composed
of agency staff with experience and expertise in regulatory,
nutritional, legal, and medical issues related to supplements.
The Commissioner asked the Task Force to examine a number of
issues, including whether safety concerns exist regarding dietary
supplements and, if so, to recommend a regulatory framework
to distinguish supplements that raise safety concerns from those
that do not.
   The Task Force attempted to balance the agency's statutory
mandate to protect the public health with some accommodation
of the desire of a substantial segment of the public to obtain
dietary supplements, including ones with possibly little or
no documented nutritive value. The Task Force focused on products
sold in capsule, tablet, liquid, and powder form. To facilitate
its deliberations, the Task Force divided supplements into three
categories: (1) Vitamin- and mineral-containing products; (2)
amino acid-containing products; and (3) products containing
all other ingredients, a category that included herbs without
a history of documented traditional food use, plant and animal
extracts, and certain other substances.
   The Task Force completed its work in May 1992 when it submitted
a report with recommendations to the Commissioner (Ref. 2).
The Task Force identified the safety of ingredients in dietary
supplements as the overriding concern for FDA as it develops
a regulatory framework to distinguish among dietary supplement
products. Details of the Task Force report with respect to specific
types of substances are discussed elsewhere in this document
under the appropriate category headings.
   FDA is making this report available and requests comments
on the recommendations in this report, including comments about
which recommendations should be considered for adoption by FDA.

F. LSRO/FASEB Report on Amino Acids

   In 1990, in the aftermath of the L-tryptophan-associated
EMS outbreaks, FDA sought an objective and accurate scientific
assessment by LSRO/FASEB on the safety of amino acids. FDA sought
this report to provide scientific information on the safety
of amino acids. This information is needed by FDA in exercising
its enforcement discretion with respect to supplements that
contain these substances.
   LSRO/FASEB reviewed the available scientific literature on

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Ä [52]  IN*TOUCH DRUGS (1:375/48) ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TALK.POLITICS.DRUGS Ä
 Msg  : #2672 [101]                                                             
 From : Nikolaos Daniel Willmore            1:2613/335      Tue 11 Jan 94 20:24 
 To   : All                                                                     
 Subj : Pt 2/6: Here's what created the public outcry against the FDA!          
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
the safety of each of the amino acids. The review gave special
emphasis to metabolism, genetic influences on metabolism, and
population groups at potentially higher risk for adverse health
effects from use of amino acids in supplements.
   The LSRO/FASEB report ``Safety of Amino Acids Used as Dietary
Supplements'' was submitted to FDA in July 1992, and its availability
was announced in the Federal Register of December 2, 1992 (57
FR 57067). LSRO/FASEB reached several conclusions:
   1. It was not able to identify a safe level of intake in
dietary supplements for any of the amino acids in the report.
   2. There was particular concern about the use of dietary
supplements containing amino acids by several subgroups of the
general healthy population (e.g., women of childbearing age,
especially if pregnant or lactating; infants, children and adolescents;
the elderly; individuals homozygous or heterozygous for inherited
disorders of amino acid metabolism; individuals who smoke; and
persons with low dietary protein intakes) and by patients with
certain diseases who were considered to be at higher risk for
possible adverse effects. The report concluded that use of dietary
supplements containing amino acids by these special groups requires
responsible medical advice and supervision.
   3. The use of D-amino acids in dietary supplements is inappropriate
because they have not been shown to have nutritional function
in humans.
   4. There is an immediate need to label dietary supplements
containing amino acids currently in the marketplace to provide
accurate information on the chemical composition and purity
of ingredients, isomeric identity, shelf life, suggested doses,
and contraindications for use.
   5. There is a need for additional information on consumption
of dietary supplements that contain amino acids, and
   6. Based on an evaluation of the limited data on patterns
of amino acid use and adverse health effects, LSRO/FASEB concluded
that the safety of unrestricted use of particular amino acids
in dietary supplements cannot be assumed.
   LSRO/FASEB recommended a systematic evaluation of certain
effects of these substances, given the scarcity of safety data
for the amino acids in dietary supplements. Specific details
of the LSRO/FASEB report findings are discussed in the amino
acids section elsewhere in this document.

G. Current Legal Framework for Dietary Supplements Under the
Act

   FDA's authority to regulate the safety and labeling of dietary
supplements derives from both the food and the drug provisions
of the act. A product is legally a food or a drug based on its
intended use. Products primarily consumed for their taste, aroma,
or nutritive value are foods under section 201(f) of the act
(21 U.S.C. 321(f)) (Nutrilab. Inc. v. Schweiker, 713 F.2d 335
(7th Cir. 1983)). While many dietary supplements are foods under
this definition, other products, although marketed as dietary
supplements, fall within the drug definition (section 201(g)
of the act) because they are intended for use in the diagnosis,
cure, mitigation, treatment or prevention of disease or to affect
the structure or a function of the body. The intended use of
a product may be determined from labeling, advertising, or other
sources.
   Because dietary supplements are subject to regulation as
foods, drugs, or both, there are a variety of statutory provisions
that come into play in the regulation of these products. These
provisions include the adulteration provisions for food and
drugs (sections 402 and 501 of the act (21 U.S.C. 342 and 351)),
the misbranding provisions (sections 403 and 502 of the act
(21 U.S.C. 343 and 352)), as well as the provisions on food
additives (section 409 of the act (21 U.S.C. 348)), prescription
drugs (section 503 of the act (21 U.S.C. 353)), and new drug
approvals (section 505 of the act (21 U.S.C. 355)).
   Fundamental to how the agency ensures the safety of foods,
including dietary supplements, are the food additive provisions
of the act (sections 201(s), 402(a)(2)(C), and 409). Before
1958, a manufacturer could use an ingredient in food, and FDA
had the burden of proving, subsequent to marketing, that the
ingredient was harmful at some level. The 1958 Food Additives
Amendment reflected a determination by Congress that marketers
of processed foods should bear the burden of establishing the
safety of the ingredients they use before exposing the public
to them.
   A food additive is broadly defined in section 201(s) of the
act as any substance, the intended use of which results, or
may reasonably be expected to result, directly or indirectly,
in its becoming a component or otherwise affecting the characteristics
of food.{1} Thus, ingredients incorporated into dietary supplements
(vitamins, minerals, amino acids, herbs, and other similar nutritional
substances that are processed in tablet, capsule, powder, or
liquid form) are food additives unless they are generally recognized
as safe (GRAS), or prior-sanctioned.{2}
        {1}  Recently, two courts of appeal have held that
      the named ingredient in a gelatin capsule that consists
      only of that ingredient, and the ingredients necessary
      to form the capsule, is not a food additive. FDA is considering
      seeking further review of these decisions.
        {2}  A substance is considered prior-sanctioned if
      its specific use in food was authorized by FDA or the
      Department of Agriculture prior to September 6, 1958.
   Section 409(b)(1) of the act requires the manufacturer to
submit a petition to establish the safety of use of a food additive,
which must include, among other information, data that establish
that the additive will accomplish its intended physical or technical
effect in the food. FDA is precluded under section 409(c)(4)(B)
of the act (21 U.S.C. 348(a)) from issuing a food additive tolerance
and under its regulation (21 CFR 184.1(b)) from affirming the
GRAS status of a substance for which a technical effect has
not been demonstrated.
   Some food ingredients are marketed based on the manufacturers'
independent determination that they are GRAS. Such manufacturers
do so at the risk that the agency will disagree and bring a
regulatory action against the product.

H. FDA's Regulatory Concerns

   The broad spectrum of dietary supplement products present
a range of safety and labeling issues. Most of the ingredients
in dietary supplements, especially vitamins and essential minerals
taken in moderate potencies, present few safety concerns. A
smaller number of ingredients of dietary supplement products
and of dietary supplement products themselves, however, do pose
direct and indirect hazards.
   Direct hazards are those adverse health effects directly
attributable to the components of dietary supplement products.
They may be the result of effects of one or more of the ingredients
(be it the desired ingredient or a binder or filler), an interactive
effect of components of the product, or an effect of a contaminant
in one or more of the ingredients of the dietary supplement.
   The agency is concerned about potential direct hazards of
some dietary supplements because information on the safety or
the nature of many of the ingredients used in dietary supplements
is not available. For example, there is considerable natural
variability in the constituents of herbs and other botanicals
and of glandular ingredients, and methods to characterize many
of these products and their constituents do not exist (e.g.,
to determine the identity and bioavailability of active ingredients
or to measure the levels of heavy metals, pesticides, or microbial
contaminants). Furthermore, there apparently are no generally
accepted current good manufacturing practices (CGMP's) that
address how supplement products are to be manufactured to ensure
that they have the claimed potency, appropriate purity, and
other quality and performance attributes that help to ensure
safety.
   Indirect hazards may occur if the use of a supplement product
delays the diagnosis or treatment of a health disorder. This
is a particular concern when exaggerated or unfounded claims
are made regarding the benefits of a product in treating or
preventing serious diseases, such as cancer and AIDS. These
indirect hazards are ordinarily dealt with through FDA's health
fraud program.
   To facilitate a more detailed examination of these concerns
the agency has divided this document into the following sections:
``II. Vitamins and Minerals,'' ``III. Amino Acids,'' ``IV. Herbs,''
and ``V. Other Components of Dietary Supplements''.

II. Vitamins and Minerals


A. Use of Vitamin and Mineral Supplements

   Vitamins and essential minerals are nutrients. They are essential
for life and must be obtained from dietary sources because they
cannot be synthesized by the body or are not present in the
body in amounts adequate to maintain health. Vitamin and mineral
dietary supplements have a long history of use at levels at
the Recommended Dietary Allowances (RDA's), below the RDA's,
or at low multiples of the RDA's, and are generally considered
safe at these levels for the general population. Intakes above
RDA levels, however, vary widely in their potential for adverse
effects. For some nutrients, such as the mineral selenium, there
is a small difference between intake levels that are safe and
levels that can be harmful. Other nutrients such as vitamin
C and thiamin have considerably larger ranges of safe intake.
   Sales of dietary supplements containing vitamins and minerals
have increased dramatically during the past two decades (Ref.
3). In 1990, sales totaled $2.9 billion. In a 1990 survey of
the dietary supplement market, multivitamins and minerals accounted
for 42 percent of the market share in dollars, vitamin C and
calcium accounted for 12 percent and 8 percent, respectively,
and vitamin B complex and vitamin E each accounted for 9 percent
(Ref. 5).
   One of the most comprehensive surveys on the use of vitamin-
and mineral-containing supplements by individuals was the National
Health Interview Survey (NHIS) conducted in 1986 (Ref. 6). This
survey covered 11,775 adults (18 years of age or older) and
1,877 children (2 to 6 years of age). A total of about 5,600
respondents reported using more than 3,400 different vitamin
or mineral-containing supplement products (Ref. 7). The more
than 3,400 products in this survey were manufactured or distributed
by about 600 different companies. About 90 percent of these
products were manufactured or distributed by national companies.
The remaining 10 percent of the products were manufactured or
distributed by a large number of local companies, which accounted
for about half of the total number of companies identified in
this survey. This survey also showed that the labeled potencies
of vitamin and mineral-containing supplements varied widely.
However, potencies of nutrients contained in children's and
prenatal products fell within a narrow range, generally at or
below 100 percent of the U. S. Recommended Daily Allowance (U.S.
RDA) per dosage unit (Ref. 7).
   Potencies of single-nutrient products (i.e., products intended
for supplementing one specific nutrient) and general multinutrient
products (i.e., products intended for supplementing two or more
nutrients that were not targeted for use by children, or pregnant
or lactating women) varied greatly. For example, potencies of
single-nutrient supplements ranged from 34 percent to 12,500
percent of the U.S. RDA per tablet for vitamin D; from 67 percent
to 33,333 percent for thiamin (vitamin B1); from 69 percent
to 50,000 percent for vitamin B6; from 17 percent to 33,333
percent for vitamin B12; and from 100 percent to 5,000 percent
for niacin. Potencies of general multi-nutrient supplements
ranged from less than 0.5 percent to 55,333 percent of the U.S.
RDA per tablet for vitamin B1; from less than 0.5 percent to
15,000 percent for vitamin B6; from 1 percent to 16,667 percent
for vitamin B12; and from less than 0.5 percent to 5,000 percent
for pantothenic acid. As seen in the range of values, some of
these products are extremely high potency, containing 5,000
to about 55,000 percent of the U.S. RDA of one or more nutrients
per tablet (Ref. 7).
   The 1986 NHIS data base also provided information on how
supplement use varied among respondents that took supplements.
About 5 percent of all self-prescribed adult users of vitamin
or mineral-containing supplements, which represents about 3
million persons in the United States, reported using at least
5 different vitamin or mineral-containing products (Ref. 6).{3}
For most vitamins, the median average daily intake of all users
of these products was between 100 percent and 200 percent of
the 1980 RDA's). However, 10 percent of adult users consumed
amounts of several vitamins (thiamin, riboflavin, vitamins C,
E, B6, and B12) ranging from 1,666 percent to 3,333 percent
of the RDA or more from the supplements alone (Ref. 6). Maximum
average daily intakes of thiamin, riboflavin, and vitamin B6
were as high as about 78,600 percent, 68,700 percent, and 51,000
percent of the RDA, respectively (Ref. 8).
        {3}  ``Self-prescribed users'' refers to those who
      use supplements without a doctor's recommendation, excluding
      pregnant or lactating females.

B. Regulatory History of Dietary Supplements of Vitamins and
Minerals

   The regulatory history of dietary supplements of vitamins
and minerals goes back over 50 years. Details of this regulatory
history are contained in the Federal Register of November 27,
1991 (56 FR 60366 at 60381). A brief discussion of its history
follows.
   In 1941, after passage of the act, FDA issued regulations
for vitamin and mineral dietary supplements expressed as minimum

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Ä [52]  IN*TOUCH DRUGS (1:375/48) ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TALK.POLITICS.DRUGS Ä
 Msg  : #2673 [101]                                                             
 From : Nikolaos Daniel Willmore            1:2613/335      Tue 11 Jan 94 20:24 
 To   : All                                                                     
 Subj : Pt 3/6: Here's what created the public outcry against the FDA!          
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
daily requirements. By the early 1960's, however, the agency
felt that these regulations were outdated. The agency's concerns
focused on high potency vitamins and on whether the potencies
of vitamins and mineral supplements should be limited to nutritionally
rational levels when these products were marketed as foods.
   In 1973, FDA adopted new regulations to govern the labeling
and composition of dietary supplements and other foods that
purported to be, or were represented for, special dietary use
because of their vitamin or mineral properties. The 1973 regulations
set forth definitions, standards of identity, and labeling statements
for vitamin and mineral dietary supplements. The standards permitted
only five basic types of preparations; prescribed the vitamin,
mineral, and other ingredient composition of multinutrient supplements;
and specified maximum and minimum potencies for vitamins and
mineral ingredients. A lawsuit was filed challenging this action,
and the reviewing court remanded the regulations to FDA. In
1975, FDA held an administrative hearing on the regulations.
   While FDA was in the process of completing the hearing and
revising the vitamin and mineral regulations pursuant to the
instructions of the court, Congress enacted legislation (Pub.
L. 94-278, Title V, April 22, 1976) that became section 411
of the act (21 U.S.C. 350) (known as the ``Proxmire Amendment'').
This amendment prevents the agency from using the food standards
or misbranding provisions of the act to place maximum limits
on the potency of vitamins or minerals in foods. It also prevents
the agency from classifying any vitamin or mineral as a drug
solely because it exceeds a potency level that is deemed to
have a nutritionally sound rationale.
   In the Federal Register of October 19, 1976 (41 FR 46156),
the agency issued a final regulation that amended the 1973 regulations
to comply with the court's 1974 remand instructions and with
the Proxmire Amendment. Another lawsuit was filed, and in February
1978, the court remanded the case to FDA. In the Federal Register
of March 16, 1979 (44 FR 16005), FDA revoked the 1976 regulations
and reinstated certain portions of the 1973 regulations. The
agency has not taken any further action on the 1976 regulations.

C. Current Regulatory Status of Vitamins and Minerals

   Some vitamins and minerals that are intended for use as dietary
supplements are listed as GRAS under part 182, subpart F (21
CFR part 182, subpart F). In most cases, the only limitation
placed on the conditions of their use is CGMP as defined in
 182.1. Some vitamins and minerals are also listed for other
intended uses, such as special dietary or nutritional additives
(part 172, subpart D (21 CFR part 172, subpart D)), or as nutrients
in processed foods (part 182, subpart I). In addition, several
vitamins and minerals have been affirmed as GRAS under part
184 (21 CFR part 184) for uses other than as dietary supplements.

D. Issues of Concern

   FDA has identified certain public health issues related to
dietary supplements of vitamins and minerals. These issues include:
(1) The need for a comprehensive science-based evaluation of
the potential toxicity of vitamins and minerals at various intake
levels; and (2) in light of that review, the need to establish
the levels of intake of vitamins and essential minerals that
are safe.
   Certain vitamins and minerals are safe when consumed at low
levels but may have adverse effects when consumed daily at higher
levels. For example, consumption of as little as 25,000 international
units (IU's) per day of preformed vitamin A (U.S. RDA is 5,000
IU's) for periods of several months or more can produce multiple
adverse effects, including hepatic cirrhosis, increased intracranial
pressure, and possibly birth defects (Refs 9 and 10). Especially
vulnerable groups include children, pregnant women, and persons
with liver pathology caused by a variety of factors including
alcohol, viral hepatitis, and severe protein-energy malnutrition
(Ref. 9).
   The preponderance of reports of adverse effects from excess
vitamin B6 (pyridoxine) supplementation have involved intakes
above 200 milligrams per day (mg/day) and have been associated
with symptoms of a sensory neuropathy. However, as little as
50 mg/day supplemental vitamin B6 (U.S. RDA is 2 mg) has caused
resumption of symptoms in an individual previously injured by
higher intakes (Refs. 11 and 12).
   Daily doses of 500 mg of niacin from a slow-release formulation
and 750 mg from an unmodified niacin product have been associated
with severe adverse effects. U.S. RDA is 20 mg. These severe
side effects include gastrointestinal distress (burning pain,
nausea, vomiting, bloating, cramping, and diarrhea) and mild
to severe liver damage (Refs. 13, 14, and 15). Several reports
have suggested that time-release formulations of niacin carry
a higher risk of side effects than do unmodified niacin products
(Ref. 13).
   Ingestion of excess selenium can cause tissue damage, especially
in tissues or organs that concentrate the element. The toxicity
of selenium depends upon the chemical form of the ingested element.
Human intoxications have occurred with high intakes after a
period of a few weeks (Ref. 16).
   Related topics on the safety of vitamin and mineral supplements
have been addressed in three LSRO/FASEB reports published since
1980. The first report, entitled ``Guidelines for Safety Evaluation
of Nutrients'' (Ref. 17), evaluated the types of scientific
evidence needed to establish the safety of vitamin and essential
mineral ingredients in supplements. This report stated that
the comprehensive systems to evaluate the safety of food additives,
food colors, and ingredients classified as GRAS have limited
application to decisions on the safety of essential nutrients.
For example, eliminating from the food supply substances that
pose a potential health hazard to the public is not a feasible
option for essential nutrients. Although the margin of safety
between current levels of ingestion and toxic levels may be
narrow for some nutrients, the report pointed out that the highest
no-adverse-effect level for most nutrients is ill-defined. Accordingly,
the report concluded that a system is needed to evaluate and
compare data on essentiality and toxicity of nutrients at various
levels of intake. This report further concluded that, in the
absence of toxicological testing, nutrients cannot be assumed
to be free of adverse effects even at intake levels possible
from normal diets.
   A second report, entitled ``Feasibility of Identifying Adverse
Effects of Vitamins and Essential Minerals in Man'' (Ref. 18),
concluded that studies with nonrandomized, self-selected treatment
groups cannot be sufficiently definitive to establish a causal
relationship between nutrient excess and subtle, long-term adverse
effects. Furthermore, according to the report, data collected
in national surveys on the normal consumption of vitamins and
essential minerals by the general U.S. population, either as
dietary components or as nutrient supplements, are of limited
value for the design of clinical protocols. The report stated,
however, that prospective clinical investigations of certain
vitamins or essential minerals can help to provide a reliable
and extensive data base that would be required for evaluating
the competing risks of nutrient deficiency and toxicity. A prime
objective of a clinical protocol would be the identification
of early and sensitive indicators of toxicity associated with
chronic ingestion of nutrient excesses. The report concluded
that the study of potential adverse effects of vitamins and
essential minerals would enhance the protection of public health.
   The usefulness of a national nutrition survey data base for
monitoring nutrient safety of the U.S. population was evaluated
through a contract study entitled ``Suggested Measures of Nutritional
Status and Health Conditions for the Third National Health and
Nutrition Examination Survey'' (Ref. 19). This study's primary
objective was to identify physiological measures useful to FDA
for monitoring both the safety and adequacy of the food supply,
for inclusion in the third National Health and Nutrition Examination
Survey (NHANES III). The report identified specific clinical
indices useful in a survey to identify the prevalence within
population subgroups of adverse health effects related to excessive
dietary intake of selected nutrients. Measures of the safety
of vitamins A, D, and B6 and the minerals iron and selenium
were suggested. Measures of the safety of other nutrients were
not available or not considered useful for this survey.

E. FDA's Task Force Discussion on Vitamin and Mineral Supplements

   The Task Force recognized that most vitamins and minerals
are generally safe when their intake is limited to small multiples
of the RDA's. However, the Task Force identified certain health
risks at higher levels of intake.
   The Task Force recommended that FDA use notice and comment
rulemaking to establish safe levels of use for vitamins and
essential minerals in dietary supplements. The Task Force recommended
that these levels be the maximum daily safe supplemental intake
for a given vitamin or essential mineral, called a ``dietary
supplement limit'' (DSL). The Task Force discussed the consequences
of regulating supplement products containing ingredients that
are not GRAS. It stated that the agency generally has not been
willing to pursue enforcement actions unless it could demonstrate
some degree of toxicity or potential toxicity. The Task Force
stated that FDA has declined to set safe levels for nutrients
in dietary supplements because the industry has shown that setting
such levels provides it with a cutoff point just below which
FDA will not take action, even though such levels are high.
Such levels then become the industry marketing norm. Nevertheless,
the Task Force stated that setting such levels is appropriate
to ensure safety. The Task Force recommended that to ensure
the safety of products containing vitamins and minerals, the
agency adopt a DSL for each vitamin and essential mineral.
   The Task Force said that the agency should initiate rulemaking
to establish these safe levels of use. Alternatively, it suggested
that the agency could call for the submission of food additive
or GRAS affirmation petitions on the use of vitamins or essential
minerals in dietary supplements. One approach, the Task Force
suggested, would be for the agency to propose to affirm as GRAS
(with certain specific exceptions) the highest RDA levels listed
by the National Academy of Sciences. The Task Force stated that
the burden would then shift to those commenting to submit evidence
that would justify a higher level that represents safe use.
Such an approach, the Task Force pointed out, would facilitate
the prompt publication of a proposals and focus the work of
agency scientists on preparing the final rules based on the
evidence submitted.
   The Task Force recommended such actions because it believed
that it is appropriate for the agency to distinguish between
those vitamin and essential mineral potencies in dietary supplements
whose use is safe, and those whose use create public health
concern.

F. Request for Public Comment on the Safety of Vitamin and Mineral
Supplements

   FDA requests comment on the appropriate procedures, both
scientific and administrative, and types of data for establishing
the safety of vitamins and essential minerals intended for consumption
in dietary supplements in quantities significantly in excess
of the amounts necessary to meet the known nutrient needs of
practically all healthy people. As stated previously, the Task
Force recommended one approach to a scientifically based determination
of the upper levels of safe use of vitamin and essential mineral
ingredients. FDA is soliciting comments on this recommendation
as well as recommendations on other approaches.
   In addition, FDA requests comments on the following questions
concerning evaluation of the safety of vitamins and minerals,
which may also be appropriate for the other ingredient categories:
   1. How should the requirement under section 409 of the act
that the tolerance limitation not be set higher than the level
necessary to accomplish the additive's intended physical or
other technical effect be satisfied?
   2. If current safety evaluation procedures are followed,
what safety factor or margin of safety is appropriate?
   3. If safety factors or margins of safety are to be applied,
how should adverse effects be identified against which these
factors or margins will be applied?
   4. Under what circumstances and how can data from nonexperimental
adverse reaction reports and other sources be utilized?
   5. Is it necessary to establish specifications and good manufacturing
practices to assure the safety of vitamin and essential mineral
products?
   As a secondary issue, the agency does not know what assumptions
and expectations consumers and health professionals have relative
to the safety of ingredients of dietary supplements. FDA requests
comments on what assumptions consumers make about the safety
of ingredients in dietary supplement products, and on what information
consumers should have on the label or in labeling to make informed
choices about the safety of these products.

III. Amino Acids


A. Current Use of Amino Acid Supplements

   Amino acids are available in the marketplace as single compounds,
in mixtures (containing two or more amino acids), as components
of protein powders, as chelated single compounds, or in chelated
mixtures. These products are marketed for a variety of uses.

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Ä [52]  IN*TOUCH DRUGS (1:375/48) ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TALK.POLITICS.DRUGS Ä
 Msg  : #2674 [101]                                                             
 From : Nikolaos Daniel Willmore            1:2613/335      Tue 11 Jan 94 20:24 
 To   : All                                                                     
 Subj : Pt 4/6: Here's what created the public outcry against the FDA!          
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
LSRO/FASEB found that amino acids in dietary supplements are
primarily used for nonnutritional purposes, i.e., for specific
therapeutic effects (Ref. 10). Amino acids were reported to
be the most frequently mentioned component on ingredient lists
for dietary supplements advertised in a survey of body building
magazines (Ref. 4).
   LSRO/FASEB estimated the quantities of individual amino acids
available for sale by members of a major trade association in
the United States from 1987 to 1989 (Ref. 20). L-lysine and
L-tryptophan (for 1987 to 1988) were available in the highest
amounts, i.e., greater than 1,000,000 pounds per year for each.
L-methionine had the next highest availability rate at more
than 20,000 pounds per year. Data on the ingestion of amino
acids by individuals have not been collected, but product labels
recommended daily intakes (RDI's) ranging from 0.25 to 4.5 grams
(g) for single amino acids, from about 1 to 15 g for partially
digested protein blends (Ref. 20), and from 0.35 to 40.0 g for
unspecified amino acids (Ref. 4).

B. Information on the Role of Amino Acids in Human Nutrition

   Amino acids are the individual structural units of proteins
and are precursors for, or may function as, biologically active
molecules such as some neurotransmitters and hormones. Nine
amino acids, histidine, isoleucine, leucine, lysine, methionine,
phenylalanine, threonine, tryptophan, and valine, must be supplied
in the diet because they are not synthesized by humans or synthesized
only in amounts inadequate for normal growth or maintenance
and are thus considered essential (Ref. 3). Other amino acids
are nonessential because they are synthesized endogenously in
amounts sufficient to support growth and nitrogen balance and
are, therefore, not specifically required in the diet.
   Most amino acids are supplied in the normal diet as constituents
of protein, not as free amino acids. Consumption of foods containing
intact proteins ordinarily provides sufficient amounts of amino
acids for growth and development of children and maintenance
of health of adults in the general U.S. population. Safety in
these forms is generally not a concern.
   Some amino acids, such as L-tryptophan and L-arginine, have
been promoted and used for their claimed pharmacologic effects.
The use of dietary supplements containing these free amino acids
appears to be a common practice among individuals interested
in increasing muscle mass and strength (Refs. 2, 4, and 20).

C. Regulatory History of Amino Acid Supplements

   In 1945, FDA issued a Trade Correspondence stating that a
food to which an amino acid is added would ordinarily be regarded
as a food for special dietary use and must be so labeled, but
may also in some cases be subject to the drug provisions of
the act (Ref. 21). Subsequently, the 1958 Food Additives Amendment
required the premarket approval of any substance whose intended
use could reasonably be expected to result in its becoming a
component of food, unless the use of the substance were GRAS
or subject to a prior sanction. In 1960 (25 FR 880, February
2, 1960, and 25 FR 7332, August 4, 1960), FDA proposed to list
a number of amino acids as GRAS for their intended use as ``nutrients
and/or dietary supplements'' with no limitations codified at
that time under 21 CFR 121.101(d)(5). This proposal was finalized
in 1961 (26 FR 1444, February 18, 1961).
   In the Federal Register of April 6, 1972 (37 FR 6938), FDA
proposed to revoke the GRAS status of all amino acids for use
as nutrients in foods and for use in dietary supplements because
of safety concerns based on studies showing that excessive intakes
of certain amino acids produced adverse effects in animals.
FDA concluded that the available information was insufficient
to support the GRAS status of amino acids. At the same time,
FDA proposed conditions for the safe use of amino acids as food
additives.
   In the same issue of the Federal Register, FDA also proposed
a food additive regulation to provide for the use of amino acids
as nutrient fortificants for addition to intact protein-containing
foods to improve the protein quality of these foods (37 FR 6938).
To prevent the random addition of amino acids to foods, the
agency proposed to limit the use of amino acids to foods that
contain naturally occurring, primarily intact, protein that
are considered significant dietary sources of protein. The agency
also addressed the use of amino acids in special formulations
for nutritional use in medical conditions.
   In the Federal Register of July 26, 1973 (38 FR 20036), FDA
published a final rule that revoked the GRAS status of amino
acids for nutritive and dietary supplement purposes. FDA promulgated
a food additive regulation that restricted the addition of amino
acids as nutrients to foods only when needed to significantly
improve the biological quality of the total protein in a food
containing naturally occurring, primarily intact protein that
is considered a significant dietary protein source. In addition,
the agency stated that no action would be taken to alter the
GRAS status of amino acids or their derivatives with recognized
nonnutritive uses (e.g., as flavor enhancers or dough conditioners).
   From 1974 through 1976, several amino acids were listed in
21 CFR 121.1002 as food additives. However, because of an editorial
error in recodifying FDA's regulations, amino acids were listed
as GRAS for use as ``nutrients and/or dietary supplements''
in the March 15, 1977, edition of title 21 of the Code of Federal
Regulations. This error was corrected by a Federal Register
notice dated October 28, 1977 (42 FR 56278 at 56279). In early
1977, prior to the correction, FDA brought a seizure action
against L-tryptophan tablets on the grounds that the tablets
contained an unapproved food additive. The court found that,
despite the fact that FDA's error had been inadvertent, the
manufacturer was entitled to rely on the GRAS regulations as
published. In another seizure initiated in 1977 against L-tryptophan
as a dietary supplement, FDA agreed to dismissal with prejudice
on September 14, 1982.

D. Current Regulatory Status of Amino Acid Supplements

   Amino acids, except L-cysteine and its hydrochloride salt,
may only be used as ingredients of food in accordance with
172.320 (21 CFR 172.320). L-cysteine and its hydrochloride salt
( 184.1271 and 184.1272) are affirmed as GRAS for use as dough
strengtheners. Under  170.50 (21 CFR 170.50), FDA has determined
that the use of glycine and its salts for certain technical
effects in human food is not GRAS. FDA considers all other uses
of amino acids in food to represent unapproved, and therefore
unlawful, uses of food additives.

E. Issues of Concern

   Products containing amino acids warrant special attention
by the agency because of several recent events, including: (1)
The recent epidemic of EMS, a serious disease associated with
consumption of L-tryptophan supplement products, (2) a recent
report by an independent organization that concluded that data
showing safety of amino acids in dietary supplements are lacking
(Ref. 20), and (3) the task force report, which discussed amino
acids and presented various options for regulating dietary supplements
that contain amino acids.

1. EMS Outbreak from L-Tryptophan

   The outbreak of EMS from the use of L-tryptophan-containing
dietary supplements has prompted FDA to reexamine its enforcement
posture regarding amino acid containing supplements. EMS is
a systemic connective tissue disease characterized by eosinophilia
(an increase in one type of the white blood cells), myalgia
(severe muscle pain), and cutaneous (skin) and neuromuscular
manifestations. This illness, which occurred in epidemic fashion
in the United States in the summer and fall of 1989, is associated
with the use of dietary supplements containing L-tryptophan
(Ref. 39). To date, more than 1,500 cases, including 38 deaths,
have met the Centers for Disease Control (CDC) case surveillance
definition of the disease, although the true incidence of the
disorder is thought to be much higher.
   FDA first learned about problems with L-tryptophan in 1989,
following a report from New Mexico about four cases of an illness
manifested by myalgia and eosinophilia, in which the common
denominator appeared to be the use of L-tryptophan. FDA subsequently
issued a strong public warning on November 11, 1989 (Ref. 22),
to discontinue the use of L-tryptophan. On November 17, 1989,
in conjunction with CDC, FDA requested a nationwide recall of
all over-the-counter dietary supplements containing 100 mg or
more of L-tryptophan (Ref. 23). The agency also issued an Import
Alert to detain all foreign shipments of L-tryptophan (Refs.
24 and 25). On March 22, 1990, the recall was extended to all
marketed products containing added manufactured L-tryptophan
because of a case of EMS in a patient consuming less than 100
mg daily (Ref. 26). (Products containing added L-tryptophan
permitted by 172.320 were excluded from this recall.) The
net effect of the recall and import alert was a ban on the oral
supplement forms of L-tryptophan because virtually all of the
raw material used to formulate U.S. products was imported.
   Despite recent intense research, the exact cause of EMS and
an understanding of how it develops have not been established.
Initial epidemiological studies implicated the L-tryptophan
produced by a single Japanese manufacturer, Showa Denko K. K.,
and further noted that certain impurities were identifiable
in batches of case-associated L-tryptophan. These findings suggested
that some impurity or other component in these batches of L-
tryptophan may have been responsible for EMS. However, both
initial and subsequent epidemiological studies on the EMS epidemic
have identified cases of EMS, and another related disease, eosinophilic
fascitis, that occurred before the 1989 epidemic and that appear
to be related to other batches or sources of L-tryptophan (Refs.
27, 40 and 41).
   EMS and other related disorders are also reported to be associated
with exposure to L-5-hydroxytryptophan, a related compound that
is not manufactured using the biofermentation process that was
used for production of L-tryptophan and is, therefore, not associated
with the same impurities or contaminants. There is also some
evidence for predisposing factors in some EMS patients. These
data, as well as data from animal experiments (Ref. 28), indicate
that L-tryptophan, either alone or in combination with some
other component in the supplement products, may be responsible
for some of the pathological features in EMS. Taken together,
these findings support previous suggestions that the L-tryptophan-
associated EMS was caused by several factors and is not necessarily
related to a contaminant in a single source of L-tryptophan.

2. Summary of LSRO/FASEB (1992) Report on Amino Acids

   As discussed earlier, LSRO/FASEB reviewed the available safety
data for the following amino acids: branched-chain amino acids
(leucine, isoleucine, and valine), histidine, lysine, methionine,
L-phenylalanine, D-phenylalanine, threonine, L-tryptophan, D-
tryptophan, alanine, arginine, ornithine and citrulline, asparagine,
aspartic acid, cysteine and cystine, glutamine, glutamic acid,
glycine, proline and hydroxyproline, serine, and tyrosine.
   For each of the amino acids, LSRO/FASEB reviewed the scientific
literature from studies with experimental animals and humans.
Special emphasis in the review was given to metabolism, genetic
influences on metabolism, and groups with potentially higher
risk for adverse health effects resulting from use of amino
acids in supplements.
   LSRO/FASEB reached several conclusions:
   1. A safe level of intake for the amino acid-containing dietary
supplements in the report could not be identified.
   2. There is a basis for particular concern about the use
of dietary supplements containing amino acids by several subgroups
of the general healthy population (e.g., women of childbearing
age, especially if pregnant or lactating; infants, children,
and adolescents; the elderly; individuals homozygous or heterozygous
for inherited disorders of amino acid metabolism; individuals
who smoke; and persons with low dietary protein intakes) and
by patients with certain diseases who were considered to be
at higher risk for possible adverse effects. The report concluded
that use by these special groups of dietary supplements containing
amino acids requires responsible medical advice and supervision.
   3. The use of D-amino acids in dietary supplements is inappropriate
because they have not been shown to have nutritional function
in humans.
   4. There is an immediate need to label dietary supplements
containing amino acids to provide accurate information on chemical
composition and purity of ingredients, isomeric identity, shelf
life, suggested doses, and contraindications for use. LSRO/FASEB
also noted the need for additional information on consumption
of dietary supplements containing amino acids.
   5. Based on an evaluation of the limited data on patterns
of amino acid use and adverse health effects, LSRO/FASEB concluded
that the safety of unrestricted use of particular amino acids
in dietary supplements cannot be assumed. LSRO/FASEB recommended
a systematic evaluation of certain effects of these substances,
given the paucity of safety data on the amino acids in dietary
supplements.
   FDA has reviewed the LSRO/FASEB report and notes that it
is consistent with the agency's previous determination that
amino acids for nutritive purposes are not GRAS. FDA solicits
comments on the report and submission of data that was not included
in the report.

F. FDA's Task Force Discussion on Amino Acids


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 * Origin: COBRUS - Usenet-to-Fidonet Distribution System (1:2613/335.0)

Ä [52]  IN*TOUCH DRUGS (1:375/48) ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TALK.POLITICS.DRUGS Ä
 Msg  : #2675 [101]                                                             
 From : Nikolaos Daniel Willmore            1:2613/335      Tue 11 Jan 94 20:24 
 To   : All                                                                     
 Subj : Pt 5/6: Here's what created the public outcry against the FDA!          
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
   As discussed earlier, amino acids were one category of ingredients
of dietary supplements considered by the Task Force. The Task
Force suggested several options for the agency to consider in
the regulation of amino acid-containing dietary supplements.
One option is to regulate single amino acids and mixtures of
amino acids as drugs when marketed for any use other than those
specified in the GRAS and food additive regulations.
   A second regulatory option identified in the report is to
regulate amino acids in supplements as food additives or GRAS
substances with a DSL low enough to ensure safety, unless drug
claims are made, in which case the products would be drugs.
The Task Force recognized that if the latter option were adopted
by the agency, a DSL for each amino acid would have to be established.
   The Task Force recommended that amino acid-containing dietary
supplements be regulated as drugs. This recommendation was based,
in part, on information presented indicating that the primary
intended use of these products is for therapeutic rather than
nutritional purposes. The Task Force pointed to the wide marketing
of amino acids for use in the diagnosis, cure, mitigation, treatment,
or prevention of disease or to affect the structure of the body
through such claims as ``Nature's Tranquilizer,'' `` * * * stimulates
the immune system * * *,'' `` * * * reduce craving for alcohol
and sweets * * *,'' `` * * * used in the treatment of alcoholism,
* * * '' and ``used in the treatment of schizophrenia and senility.''

G. Request for Public Comment on Regulatory Approach to Amino
Acid Dietary Supplement Products

   Based on the foregoing, it is clear that many amino acid
products are being marketed in violation of the act because
they are unapproved food additives, and adequate scientific
evidence to ensure their safe use does not exist, or because
they are being marketed for therapeutic uses, and the drug requirements
of the act have not been satisfied for these uses.
   FDA intends to bring amino acid-containing supplements into
compliance with the law. As part of this effort, FDA is providing,
with the publication of this document, an opportunity for interested
persons to submit data and information on the safety and intended
uses of amino acids, as well as support for claims being made
for them.
   Amino acid-containing supplements that are marketed for use
as drugs must comply with the drug provisions of the act. In
this regard, FDA will consider whether the drug uses of particular
amino acids are so well established and widespread as to justify
rulemaking to establish as a matter of law that these products
are drugs.
   For those amino acid supplements intended for food (nutritional)
use, interested parties should provide FDA with data or other
information that provide a basis upon which these products can
be legally marketed under the food provisions of the act. Issues
for consideration include how to satisfy the requirement under
section 409 of the act ``that intended effects be demonstrated,''
whether amino acids in dietary supplements have a nutritional
purpose, and on what evidence the agency can determine that
the use of amino acids in dietary supplements is safe.
   FDA will consider any data and comments submitted in response
to this document in forming its regulatory and enforcement strategy
with respect to amino acid-containing products. However, FDA
notes that while it will review the comments that it receives,
the agency will continue to take regulatory action as appropriate
to address safety or other consumer protection concerns.

IV. Herbs


A. Use of Herbal Dietary Supplements

   Herbal and other botanical ingredients of dietary supplements
include processed or unprocessed plant parts (bark, leaves,
flowers, fruits, and stems) as well as extracts of essential
oils. They are available in a variety of forms, such as teas,
powders, tablets, capsules, and elixirs. Botanicals are marketed
either as single substances or in combination with other materials,
including vitamins and minerals, amino acids, and nonnutrient
ingredients. They are marketed for children and adults. Data
on the availability of, and consumer use of, botanical products
are very limited.

B. Regulatory History and Current Regulatory Status of Herbs

   Many herbs and other botanical ingredients have been used
in foods as flavoring agents. However, there are also many herbs
that have no known history of food use and, even without drug
claims, are used for medical purposes. Many of these herbs have
a history of use as traditional medicines in many countries
outside of the United States.
   The GRAS and food additive regulations list a number of herbs
and herbal products and vegetable gums. However, the data that
were used to form the basis for most of these regulations were
related to such intended uses as flavoring agent, stabilizer,
thickener, formulation aid, emulsifier, or firming agent and
did not necessarily reflect the levels at which, or forms in
which, they have been used in dietary supplements.
   Food-use herbs are subject to the food additive provisions
of the act (sections 201(s) and 409 of the act). Because the
act does not explicitly restrict marketing to substances whose
safety has been determined by FDA, many of these substances
are marketed without any safety review by the agency, based,
presumably, on a GRAS determination by the marketer.

C. Issues of Concern

   While many ingredients in herbal dietary supplements have
not been associated with specific health concerns, some components
contained in these products have been associated with reports
of adverse health effects or toxicities in animals and humans.
For example, recently, at least six documented cases of toxic
hepatitis have been associated with the consumption of chaparral
(Larrea tridentata) (Refs. 29, 30, 34, and 35). There have been
several cases of adverse reactions associated with the consumption
of dietary supplements containing Lobelia inflata (lobelia,
Indian tobacco) (Ref. 36). Germander (genus Teucrium) has been
recently implicated in at least seven cases of acute nonviral
hepatitis in France (Ref. 32). Chronic renal failure has been
reported to have occurred as the result of consumption of herbal
powders containing Stephania tetrandra and Magnolia officinalis
(Ref. 43).
   The use of yohimbe (Pausinystalia yohimbe) in dietary supplements
such as body building products appears to be increasing. The
known pharmacologically active components of yohimbe are yohimbine
and related alkaloids. Yohimbine causes vasodilation, thereby
lowering blood pressure. Other actions of yohimbine include
antagonism of neurotransmitters and their precursors. Its use
is contraindicated for certain medical conditions or with concurrent
use of drugs or foods that exhibit monamine oxidase activity
because of increased potential for adverse effects.
   Human toxicity, including fatalities, have been associated
with consumption of the Symphytum (comfrey and Russian comfrey)
Heliotropium and Senecio species (Ref. 33). The scientific literature
documents the toxicity of these and other pyrrolizidine alkaloid
(PA)-containing plants (Refs. 43 and 44). Some of these plant
materials are taken as teas or in capsules for a variety of
suggested medical effects or simply as beverages. There are
reports that PA causes liver injury and failure secondary to
veno-occlusive disease (i.e., blocking the veins that remove
blood from the liver). There have been sporadic cases reported,
as well as reported epidemics, involving many thousand of people,
of serious liver injury from consumption of flours contaminated
with pyrrolizidine alkaloid (Refs. 45 and 46). Toxicity associated
with PA-containing plants can occur, and has occurred, after
relatively short use (a few weeks and at relatively low doses).
Liver failure, cirrhosis, and death (approximately 25 percent
of 7,500 affected individuals in an outbreak in Afghanistan)
can result. PA toxicity can even occur in newborns whose mothers
have ingested PA-containing plant materials. Infants appear
to be particularly sensitive to the effects of PA's, and fatal
hepatic disease has been reported in a newborn infant whose
mother consumed PA-containing products during pregnancy (Ref.
47). Several animal studies have demonstrated that the toxicity
of PA's and PA-containing plants, including comfrey, can cause
cancer in test animals (Refs. 48, 49, and 50).

D. Request for Public Comment

   FDA requests data and information from marketers of herbal
products and other interested parties that will assist the agency
in evaluating the safety of particular herbal products and herbal
products as a category. FDA intends to explore approaches to
regulations that will enable it to ensure the safety of herbal
products in an effective and efficient manner.
   FDA's immediate goal with respect to herbal products is to
ensure their safety and to remove hazardous products from the
market. FDA is aware that many herbal products are marketed
for drug uses without having complied with the drug approval
requirements. When appropriate, FDA will take regulatory action
against these products on a case-by-case basis in accordance
with the priorities established in FDA's health fraud program.
   FDA requests comments on the following questions:
   1. How should the requirement under section 409 of the act
that the tolerance limitation not be set higher than the level
necessary to accomplish the additive's intended physical or
other technical effect be satisfied?
   2. Should FDA consider another approach to regulating the
safety of herbs? If so, what should it be? What should the standard
be for determining when the use of the herb is safe?
   3. What types of data are necessary for establishing safe
levels of use for herbs (e.g., no effect levels, clinical studies,
reports of adverse effects)?
   4. What information should be included on the label to assure
safe use of herbal products?
   5. It is necessary to establish specifications and good manufacturing
practices to assure the safety of herbal products?

V. Other Components of Dietary Supplements


A. Use of ``Other'' Category Supplements

   This category includes a broad array of substances that are
offered for sale as components of dietary supplements, including
fish and plant oils, fatty acids, fibers and vegetable gums,
and carnitine. Some of the ingredients in this broad category
are concentrated substances that occur naturally in plant and
animal products. In addition, many of these substances have
no recognized nutritive value or technical effects.
   Fish and plant oil fatty acids and other lipids are available
as ingredients in capsules or as oils. They include the ingredients
menhaden oil, flax seed oil, black currant oil, oil of evening
primrose, fish oils and omega-3-fatty acids, essential fatty
acids, phytosterols, and others. A recent dietary supplement
advertising survey (Ref. 4) found that lipid ingredients accounted
for about 4 percent of the ingredients in products advertised
in health magazines.
   Dietary fiber is available in products either singly or as
mixtures. Major types of fiber include cellulose, hemicellulose,
pectins, mucilages, gums, algal polysaccharides, and lignins.
Common sources of some of these substances are wheat bran, psyllium,
guar gum, and apple pectin. Products containing dietary fiber
have been offered for nonfood uses, e.g., as an appetite suppressant.
   Data and information on the current marketing and use of
these ``other'' dietary supplement products are sparse. The
following discussion reflects the information that is available.

B. Regulatory History and Current Status of ``Other'' Category
Supplements

   The agency has considered these products to be subject to
the food provisions of the act, except when therapeutic, disease
prevention, or structure/function claims not related to nutritive
value are made about the products. As food ingredients, these
substances are subject to the food additive provisions of the
act (sections 201(s) and 409 of the act). However, because,
as stated previously, the act does not restrict marketing to
substances whose safety has been determined by FDA, many of
these substances have been marketed without any safety review
by the agency, although they are subject to regulatory action
by the agency.
   The GRAS regulations list a number of vegetable gums, but
the data that were used as the basis for most of these regulations
were related to intended uses such as stabilizer, thickener,
formulation aid, emulsifier, or firming agent and did not necessarily
reflect the amounts or forms in which they are used as sources
of fiber in dietary supplements. For many of these ingredients,
there are no GRAS or food additive regulations in effect, and
FDA has no basis on which to determine if the ingredient is
GRAS.

C. Issues of Concern

   Products in this ``other'' category are readily available
in the marketplace, even though generally very little is known
about their safety. Although many of these products contain
ingredients that are known to be present in the human body,
these ingredients may be part of the normal diet. Some of these
compounds have been associated with serious toxicity. For example,
the compound gamma hydroxy butyrate (GHB) is ubiquitous in the
human body, although its function is unknown. In the recent
past, use of GHB in dietary supplements became popular as a
sleep aid and also as a weightlifting aid. However, reports
of serious adverse reactions observed in association with GHB
became common throughout the country. These reports included
respiratory depression, coma, seizures, and other serious reactions.

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Ä [52]  IN*TOUCH DRUGS (1:375/48) ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TALK.POLITICS.DRUGS Ä
 Msg  : #2676 [101]                                                             
 From : Nikolaos Daniel Willmore            1:2613/335      Tue 11 Jan 94 20:24 
 To   : All                                                                     
 Subj : Pt 6/6: Here's what created the public outcry against the FDA!          
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
As a result of these reports, FDA issued a consumer alert on
this product.
   Toxicity from chronic use of germanium supplements includes
nephrotoxicity that has resulted in death. In surviving patients,
renal function has improved after discontinuation of germanium
supplementation. However, in no case has recovery been complete
(Ref. 38).

D. Task Force Report on ``Other Components''

   The Task Force's description of the ``all other substances''
category included nonessential chemical compounds, herbs without
a history of documented traditional food use, and plant and
animal extracts. Dietary fiber and certain fatty acids were
not considered in the Task Force report. The Task Force recommended
that the agency find an effective means of ensuring safe use
of this ``other'' category of ingredients. Among the possible
options suggested by the Task Force were to continue regulating
these ingredients as food additives, to require a description
of the nutrient value on the label of foods containing these
ingredients, and to bring actions against these substances when
they are represented as drugs.

E. Request for Public Comment

   FDA requests comment on the following:
   1. How should the requirement under section 409 of the act
that the tolerance limitation not be set higher than the level
necessary to accomplish the additive's intended physical or
other technical effect be satisfied?
   2. If current procedures are followed, what safety factor
or margin of safety is appropriate?
   3. Should FDA consider another approach to regulating safety?
If so, what should it be? What should the standard be for determining
when the use of the substance is safe?
   4. What types of data are necessary for establishing safe
levels of use for these substances (e.g., no effect levels,
clinical studies, reports of adverse effects)?
   5. What information should be included on the label to assure
safe use of these substances?
   6. Is it necessary to establish specifications and good manufacturing
practices to assure the safety of these substances?
   FDA is also soliciting comments on the availability, sources,
ranges, and current uses of ``other'' ingredients, as well as
information/comments on changing patterns of use of these substances
over the last 20 to 30 years. Additionally, FDA is seeking suggestions
to further define this category of ingredients.

VI. Possible Future Actions

   The agency will review the data and information that it receives
in response to this document and will develop appropriate steps
to assure the safety and proper labeling of dietary supplements.
The agency will consider the array of options presented in this
document and suggested in comments received to plan next steps.
These next steps may include rulemaking, enforcement action,
or other appropriate activities.

VII. References

   The following references have been placed on display in the
Dockets Management Branch (address above) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through
Friday.

   1. Bender, M. M., A. S. Levy, R. S. Schucker, E. A. Yetley,
``Trends in Prevalence and Magnitude of Vitamin and Mineral
Supplement Usage and Correlation With Health Status,'' Journal
of the American Dietetic Association, 92:1096-1101, 1992.
   2. FDA, ``Task force on Dietary Supplements Final Report,''
May 1992.
   3. Committee on Diet and Health, Food and Nutrition Board,
Commission of Life Sciences, National Research Council, ``Dietary
Supplements, ``Diet and Health: Implications for Reducing Chronic
Disease Risk,'' National Academy Press, Washington, DC, 1989.
   4. Philen, R. M., D. I. Oritz, S. B. Auerbach, H. Falk, ``Survey
of Advertising for Nutritional Supplements in Health and Bodybuilding
Magazines,'' Journal of the American Medical Association, 268:1008-
1011, 1992.
   15. Council for Responsible Nutrition, 1990 Overview of the
Nutritional Supplement Market, 1991.
   6. Moss, A. J., A. S. Levy, I. Kim, Y. K. Park, ``Use of
Vitamin and Mineral Supplements in the United States: Current
Users, Types of Products and Nutrients,'' Advance Data, National
Center for Health Statistics, U.S. Department of Health and
Human Services, No. 174, July 18, 1989.
   7. Park, Y. K., I. Kim, E. A. Yetley, ``Characteristics of
Vitamin and Mineral Supplement Products in the United States,''
American Journal of Clinical Nutrition, 54L:750-59, 1991.
   8. Park, Y. K., memo to file, 1993.
   9. Hathcock, J. N., D. G. Hattan, M. Y. Jenkins, et at.,
``Evaluation of Vitamin A Toxicity,'' American Journal of Clinical
Nutrition, 52:183-202.
   10. Geubel, A. P., C. DeGalocsy, N. Alves, et al., ``Liver
Damage Caused by Therapeutic Vitamin A Administration: Estimate
of Dose-Related Toxicity in 41 Cases,'' Gastroenterology, 100:1701-
1706, 1991.
   11. Dalton, K. I., M. J. Dalton, ``Characteristics of Pyridoxine
Overdose Neuropathy Syndrome,'' Acta Neurological Scandinavica,
76:8-11, 1987.
   12. Parry, G. J., D. E. Bredesen, ``Sensory Neuropathy With
Low-Dose Pyridoxine,'' Neurology, 35:1446-1468, 1985.
   13. Rader, J. I., R. J. Calvert, J. N. Hathcock, ``Hepatic
Toxicity of Unmodified and Time-Release Preparations of Niacin,''
American Journal of Medicine, 92:77-81, 1992.
   14. Dearing, B. D., C. J. Lavie, T. P. Lohman, E. Genton,
``Niacin-Induced Clotting Factory Synthesis Deficiency With
Coagulopathy,'' Archives of Internal Medicine, 152:861-863,
1992.
   15. Dalton, T. A., R. S. Berry, ``Hepatoxicity Associated
With Sustained-Release Niacin,'' American Journal of Medicine,
93:102-104, 1992.
   16. Hathcock, J. N., J. I. Rader, ``Micronutrient Safety,''
Annals of the New York Academy of Sciences, 587:257-266, 1990.
   17. LSRO, ``Guidelines for Safety Evaluation of Nutrients,''
June 1980, Life Sciences Research Office, Federation of American
Societies for Experimental Biology, 9650 Rockville Pike, Bethesda,
MD 20814.
   18. LSRO/FASEB, ``Feasibility of Identifying Adverse Health
Effects of Vitamins and Essential Minerals in Man,'' Bethesda,
MD, June 1980.
   19. LSRO/FASEB, ``Suggested Measures of Nutritional Status
and Health Conditions for the Third National Health and Nutrition
Examination Survey,'' Bethesda, MD, November 1985.
   20. LSRO/FASEB, ``Safety of Amino Acids Used as Dietary Supplements,''
Bethesda, MD, July 1992.
   21. FDC Act Trade Correspondence, TC-387, June 23, 1942.
   22. HHS News, P89-47, November 11, 1989.
   23. HHS News, P89-49, November 17, 1989.
   24. FDA Import Alert No. 54-04 (Revision).
   25. FDA Import Alert No. 54-04 (Revision), March 22, 1990.
   26. HHS News, P90-21, March 22, 1990.
   27. Swygert, L. A., E. F. Maes, L. E. Sewell, et al., ``Eosinophilia-
Myalgia Syndrome Results of National Surveillance,'' Journal
of the American Medical Association, 264:1698-1703, 1990.
   28. Love, A. L., J. I. Rader, L. J. Crofford et al., R. B.
Raybourne, M. A. Principato, S. W. Page, M. W. Trucksess, M.
J. Smith, E. M. Dugan, M. L. Turner, E. Zelazowski, P. Zelazowski,
E. M. Sternber, ``Pathological and Immunological Effects of
Ingesting L-Tryptophan and 1,1-Ethylidenebis (L-Tryptophan)
in Lewis Rats,'' Journal of Clinical Investigation, 91:804-811,
1993.
   29. ``Chaparral-Induced Toxic Hepatitis-California and Texas,''
Morbidity and Mortality Weekly Report, 41:812-4, 1992.
   30. HHS News, P92-38, December 10, 1992.
   31. Varro, T. E., ``The New Honest Herbal,'' George F. Stickley
Co., Philadelphia, PA, 1987.
   32. Larrey, D., T. Vial, A. Pauwels, et al., ``Hepatitis
After Germander (Teucrium Chamaedrys) Administration: Another
Instance of Herbal Medicine Hepatoxicity,'' Annals of Internal
Medicine, 117:129-1322, 1992.
   33. Winship, ``Toxicity of Comfrey,'' Adverse Drug React
Toxicology Review,'' 10:47-59, 1991.
   34. FDA Talk Paper, T-92-70, December 11, 1992.
   35. Katz, M., Saibil, F., ``Herbal Hepatitis: Subacute Hepatic
Necrosis Secondary to Chaparral Leaf,'' Journal of Clinical
Gastroenterology, 12:203-206, 1990.
   36. FDA Consumer, 19:41, 1985.
   37. HHS News, P-90-53, November 8, 1990.
   38. Takeuchi, A., N. Yoshizawa, S. Oshima, et al., ``Nephrotoxicity
of Germanium Compounds: Report of a Case and Review of the Literature,''
Nephron, 60:436-442, 1992.
   39. Varga, J., J. Uitto, S. Jimenez, ``The Cause and Pathogenesis
of Eosinophilia-Myalgia Syndrome,'' Annals of Internal Medicine,
116:140-147, 1992.
   40. Blauvelt, A., V. Falanga, ``Idiopathic and L-tryptophan-
Associated Eosinophilic Fasciitis Before and After L-Tryptophan
Contamination,'' Archives of Dermatology, 127:1159-1166, 1991.
   41. Hibbs, J. R., B. Mittleman, P. Hill, T. A. Medsger, ``L-
Tryptophan-Associated Eosinophilic Fasciitis Prior to the 1989
Eosinophilia-Myalgia Syndrome Outbreak,'' Arthritis and Rheumatism,
35:299-303, 1992.
   42. Van Herweghem, J. L., M. Depierreux, et al., ``Rapidly
Progressive Interstitial Renal Fibrosis in Young Women: Association
With Slimming Regimen Including Chinese Herbs,'' Lancet, 34:387-
391, February 1993.
   43. Huxtable, R. J., ``The Myth of Beneficent Nature: The
Roles of Herbal Preparations,'' Annals of Internal Medicine,
117:165-166, 1992.
   44. Huxtable, R. J., ``The Harmful Potential of Herbal and
Other Plant Products,'' Drug Safety, 5:126-136, 1990.
   45. Tandon, B. N. et al., ``An Epidemic of Veno-Occlusive
Disease of Liver in Central India,'' Lancet, 2:271-272, 1976.
   46. Tandon, B. N. et al., ``An Epidemic of Veno-Occlusive
Disease of the Liver in Afghanistan, American Journal of Gastroenterology,
70:607-613, 1978.
   47. Huxtable, R. J., ``Human Embryotoxicity of Pyrrolizidine-
Containing Drugs,'' Hepatology, 9:510-511, 1989.
   48. Svoboda D. J. and J. K. Reddy, ``Malignant Tumors in
Rats Given Lasiocarpine,'' Cancer Research, 32:908-912, 1972.
   49. Hirono, I. et al., ``Carcinogenic Activity of Symphytum
Officinale,'' Journal of the National Cancer Institute, 61:865-
869, 1978.
   50. Morton J. F., ``The Potential Carcinogenicity of Herbal
Tea,'' Environmental Carcinogenesis Reviews, Journal of Environmental
Science and Health, 4:203-223, 1986.

VIII. Comments

   Interested persons may, on or before August 17, 1993, submit
to the Dockets Management Branch (HFA-305), Food and Drug Administration,
rm. 1-23, 12420 Parklawn Dr., Rockville, MD 20857, written comments
regarding this proposal. Two copies of any comments are to be
submitted, except that individuals may submit one copy. Comments
are to be identified with the docket number found in brackets
in the heading of this document. Received comments may be seen
in the office above between 9 a.m. and 4 p.m., Monday through
Friday.
   This document is issued under sections 201, 301, 402, 403,
409, 501, 502, 505, 701 of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 321, 331, 342, 343, 348, 351, 352, 355, 371);
and the Dietary Supplement Act (Pub. L. 102-571).

   Dated: June 9, 1993.

Michael R. Taylor,
Deputy Commissioner for Policy.

[FR Doc. 93-14271 Filed 6-15-93; 8:45 am]
BILLING CODE 4160-01-P




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Ä [52]  IN*TOUCH DRUGS (1:375/48) ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TALK.POLITICS.DRUGS Ä
 Msg  : #2677 [101] - 2646 + 2700                                               
 From : Nikolaos Daniel Willmore            1:2613/335      Tue 11 Jan 94 20:40 
 To   : All                                                                     
 Subj : Here's what created the public outcry against the FDA!                  
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
From: ndw1@bonjour.cc.columbia.edu (Nikolaos Daniel Willmore)
Organization: Columbia University

Here is but a summary of the ACTUAL regulations that the FDA has put into
place, as stated in the FDA's press release about them. I am still looking
for the full electronic text versions of the regulations themselves. If
they do indeed reflect what the FDA claims here, then we the public have
"stopped them in their tracks" as per their attempt to limit access to
supplements. The bills S.784 and H.R.1709, coming before congress very
soon, would limit FUTURE FDA motions to limit access to supplements. NOW is
the time to write those letters! If these bills pass we wont have to go
though this again and again every few years, as the FDA chips away our
access to preventive health care. -Nik

From FDA BBS (telnet to fdabbs.fda.gov, login as "bbs"):

P93-46                                 Food and Drug Administration
FOR IMMEDIATE RELEASE                Brad Stone (202) 205-4144
Dec. 29, 1993                        (Home) -- (703) 892-0468

     The Food and Drug Administration today announced standards
to ensure that the labeling of dietary supplements is truthful
and scientifically valid.  Consumer access to dietary supplements
will not be affected by the new rules.
     The new regulations provide that dietary supplement labels
will have to provide the same basic nutritional information that
is found on the labels of nearly all conventional foods.  The new
rules also make dietary supplements subject to the same standard
for providing disease-related health information as Congress
previously mandated for conventional foods.
     In addition, the rules announce that a health claim on folic
acid and the risk of neural tube birth defects has been
authorized on dietary supplements.  FDA earlier approved a health
claim for calcium and osteoporosis.
     "Consumers should have access to dietary supplements that
are truthfully labeled and marketed," said FDA Commissioner David
A. Kessler, M.D.  "These rules enable the public to make informed
choices. They will not restrict access."
     Health claims made for the products will have to be
scientifically valid, and a nutrition information panel on the
label will declare the nutrient content per serving.  Health
claims will be authorized under the new rules if there is
significant scientific agreement among qualified experts that
these claims are valid.
     "This is the standard Congress established for health claims
on labeling of conventional foods,"  said Kessler.  "It's a
flexible standard that will keep unsubstantiated claims out of
the marketplace."
     The health claim standard is scheduled to take effect in
July 1994.  The additional rules on nutrition labeling and
nutrient content claims ("high," "low," etc.) become effective in
July 1995.
     FDA is one of eight Public Health Service agencies in HHS.

   FACT SHEET ON FDA'S DIETARY SUPPLEMENT LABELING REGULATIONS

     The Food and Drug Administration (FDA) is required by law to
publish final dietary supplement labeling regulations by December
31, 1993.  FDA is publishing 7 regulations that will help ensure
that consumers have access to dietary supplements that bear
truthful and scientifically valid nutritional and health claim
information on product labels.

     o    The label changes do not become effective immediately.
          The new health claims standard becomes effective in
          July 1994.  Other changes do not become mandatory until
          July 1995.

     o    Consumer access to dietary supplements will not change
          nor will consumers need prescriptions for dietary
          supplements after these regulations are published and
          become effective.

     o    Effective immediately, dietary supplement manufacturers
          may market folic acid products with a health claim
          stating that folic acid may reduce the risk of certain
          birth defects.


WHAT ARE THE 7 DOCUMENTS?


1.   GENERAL REQUIREMENTS FOR HEALTH CLAIMS FOR DIETARY
     SUPPLEMENTS - Final rule

     o    Dietary supplements of vitamins, minerals, herbs, or
          other similar nutritional substances will be subject to
          the general requirements for health claims that already
          apply to conventional food.

     o    A health claim touting the relationship between a
          substance and a disease or health-related condition
          must be supported by significant scientific agreement
          among qualified experts.

     o    This rule becomes effective in July 1994.


2.   GENERAL REQUIREMENTS FOR NUTRITION LABELING FOR DIETARY
     SUPPLEMENTS - Final rule

     o    Requires nutrition labeling for dietary supplements.

     o    This rule becomes effective in July 1995.


     o    Permits 7 additional nutrients to be included in the
          "Nutrition Facts" portion of the label.
     o    Permits reduced type size on smaller labels.



3.   REQUIREMENTS FOR NUTRIENT CONTENT CLAIMS FOR DIETARY
     SUPPLEMENTS - Final rule

     o    Provides for the use of nutrient content claims on
          labels or in labeling of dietary supplements (e.g.
          "high," "low," "less").

     o    This rule becomes effective in July 1995.


4.   FOLIC ACID HEALTH CLAIM - Notice

     o    Announces that the October 14, 1993, proposal to
          authorize a health claim about the relationship between
          folate and the risk of neural tube defects is now a
          final regulation for dietary supplements.


5.   SPECIFIC HEALTH CLAIMS - Notice

     o    Announces that the October 14, 1993, proposal not to
          authorize health claims relating an association between
          dietary fiber and cancer; dietary fiber and
          cardiovascular disease; antioxidant vitamins and
          cancer; omega-3 fatty acids and coronary heart disease;
          and zinc and immune deficiency in the elderly on the
          labels and in the labeling of dietary supplements is
          now a final regulation.

     o    Separately, FDA recently convened a symposium on the
          possible health benefits of antioxidant vitamins and is
          awaiting the publication of a major study in early
          1994.  FDA stands ready to approve antioxidant vitamin
          claims that are supported by significant scientific
          agreement.


6.   DAILY INTAKE LEVELS - Proposed rule

     o    Establishes Reference Daily Intakes for vitamin K,
          selenium, chloride, manganese, fluoride, chromium, and
          molybdenum for use in declaring the nutrient content of
          a food on its label or labeling.


7.   DELAY OF APPLICATION - Final rule

     o    FDA is invoking provisions that permit up to a 1 year
          delay inthe effective date of the nutrition labeling
          and nutrient content claims regulations to minimize the
          cost of compliance with the new regulations.


     o    These regulations become effective in July 1995, 18
          months after publication of the final rules.



             @@@@@  @@@@@@    @
             @      @     @  @ @                    THE FDA
             @@@@@  @     @ @@@@@          ELECTRONIC BULLETIN BOARD
             @      @@@@ @ @     @


    Thank you for using the FDA's electronic bulletin board,
    a public service of the Food and Drug Administration.

    Good Bye.





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Ä [52]  IN*TOUCH DRUGS (1:375/48) ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ TALK.POLITICS.DRUGS Ä
 Msg  : #2700 [101] - 2677                                                      
 From : Nikolaos Daniel Willmore            1:2613/335      Tue 11 Jan 94 21:28 
 To   : All                                                                     
 Subj : Here's what created the public outcry against the FDA!                  
ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ
From: ndw1@konichiwa.cc.columbia.edu (Nikolaos Daniel Willmore)
Organization: Columbia University

The NAME of the bills are:

Hatch-Richardson Dietary Supplement Health and Education Act, bills S. 784
and HR 1709." The legislation, which has the support of 63 U.S. senators
and 211 House members continues to draw support despite the efforts of
opponents to the legislation.

That's from the Nutrional Alliance Hotline people, who you can call at
(800)226-4642 for updates on Congress and more info. The easiest way to
write a letter is to take a stolen piece of photcopy paper, fold it in
thirds, address it and mail it off ;-).

-Nik

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