Food Labeling; Declaration of Free Glutamate in Food

DEPARTMENT OF HEALTH AND HUMAN SERVICES

21 CFR Part 101

[Docket No. 96N-0244]

Food Labeling; Declaration of Free Glutamate in Food

AGENCY: Food and Drug Administration, HHS.

ACTION: Advance notice of proposed rulemaking.

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SUMMARY: The Food and Drug Administration (FDA) is considering

establishing requirements for label information about the free

glutamate content of foods. The recent finding of the Federation of

American Societies for Experimental Biology (FASEB) that oral ingestion

of 3 or more grams (g) of monosodium glutamate (MSG) without food can

cause adverse reactions in certain otherwise healthy individuals has

prompted the agency to consider what action is necessary to protect

consumers from inadvertently ingesting levels of MSG or other forms of

free glutamate that could cause an adverse reaction. Thus, the agency

seeks public comment on whether additional labeling requirements are

necessary to protect glutamate-intolerant consumers from adverse

reactions, and, if so, how such labeling requirements should be

implemented. The agency also solicits comment on establishing formal

criteria for the use of claims about the absence of MSG to ensure that

labels bearing such claims are not misleading. The agency solicits

comment on whether such criteria should be based on a defined threshold

level of free glutamate in a finished food, on the ingredients used in

the food, or both.

DATES: Written comments by November 12, 1996.

ADDRESSES: Submit written comments to the Dockets Management Branch

(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Felicia B. Satchell, Center for Food

Safety and Applied Nutrition (HFS-158), Food and Drug Administration,

200 C St. SW., Washington, DC 20204, 202-205-5099.

SUPPLEMENTARY INFORMATION:

I. Background

A. Introduction

it written comments to the Dockets Management Branch

(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Felicia B. Satchell, Center for Food

Safety and Applied Nutrition (HFS-158), Food and Drug Administration,

200 C St. SW., Washington, DC 20204, 202-205-5099.

SUPPLEMENTARY INFORMATION:

I. Background

A. Introduction

Glutamic acid, one of the amino acids found in nature, is a

building block of virtually all proteins and is a normal component of

the human body. In the human body and in most foods, glutamic acid

exists primarily in its salt form, glutamate. Glutamate is a naturally

occurring component of many foods, including tomatoes, cheese, meat,

mushrooms, and milk. ``Free'' glutamate is glutamate that is not

incorporated into a protein; ``bound'' glutamate is glutamate that is a

component of an intact protein. Meat and milk contain primarily bound

glutamate, while tomatoes, mushrooms, and certain cheeses contain, in

addition to bound glutamate, relatively high levels of free glutamate.

It is the free form of glutamate that has been shown to have

flavor-enhancing properties in food. As noted previously, some foods

contain relatively high levels of naturally occurring free glutamate.

Free glutamate may be introduced into foods as a component of various

food ingredients, such as tomato sauce and hydrolyzed protein products,

or it may be added in one of its various salt forms, such as MSG.

MSG is the most commonly used form of free glutamate added to food

for flavor-enhancing purposes. It is a white, practically odorless,

free-flowing crystalline powder (Ref. 1), similar in appearance to salt

or sugar. MSG has been used for many years as a flavor enhancer for a

variety of foods prepared in homes and restaurants and by food

processors. MSG is manufactured commercially by a fermentation process

using starch, beet sugar, cane sugar, or molasses

for flavor-enhancing purposes. It is a white, practically odorless,

free-flowing crystalline powder (Ref. 1), similar in appearance to salt

or sugar. MSG has been used for many years as a flavor enhancer for a

variety of foods prepared in homes and restaurants and by food

processors. MSG is manufactured commercially by a fermentation process

using starch, beet sugar, cane sugar, or molasses. The American food

processing industry has used MSG widely since the late 1940's (Ref. 2),

and consumption in the United States is estimated to be 28,000 tons per

year. As a food ingredient, MSG is used to enhance the flavor of meat,

poultry, vegetables, and many processed foods. MSG is described in 21

CFR 182.1 as an example of a common food ingredient that is generally

recognized as safe (GRAS) under section 201(s) of the Federal Food,

Drug, and Cosmetic Act (the act) (21 U.S.C. 321(s)). When used as an

ingredient in a food, MSG must be declared in the ingredient statement

by its common or usual name, in accordance with section 403(i) of the

act (21 U.S.C. 343(i)) and 21 CFR part 101. Thus, ``monosodium

glutamate'' must appear in the ingredient list of any food to which MSG

has been added (21 CFR 101.22(h)(5)). This is true even when MSG has

been added indirectly as part of another ingredient to which MSG has

been added (e.g., a spice blend that includes MSG).

While MSG is the most well-known and widely used form of free

glutamate used to enhance the flavor of foods, other salts of free

glutamate, such as monopotassium glutamate and monoammonium glutamate

also have flavor-enhancing properties. GRAS uses of glutamic acid,

glutamic acid hydrochloride, monoammonium glutamate, and monopotassium

glutamate are codified in 21 CFR 182.1045, 182.1047, 182.1500, and

182.1516, respectively. Like MSG, these substances must be declared in

the ingredient statement of any food to which they are added

such as monopotassium glutamate and monoammonium glutamate

also have flavor-enhancing properties. GRAS uses of glutamic acid,

glutamic acid hydrochloride, monoammonium glutamate, and monopotassium

glutamate are codified in 21 CFR 182.1045, 182.1047, 182.1500, and

182.1516, respectively. Like MSG, these substances must be declared in

the ingredient statement of any food to which they are added.

Free glutamate occurs naturally in various foods and in food

substances that are used as ingredients in finished foods, or it can be

produced by hydrolysis of proteins; in such cases, the presence of free

glutamate in the food is not required to be declared on the label under

existing regulations. Naturally occurring free glutamate is not

required to be declared in the ingredient statement because it is not

an added ingredient; rather, it is a natural constituent of the food,

like protein or a vitamin. Similarly, when a food that contains

naturally occurring free glutamate is used as an ingredient in another

food, the free glutamate is not required to be declared in the

ingredient statement of the finished food. Rather, the ingredient

containing the free glutamate is declared in the ingredient statement

by its common or usual name. The principle that it is the ingredients

and not the constituents of a food that must be declared also applies

when a food that contains free glutamate produced by protein hydrolysis

is used as an ingredient in another food. In that situation too, the

glutamate-containing ingredient must be declared in the ingredient

statement of the finished food, but free glutamate need not be declared

as an ingredient

that it is the ingredients

and not the constituents of a food that must be declared also applies

when a food that contains free glutamate produced by protein hydrolysis

is used as an ingredient in another food. In that situation too, the

glutamate-containing ingredient must be declared in the ingredient

statement of the finished food, but free glutamate need not be declared

as an ingredient. Because the average consumer is not aware that

ingredients like hydrolyzed soy protein, autolyzed yeast extract,

tomato paste, and parmesan cheese contain free glutamate or that free

glutamate is essentially equivalent to MSG, declaration of these

ingredients by their common or usual names does not indicate to the

consumer that an MSG-like substance is present in the food.

A number of consumers, particularly consumers who report adverse

reactions to MSG, have stated to FDA (Ref. 3) their belief that

manufacturers use ingredients such as hydrolyzed proteins and autolyzed

yeast extracts for the express purpose of adding free glutamate to a

food while hiding its presence. These consumers report the same types

of adverse reactions to foods containing hydrolyzed proteins, autolyzed

yeast extracts, and forms of ``manufactured'' glutamate (other than

MSG) that they experience when they inadvertently consume foods that

have MSG declared in the ingredient list. Consequently, FDA has

received numerous requests that labels of all foods containing these

ingredients be required to declare the presence of free glutamate in

the finished food, on the ground that free glutamate presents a health

concern to consumers. Some consumers have also requested that FDA

require that the amount of free glutamate be declared on the label.

Until recently, the agency's response has been that the scientific

literature does not provide a public health basis on which to impose

special labeling requirements for such ingredients or for foods that

contain free glutamate

free glutamate presents a health

concern to consumers. Some consumers have also requested that FDA

require that the amount of free glutamate be declared on the label.

Until recently, the agency's response has been that the scientific

literature does not provide a public health basis on which to impose

special labeling requirements for such ingredients or for foods that

contain free glutamate. However, in light of the recent findings of the

Life Sciences Research Office (LSRO) of FASEB, the agency is

reconsidering the need for labeling to inform individuals who

experience adverse reactions to glutamate about its presence in a food.

(The agency notes that in the Federal Register of January 6, 1993 (58

FR 2950), it proposed to require the term ``(contains glutamate)'' as

part of the common or usual name for autolyzed yeast extracts and

highly hydrolyzed proteins. That proposal was not based on any health

concern regarding the use of these ingredients in food; therefore, the

comments to that proposal and the agency's decision with respect to

those comments will not be addressed in this document.)

B. Previous Safety Reviews

Until the recent findings of the FASEB report (discussed in section

I.C. of this document) that a subgroup of otherwise healthy individuals

experiences a complex of symptoms following ingestion of 3 or more (g)

of MSG without food, FDA relied on

previous safety review studies in deciding that special labeling for

free-glutamate-containing (hereinafter referred to as ``glutamate-

containing'') foods was not warranted. These studies indicated that

while anecdotal reports of adverse reactions to MSG and other

glutamate-containing ingredients existed, there were no verifiable

scientific data establishing that the levels of these ingredients used

in the food supply could cause adverse reactions in the general

population

-containing (hereinafter referred to as ``glutamate-

containing'') foods was not warranted. These studies indicated that

while anecdotal reports of adverse reactions to MSG and other

glutamate-containing ingredients existed, there were no verifiable

scientific data establishing that the levels of these ingredients used

in the food supply could cause adverse reactions in the general

population. Historically, the agency has not issued labeling

requirements on the basis of anecdotal reports alone because such

reports do not by themselves establish a cause-and-effect relationship

between the suspected substance and the occurrence of an adverse

reaction.

MSG and other glutamate-containing ingredients have been the

subject of numerous safety reviews during the past decade. In 1969,

largely as a result of a recommendation by the White House Conference

on Food, Nutrition and Health, FDA proceeded to reevaluate the safety

of all GRAS substances for food use. The Select Committee on GRAS

Substances (SCOGS), convened by FASEB in 1972 under a contract with

FDA, independently reviewed the health aspects of MSG and of glutamate-

containing protein hydrolysates in 1978 and 1980 (Refs. 4, 5, 6, and

7). Although protein hydrolysates are not listed as GRAS food

ingredients by regulation, they are described as GRAS in a number of

FDA opinion letters (Refs. 8, 9, 10, and 11). SCOGS concluded that MSG

and hydrolyzed proteins were safe for the general population at then-

current levels of use but recommended additional evaluation to

determine their safety at significantly higher levels of consumption.

In 1986, FDA's Advisory Committee on Hypersensitivity to Food

Constituents (Ref. 12) concluded that MSG posed no threat to the

general public but that reactions of brief duration might occur in some

people. Other reports gave similar findings. A 1991 report by the

European Community's (EC) Scientific Committee for Foods (Ref

etermine their safety at significantly higher levels of consumption.

In 1986, FDA's Advisory Committee on Hypersensitivity to Food

Constituents (Ref. 12) concluded that MSG posed no threat to the

general public but that reactions of brief duration might occur in some

people. Other reports gave similar findings. A 1991 report by the

European Community's (EC) Scientific Committee for Foods (Ref. 13)

reaffirmed the safety of MSG and other forms of free glutamate and

classified the ``acceptable daily intake'' for MSG as ``not

specified,'' the most favorable designation for a food ingredient. In

addition, the EC committee said, ``infants, including prematures, have

been shown to metabolize glutamate as efficiently as adults and,

therefore, do not display any special susceptibility to elevated oral

intakes of glutamate.''

A 1992 report from the Council on Scientific Affairs of the

American Medical Association (Ref. 14) stated that glutamate in any

form has not been shown to be a ``significant health hazard.'' Also,

the 1987 Joint Expert Committee on Food Additives of the United Nations

Food and Agriculture Organization and the World Health Organization

(Ref. 15) placed MSG and other glutamate salts in the safest category

of food ingredients.

Although the general consensus of the many safety reviews that have

been done on the use of MSG and other glutamate-containing ingredients

in foods is that they are safe for the general population, the use of

these ingredients has been very controversial. FDA has received many

anecdotal reports of adverse reactions following ingestion of

glutamate-containing foods. Between 1980 and 1995, the Adverse Reaction

Monitoring System in FDA's Center for Food Safety and Applied Nutrition

received 661 reports of complaints about adverse reactions to MSG (Ref.

16). Headache was the most frequently reported symptom

ingredients has been very controversial. FDA has received many

anecdotal reports of adverse reactions following ingestion of

glutamate-containing foods. Between 1980 and 1995, the Adverse Reaction

Monitoring System in FDA's Center for Food Safety and Applied Nutrition

received 661 reports of complaints about adverse reactions to MSG (Ref.

16). Headache was the most frequently reported symptom. However, other

symptoms, such as a ``burning sensation'' on the back of the neck,

forearms, and chest, facial pressure or tightness, neck and chest pain,

palpitations, numbness, nausea, and vomiting, were also reported. These

symptoms were transient, typically beginning within 25 minutes after

consumption of MSG or of a glutamate-containing food and subsiding

within about 2 hours. Initially many of these symptoms became known

popularly as ``Chinese Restaurant Syndrome.'' As discussed in section

I.C. of this document, FASEB refers to these symptoms collectively as

the ``MSG symptom complex.''

C. The FASEB Report

Because of the agency's concern regarding the continued reports of

adverse reactions to MSG and other glutamate-containing ingredients and

because of the expanding base of scientific knowledge on the role of

glutamate in brain function, FDA decided that an up-to-date review of

the safety of MSG and other glutamate-containing ingredients was

warranted. Thus, as part of its ongoing evaluation of GRAS ingredients

and in response to the concerns raised by consumers, FDA contracted

with FASEB in 1992 to do an up-to-date scientific safety review of the

effects of the use of MSG and hydrolyzed protein products as food

ingredients. The agency announced the study in the Federal Register of

December 4, 1992 (57 FR 57467)

ingredients was

warranted. Thus, as part of its ongoing evaluation of GRAS ingredients

and in response to the concerns raised by consumers, FDA contracted

with FASEB in 1992 to do an up-to-date scientific safety review of the

effects of the use of MSG and hydrolyzed protein products as food

ingredients. The agency announced the study in the Federal Register of

December 4, 1992 (57 FR 57467). As discussed in that document, the

objectives of the review were to: (1) Determine whether MSG and

hydrolyzed protein products, as used in the American food supply,

contribute to the presentation of a complex of symptoms (initially

described as the Chinese Restaurant Syndrome) after oral ingestion of

levels up to or beyond 5 g per eating occasion (i.e., a meal or snack),

and/or the elicitation of other reactions, including more serious

adverse reactions that have been reported to occur following ingestion

of 25 to 100 milligrams per eating occasion; (2) to determine whether

MSG and hydrolyzed protein products, as used in the American food

supply, have the potential to contribute to brain lesions in neonatal

or adult nonhuman primates and whether there is any risk to humans

ingesting dietary MSG; (3) to assess whether hormones are released from

the pituitary of nonhuman primates following ingestion of MSG or

hydrolyzed protein products and whether any comparable risk to humans

ingesting food containing these substances exists; and (4) to define

the metabolic basis that might underlie any adverse reactions to MSG

and hydrolyzed protein products.

FASEB convened an ad hoc expert panel to perform a comprehensive

review of the scientific literature and adverse report submissions to

both FDA and LSRO. The expert panel also considered oral and written

testimony received at a 2-day open meeting held in 1993. The expert

panel used a weight of evidence approach in reaching its conclusions

about the evidence of adverse effects of MSG

roducts.

FASEB convened an ad hoc expert panel to perform a comprehensive

review of the scientific literature and adverse report submissions to

both FDA and LSRO. The expert panel also considered oral and written

testimony received at a 2-day open meeting held in 1993. The expert

panel used a weight of evidence approach in reaching its conclusions

about the evidence of adverse effects of MSG. In other words, the

expert panel analyzed the data by considering the totality of the

scientific evidence in a given area rather than weighing one

interpretation against another.

The expert panel reported its findings to FASEB, which reviewed the

expert panel's work and prepared a report entitled ``Analysis of

Adverse Reactions to Monosodium Glutamate (MSG)'' (Ref. 17). The FASEB

report was submitted to FDA on July 31, 1995. While FASEB found no

scientifically verifiable evidence of adverse effects in most

individuals exposed to high levels of MSG, it concluded that there is

sufficient documentation to define an acute, temporary, and self-

limiting ``MSG symptom complex'' in a subgroup of the population. The

symptoms characteristic of the complex include: (1) A burning sensation

of the back of the neck, forearms, and chest; (2) facial pressure or

tightness; (3) chest pain; (4) headache; (5) nausea; (6) upper body

tingling and weakness; (7) palpitation; (8) numbness in the back of

neck, arms and back; (9) bronchospasm, i.e., constriction of the

bronchial tubes

resulting in difficulty in breathing (observed in asthmatics only); and

ex include: (1) A burning sensation

of the back of the neck, forearms, and chest; (2) facial pressure or

tightness; (3) chest pain; (4) headache; (5) nausea; (6) upper body

tingling and weakness; (7) palpitation; (8) numbness in the back of

neck, arms and back; (9) bronchospasm, i.e., constriction of the

bronchial tubes

resulting in difficulty in breathing (observed in asthmatics only); and

(10) drowsiness. These symptoms were judged to be related to the amount

of MSG consumed and whether the MSG was consumed with or without food.

FASEB identified this group of symptoms as the ``MSG symptom complex,''

stating that the previously used term, ``Chinese restaurant syndrome,''

was pejorative and did not reflect the extent or nature of the symptoms

that have been associated with the myriad of exposure scenarios. FASEB

concluded that ``Based on scientifically verifiable evidence, there is

a subgroup of presumably healthy individuals within the general

population that responds, generally within one hour of exposure, with

manifestations of the MSG Symptom Complex to an oral bolus [dose] of

MSG 3 g in the absence of food.''

FASEB also identified a subgroup of asthmatics reported to respond

to oral doses of MSG with bronchospasm. The study conducted by Allen,

Delohery, and Baker (Ref. 18) described severe bronchospasm in

individuals with unstable asthmatic conditions in conjunction with

symptoms of the MSG symptom complex following an oral dose of MSG. In

addition, the study reported that some asthmatic subject experienced a

6 to 12 hour delayed bronchospasm without other MSG-related symptoms.

While FASEB recognized and described limitations in the study design

used by Allen, et al., it concluded that the study was a reasonably

well-designed scientific oral dose study in asthmatic subjects, and

that the study provided evidence to support the existence of a subgroup

of asthmatic responders to MSG

ct experienced a

6 to 12 hour delayed bronchospasm without other MSG-related symptoms.

While FASEB recognized and described limitations in the study design

used by Allen, et al., it concluded that the study was a reasonably

well-designed scientific oral dose study in asthmatic subjects, and

that the study provided evidence to support the existence of a subgroup

of asthmatic responders to MSG.

With regard to hydrolyzed proteins, FASEB identified no scientific

reports of glutamate-related adverse effects of ingesting protein

hydrolysates, whether microbial, vegetable, or animal in origin.

Protein hydrolysates are used at very low levels, typically

constituting only a small percentage (less than 1 percent) of a

finished food.

Because of glutamate's role as a stimulatory neurotransmitter in

the brain, the scientific community has speculated about the potential

influence of dietary glutamate on brain glutamate metabolism and the

potential role of dietary glutamate in provoking or exacerbating long-

term illnesses. At FDA's request, FASEB reviewed the scientific

literature on these issues. Although FASEB acknowledged the neurotoxic

potential of glutamate produced in the body (as opposed to glutamate

consumed in food), it found no studies or corroborating evidence

linking adverse effects associated with consuming free glutamate in

food to changes in brain function or to levels of glutamate in the

bloodstream. Consequently, FASEB concluded that no evidence exists to

support a role for dietary MSG or other forms of free glutamate

consumed in food in causing or exacerbating serious, long-term medical

problems resulting from degenerative nerve cell damage, such as

Alzheimer's disease, Huntington's chorea, or amyotrophic lateral

sclerosis, or to any other long-term or chronic illness

the

bloodstream. Consequently, FASEB concluded that no evidence exists to

support a role for dietary MSG or other forms of free glutamate

consumed in food in causing or exacerbating serious, long-term medical

problems resulting from degenerative nerve cell damage, such as

Alzheimer's disease, Huntington's chorea, or amyotrophic lateral

sclerosis, or to any other long-term or chronic illness. However, FASEB

recommended that future efforts to explain reported adverse effects

from ingested MSG be designed to test potential relationships between

dietary glutamate and the physiological functions of the central

nervous system.

FASEB also reviewed the chemical characteristics of various forms

of free glutamate to determine if there was some structural or chemical

difference in free glutamate occurring in the form of MSG or hydrolyzed

protein products, as compared to free glutamate that naturally occurs

in foods. FDA asked FASEB to include this issue in its review because

of the contention by some consumers that manufactured forms of

glutamate, such as MSG and hydrolyzed protein products, are in some way

different from naturally occurring glutamates, and that the

manufactured forms of glutamate are the only forms that trigger adverse

reactions.

Free glutamate can exist in two possible stereoisomeric forms: D-

glutamate and L-glutamate. L-glutamate is the predominant natural form

and the only form with flavor-enhancing activity. FASEB concluded that

MSG symptom complex reactions are related to L-glutamate exposure and

that the chemical nature of L-glutamate is the same regardless of the

source, i.e., whether manufactured or naturally occurring in the food.

Thus, FASEB found no evidence to support the contention that adverse

reactions occur with manufactured but not naturally occurring

glutamate

r-enhancing activity. FASEB concluded that

MSG symptom complex reactions are related to L-glutamate exposure and

that the chemical nature of L-glutamate is the same regardless of the

source, i.e., whether manufactured or naturally occurring in the food.

Thus, FASEB found no evidence to support the contention that adverse

reactions occur with manufactured but not naturally occurring

glutamate.

FASEB further concluded that with regard to determining glutamate

levels and assessing risk from consumption of specific foods, a clear

distinction must be made between free glutamate and glutamate as a

component of protein (i.e., bound glutamate). Free glutamate is readily

available for use in the body, whereas bound glutamate becomes

available to body tissues more slowly, as the intestines chemically

break down foodstuffs. FASEB also noted that the presence of food, as

when MSG is consumed as part of a meal, attenuates the rise in blood

glutamate levels and perhaps the effect, at least with regard to the

potential for any direct central nervous system effect. However, FASEB

was unable to identify any studies that have effectively compared blood

glutamate levels between responders (i.e., persons who experience

adverse reactions following exposure to MSG) and nonresponders, or any

studies in which responders have been given a dose of MSG with a meal

or 20 to 30 minutes before a meal.

FDA has reviewed the findings and conclusions contained in the

FASEB report (Ref. 19). Based on FASEB's findings, FDA has tentatively

concluded that requirements for label information about glutamate

content may be warranted under certain conditions.

II. The Agency's Response

ers, or any

studies in which responders have been given a dose of MSG with a meal

or 20 to 30 minutes before a meal.

FDA has reviewed the findings and conclusions contained in the

FASEB report (Ref. 19). Based on FASEB's findings, FDA has tentatively

concluded that requirements for label information about glutamate

content may be warranted under certain conditions.

II. The Agency's Response

FASEB's conclusion that oral ingestion of 3 or more grams of MSG

without food can cause adverse reactions in certain otherwise healthy

individuals has prompted the agency to consider what action is

necessary to protect these consumers from inadvertently ingesting

levels of free glutamate that could trigger an adverse reaction. The

agency believes that it may be appropriate to establish labeling

requirements to alert free-glutamate-intolerant (hereinafter referred

to as ``glutamate-intolerant'') consumers to the presence of free

glutamate in a food.

The agency has carefully evaluated FASEB's findings and has reached

several tentative conclusions regarding the basis on which any labeling

policy to alert glutamate-intolerant consumers should be established.

A. Total Free Glutamate

Based on FASEB's findings that it is the free glutamate component

of MSG that appears to be linked to the occurrence of the MSG symptom

complex, that free glutamate is the same chemically in both its natural

and manufactured forms, and that free glutamate has the same function

regardless of source, i.e., free glutamate in MSG functions the same as

free glutamate in hydrolyzed proteins or tomato products, the agency

tentatively finds that any labeling policy it establishes should be

based on the total amount of free glutamate in a serving of food,

rather than on the number or kind of glutamate-containing ingredients

in the food.

FDA has received correspondence suggesting that adverse reactions

result only from exposure to manufactured free glutamate in food (Ref.

3)

teins or tomato products, the agency

tentatively finds that any labeling policy it establishes should be

based on the total amount of free glutamate in a serving of food,

rather than on the number or kind of glutamate-containing ingredients

in the food.

FDA has received correspondence suggesting that adverse reactions

result only from exposure to manufactured free glutamate in food (Ref.

3). Based on FASEB's findings, the agency rejects this view. As

previously discussed,

FASEB reported that all free glutamate found in food is the same

regardless of the source. Further, in examining the scientific reports

relating to physiological mechanisms of action, FASEB found no evidence

indicating that manufactured free glutamate functions differently in

the body than free glutamate naturally occurring in foods. The agency

agrees with FASEB that all forms of free glutamate are chemically and

functionally the same. Moreover, the agency notes that the available

analytical methodology measures the total amount of free glutamate in a

finished food and does not distinguish among free glutamate occurring

in the form of MSG, as a constituent of ingredients such as hydrolyzed

proteins, or as a natural constituent of food such as cheese,

mushrooms, or meat. Accordingly, the agency tentatively finds that any

labeling requirement for glutamate-containing foods should apply to

foods that contain free glutamate from any source.

B. Food Matrix

and does not distinguish among free glutamate occurring

in the form of MSG, as a constituent of ingredients such as hydrolyzed

proteins, or as a natural constituent of food such as cheese,

mushrooms, or meat. Accordingly, the agency tentatively finds that any

labeling requirement for glutamate-containing foods should apply to

foods that contain free glutamate from any source.

B. Food Matrix

Although FASEB noted that the presence of food may attenuate the

rise of blood glutamate levels, the FASEB report cited no scientific

evidence establishing a relationship between the occurrence of MSG

symptom complex reactions and metabolic responses to ingestion of MSG,

such as changes in blood glutamate levels. The agency requests data

describing the effect of the food matrix (i.e., the food in which free

glutamate is present or with which it is eaten) on the occurrence of

the MSG symptom complex. If the food matrix does have an effect, does

the effect vary depending on the type of food?

In the absence of sound scientific data demonstrating that the food

matrix reduces the risk or severity of adverse effects following

ingestion of free glutamate, the agency's likely approach would be to

assume that the food matrix has no predictable mitigating effect on the

occurrence of the MSG symptom complex and to develop a labeling policy

based on the level of free glutamate reported to cause reactions when

consumed without food. Because the agency does not yet have such data,

this assumption is adopted for purposes of the preliminary discussion

in this document.

C. Materiality

be to

assume that the food matrix has no predictable mitigating effect on the

occurrence of the MSG symptom complex and to develop a labeling policy

based on the level of free glutamate reported to cause reactions when

consumed without food. Because the agency does not yet have such data,

this assumption is adopted for purposes of the preliminary discussion

in this document.

C. Materiality

Section 403(a) of the act (21 U.S.C. 343(a)) states that a food is

misbranded if its labeling is false or misleading in any particular.

Under section 201(n) of the act, labeling is misleading if it ``fails

to reveal facts material * * * with respect to consequences which may

result from the use of the article to which the labeling or advertising

relates under the conditions of use prescribed in the labeling * * * or

under such conditions of use as are customary or usual.'' Thus, a food

label is misleading if it does not disclose consequences that may

result from consumption of the food.

The agency believes that information on the presence of free

glutamate in a food becomes a material fact for the glutamate-

intolerant consumer in the decision to purchase a food (and in the

subsequent use of the food) when free glutamate is present at a level

such that a glutamate-intolerant person who consumes the food alone or

as part of a meal that includes other glutamate-containing foods may

suffer an adverse reaction. The presence of free glutamate below this

level is not material because it would not cause a reaction or

contribute significantly toward a total intake of free glutamate that

might cause a reaction. Moreover, special glutamate labeling on

products that contain levels of free glutamate below the material level

could cause the label statement to lose its significance for glutamate-

intolerant consumers, especially if such labeling appeared on products

previously consumed by such consumers without subsequent occurrence of

any adverse reaction

n

included: (1) A 5-day pretest diet excluding chemicals known to provoke

asthma (not otherwise defined), but lacked data with regard to patient

compliance with the pretest diet; (2) ingestion of unidentified

substances other than MSG; (3) limited placebo-control testing; and,

most importantly, (4) the withdrawal of asthma medication that could

have prevented or delayed an asthmatic response. Because of the

questions raised by the study design and the limited data in this area,

FDA's current view is that a cause-and-effect relationship has not been

established between exposure to MSG at levels of 0.5 to 2.5 g and

adverse reactions in this subgroup of asthmatics. The agency requests

comments on this aspect of the FASEB report, as well as any new data

demonstrating a relationship between exposure to free glutamate at

levels below 2.4 g (3 g of MSG) and adverse reactions in asthmatics. If

such data are received, FDA will be better able to evaluate the need

for a labeling policy to enable glutamate-intolerant asthmatics to

protect themselves from adverse reactions.

FDA's preliminary view is that a policy requiring glutamate

labeling should be based on the amount of free glutamate in a serving

of a food. Foods are labeled individually to reflect the nutrient

content and other characteristics of the particular food. Because a

food's contribution to the diet is based on an individual serving of

the food, current regulations require foods to be labeled with

nutrition information on a per-serving basis. Since the regulations

implementing the Nutrition Labeling and Education Act (Pub. L. 101-445)

became effective in 1994, consumers have become adept at using label

information to monitor their intake of certain nutrients (Ref. 20)

ibution to the diet is based on an individual serving of

the food, current regulations require foods to be labeled with

nutrition information on a per-serving basis. Since the regulations

implementing the Nutrition Labeling and Education Act (Pub. L. 101-445)

became effective in 1994, consumers have become adept at using label

information to monitor their intake of certain nutrients (Ref. 20). A

glutamate labeling policy based on the amount of free glutamate in a

serving of a food would be consistent with current labeling

regulations, and FDA tentatively finds that such a policy would be

useful to consumers who wish to avoid intake of free glutamate at

levels that may cause an adverse reaction.

D. Labeling Threshold Approach

Applying these principles, the question then becomes how to

calculate an appropriate labeling threshold, i.e., the level of free

glutamate in a serving of an individual food that should trigger a

labeling requirement because consumption of the food as part of a meal

that may include other glutamate-containing foods could result in

overall intake of free glutamate at levels that have been demonstrated

to cause an adverse reaction. That is, what is the appropriate

mechanism to relate a total

intake of 2.4 g of free glutamate (from all servings of foods consumed

at the meal) to the contribution of an individual food?

One possible approach is to assume that the average daily

consumption of a U.S. consumer is 20 servings per day, spread over

approximately 3 meals and a snack. A snack is considered roughly two

servings and a meal five to six servings. (The agency used a similar

approach in determining disclosure levels for nutrient content claims

and disqualifying levels for health claims. (56 FR 60426, 56 FR 60543-

60544, 58 FR 2492, and 59 FR 24239))

verage daily

consumption of a U.S. consumer is 20 servings per day, spread over

approximately 3 meals and a snack. A snack is considered roughly two

servings and a meal five to six servings. (The agency used a similar

approach in determining disclosure levels for nutrient content claims

and disqualifying levels for health claims. (56 FR 60426, 56 FR 60543-

60544, 58 FR 2492, and 59 FR 24239)). Assuming that a meal consists of

approximately six servings, the glutamate-intolerant consumer would be

at risk if the total amount of free glutamate from all six servings in

the meal were equal to or greater than 2.4 g. Spreading this amount

equally over each of the six servings would suggest that each serving

of food should contain no more than 0.4 g of free glutamate. Thus, one

approach could be to require any food containing 0.4 g or more free

glutamate per serving to bear a label statement about its free

glutamate content. Such labeling would alert the glutamate-intolerant

consumer to foods that contribute significant levels of free glutamate

to a meal. With such information, the consumer could avoid foods with

significant levels of free glutamate or, as an alternative, include

limited quantities of a labeled food in the meal while being careful

not to eat other glutamate-containing foods. Using 0.4 g as a labeling

threshold would require foods like tomato juice and some soup mixes and

canned soups to bear glutamate labeling (Ref. 21).

Although a labeling threshold or ``trigger'' of 0.4 g per serving

based on average consumption estimates would adequately protect most

glutamate-intolerant consumers, it might not be sufficient to protect

those whose food intake is in the high range, that is, at or above the

90th percentile. According to food consumption and food frequency

surveys (Refs. 22 and 23) conducted in the United States, intake at the

90th percentile for most commonly consumed foods is roughly 2 times the

mean intake for that food (Ref. 24)

ct most

glutamate-intolerant consumers, it might not be sufficient to protect

those whose food intake is in the high range, that is, at or above the

90th percentile. According to food consumption and food frequency

surveys (Refs. 22 and 23) conducted in the United States, intake at the

90th percentile for most commonly consumed foods is roughly 2 times the

mean intake for that food (Ref. 24). Thus, a high-intake consumer could

be exposed to levels close to 0.8 g from a single food if a regular-

size serving of the food contained just under 0.4 g of free glutamate.

In such a case, the food would not be required to bear a glutamate

content statement, yet the amount eaten by high-intake consumers would

contain a significant level of free glutamate. Taking into

consideration the number of products that may contain free glutamate

and the acute nature of the effects of free glutamate exposure for

certain individuals, the agency is concerned that a label trigger of

0.4 g would not sufficiently protect high-intake consumers. The agency

believes, therefore, that it is prudent to build in a safety factor to

ensure that high-intake consumers are adequately informed of any

potential risk.

Allowing for intakes up to twice the mean intake, to provide an

additional margin of safety, would result in a labeling threshold of

0.2 g free glutamate (0.4 divided by 2) per serving of food. If the

agency were to take this approach and require a glutamate label

statement for foods that contain 0.2 or more grams free glutamate per

serving, additional foods such as blue cheese, spaghetti sauce, and

some brands of soy sauce and tomato paste would be required to bear a

label statement about free glutamate content (Ref. 21).

FDA notes that the use of labeling thresholds is not new. Existing

regulations establish labeling thresholds for certain ingredients that

have been identified as causing adverse reactions either in sensitive

individuals or in the general population

paghetti sauce, and

some brands of soy sauce and tomato paste would be required to bear a

label statement about free glutamate content (Ref. 21).

FDA notes that the use of labeling thresholds is not new. Existing

regulations establish labeling thresholds for certain ingredients that

have been identified as causing adverse reactions either in sensitive

individuals or in the general population. These regulations require

special labeling for foods that exceed the labeling threshold. For

example, the statement ``Excess consumption may have a laxative

effect'' is required on foods that contain sorbitol when ``reasonably

foreseeable'' consumption of the food could result in a daily sorbitol

intake of 50 g or more (21 CFR 184.1835). To cite another example, the

label statement ``Sensitive individuals may experience a laxative

effect from excessive consumption of this product'' is required when a

single serving of a food contains more than 15 grams of polydextrose

(21 CFR 172.841). To the best of the agency's knowledge, the use of a

labeling threshold has worked well in protecting consumers from adverse

reactions caused by excessive consumption of sorbitol and polydextrose.

E. Request for Comments

FDA is soliciting comments on all aspects of this advance notice of

proposed rulemaking (ANPRM), and specifically requests comments on the

following:

1. The agency invites comments on whether additional labeling

requirements should be established to protect glutamate-intolerant

consumers from adverse reactions. The agency also solicits comments on

the effectiveness of the regulatory approach described previously, as

well as suggestions for other approaches that would adequately inform

and assist glutamate-intolerant consumers to avoid exposure to levels

of free glutamate that might cause a reaction. Suggestions for other

approaches should include data or other information to substantiate the

effectiveness of the approach

s comments on

the effectiveness of the regulatory approach described previously, as

well as suggestions for other approaches that would adequately inform

and assist glutamate-intolerant consumers to avoid exposure to levels

of free glutamate that might cause a reaction. Suggestions for other

approaches should include data or other information to substantiate the

effectiveness of the approach. In particular, the agency solicits

comments on whether the labeling threshold should be set higher or

lower than 0.2 g free glutamate per serving, and on the costs and

benefits of labeling policies using different possible labeling

thresholds. The agency notes that regulations based on this ANPRM may

have a significant impact on a substantial number of small entities.

Therefore, the agency particularly requests information on the costs to

small businesses of alternative MSG labeling policies and on policy

options that would reduce the burden on small businesses while meeting

the objectives of MSG labeling. Recognizing that foods would have to be

chemically analyzed to determine the free glutamate content and that

labels would have to be changed for some foods, the agency solicits

data and comments on the economic impact associated with various

labeling policies.

2. The agency solicits data on the levels of glutamate in foods to

assist it in determining how many and what kinds of foods would be

affected by various regulatory approaches.

3. The agency also solicits comments on the advantages or

disadvantages of a simple label statement that the food contains free

glutamate, as compared to a quantitative statement of the amount of

free glutamate in a serving of the food either in absolute terms (i.e.,

g) or as a percentage of the intake level that might lead to adverse

reactions in some consumers

arious regulatory approaches.

3. The agency also solicits comments on the advantages or

disadvantages of a simple label statement that the food contains free

glutamate, as compared to a quantitative statement of the amount of

free glutamate in a serving of the food either in absolute terms (i.e.,

g) or as a percentage of the intake level that might lead to adverse

reactions in some consumers. As a preliminary matter, FDA's view is

that quantitative labeling is not necessarily any more useful than a

general label statement alerting the glutamate-intolerant consumer to

the presence of free glutamate in the food when the level is

significant. The agency notes that because almost all foods contain

trace levels of free glutamate, quantitative labeling for all foods

with detectable levels of free glutamate might cause confusion among

glutamate-intolerant consumers about which foods could be consumed

without risking a reaction. Consumers might unnecessarily limit their

food choices by assuming that they should not eat any food labeled to

contain any amount of free glutamate, however small. FDA's preliminary

view is that, if quantitative labeling is required, a labeling

threshold should be established to prevent this problem. The agency

solicits comments on this view and on whether the optimal threshold for

quantitative free glutamate labeling

would be the same as the optimal threshold for a label statement that

the food contains free glutamate.

4. Finally, the agency solicits comments on the following questions

regarding the content, wording, and placement of labeling for

glutamate-containing foods, and on any other aspects of such labeling:

(a) What information should be included in labeling for glutamate-

containing foods? How should any required label statement be worded?

Should the scientifically accurate term ``free glutamate'' be used in

such labeling, or should the term ``MSG'' be used for all forms of free

glutamate because consumers are more familiar with it?

te-containing foods, and on any other aspects of such labeling:

(a) What information should be included in labeling for glutamate-

containing foods? How should any required label statement be worded?

Should the scientifically accurate term ``free glutamate'' be used in

such labeling, or should the term ``MSG'' be used for all forms of free

glutamate because consumers are more familiar with it?

(b) Should a label statement such as ``contains free glutamate'' be

included in the ingredient list because consumers traditionally use the

ingredient list to determine if the food contains ingredients they wish

to avoid? Alternatively, should such a label statement be placed

adjacent to the ingredient list or elsewhere on the information panel,

or should the label statement be placed on the principal display panel?

Suggestions for placement of the label statement should include the

comment's rationale for choosing one location over another.

(c) Is a separate label statement about free glutamate content

necessary when MSG is an ingredient in the food and is therefore

declared in the ingredient list? Current information in the agency's

possession suggests that glutamate-intolerant consumers already

identify and avoid foods that declare MSG as an ingredient, although

they often fail to recognize the presence of free glutamate when it

occurs in forms other than MSG (Ref. 3). Thus, the agency solicits

comments on the need for a statement about free glutamate content in

foods that contain MSG as a declared ingredient.

III. The ``No MSG'' Labeling Policy

A. Current Label Claims

ers already

identify and avoid foods that declare MSG as an ingredient, although

they often fail to recognize the presence of free glutamate when it

occurs in forms other than MSG (Ref. 3). Thus, the agency solicits

comments on the need for a statement about free glutamate content in

foods that contain MSG as a declared ingredient.

III. The ``No MSG'' Labeling Policy

A. Current Label Claims

The controversy over the use and safety of MSG in foods has

prompted some food manufacturers to make label claims such as ``No

MSG'' or ``No added MSG'' when MSG is not used as an ingredient in the

food. Several manufacturers have opted to reformulate their products to

remove MSG as an ingredient, or to substitute for MSG other ingredients

that have similar flavor-enhancing properties. Many of these

reformulated foods bear label claims about the absence of MSG. In some

cases manufacturers replace MSG with ingredients like hydrolyzed

proteins, autolyzed yeast extracts, or other flavor-enhancing

ingredients that contain substantial amounts of free glutamate.

Based on correspondence submitted to the agency and arguments

raised in a citizen petition submitted on behalf of Jack L. Samuels,

Adrienne Samuels, John Olney, et al., (Docket No. 94P-0444), FDA

recognizes that many consumers, especially those who report having

adverse reactions to MSG, refer to all forms of manufactured glutamate

as MSG. As previously discussed, the scientific evidence does not

support the assertion that manufactured free glutamate functions

differently in the body than naturally occurring free glutamate.

Moreover, even though FDA has attempted to clarify the distinction

between the ingredient monosodium glutamate (MSG) and other ingredients

that contain free glutamate in correspondence and other FDA documents,

such as FDA's Backgrounder on MSG (Ref. 25), consumers either do not

fully understand or do not acknowledge this distinction

erently in the body than naturally occurring free glutamate.

Moreover, even though FDA has attempted to clarify the distinction

between the ingredient monosodium glutamate (MSG) and other ingredients

that contain free glutamate in correspondence and other FDA documents,

such as FDA's Backgrounder on MSG (Ref. 25), consumers either do not

fully understand or do not acknowledge this distinction. Consequently,

consumers continue to use the term ``MSG'' to mean all forms of free

glutamate that are added to food. For example, FDA has received

numerous written and oral complaints (Ref. 3) charging manufacturers

with hiding the presence of ``MSG'' by declaring the substance under

other names such as ``flavorings,'' ``hydrolyzed protein,'' ``autolyzed

yeast extract,'' and similar terms.

FDA tentatively finds that consumers are likely to perceive a ``No

MSG'' or ``No added MSG'' claim on a label as indicating the absence of

all forms of free glutamate in the food. Such claims encourage

consumers wishing to avoid free glutamate to purchase a food by

representing the food as free of MSG. Moreover, manufacturers of

hydrolyzed proteins and other glutamate-containing ingredients often

promote them to manufacturers of finished foods as functional

substitutes for MSG that permit a ``clean'' ingredient statement and a

``No MSG'' claim on the label of the finished food. In this context,

``clean'' means an ingredient list that does not include ``monosodium

glutamate.'' Thus, while technically such foods bearing a claim about

the absence of MSG do not contain the ingredient monosodium glutamate,

they frequently contain levels of free glutamate that cause claims like

``No MSG'' and ``No added MSG'' to be misleading. Some manufacturers

attempt to evade the ingredient declaration requirement for MSG by

reformulating their products with MSG-containing ingredients (for

example, certain spice blends) that are added to the product in lieu of

MSG itself

the ingredient monosodium glutamate,

they frequently contain levels of free glutamate that cause claims like

``No MSG'' and ``No added MSG'' to be misleading. Some manufacturers

attempt to evade the ingredient declaration requirement for MSG by

reformulating their products with MSG-containing ingredients (for

example, certain spice blends) that are added to the product in lieu of

MSG itself. They then modify the ingredient list on the product label

to delete MSG and replace it with a generic term such as ``spices.''

(As noted in section I. of this document, this practice violates

existing ingredient labeling requirements; when MSG is added to a food

as an ingredient of a spice blend, MSG must still be declared in the

ingredient statement by its common or usual name, monosodium

glutamate.) In some cases, these manufacturers also add a ``No MSG''

claim to the label.

A related problem is the use of claims such as ``No MSG'' and ``No

added MSG'' on foods that contain substantial amounts of naturally

occurring free glutamate, such as tomato paste and certain cheeses.

Although such foods do not contain MSG itself, they contain ingredients

with concentrations of free glutamate that function as flavor enhancers

like MSG. Because of their free glutamate content, these foods are as

likely to cause or contribute to an MSG symptom complex reaction as a

food that contains a comparable amount of MSG. A claim such as ``No

MSG'' is misleading because it implies that the food may be consumed by

glutamate-intolerant consumers without risk of a reaction.

A food that bears a false or misleading claim about the absence of

MSG is misbranded under section 403(a) of the act. FDA has repeatedly

advised consumers and industry that it considers such claims as ``No

MSG'' and ``No added MSG'' to be misleading when they are used on the

labels of foods made with ingredients that contain substantial levels

of free glutamate (Refs. 25, 26, and 27)

action.

A food that bears a false or misleading claim about the absence of

MSG is misbranded under section 403(a) of the act. FDA has repeatedly

advised consumers and industry that it considers such claims as ``No

MSG'' and ``No added MSG'' to be misleading when they are used on the

labels of foods made with ingredients that contain substantial levels

of free glutamate (Refs. 25, 26, and 27). FDA has authority to take

action against such misbranded foods under existing law, but because of

the proliferation of such claims on products made with ingredients that

contain substantial levels of free glutamate, the agency believes that

formal criteria would be useful to define more precisely the

circumstances under which labels bearing claims about the absence of

MSG are misleading. While such criteria are being developed, however,

FDA will continue to take regulatory action as appropriate against

false or patently misleading claims about the absence of MSG, such as

``No MSG'' claims on products made with MSG-containing ingredients,

hydrolyzed proteins, or autolyzed yeast extracts.

B. Approaches Under Consideration

The agency is considering a variety of approaches to address

misleading claims about the absence of MSG. As a

starting point, a food that contains MSG, or ingredients to which MSG

has been added, is misbranded if it bears a ``No MSG'' or similar

claim. Such claims are false and, therefore, their regulatory status

needs no further clarification. The discussion below concerns the

development of criteria to prevent misbranding because of misleading

``No MSG'' and ``No added MSG'' claims on foods that contain free

glutamate but to which MSG itself has not been added, directly or

indirectly.

1. Cutoff levels

One strategy the agency is considering involves establishing a

``cutoff level'' for claims about the absence of free glutamate. If the

finished food contains free glutamate above the cutoff level, a ``No

MSG'' or similar label statement would be prohibited

ed MSG'' claims on foods that contain free

glutamate but to which MSG itself has not been added, directly or

indirectly.

1. Cutoff levels

One strategy the agency is considering involves establishing a

``cutoff level'' for claims about the absence of free glutamate. If the

finished food contains free glutamate above the cutoff level, a ``No

MSG'' or similar label statement would be prohibited. There are several

ways in which such a level could be defined:

a. Quantitation limit for free glutamate. One approach would be to

use the analytical limit of quantitation (LOQ) for free glutamate as

the cutoff level. The enzymatic procedure of Hattula and Wallin (Ref.

28), a commonly used, collaboratively studied analytical method for

determining free glutamate content, has an estimated quantitation limit

of 100 parts per million (ppm) (Ref. 29). Under this approach, any food

with a level of free glutamate above the LOQ, i.e., a level above 100

ppm using the Hattula and Wallin method, would be disqualified from

bearing a ``No MSG'' claim. However, because glutamate is ubiquitous in

the food supply and low levels of free glutamate typically occur in

many raw or minimally processed foods, using the LOQ as the cutoff

level would disqualify almost all foods from bearing a ``No MSG''

claim. For example, typical levels of free glutamate in canned peas and

canned corn are 320 ppm (.032 g) and 470 ppm (.047 g) respectively

(Ref. 30). Although these levels are lower than the level generally

associated with flavor-enhancing function (500 ppm) and lower than the

amount of free glutamate found in most foods containing monosodium

glutamate, hydrolyzed proteins, or yeast extracts, they are above the

LOQ of 100 ppm. Consequently, relying on a ``limit of quantitation''

criterion would disqualify foods like canned peas and canned corn from

bearing a ``No MSG'' claim.

b. Functional level. According to the scientific literature (Ref.

31), free glutamate has a flavor-enhancing effect at levels as low as

500 ppm

monosodium

glutamate, hydrolyzed proteins, or yeast extracts, they are above the

LOQ of 100 ppm. Consequently, relying on a ``limit of quantitation''

criterion would disqualify foods like canned peas and canned corn from

bearing a ``No MSG'' claim.

b. Functional level. According to the scientific literature (Ref.

31), free glutamate has a flavor-enhancing effect at levels as low as

500 ppm. Using 500 ppm as the cutoff level for claims about the absence

of MSG would allow a ``No MSG'' label statement on most raw or

minimally processed foods that naturally contain free glutamate, while

prohibiting such claims on MSG substitutes like protein hydrolysates

and autolyzed yeast extracts. Under this approach, foods such as canned

peas and canned corn would be permitted to bear a ``No MSG'' claim.

However, tomato sauce and fresh tomatoes, because of their relatively

high natural free glutamate content, would be prohibited from bearing

such a claim, as would parmesan cheese.

c. Labeling threshold. As discussed in section II. of this

document, the agency is considering whether to require a label

statement about free glutamate content on foods that contain 0.2 g or

more free glutamate per serving. For consistency, the cutoff for claims

about the absence of MSG could be set at the same level. Under this

approach, a ``No MSG'' claim would be permitted on foods like canned

peas and canned corn. However, bacon flavored toppings made from

hydrolyzed vegetable protein would also qualify to bear a ``No MSG''

claim because the serving size for toppings is so small. Claims about

the absence of MSG would be prohibited on any food required to bear a

label statement about the presence of free glutamate.

The agency solicits comment on whether an approach based on a

cutoff level of free glutamate in the finished food should be adopted

to determine whether a food may bear a ``No MSG'' or ``No added MSG''

claim

ecause the serving size for toppings is so small. Claims about

the absence of MSG would be prohibited on any food required to bear a

label statement about the presence of free glutamate.

The agency solicits comment on whether an approach based on a

cutoff level of free glutamate in the finished food should be adopted

to determine whether a food may bear a ``No MSG'' or ``No added MSG''

claim. Further, the agency solicits comment on whether such a cutoff

level should be: (a) The analytical limit of quantitation for free

glutamate; (b) the level at which free glutamate functions as a flavor

enhancer; (c) the level of free glutamate that would trigger a label

statement about the food's glutamate content; or (d) some other level.

2. Ingredients

The second approach the agency is considering would prohibit ``No

MSG'' and similar claims on foods made from ingredients that contain

substantial amounts of free glutamate. In the agency's opinion,

ingredients like hydrolyzed vegetable proteins, autolyzed yeast

extracts, soy sauce, parmesan cheese, and tomato paste contain enough

free glutamate to cause a ``No MSG'' label claim to be misleading. To

adopt this approach, the agency would have to define what constitutes a

``substantial'' amount of free glutamate in an ingredient. Should a

``substantial'' amount of free glutamate be defined as the amount

reported to have flavor-enhancing properties, i.e., 500 ppm (Ref. 31),

or in some other way?

Further, is an approach that prohibits a ``No MSG'' claim if an

ingredient in a food contains a ``substantial'' amount of free

glutamate equitable in all cases, or should the amount of an ingredient

added to a food also be considered in determining whether a claim is

misleading? For example, could ingredients like tomato paste or soy

protein isolate be added to a food in trace amounts without rendering a

``No MSG'' claim misleading?

3

o MSG'' claim if an

ingredient in a food contains a ``substantial'' amount of free

glutamate equitable in all cases, or should the amount of an ingredient

added to a food also be considered in determining whether a claim is

misleading? For example, could ingredients like tomato paste or soy

protein isolate be added to a food in trace amounts without rendering a

``No MSG'' claim misleading?

3. Combination or Other Approaches

The agency also invites comments on possibilities for combining any

of the approaches described in this section to develop a comprehensive

labeling policy to ensure that ``No MSG'' claims are truthful and not

misleading. For example, would a labeling policy that allowed a ``No

MSG'' or similar claim only on foods that: (1) Contain no ingredients

that have a ``substantial'' amount of free glutamate, and (2) contain

levels of total free glutamate per serving below a cutoff level of 0.2

g, be more desirable than a policy that relied on one criterion alone?

This approach would permit claims about the absence of MSG on foods

like canned peas and canned corn, but prohibit such claims on foods

like bacon flavored toppings made with hydrolyzed protein and on foods

that have a relatively high natural free glutamate content, including

tomato sauce and parmesan cheese. Alternatively, is there another

combination of approaches that would be more effective in ensuring that

label claims about the absence of MSG are not misleading? Suggestions

for other approaches or combinations of approaches should include data

or other information to substantiate the effectiveness of the approach.

IV. References

glutamate content, including

tomato sauce and parmesan cheese. Alternatively, is there another

combination of approaches that would be more effective in ensuring that

label claims about the absence of MSG are not misleading? Suggestions

for other approaches or combinations of approaches should include data

or other information to substantiate the effectiveness of the approach.

IV. 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. National Academy of Science, ``Food Chemicals Codex,'' 4 ed.,

1996, p. 260.

2. Taliaferro, P. T., ``Monosodium Glutamate and the Chinese

Restaurant Syndrome: A Review of Food Additive Safety,'' Journal of

Environmental Health, vol. 57, No. 10, pp. 8-12, 1995.

3. Satchell, F. B., Division of Programs and Enforcement Policy

(HFS-158), Center for Food Safety and Applied Nutrition, memorandum

to file: ``Consumer Correspondence to FDA Regarding the Use and

Labeling of MSG in Foods,'' July 3, 1996.

4. Select Committee on GRAS Substances, Life Sciences Research

Office, Federation of American Societies for Experimental Biology,

``Evaluation of the Health Aspects of Certain Glutamates as Food

Ingredients-Report 37a,'' (PB 283-475/AS), 1978.

5. Select Committee on GRAS Substances, Life Sciences Research

Office, Federation of American Societies for Experimental Biology,

``Evaluation of the Health Aspects of Protein Hydrolysates as Food

Ingredients- Report 37b,'' (PB 283-440/AS), 1978.

6. Select Committee on GRAS Substances, Life Sciences Research

Office, Federation of American Societies for Experimental Biology,

``Evaluation of the Health Aspects of Certain Glutamates as Food

Ingredients, Supplemental Review and Evaluation-Report 37a-Suppl.,''

(PB 178635), 1980.

7

tion of the Health Aspects of Protein Hydrolysates as Food

Ingredients- Report 37b,'' (PB 283-440/AS), 1978.

6. Select Committee on GRAS Substances, Life Sciences Research

Office, Federation of American Societies for Experimental Biology,

``Evaluation of the Health Aspects of Certain Glutamates as Food

Ingredients, Supplemental Review and Evaluation-Report 37a-Suppl.,''

(PB 178635), 1980.

7. Select Committee on GRAS Substances, Life Sciences Research

Office, Federation of American Societies for Experimental Biology,

``Evaluation of the Health Aspects of Protein Hydrolysates as Food

Ingredients, Supplemental Review and Evaluation-Report 37b-Suppl.,''

(PB80-178643), 1980.

8. FDA opinion letter from Einar T. Wulfsberg, Food and Drug

Officer to Mr. Ratton B. Rogers, the Nestle Co., November 12, 1959.

9. FDA opinion letter from Einar T. Wulfsberg, Food and Drug

Officer to Mr. J. Ter Marsch, August 25, 1961.

10. FDA opinion letter from D. R. Kleber, Jr., Division of

Advisory Opinions Bureau of Enforcement to Yeast Products, Inc.,

January 22, 1962.

11. FDA opinion letter from Virgil O. Wodicka, Director, Bureau

of Foods to Mr. William H. Honstead, The ESU Research Foundation,

Kansas State University, 1972.

12. Advisory Committee on Hypersensitivity to Food

Constituents--Proceedings Ad Hoc, May 8, 1986, pp. 13-28.

13. Reports of the Scientific Committee for Food on a First

Series of Food Additives of Various Technological Functions,

Commission of the European Communities, Reports of the Scientific

Committee for Food, 25th series, 1991.

14. Report of the Council on Scientific Affairs, American

Medical Association, ``Food and Drug Administration Regulations

Regarding the Inclusion of Added L-Glutamic Acid Content on Food

Labels,'' Report: D (A-92), 1992.

15

st

Series of Food Additives of Various Technological Functions,

Commission of the European Communities, Reports of the Scientific

Committee for Food, 25th series, 1991.

14. Report of the Council on Scientific Affairs, American

Medical Association, ``Food and Drug Administration Regulations

Regarding the Inclusion of Added L-Glutamic Acid Content on Food

Labels,'' Report: D (A-92), 1992.

15. The Joint Food Agriculture Organization/World Health

Organization Expert Committee on Food Additives, ``L-Glutamic Acid

and its Ammonium, Calcium, Monosodium and Potassium Salts-

Toxicological Evaluation of Certain Food Additives,'' WHO Food

Additive Series, No. 22, pp. 97-161, 1988.

16. Gray, D., FDA memorandum, May 23, 1996.

17. Life Sciences Research Office, Federation of American

Societies for Experimental Biology, ``Analysis of Adverse Reactions

to Monosodium Glutamate (MSG),'' Report, 1995.

18. Allen, D. H., J. Delohery, and G. Baker, ``Monosodium L-

Glutamate-Induced Asthma,'' Journal of Allergy and Clinical

Immunology, vol. 80, pp. 530-537, 1987.

19. FDA memorandum concerning evaluation of the Federation of

American Societies for Experimental Biology (FASEB) (July 1995

Report) from the Director, Division of Health Effects Evaluation to

Lawrence Lin, ``Analysis of Adverse Reactions to Monosodium

Glutamate (MSG),'' August 30, 1996.

20. Levy, A. S., B. M. Derby, Consumer Studies Branch, Center

for Food Safety and Applied Nutrition, FDA, ``The Impact of the NLEA

on Consumers: Recent Findings From FDA's Food Label and Nutrition

Tracking System,'' 1996.

21. Warner, C., and D. Daniels, FDA memorandum, August 14, 1996.

22. United States Department of Agriculture, ``Continuing Survey

of Food Intake by Individuals'' (1989-90, 1990-91, 1991-92),

Nationwide Food Consumption Survey, 1987.

23. Market Research Corporation of America (1992), 5-Year Menu

Census, 1982-87, FDA Contract No. 223-87-2088.

24. DiNovi, M., FDA memorandum, ``Basis for High-Intake

Estimates,'' July 1, 1996.

25

memorandum, August 14, 1996.

22. United States Department of Agriculture, ``Continuing Survey

of Food Intake by Individuals'' (1989-90, 1990-91, 1991-92),

Nationwide Food Consumption Survey, 1987.

23. Market Research Corporation of America (1992), 5-Year Menu

Census, 1982-87, FDA Contract No. 223-87-2088.

24. DiNovi, M., FDA memorandum, ``Basis for High-Intake

Estimates,'' July 1, 1996.

25. FDA Backgrounder (BG95-16), ``Monosodium Glutamate (MSG),''

August 31, 1995.

26. FDA Warning Letter from Elaine C. Messa, District Director,

Irvine, CA to Patricia Bragg, President, Live Food Products, May 29,

1996.

27. FDA correspondence from John E. Thomas to Sonja L. Valiulis,

October 14, 1992.

28. Hattula, M. T., and H. C. Wallin, ``Enzymatic Determination

of Free Glutamic Acid in Dried Soups and in Minced Sausages: NMKL1

Collaborative Study,'' Journal of the Association of Official

Analytical Chemists, vol. 74, No. 6, pp. 921-925, 1991.

29. Facsimile from H. C. Wallin to C. Warner, May 6, 1996.

30. Daniels, D. H., F. L. Joe, and G. W. Diachenko,

``Determination of Free Glutamic Acid in a Variety of Foods by High-

Performance Liquid Chromatography,'' Food Additives and

Contaminants, vol. 12, No. 1, pp. 21-29, 1995.

31. Yamaguchi, S., and A. Kimizuka, ``Psychometric Studies on

the Taste of Monosodium Glutamate,'' Glutamic Acid: Advances in

Biochemistry and Physiology, Raven Press, New York, pp. 35-54, 1979.

V. Comments

. W. Diachenko,

``Determination of Free Glutamic Acid in a Variety of Foods by High-

Performance Liquid Chromatography,'' Food Additives and

Contaminants, vol. 12, No. 1, pp. 21-29, 1995.

31. Yamaguchi, S., and A. Kimizuka, ``Psychometric Studies on

the Taste of Monosodium Glutamate,'' Glutamic Acid: Advances in

Biochemistry and Physiology, Raven Press, New York, pp. 35-54, 1979.

V. Comments

Interested persons may, on or before November 12, 1996, submit to

the Dockets Management Branch (address above) written comments

regarding this ANPRM. 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 Dockets Management

Branch (address above) between 9 a.m. and 4 p.m., Monday through

Friday.

This advance notice of proposed rulemaking is issued under sections

5 and 6 of the Fair Packaging and Labeling Act (15 U.S.C. 1454, 1455),

sections 201, 301, 403, 701 of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 321, 331, 343, 371), and under the authority of the

Commissioner of Food and Drugs.

Dated: August 29, 1996.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 96-23159 Filed 9-5-96; 4:43 pm]

BILLING CODE 4160-01-F