Food Labeling: Health Claims; Soy Protein and Coronary Heart Disease

SUMMARY: The Food and Drug Administration (FDA) is authorizing the use,

on food labels and in food labeling, of health claims on the

association between soy protein and reduced risk of coronary heart

disease (CHD). Based on its review of evidence submitted with comments

to the proposed rule, as well as evidence described in the proposed

rule, the agency has concluded that soy protein included in a diet low

in saturated fat and cholesterol may reduce the risk of CHD by lowering

blood cholesterol levels.

DATES: This regulation is effective October 26, 1999, except for

Sec. 101.82(c)(2)(ii)(B), which contains information collection

requirements that have not been approved by the Office of Management

and Budget (OMB). Upon approval, the FDA will publish a document in the

Federal Register announcing the effective date of those requirements.

FOR FURTHER INFORMATION CONTACT: Susan M. Pilch, Center for Food Safety

and Applied Nutrition (HFS-465), Food and Drug Administration, 200 C

St. SW., Washington, DC 20204, 202-205-4500.

SUPPLEMENTARY INFORMATION:

I. Background Information

On November 8, 1990, the President signed into law the Nutrition

Labeling and Education Act of 1990 (the 1990 amendments) (Public Law

101-535). This new law amended the Federal Food, Drug, and Cosmetic Act

(the act) in a number of important ways. One notable aspect of the 1990

amendments was that they provided procedures whereby FDA is to regulate

health claims on food labels and in food labeling.

In the Federal Register of January 6, 1993 (58 FR 2478), FDA issued

a final rule that implemented the health claim provisions of the act

(hereinafter referred to as the 1993 health claims final rule). In that

final rule, FDA adopted Sec. 101.14 (21 CFR 101.14), which sets out

rules for the authorization and use of health claims by regulation.

Additionally, Sec. 101.70 (21 CFR 101.70) establishes a process for

petitioning the agency to authorize by regulation the use of health

claims about a substance-disease relationship (Sec. 101.70(a)) and sets

out the types of information that any such petition must include

(Sec. 101.70(f)).

In response to the 1990 amendments, FDA also conducted an extensive

review of the evidence on 10 substance-disease relationships. As a

result of its review, FDA has authorized claims for 8 of these 10

relationships, one of which focused on the relationship between dietary

saturated fat and cholesterol and reduced risk of CHD. CHD is the most

common, most frequently reported, and most serious form of

cardiovascular disease (CVD) (58 FR 2739, January 6, 1993). Further,

although the agency denied the use on food labeling of health claims

relating dietary fiber to reduced risk of CVD (58 FR 2552), it

authorized a health claim relating diets low in saturated fat and

cholesterol and high in fruits, vegetables, and grain products that

contain dietary fiber (particularly soluble fiber) to a reduced risk of

CHD.

In the proposed rule entitled ``Health Claims and Label Statements;

Lipids and Cardiovascular Disease'' (56 FR 60727, November 27, 1991)

(hereinafter referred to as the saturated fat/cholesterol proposed

rule), FDA set out criteria for evaluating evidence on diet and CVD

relationships. The agency focused on those aspects of the dietary lipid

and CVD relationship for which the strongest scientific evidence

andagreement existed. FDA noted that, because of the public health

importance of CHD, identification of ``modifiable'' risk factors for

CHD had been the subject of considerable research and public policy

attention. The agency also noted that there is general agreement that

elevated blood cholesterol levels are one of the major ``modifiable''

risk factors in the development of CHD. FDA cited Federal Government

and other reviews that concluded that there is substantial

epidemiologic and clinical evidence that high blood levels of total and

low density lipoprotein (LDL)-cholesterol are a cause of

atherosclerosis and represent major contributors to CHD. Further,

factors that decrease total blood cholesterol and LDL-cholesterol will

also decrease the risk of CHD. FDA concluded that it is generally

accepted that blood total and LDL-cholesterol levels are major risk

factors for CHD, and that dietary factors affecting blood cholesterol

levels affect the risk of CHD. High intakes of dietary saturated fat

and, to a lesser degree, of dietary cholesterol are consistently

associated with elevated blood cholesterol levels. FDA tentatively

concluded that the publicly available data supported an association

between diets low in saturated fat and cholesterol and reduced risk of

CHD (56 FR 60727 at 60737), and it confirmed that conclusion in the

saturated fat/cholesterol final rule (58 FR 2739 at 2751).

Based on its review using the stated criteria, and on its

consideration of comments received in response to the proposed rule

entitled ``Health Claims; Dietary Fiber and Cardiovascular Disease''

(56 FR 60582), FDA concluded that the publicly available scientific

information supported an association between diets low in saturated fat

and cholesterol and high in fruits, vegetables, and grain products

(i.e., foods that are low in saturated fat and cholesterol and that are

good sources of dietary fiber) and reduced risk of heart disease (58 FR

2552 at 2572). In the 1993 dietary fiber and CVD final rule, in

response to a comment regarding the apparent hypocholesterolemic

properties of specific food fibers, FDA again articulated its criteria

for evaluating diet and CHD relationships (58 FR 2552 at 2567). FDA

agreed that the effectiveness of naturally occurring fibers in foods in

reducing the risk of CHD may be documented for specific food products.

Further, the agency indicated that if manufacturers could document,

through appropriate studies, that dietary consumption of the soluble

fiber in a particular food has a beneficial effect on blood lipids

predictive of CHD risk, they should petition for a health claim for

that particular product. In response to two petitions that documented

such evidence, FDA has authorized health claims for soluble fiber from

certain foods and reduced risk of CHD in Sec. 101.81 (21 CFR 101.81)

(62 FR 3600, January 23, 1997, and amended at 62 FR 15344, March 31,

1997, and 62 FR 8119, February 18, 1998).

In the Federal Register of November 10, 1998 (63 FR 62977), and in

response to a petition from Protein Technologies International, Inc.

(Ref. 1 and Ref. 2), the agency proposed Sec. 101.82 to provide for

health claims on the relationship of soy protein and reduced risk of

CHD (hereinafter referred to as the soy protein proposed rule). In the

soy protein proposed rule, FDA considered the relevant scientific

studies and data presented in the petition as part of its review of the

scientific literature on soy protein and CHD. The agency summarized

this evidence in the soy protein proposed rule and presented the

rationale for a health claim on this food-disease relationship as

provided for under the significant scientific

[[Page 57701]]

agreement standard in section 403(r)(3)(B)(i) of the act and

Sec. 101.14(c) of FDA's regulations.

Proposed Sec. 101.82(c)(2)(ii)(A) identified the substance that is

the subject of the proposed claim as soy protein from the legume seed

Glycine max. The soy protein proposed rule included qualifying criteria

for the purpose of identifying soy protein-containing foods eligible to

bear the proposed health claim. The proposal also specified mandatory

content for health claim statements; identified additional, optional

information for such statements; and provided model health claims.

In its evaluation of the scientific evidence for a relationship

between consumption of soy protein and blood total and LDL-cholesterol

levels, the agency found the data suggestive but not sufficient to

establish a dose-response for this relationship. However, the agency

did find consistent, clinically significant reductions of total and

LDL-cholesterol levels in controlled trials that used at least 25 grams

(g) of soy protein per day. Thus, the agency proposed to base the

qualifying level of soy protein on a total daily intake of 25 g, as

suggested by the petitioner. Therefore, in Sec. 101.82(c)(2)(iii)(A),

FDA proposed the qualifying criterion for a food to bear the claim as

6.25 g of soy protein per reference amount customarily consumed (RACC)

(i.e., 25 g divided by 4 eating occasions per day).

In the soy protein proposed rule, FDA had tentatively indicated its

intention to use a specific analytical method to measure soy protein

for assessing compliance with the qualifying criterion. Comments

persuaded the agency that the method would be inadequate for many

products. Therefore, in the Federal Register of August 23, 1999 (64 FR

45932), FDA issued a proposed rule to provide for an alternative

procedure for assessing compliance (hereinafter referred to as the soy

protein reproposal). In the soy protein reproposal, in

Sec. 101.82(c)(2)(ii)(B) FDA proposed that it would rely on measurement

of total protein and require manufacturers, when soy is not the sole

source of protein in foods, to maintain records that document the

amount of soy protein in products and to make these records available

to appropriate regulatory officials for inspection and copying upon

request.

II. Summary of Comments and the Agency's Responses

In response to the soy protein proposed rule, the agency received

approximately 130 submissions, each containing one or more comments,

from consumers, consumer organizations, professional organizations,

government agencies, industry, trade associations, health care

professionals, and research scientists.

About half of these submissions supported the proposed rule without

providing grounds for this support other than those provided by FDA in

the preamble to the soy protein proposed rule. The majority of the

remaining comments were generally supportive, but requested

modification of one or more provisions of the proposed rule. Some

comments provided additional data on the relationship between soy

protein and CHD, including one submission, originally submitted as a

health claim petition and converted to a comment on the soy protein

proposed rule (Ref. 3), that included a comprehensive review of

available scientific evidence about the relationship. Some of the

comments that disagreed with the soy protein proposed rule provided

specific support for their positions. Some of the comments were

received after the date for submitting comments had passed. Although

the agency is not obligated to respond to late comments, in the

interest of assessing the totality of the available data, it has

considered each of these comments to the extent that it provided

complete information for review or references accessible to the agency

and addressed issues not raised in earlier comments. The agency has

summarized and addressed the relevant issues raised in the comments in

the sections of this document that follow.

In response to the soy protein reproposal, the Agency received

approximately 10 submissions, each containing one or more comments. The

agency has summarized and addressed these comments in section II.C.2 of

this document.

A. Eligibility of Soy Protein as the Subject of a Health Claim

In the soy protein proposed rule, the agency assessed whether soy

protein satisfied the preliminary requirement that a substance that is

the subject of a health claim is associated with a disease for which

the U.S. population is at risk (63 FR 62977 at 62978). Based on

analyses presented in earlier rulemakings and its review of data on the

mortality, morbidity, and costs of CHD and prevalence of ``high risk''

and ``borderline high'' total and LDL-cholesterol levels in the United

States (Refs. 4 through 8), the agency tentatively concluded that, as

required in Sec. 101.14(b)(1), CHD is a disease for which the U.S.

population is at risk. One comment reviewed additional sources of

information and reached the same conclusion.

In the soy protein proposed rule, FDA also tentatively concluded

that soy protein from Glycine max satisfied the preliminary requirement

of Sec. 101.14(b)(3)(i) that the substance be a food that contributes

taste, aroma, or nutritive value (63 FR 62977 at 62978). Sources of soy

protein identified in the soy protein proposed rule included foods

composed of or derived from whole soybeans and foods that contain

processed soy protein ingredients: Isolated soy protein (ISP), soy

protein concentrate (SPC), soy flour (SF), texturized soy protein, or

texturized vegetable protein (TVP). In addition to protein, these foods

and ingredients contain other naturally occurring soy constituents,

such as isoflavones, fiber, and saponins. The specific processing steps

employed determine the extent of retention of such naturally occurring

constituents in the final product.

In assessing whether the petitioner had demonstrated that soy

protein is safe and lawful at the level necessary to justify the claim,

FDA noted that the petitioner stated that soy protein ingredients were

in common use in food before January 1, 1958, and that they are

generally recognized as safe (GRAS) by self-determination (63 FR 62977

at 62978). Because the fractionation procedures used to convert

vegetable flours to vegetable protein isolates and concentrates were

commonplace prior to 1958, the petitioner also asserted that ISP and

SPC can be defined as soy flour ``subject only to conventional

processing as practiced prior to January 1, 1958.'' In addition, FDA

reviewed information submitted by the petitioner about potential risks

of consuming soy products: allergenicity (Refs. 9 and 10), exposure to

trypsin inhibitors (Refs. 11 through 16), reduced bioavailability of

minerals (Refs. 13, 17, 18, 19, and 20), and hormonal disturbances due

to soy isoflavones (Refs. 21 through 26). Based on the totality of the

evidence and, in particular, its common use in food, the agency did not

take issue with the petitioner's view that the use of soy protein is

safe and lawful as required in Sec. 101.14(b)(3)(ii). Thus, FDA

tentatively concluded that the petitioner provided evidence that

satisfied the requirement in Sec. 101.14(b)(3)(ii) that use of soy

protein at the levels necessary to justify a claim is safe and lawful

under the applicable food safety provisions of the act (63 FR 62977 at

62979).

Several comments agreed with the agency's conclusion and some

provided the rationale for their support. A number of comments disputed

the

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petitioner's assertion of GRAS status for soy protein and raised

questions about the safety of soy protein-containing foods. The

specific aspects of disagreement are summarized and discussed in the

following sections of this document.

1. Concerns About the Safety of Soy Protein-Based Infant Formulas

(Comment 1). Many of the comments that raised concerns about the

safety of consuming soy protein-containing foods addressed the safety

of soy protein-based infant formulas. The observed or hypothesized

detrimental effects of such formulas discussed in these comments

included: hormonal disturbances due to estrogenic effects of soy

isoflavones; thyroid abnormalities; altered mineral balance, especially

for zinc; and diabetogenic effects in infants.

FDA is aware of concerns raised about the safety of soy infant

formulas, but notes that these are speculative at this time, pending

the results of definitive research. FDA also notes that the American

Academy of Pediatrics (Ref. 73) and the New Zealand Ministry of Health

(Ref. 74) have recently issued guidelines for the safe and suitable use

of soy-based infant formulas. Some issues regarding effects of infant

formula are unique because infants may be entirely dependent on formula

as a sole source of nutrition and the relevance of such issues for soy

protein consumed as part of a mixed diet by the general U.S. population

is not clear.

In any case, concerns about effects of soy protein specific to

infant formulas are beyond the scope of the current rule, which

authorizes a health claim about the relationship of soy protein and CHD

for foods intended for use by the general population. Health claims are

not permitted on foods represented or purported for use by infants and

toddlers less than 2 years of age unless specifically provided for in

the authorizing regulation (21 CFR 101.14(e)(5)). Diets restricted in

fat, saturated fat, and cholesterol are not recommended for infants and

young children, and the current rule (Sec. 101.82) contains no

provisions for use of the health claim about the relationship between

soy protein and CHD on foods for infants and toddlers.

2. Comments on Petitioner's Self-Determination of GRAS Status for Soy

Protein

(Comment 2). One comment specifically agreed with the petitioner's

assertion that soy protein-containing food ingredients are generally

recognized as safe (GRAS) by self-determination and based on common use

in food before January 1, 1958, in conformance with Sec. 201(s) of the

act. The comment also noted that, although soy protein is not listed as

GRAS or prior sanctioned in Title 21 of the CFR, FDA has noted that

these lists ``do not include all substances generally recognized as

safe for their intended use'' and, as stated at 21 CFR 182.1, ``[i]t is

impracticable [for FDA] to list all substances that are GRAS for their

intended use.'' This comment also agreed with the petitioner's

conclusion that fractionation procedures used to convert vegetable

flours to vegetable protein concentrates and isolates were commonplace

in various sectors of the grain industry, such as corn processing, well

before 1958. Therefore, SPC and ISP can be defined as soy flour

``subject only to conventional processing as practiced prior to January

1, 1958.'' The comment concluded that SF (including steam-treated SF),

SPC, and ISP all fall within the category of ingredients that are GRAS

through experience based on their common use. Several comments objected

to the petitioner's self-determination of GRAS status, citing a variety

of reasons. As stated previously, FDA does not take issue with the

petitioner's self-determination of GRAS status, and the comments,

discussed below, have not convinced the agency to change that

conclusion.

(Comment 3). Some comments raised objections on the basis that FDA

has not approved the GRAS status of soy protein.

Although FDA has not ruled formally on the GRAS status of soy

protein ingredients, it has not challenged determinations that soy's

use as dietary protein is GRAS. Food ingredients whose use is generally

recognized as safe by qualified experts are not required by law to

receive FDA approval. Under the health claim petition process, FDA

evaluates whether the substance is ``safe and lawful'' under the

applicable food safety provisions of the act (Sec. 101.14(b)(3)(ii)).

As discussed in greater detail below, FDA did not receive sufficient

evidence from comments to challenge the petitioner's assertion that soy

protein ingredients are GRAS by self-determination. The petitioner met

the showing required by Sec. 101.14(b)(3)(ii) that the substance be

``safe and lawful.''

(Comment 4). One comment claimed that the Center for Food Safety

and Applied Nutrition recently returned a petition requesting GRAS

recognition for soy protein.

The document referred to by the comment was a notification by

Archer Daniels Midland Company (GRN 000001), rather than a petition for

FDA action, and the subject of the notification was soy isoflavone

extract, rather than soy protein. At the company's request, FDA ceased

evaluation of the GRAS Notification pending the company's updating of

the file (Ref. 75). Thus, this comment was incorrect.

(Comment 5). A comment asserted that petitioner's basis for GRAS

self-determination of the use of soy protein as a dietary protein

ingredient (i.e., common use in food before January 1, 1958) was

incorrect. Because the 1979 Select Committee on GRAS Substances (SCOGS)

report (Ref. 76) determined that, at the time of the report, likely

average dietary exposure to soy protein isolate was only about 150

milligrams (mg) from food items, the comment asserted that soy protein

isolates could not have been in common use before 1958.

FDA finds that this comment is groundless and inaccurately

characterizes the findings of the SCOGS. The 1979 SCOGS report includes

the background statement ``Edible soy protein isolates for food uses

appeared about 1957 as a major article of commerce.'' The 1979 SCOGS

Report also cited a 1972 National Research Council survey of GRAS

ingredients that listed 14 food categories in which soy protein

isolates were used and calculated an average daily intake of several

grams. Soy protein isolates represent only one of several possible

sources of soy protein in foods. In addition, for purposes of

determining if a substance is GRAS, common use is not restricted to

common use in the United States.

(Comment 6). A comment supporting the petitioner's self-

determination of GRAS status noted that use of soy as a food dates to

about the 11th century BC in the eastern half of north China. From

about the first century AD to the 15th-16th century, soybeans were

introduced in Korea, Japan, Indonesia, the Philippines, Vietnam,

Thailand, Malaysia, Burma, Nepal, and northern India. Soybeans first

grew in the United States in 1765 and were used then to manufacture soy

sauce and vermicelli (soybean paste) (Ref. 77). A comment that disputed

the petitioner's self-determination of GRAS status speculated that the

species of soybean grown early in its history in Asia may have differed

significantly in its content of nutrients and other active components

from the modern species that is cultivated in this country.

FDA does not find this comment compelling. Although the composition

of soybeans has likely changed over time, modern soybean species and

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cultivars are, in any case, encompassed within the period of common use

of soy and soy protein in food.

(Comment 7). One comment questioned whether the Asian experience

could provide assurance that soy is safe. Drawing parallels with herbal

medicine in terms of attitudes, monitoring deficiencies, and the

general difficulty in detecting toxicities with long latency, this

comment concluded that the long history of apparent safe use of soy

products cannot assure they are without risk (Ref. 78).

The comment did not provide evidence to document that soy products,

consumed at levels necessary to justify the claim, are not generally

recognized as safe. Moreover, considerable research is underway at this

time because of the hypothesized benefits of the historical use of soy

products by certain population groups. FDA supports the ongoing

research to clarify the effects, both potentially beneficial and

potentially adverse, of soy and agrees that any effects due to changes

in the conditions of use should be monitored. However, the information

currently available does not lead FDA to object to the petitioner's

self-determination of GRAS status of soy protein.

(Comment 8). Several other comments asserted that the proposal did

not adequately establish the GRAS status of soy protein food

ingredients in that the proposal did not include a thorough evaluation

of the safety of potentially harmful components, e.g., lysinoalanine,

nitrites and nitrosamines, trypsin inhibitors, phytate, and

isoflavones.

FDA notes that the 1979 SCOGS report (Ref. 76) discussed several of

these components extensively and recommended that it would be prudent

to develop food grade specifications for soy protein isolates that

would set acceptable limits on the levels of lysinoalanine, nitrites,

and nitrosamines. But, the possible presence of these components in soy

protein isolates did not lead the SCOGS panel to recommend against GRAS

status of soy protein isolates.

As noted above, the agency finds the petitioner met the showing

required by Sec. 101.14(b)(3)(ii) that soy protein is ``safe and

lawful.'' The agency lacks documented evidence of adverse effects in

humans and has received no information about actual levels of

potentially harmful components or about threshold levels for adverse

effects in humans. Accordingly, the agency has no basis to conclude

that soy protein is not safe and lawful. The specific comments about

potentially harmful components of soy are discussed below.

3. Lysinoalanine: Potential Toxic Effects

(Comment 9). A few comments noted concerns about the presence of

lysinoalanine in soy protein isolates and cited the SCOGS report (Ref.

76), which indicated that lysinoalanine was implicated as a renal toxic

factor in rats.

FDA finds that the comments inaccurately reflected the findings of

the SCOGS report. The SCOGS report noted that the relatively severe

alkali treatment used to modify viscosity and adhesive properties of

soy protein isolates used as sizing and coating adhesives in the

production of paper and paperboard products can cause formation of

lysinoalanine. The report evaluated the risk of lysinoalanine exposure

from soy protein adhesives and binders used in paper and paperboard

food packaging. The 1979 SCOGS report noted that, ``For edible isolated

protein production, extraction is usually carried out at a pH below 9

to avoid hydrolytic or rheological changes'' and concluded that, while

relatively low levels of lysinoalanine had been reported in some

samples of food grade soy protein isolate, available information

indicated that the levels of lysinoalanine in food grade soy protein

isolates pose no hazard to the consumer (Ref. 76).

FDA notes that the comments that expressed concern about

lysinoalanine in soy protein ingredients did not provide any

information about lysinoalanine levels in food grade soy protein

ingredients nor about use of alkali-processed soy protein as a food

ingredient. FDA finds that the potential presence of lysinoalanine in

soy protein isolates used for sizing and coating adhesives in paper and

paperboard products is not relevant to the safe and lawful use of soy

protein in food. FDA also notes that the production of small amounts of

lysinoalanine during alkali processing has also been documented with

casein and lactalbumin, so it is not unique to soy. Good manufacturing

practices are and should be employed to minimize the production of

lysinoalanine because of its deleterious effects on protein quality.

4. Nitrites and Nitrosamines: Potential Carcinogenic Effects

(Comment 10). Some comments expressed concerns about the potential

presence of nitrites in soy protein and the potential their presence

poses for the in vivo formation of nitrosamines, which have been shown

to be carcinogenic in experimental animals.

FDA notes that many natural and processed foods contribute to the

total human intake of nitrite. In an appendix titled ``Health Aspects

of Nitrites in Soy Protein Isolates,'' the SCOGS report (Ref. 76)

presented an estimate of the consumer exposure to nitrite contributed

by soy protein in perspective to nitrite from other dietary sources and

that formed in the gastrointestinal tract by reduction of salivary and

dietary nitrate. The SCOGS report estimated the maximum daily nitrite

consumption for a vegetarian eating meat alternatives prepared from soy

protein to be 0.04 mg/kilogram (kg) body weight (or 2.8 mg for a 70-kg

person). The report estimated daily per capita intake of nitrite from

other foods of plant origin and cured meats to be about 2.4 mg and

daily exposure to nitrite from saliva to be 15 mg. The report estimated

that nitrite formed in the intestine from reduction of ammonia or

organic nitrogen compounds contributed about 90 mg/day. Given the

relatively minor potential contribution of soy protein to total nitrite

exposure, and the fact that no data were submitted to document the

current levels of nitrites or nitrosamines in soy protein isolates, FDA

is not persuaded of the necessity for establishing specifications for

acceptable levels of these compounds.

5. Trypsin Inhibitors: Potential Effects on Pancreatic Function

(Comment 11). A number of comments presented evidence that modern

heat treatment and other processing do not entirely eliminate the

activity of trypsin inhibitors in soy protein-containing products.

Additional references provided in comments (Refs. 79, 80, 81, and 82)

suggested that the mechanism of feedback regulation of pancreatic

enzyme secretion may be responsible for deleterious effects on the

pancreas--hyperplasia and formation of nodules--seen in animal studies.

Further, Leiner (Ref. 80) demonstrated that infusion of high levels of

isolated trypsin inhibitor in humans can evoke this mechanism but noted

that further research was needed to assess whether frequent exposures

to low levels of trypsin inhibitors consumed in the diet could have the

same effect. Other comments cited evidence for potential

anticarcinogenic effects of these and other protease inhibitors (Ref.

83). Leiner (Ref. 82) hypothesized that any anticarcinogenic effect of

protease inhibitors would likely be manifested at levels too low to

evoke their adverse effects on the pancreas.

FDA notes that the observed adverse effects have been limited to

animal

[[Page 57704]]

studies. To date, deleterious effects of consumption of low levels of

soybean trypsin inhibitors have not been documented in humans. For

example, Mills et al. (Ref. 84) conducted a prospective study of fatal

pancreas cancer among 34,000 California Seventh-day Adventists, a group

with high soy consumption. Compared to all U.S. whites, Adventists

experienced decreased risk from pancreas cancer death, which was not

statistically significant. Although there was a suggestive relationship

between increasing meat, egg, and coffee consumption and increased

pancreatic cancer risk, these variables were not significantly related

to risk after controlling for cigarette smoking. However, increasing

consumption of vegetarian protein products, beans, lentils, and peas as

well as dried fruit was associated with highly significant protective

relationships to pancreas cancer risk.

Therefore, FDA finds that the information presented in these

comments has not documented deleterious effects of dietary intake of

trypsin inhibitors from soy in humans and, thus, does not lead the

agency to take issue with the petitioner's conclusion that the use of

soy protein is safe and lawful as required by Sec. 101.14(b)(3)(iii).

6. Phytate: Effects on Mineral Balance

Comments raised concerns about the potential deleterious effect of

soy protein and its phytate content on mineral status. Phytate, the

salt of phytic acid or inositol hexaphosphate, is a natural plant

constituent containing six negatively charged phosphate groups that can

form strong complexes with divalent cations such as calcium, magnesium,

iron, zinc, and copper. Concerns relative to soy have concentrated

mainly on iron and zinc, based primarily on studies of the absorption

and bioavailability of these minerals.

(Comment 12). One comment cited a study in which a soy protein-

based purified diet induced iron deficiency in monkeys (Ref. 85). The

same comment also noted two studies in humans--one that found

inhibition of the absorption of nonheme iron from both semisynthetic

meals and meals comprising conventional foods by various soy protein-

containing ingredients (Ref. 86), and one that found increasing

inhibition of nonheme iron absorption with increasing amounts of

phytate in liquid formula meals that contained soy protein isolates

(Ref. 87). In a study cited in another comment, the substitution of

some meat in a mixed meal by soy protein caused a decrease in the

absorption of nonheme iron and an increase in the absorption of heme

iron (Ref. 88), so that overall iron absorption was not compromised.

Another comment reported that human feeding studies with soy protein

that have examined measures of iron status have not shown detrimental

effects (Ref. 89).

A comment raised concerns about the effect of soy protein on zinc

status based on studies of absorption of zinc from soy infant formula

(Ref. 90) and a study that showed decreased serum thymulin in subjects

fed a low-zinc, soy protein-based experimental diet designed to produce

mild zinc deficiency (Ref. 91). As noted earlier, issues specific to

infant formula are outside the scope of this rulemaking and the

experimental diet in the latter study (Ref. 91) is of limited relevance

to the likely conditions of consumption of soy protein in the

population that is the target of the health claim. Another comment

cited two studies (Refs. 92 and 93) showing no adverse effects of soy

protein on absorption of zinc from meals in subjects with adequate zinc

status.

One comment provided additional information on the mechanism of

phytate interference with zinc homeostasis (Ref. 94) and characterized

the problem as more than a matter of decreased bioavailability of the

zinc consumed in a meal. The comment noted that phytate can remove from

the duodenum zinc that is mainly derived from pancreatic secretions,

that is, zinc that may have been consumed 1-2 weeks earlier. Although

these data are derived from animal studies, the comment indicated that

the physiology of zinc homeostasis is not qualitatively different

across species.

This comment expressed concern that high consumption of soy protein

might exacerbate marginal zinc deficiency, which is difficult to

diagnose, and suggested that labeling should include the content of

both zinc and phytate so consumers can be educated that a molar ratio

of phytate:zinc of less than 10 is needed to avoid detrimental effects

on zinc status, as suggested by research in animals (including Ref.

95). The comment acknowledged that education would be needed for the

public to utilize such labeling. The agency recognizes that adequacy of

iron and zinc status in largely plant-based diets is a legitimate

concern.

FDA finds that the evidence of potential adverse effects of soy

protein on iron and zinc status is equivocal. Interpretation of the

evidence is difficult because findings in human studies are often

inconsistent with results of animal studies. Moreover, many factors

affect the absorption of these minerals, including the amount consumed

in a meal, the enhancing and inhibiting effects of other components of

the meal, and the nutritional status of the subject. Animal studies

suggest that zinc status is a strong determinant of effects of phytate/

soy on zinc absorption: zinc absorption is more impaired with zinc

deficiency, in contrast to the effect of low iron status, which

enhances iron absorption. However, given the lack of documented

evidence for impaired iron and zinc status in humans consuming soy

protein as part of a mixed diet, FDA is not persuaded of the necessity

for the suggested labeling with respect to the phytate: zinc molar

ratio. Nor is it persuaded that many consumers would find the suggested

information, which is highly technical, useful at this time.

7. Soy Isoflavones: Estrogenic Effects

Many comments addressed concerns about the possible deleterious

consequences of phytoestrogen effects of the soy isoflavones, genistein

and daidzein. Most of these addressed proliferative (and potentially

carcinogenic) effects on estrogen-sensitive tissues, effects on

circulating hormone levels and potential deleterious effects on

fertility, and potentially adverse effects on sexual development.

a. Proliferative effects. (Comment 13). Several comments cited a

number of studies of in vitro effects of individual isoflavones on

proliferation of estrogen-sensitive cells. For example, Dees et al.

(Ref. 96) found that genistein increased a number of indices for

proliferative activity in MCF-7 human breast cancer cells. As the

authors noted, these findings are consistent with the conclusion that

dietary estrogens at low concentrations do not act as antiestrogens,

but act like estradiol to stimulate human breast cancer cells to enter

the cell cycle. However, many other studies (reviewed in Refs. 97 and

98) have found that the phytoestrogens present in soybeans inhibit

breast cancer cell proliferation in vitro (at lower concentrations,

closer to physiological levels) and inhibit mammary cancer development

in various animal models. FDA concludes that studies in transformed

cells cannot predict with certainty whether effects will be beneficial

or detrimental in humans consuming soy protein.

(Comment 14). Comments argued that two reports showed effects of

dietary intake of soy isoflavones on breast tissue in women. Petrakis

et al. (Ref. 99) studied 24 normal pre- and postmenopausal white women,

ages 30

[[Page 57705]]

to 58 years, who underwent monthly nipple aspiration of breast fluid

and gave blood and 24-hour urine samples for biochemical studies. The

women consumed no soy in months 1-3 and 10-12. During months 4-9 the

women ingested daily 38 grams (g) of soy protein isolate containing 38

mg of genistein (daidzein content was not reported). This study's

findings indicated that prolonged consumption of soy protein isolate

had a stimulatory effect on the breast of premenopausal women,

characterized by increased secretion of breast fluid and elevated

levels of plasma estradiol. The study also detected evidence of

epithelial proliferation (hyperplasia) in 7 of the 24 subjects during

consumption of soy. McMichael-Phillips et al. (Ref. 100) examined the

effects of dietary soy supplementation on the proliferation rate of

premenopausal, histologically normal breast epithelium and the

expression of progesterone receptor. Women (n = 48) with benign or

malignant breast disease were randomly assigned to receive their normal

diet either alone or with a 60-g soy supplement (containing 45 mg

isoflavones) taken daily for 14 days. Serum concentrations of the

isoflavones genistein and daidzein increased in the soy group at 14

days. The proliferation rate of breast lobular epithelium significantly

increased after soy supplementation when both the day of menstrual

cycle and the age of patient were accounted for. Progesterone receptor

expression increased significantly in the soy group. The authors

concluded that further studies are required to determine whether the

short-term stimulation of breast proliferation is due to estrogen

agonist activity and to examine the long-term effects of soy on both

the pituitary gland and breast.

FDA finds that the detection of proliferative effects in these two

studies suggests the need for additional research. The findings do not,

however, establish that the observed effects are detrimental and are

not supported by the findings of epidemiologic studies of soy intake

and risk of premenopausal breast cancer (Ref. 101).

b. Fertility and Hormone Levels. (Comment 15). Some comments

referenced a number of studies that reported reduced fertility in

animals exposed to phytoestrogens (including Refs. 102, 103, and 104).

Some of these studies involved phytoestrogens other than those found in

soy or consumption of soy under extreme or unusual conditions. FDA is

not convinced of the relevance of these studies to human consumption of

soy protein.

(Comment 16). Comments cited the study of Cassidy et al. 1994 (Ref.

105) as suggesting the potential for deleterious effects on human

fertility. These investigators examined the influence of a diet

containing soy protein on the hormonal status and regulation of the

menstrual cycle in six premenopausal women. Soy protein (60 g

containing 45 mg isoflavones) given daily for 1 month significantly

(p1

----------------------------------------------------------------------------------------------------------------

Annual Total

21 CFR No. of frequency per annual Hours per Total Hours

respondents response responses response

----------------------------------------------------------------------------------------------------------------

101.82(c)(2)(ii)(B)................. 25 1 25 1 25

----------------------------------------------------------------------------------------------------------------

\1\ There are no capital costs or operating and maintenance costs associated with this collection.

Table 3.--Estimated Annual Reporting Burden \1\

----------------------------------------------------------------------------------------------------------------

No. of Total

21 CFR Section No. of responses per annual Hours per Total hours

respondents respondent responses response

----------------------------------------------------------------------------------------------------------------

101.82(c)(2)(ii)(B)................. 5 1 5 1 5

----------------------------------------------------------------------------------------------------------------

\1\ There are no capital costs or operating and maintenance costs associated with this collection.

Manufacturers must determine that their products are qualified to

bear any claim used on foods labels or in labeling, including meeting

the requirement for a qualifying amount of soy protein to bear the

health claim authorized for use by this regulation. In the absence of a

validated analytical methodology for soy protein in foods that contain

other proteins, manufacturers will need to use records, e.g., the

food's formulation or recipe, to determine if such a food contains 6.25

g per RACC. In this rule, FDA is requiring that firms maintain the

records they use to determine that a food is qualified to bear the

claim, and that those records be submitted to FDA upon written request.

Based upon its experience with the use of health claims, FDA estimated

that 25 firms would market products bearing a soy protein and CHD

health claim and that one of each firm's products would contain a

source or sources of protein in addition to soy. FDA received no

comments that challenged this estimate. FDA estimates that, annually,

it would request records to assess compliance from 20 percent of firms

subject to the

[[Page 57728]]

recordkeeping requirement. The records that would be required to be

retained by Sec. 101.82(c)(ii)(B)(2) are records that, as described

above, FDA believes a prudent and responsible manufacturer uses and

retains as a normal part of doing business. Thus, the burden to the

food manufacturer would be that involved in assembling and providing

the records to appropriate regulatory officials upon written request.

The requirements contained in this rule would require only a minimal

burden, no more than one hour per response, from respondents.

The information collection provisions of this final rule have been

submitted to OMB for review. FDA will publish a notice in the Federal

Register announcing OMB's decision to approve, modify, or disapprove

the information collection provisions in this final rule. An agency may

not conduct or sponsor, and a person is not required to respond to, a

collection of information unless it displays a currently valid OMB

control number.

VI. 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. Protein Technologies International, Inc., ``Health Claim

Petition,'' May 4, 1998 [CP1, vol. 1-3].

2. Protein Technologies International, Inc., ``Addendum to

Health Claim Petition,'' August 10, 1998 [CP1, vol. 4].

3. American Soybean Association, ``Health Claim Petition for Soy

Protein,'' October 29, 1998 [C1, vol. 8-12].

4. DHHS, Public Health Service (PHS), ``The Surgeon General's

Report on Nutrition and Health,'' U.S. Government Printing Office,

Washington, DC, pp. 83-137, 1988.

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1989.

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20. Portale, A. A., B. P. Halloran, M. M. Murphy, and R. C.

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24. Cline, J. M., J. C. Paschold, M. S. Anthony, I. O. Obasanjo,

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26. Cassidy, A., S. Bingham, and K. D. R. Setchell, ``Biological

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27. Bakhit, R. M., B. P. Klein, D. Essex-Sorlie, J. O. Ham, J.

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124:213-222, 1994.

28. Baum, J. A., H. Teng, J. W. Erdman, Jr., R. M. Weigel, B. P.

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68:545-551, 1998.

29. Bosello, O., L. Cominacini, I. Zocca, U. Garbin, R. Compri,

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Hypocaloric Diets Containing Proteins of Different Sources on Plasma

Lipids and Apoproteins of Obese Subjects,'' Annals of Nutrition

Metabolism, 32:206-214, 1988.

30. Carroll, K. K., P. M. Giovannetti, M. W. Huff, O. Moase, D.

C. K. Roberts, and B. M. Wolfe, ``Hypocholesterolemic Effect of

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31:1312-1321, 1978.

31. Crouse, J. R., III, T. Morgan, J. G. Terry, J. Ellis, M.

Vitolins, and G. L. Burke, ``A Randomized Trial Comparing the Effect

of Casein with That of Soy Protein Containing Varying Amounts of

Isoflavones on Plasma Concentrations of Lipids and Lipoproteins,''

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32. Cruz, M. L. A., W. W. Wong, F. Mimouni, D. L. Hachey, K. D.

R. Setchell, P. D. Klein, and R. C. Tsang, ``Effects of Infant

Nutrition on Cholesterol Synthesis Rates,'' Pediatric Research,

35:135-140, 1994.

33. Descovich, G. C., C. Ceredi, A. Gaddi, M. S. Benassi, G.

Mannino, L. Colombo, L. Cattin, G. Fontana, U. Senin, E. Mannarino,

C. Caruzzo, E. Bertelli, C. Fragiacomo, G. Noseda, M. Sirtori, and

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34. A. Gaddi, G. C. Descovich, G. Noseda, C. Fragiacomo, A.

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35. Gaddi, A., A. Ciarrocchi, A. Matteucci, S. Rimondi, G.

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[[Page 57729]]

36. Giovannetti, P. M., K. K. Carroll, and B. M. Wolfe,

``Constancy of Fasting Serum Cholesterol of Healthy Young Women Upon

Substitution of Soy Protein Isolate for Meat and Dairy Protein in

Medium and Low Fat Diets,'' Nutrition Research, 6:609-618, 1986.

37. Goldberg, A. P., A. Lim, J. B. Kolar, J. J. Grundhauser, F.

H. Steinke, and G. Schonfeld, ``Soybean Protein Independently Lowers

Plasma Cholesterol Levels in Primary Hypercholesterolemia,''

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38. Gooderham, M. J., H. Adlercreutz, S. T. Ojala, K. Wahala,

and B. J. Holub, ``A Soy Protein Isolate Rich in Genistein and

Daidzein and its Effects on Plasma Isoflavone Concentrations,

Platelet Aggregation, Blood Lipids and Fatty Acid Composition of

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2006, 1996.

39. Grundy, S. M. and J. J. Abrams, ``Comparison of Actions of

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Cholesterol in Humans,'' American Journal of Clinical Nutrition,

38:245-252, 1983.

40. Holmes, W. L., G. B. Rubel, and S. S. Hood, ``Comparison of

the Effect of Dietary Meat Versus Dietary Soybean Protein on Plasma

Lipids of Hyperlipidemic Individuals,'' Atherosclerosis, 36:379-387,

1980.

41. Huff, M. W., P. M. Giovannetti, and B. M. Wolfe, ``Turnover

of Very Low-density Lipoprotein-Apoprotein B is Increased by

Substitution of Soybean Protein for Meat and Dairy Protein in the

Diets of Hypercholsterolemic Men,'' American Journal of Clinical

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42. Jacques, H., D. Laurin, S. Moorjani, F. H. Steinke, C.

Gagne, D. Brun, and P. J. Lupien, ``Influence of Diets Containing

Cow's Milk or Soy Protein Beverage on Plasma Lipids in Children with

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43. Jenkins, D. J. A., T. M. S. Wolever, G. Spiller, G. Buckley,

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44. Kurowska, E. M., J. Jordan, J. D. Spence, S. Wetmore, L. A.

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45. Laurin, D., H. Jacques, S. Moorjani, F. H. Steinke, C.

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54:98-103, 1991.

46. Lovati, M. R., C. Manzoni, A. Canavesi, M. Sirtori, V.

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47. Meinertz, H., O. Faergeman, K. Nilausen, M. J. Chapman, S.

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48. Meinertz, H., K. Nilausen, and O. Faergeman, ``Soy Protein

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49. Mercer, N. J. H., K. K. Carroll, P. M. Giovannetti, F. H.

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Office, ``Evaluation of the Health Aspects of Soy Protein Isolates

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77. Hymowitz, T. and J.R. Harlan, ``Introduction of the Soybean

to North America by Samuel Bowen in 1765, Georgia, Gazette,

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78. Sheehan, D.M., ``Herbal Medicines, Phytoestrogens, and

Toxicity: Risk:Benefit Considerations,'' Proceedings of the Society

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79. Liener, I.E., ``Trypsin Inhibitors: Concern for Human

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80. Liener, I.E., R.L. Goodale, A. Deshmukh, T.L. Satterberg, G.

Ward, C.M. DiPietro, P.E. Bankey, and J.W. Borner, ``Effect of a

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List of Subjects in 21 CFR Part 101

Food labeling, Nutrition, Reporting and recordkeeping requirements.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under

authority delegated to the Commissioner of Food and Drugs, 21 CFR part

101 is amended as follows:

PART 101--FOOD LABELING

The authority citation for 21 CFR part 101 continues to read as

follows:

1. Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331,

342, 343, 348, 371.

2. Add Sec. 101.82 to subpart E to read as follows:

Sec. 101.82 Health claims: Soy protein and risk of coronary heart

disease (CHD).

(a) Relationship between diets that are low in saturated fat and

cholesterol and that include soy protein and the risk of CHD. (1)

Cardiovascular disease means diseases of the heart and circulatory

system. CHD is one of the most common and serious forms of

cardiovascular disease and refers to diseases of the heart muscle and

supporting blood vessels. High blood total cholesterol and low density

lipoprotein (LDL)-cholesterol levels are associated with increased risk

of developing CHD. High CHD rates occur among people with high total

cholesterol levels of 240 milligrams per deciliter (mg/dL) (6.21

millimole per liter (mmol/L)) or above and LDL-cholesterol levels of

160 mg/dL (4.13 mmol/L) or above. Borderline high risk total

cholesterol levels range from 200 to 239 mg/dL (5.17 to 6.18 mmol/L)

and 130 to 159 mg/dL (3.36 to 4.11 mmol/L) of LDL-cholesterol. The

scientific evidence establishes that diets high in saturated fat and

cholesterol are associated with increased levels of blood total and

LDL-cholesterol and, thus, with increased risk of CHD.

(2) Populations with a low incidence of CHD tend to have relatively

low blood total cholesterol and LDL-cholesterol levels. These

populations also tend to have dietary patterns that are not only low in

total fat, especially saturated fat and cholesterol, but are also

relatively high in plant foods that contain dietary fiber and other

components.

(3) Scientific evidence demonstrates that diets low in saturated

fat and cholesterol may reduce the risk of CHD. Other evidence

demonstrates that the addition of soy protein to a diet that is low in

saturated fat and cholesterol may also help to reduce the risk of CHD.

(b) Significance of the relationship between diets that are low in

saturated fat and cholesterol and that include soy protein and the risk

of CHD. (1) CHD is a major public health concern in the United States.

It accounts for more deaths than any other disease or group of

diseases. Early management of risk factors for CHD is a major public

health goal that can assist in reducing risk of CHD. High blood total

and LDL-cholesterol are major modifiable risk factors in the

development of CHD.

(2) Intakes of saturated fat exceed recommended levels in the diets

of many people in the United States. One of the major public health

recommendations relative to CHD risk is to consume less than 10 percent

of calories from saturated fat and an average of 30 percent or less of

total calories from all fat. Recommended daily cholesterol intakes are

300 mg or less per day. Scientific evidence demonstrates that diets low

in saturated fat and cholesterol are associated with lower blood total

and LDL-cholesterol levels. Soy protein, when included in a low

saturated fat and cholesterol diet, also helps to lower blood total and

LDL-cholesterol levels.

(c) Requirements. (1) All requirements set forth in Sec. 101.14

shall be met.

(2) Specific requirements--(i) Nature of the claim. A health claim

associating diets that are low in saturated fat and cholesterol and

that include soy protein with reduced risk of heart disease may be made

on the label or labeling of a food described in paragraph (c)(2)(iii)

of this section, provided that:

(A) The claim states that diets that are low in saturated fat and

cholesterol and that include soy protein ``may'' or ``might'' reduce

the risk of heart disease;

(B) In specifying the disease, the claim uses the following terms:

``heart disease'' or ``coronary heart disease'';

(C) In specifying the substance, the claim uses the term ``soy

protein'';

(D) In specifying the fat component, the claim uses the terms

``saturated fat'' and ``cholesterol'';

(E) The claim does not attribute any degree of risk reduction for

CHD to diets that are low in saturated fat and cholesterol and that

include soy protein;

(F) The claim does not imply that consumption of diets that are low

in saturated fat and cholesterol and that include soy protein is the

only recognized means of achieving a reduced risk of CHD; and

(G) The claim specifies the daily dietary intake of soy protein

that is necessary to reduce the risk of coronary heart disease and the

contribution one serving of the product makes to the specified daily

dietary intake level. The daily dietary intake level of soy protein

that has been associated with reduced risk of coronary heart disease is

25 grams (g) or more per day of soy protein.

(ii) Nature of the substance. (A) Soy protein from the legume seed

Glycine max.

(B) FDA will assess qualifying levels of soy protein in the

following fashion: FDA will measure total protein content by the

appropriate method of analysis given in the ``Official Methods of

Analysis of the AOAC International,'' as

[[Page 57733]]

described at Sec. 101.9(c)(7). For products that contain no sources of

protein other than soy, FDA will consider the amount of soy protein as

equivalent to the total protein content. For products that contain a

source or sources of protein in addition to soy, FDA will, using the

measurement of total protein content, calculate the soy protein content

based on the ratio of soy protein ingredients to total protein

ingredients in the product. FDA will base its calculation on

information identified and supplied by manufacturers, such as nutrient

data bases or analyses, recipes or formulations, purchase orders for

ingredients, or any other information that reasonably substantiates the

ratio of soy protein to total protein. Manufacturers must maintain

records sufficient to substantiate the claim for as long as the

products are marketed and provide these records, on written request, to

appropriate regulatory officials.

(iii) Nature of the food eligible to bear the claim. (A) The food

product shall contain at least 6.25 g of soy protein per reference

amount customarily consumed of the food product;

(B) The food shall meet the nutrient content requirements in

Sec. 101.62 for a ``low saturated fat'' and ``low cholesterol'' food;

and

(C) The food shall meet the nutrient content requirement in

Sec. 101.62 for a ``low fat'' food, unless it consists of or is derived

from whole soybeans and contains no fat in addition to the fat

inherently present in the whole soybeans it contains or from which it

is derived.

(d) Optional information. (1) The claim may state that the

development of heart disease depends on many factors and may identify

one or more of the following risk factors for heart disease about which

there is general scientific agreement: A family history of CHD;

elevated blood total and LDL-cholesterol; excess body weight; high

blood pressure; cigarette smoking; diabetes; and physical inactivity.

The claim may also provide additional information about the benefits of

exercise and management of body weight to help lower the risk of heart

disease;

(2) The claim may state that the relationship between intake of

diets that are low in saturated fat and cholesterol and that include

soy protein and reduced risk of heart disease is through the

intermediate link of ``blood cholesterol'' or ``blood total and LDL-

cholesterol'';

(3) The claim may include information from paragraphs (a) and (b)

of this section, which summarize the relationship between diets that

are low in saturated fat and cholesterol and that include soy protein

and CHD and the significance of the relationship;

(4) The claim may state that a diet low in saturated fat and

cholesterol that includes soy protein is consistent with ``Nutrition

and Your Health: Dietary Guidelines for Americans,'' U.S. Department of

Agriculture (USDA) and Department of Health and Human Services (DHHS),

Government Printing Office (GPO);

(5) The claim may state that individuals with elevated blood total

and LDL-cholesterol should consult their physicians for medical advice

and treatment. If the claim defines high or normal blood total and LDL-

cholesterol levels, then the claim shall state that individuals with

high blood cholesterol should consult their physicians for medical

advice and treatment;

(6) The claim may include information on the number of people in

the United States who have heart disease. The sources of this

information shall be identified, and it shall be current information

from the National Center for Health Statistics, the National Institutes

of Health, or ``Nutrition and Your Health: Dietary Guidelines for

Americans,'' USDA and DHHS, GPO;

(e) Model health claim. The following model health claims may be

used in food labeling to describe the relationship between diets that

are low in saturated fat and cholesterol and that include soy protein

and reduced risk of heart disease:

(1) 25 grams of soy protein a day, as part of a diet low in

saturated fat and cholesterol, may reduce the risk of heart disease. A

serving of [name of food] supplies ____ grams of soy protein.

(2) Diets low in saturated fat and cholesterol that include 25

grams of soy protein a day may reduce the risk of heart disease. One

serving of [name of food] provides ____ grams of soy protein.

Dated: October 19, 1999.

Margaret M. Dotzel,

Acting Associate Commissioner for Policy.

[FR Doc. 99-27693 Filed 10-20-99; 10:35 a.m.]

BILLING CODE 4160-01-P