[Federal Register Volume 72, Number 3 (Friday, January 5, 2007)]
[Proposed Rules]
[Pages 497-519]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-22573]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 101
[Docket No. 2004P-0464]
Food Labeling: Health Claims; Calcium and Osteoporosis, and
Calcium, Vitamin D, and Osteoporosis
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
the regulation authorizing a health claim on the relationship between
calcium and a reduced risk of osteoporosis to: Include vitamin D so
that, in addition to claims for calcium and osteoporosis, additional
claims can be made for calcium and vitamin D and osteoporosis;
eliminate the requirement in Sec. 101.72(c)(2)(i)(A) (21 CFR
101.72(c)(2)(i)(A)) that the claim list sex, race, and age as specific
risk factors for the development of osteoporosis; eliminate the
requirement in Sec. 101.72(c)(2)(i)(B) that the claim does not state
or imply that the risk of osteoporosis is equally applicable to the
general U.S. population, and that the claim identify the populations at
particular risk for the development of osteoporosis; eliminate the
requirement in Sec. 101.72(c)(2)(i)(C) that the claim identify the
mechanism by which calcium reduces the risk of osteoporosis and instead
make it optional; and eliminate the requirement in Sec.
101.72(c)(2)(i)(E) that the claim include a statement that reflects the
limit of the benefits derived from dietary calcium intake, when the
level of calcium in the food exceeds a set threshold level. FDA is
taking these actions, in part, in response to a health claim petition
submitted by The Beverage Institute for Health and Wellness, LLC.
Elsewhere in this issue of the Federal Register, FDA is withdrawing
certain proposed amendments to a proposed rule that published in the
Federal Register of December 21, 1995 (60 FR 66206) related to the
calcium and osteoporosis health claim.
DATES: Submit written or electronic comments by March 21, 2007.
ADDRESSES: You may submit comments, identified by Docket No. 2004P-
0464, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following ways:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
Submit written submissions in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
To ensure more timely processing of comments, FDA is no longer
accepting comments submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic comments by using the Federal
eRulemaking Portal or the agency Web site, as described in the
Electronic Submissions portion of this paragraph.
Instructions: All submissions received must include the agency name
and Docket No(s). and Regulatory Information Number (RIN) (if a RIN
number has been assigned) for this rulemaking. All comments received
may be posted without change to http://www.fda.gov/ohrms/dockets/default.htm, including any personal information provided. For
additional information on submitting comments, see the ``Comments''
heading of the SUPPLEMENTARY INFORMATION section of this document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm
and insert the docket number(s), found in brackets in the heading of
this document, into the ``Search'' box and follow the prompts and/or go
to the Division of Dockets Management, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Jillonne Kevala, Center for Food
Safety and Applied Nutrition (HFS-830), Food and Drug Administration,
5100 Paint Branch Pkwy., College Park, MD 20740-3835, 301-436-1450.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Background
II. Petition and Grounds for Amending the Health Claim on Calcium and
Osteoporosis
A. The Petition
B. Nature of the Substance
III. Review of Scientific Evidence of the Substance-Disease
Relationship
A. Basis for Evaluating the Relationship between Calcium and
Vitamin D and Osteoporosis
B. Review of the Scientific Evidence of the Substance-Disease
Relationship
IV. Decision to Amend the Calcium and Osteoporosis Health Claim
A. Addition of Vitamin D
B. Amendments to the Calcium and Osteoporosis Health Claim Other
than the Inclusion of Vitamin D
C. Elimination of the Requirement to List Race, Age and Sex as Risk
Factors for the Development of Osteoporosis
D. Elimination of the Requirement that the Claim Not State or Imply
that the Risk of Osteoporosis is Equally Applicable to the General
Population, and that the Claim Identify the Populations at Particular
Risk for the Development of Osteoporosis
E. Elimination of the Requirement that the Claim Identify the
Mechanism by Which Calcium Reduces the Risk of Osteoporosis
F. Elimination of the Requirement in Sec. 101.72(c)(2)(i)(E) that
Certain Products Bearing the Claim Include a Statement that Reflects
the Limits on the Benefits from Calcium
V. Description of Modifications to Sec. 101.72
A. Title of the Regulation
B. General Requirements
VI. Analysis of Economic Impacts
A. Preliminary Regulatory Impact Analysis
B. Small Entity Analysis (or Initial Regulatory Flexibility
Analysis)
VII. Environmental Impact
VIII. Paperwork Reduction Act
IX. Federalism
X. Comments
XI. References
I. Background
The Nutrition Labeling and Education Act of 1990 (NLEA) (Public Law
101-535) amended the Federal Food, Drug, and Cosmetic Act (the act) in
a number of important ways. The NLEA clarified FDA's authority to
regulate health claims on food labels and in food labeling by amending
the act to add section 403(r) to the act (21 U.S.C. 343(r)). Section
403(r) specifies, in part,
[[Page 498]]
that a food is misbranded if it bears a claim that expressly or by
implication characterizes the relationship of a nutrient to a disease
or health-related condition unless the claim is made in accordance with
section 403(r)(3) (for conventional foods) or 403(r)(5)(D) (for dietary
supplements).
The NLEA directed FDA to issue regulations authorizing health
claims (i.e., labeling claims that characterize the relationship of a
substance to a disease or health-related condition) for conventional
foods only if the agency determines, based upon the totality of
publicly available scientific evidence (including evidence from well-
designed studies conducted in a manner which is consistent with
generally recognized scientific procedures and principles), that there
is significant scientific agreement (SSA), among experts qualified by
scientific training and experience to evaluate such claims, that the
claim is supported by such evidence (21 U.S.C. 343(r)(3)(B)(i)).
Congress delegated to FDA the authority to establish the procedure and
standard for health claims for dietary supplements (21 U.S.C.
343(r)(5)(D)).
FDA issued regulations establishing general requirements for health
claims in labeling for conventional foods (58 FR 2478; January 6,
1993). By regulation (59 FR 395; January 4, 1994), and under
Congressional authority,\1\ FDA adopted the same general requirements,
including the procedure and standard, for health claims in dietary
supplement labeling that Congress had prescribed in the NLEA for health
claims in the labeling of conventional foods. (See 21 U.S.C. 343(r)(3)
and (r)(4)).
---------------------------------------------------------------------------
\1\FDA issued regulations establishing general requirements for
health claims in dietary supplement labeling (59 FR 395) under the
NLEA and the Dietary Supplement Act of 1992 (Public Law 102-571).
---------------------------------------------------------------------------
The regulations require the evidence supporting a health claim to
be presented to FDA for review before the claim may appear in labeling
(Sec. Sec. 101.14(d) and (e) and 101.70 (21 CFR 101.14(d) and (e) and
21 CFR 101.70)). The standard requires a finding of ``significant
scientific agreement'' (SSA) before FDA may authorize a health claim by
regulation (Sec. 101.14(c)).
Among its provisions regulating claims, the NLEA required FDA to
determine whether claims respecting 10 specific substance/disease
relationships met the requirements for a health claim (NLEA section
3(b)(1)(A)(vi) and (x), Public Law 101-535). The relationship between
calcium and a reduced risk of osteoporosis was one of those 10
nutrient/disease relationships. On March 28, 1991, FDA published a
notice in the Federal Register requesting scientific data and
information on the 10 specific topic areas identified (56 FR 12932).
Scientific studies and data received in response to the notice, that
were relevant to the agency's review, were considered as part of the
agency's review of the scientific literature on calcium and
osteoporosis and were included in the proposed rule for the calcium and
osteoporosis health claim for use on foods, including dietary
supplements (56 FR 60689; November 27, 1991) (the 1991 proposed rule).
Before publication of the calcium and osteoporosis final rule (58 FR
2665; January 6, 1993), the agency reviewed any scientific research and
review articles relevant to calcium intake and osteoporosis that became
available after publication of the proposed rule and concluded that the
new studies were consistent with the tentative conclusions drawn in the
1991 proposed rule (58 FR 2665 at 2672). Thus, in the calcium and
osteoporosis final rule FDA concluded that, based on the totality of
the publicly available scientific evidence, there was significant
scientific agreement among qualified experts that a health claim for
calcium and a reduced risk of osteoporosis was supported by the
evidence (id.) (Codified in Sec. 101.72 (21 CFR 101.72)).
In December of 1995, in response to citizen petitions submitted by
the National Food Processors Association (Docket No. 1994P-0390) and
the American Bakers Association (Docket No. 1995P-0241), FDA proposed
to amend its regulations on health claims and nutrient content claims
to provide more flexibility in the use of these claims on food products
(60 FR 66206; December 21, 1995) (the 1995 proposal). This document
discussed many proposed amendments to FDA regulations intended to
benefit public health by encouraging manufacturers to use health claims
and nutrient content claims to assist consumers in maintaining healthy
dietary practices. In the 1995 proposal, FDA proposed, among other
things, certain amendments to simplify the current required claim
language for the calcium and osteoporosis health claim in Sec. 101.72.
In response to requests by stakeholders and other FDA initiatives
and developments, the agency reopened the comment period for the 1995
proposal several times. The most recent reopening of the comment period
was announced in the Federal Register on May 4, 2004 (69 FR 24541), and
the comment period was open until July 6, 2004. Because many of the
amendments in the 1995 proposal are similar to or exactly the same as
those requested by The Beverage Institute for Health and Wellness in
their health claim petition, and that FDA is proposing herein, the
agency considered the comments submitted in response to the 1995
proposal in the development of this proposed rule. Comments on other
aspects of the 1995 proposal are not considered in this proposed rule.
Elsewhere in this issue of the Federal Register, the agency is
withdrawing the part of the 1995 proposed rule related to the calcium
and osteoporosis claim language.
II. Petition and Grounds for Amending the Health Claim on Calcium and
Osteoporosis
A. The Petition
On July 12, 2004, the agency received a health claim petition
submitted by The Beverage Institute for Health and Wellness (the
petitioner) under section 403(r)(4) of the act.\2\ The petitioner noted
that the agency already has an authorized health claim (Sec. 101.72)
on the ability of calcium to reduce the risk of osteoporosis among teen
and young adult white and Asian women who engage in regular physical
activity, and stated that they believed that there was now significant
scientific agreement to support authorization of an expanded
osteoporosis health claim that includes vitamin D and eliminates the
restrictive language regarding age, race, gender, and physical
activity. The petitioner also noted that FDA had already proposed most
of the petitioner's proposed amendments in the 1995 proposal (60 FR
66206).
---------------------------------------------------------------------------
\2\Although the petitioner cited only section 403(r)(4) of the
act, which applies to the use of the claim on conventional foods,
the agency is including within its review the use of the claim in
dietary supplement labeling under section 403(r)(5)(D) of the act.
This is consistent with the calcium and osteoporosis health claim in
Sec. 101.72, which applies to both conventional food and dietary
supplements.
---------------------------------------------------------------------------
Specifically, the petitioner's proposed amendments to Sec. 101.72
would: (1) Include vitamin D so that, in addition to claims for calcium
and osteoporosis, additional claims can be made for calcium and vitamin
D and osteoporosis; (2) eliminate the required claim language in Sec.
101.72(c)(2)(i)(A) regarding race, age, gender, and the need for
physical activity; (3) eliminate the requirement in Sec.
101.72(c)(2)(i)(B) that the claim identify the population at particular
risk for osteoporosis; (4) eliminate the requirement in Sec.
101.72(c)(2)(i)(C) that the claim identify the mechanism by which
calcium reduces the risk of osteoporosis and instead make this
information
[[Page 499]]
optional; (5) simplify the language used in the claim; and (6) increase
the amount of calcium present in the food (from 400 milligrams (mg) of
calcium per reference amount customarily consumed or per daily
recommended supplement intake to more than 1,500 mg calcium per day)
before the claim must include a statement that reflects the limit on
the benefit derived from dietary calcium intake. The petitioner
concluded that amending the osteoporosis and calcium health claim in
the above manner would provide the availability of a simplified,
understandable health claim that would allow food manufacturers to help
address the public health issue of osteoporosis by educating consumers
about the importance of both vitamin D and calcium in reducing the risk
of osteoporosis in later life (Ref. 1). Finally, the petitioner
requested that the agency exercise its authority under section
403(r)(7) of the act to make any proposed regulation based on their
petition effective upon publication, pending consideration of public
comment and publication of a final rule.
On October 20, 2004, we notified the petitioner that we had
completed our initial review of the petition and that the petition had
been filed for further action (Docket No. 2004P-0464, Let 1) in
accordance with section 403(r)(4) of the act. The October 20, 2004,
letter stated that if the agency did not act, by either denying the
petition or issuing a proposed regulation to authorize the health
claim, within 90 days of the date of filing, the petition would be
deemed to be denied unless an extension was mutually agreed upon by the
agency and the petitioner (section 403(r)(4)(A)(i) of the act and Sec.
101.70(j)(3)(iii)). FDA and the petitioner agreed to extend the
publication date of a regulation until January 18, 2007 (Docket No.
2004P-0464, Let 6).
B. Nature of the Substance
The petition requested, among other things, that FDA amend the
calcium and osteoporosis health claim (Sec. 101.72) to include vitamin
D so that, in addition to claims for calcium and osteoporosis, claims
can be made for calcium and vitamin D and osteoporosis. Thus, FDA
considered two substances that are the subject of the petition: (1)
Calcium and (2) calcium and vitamin D. Unless specified, the term
`vitamin' D means D2 (ergocalciferol), D3
(cholecalciferol) or a combination of vitamin D2 and
D3.
C. Review of the Preliminary Requirements
1. The Substance is Associated With a Disease for Which the U.S.
Population is at Risk
Osteoporosis, which is defined as a skeletal disorder characterized
by compromised bone strength, continues to be a major public health
problem in the United States, even after authorization of the calcium
and osteoporosis health claim in 1993. The continued public health
problem is reflected, in part, by the observation that the number of
bone fractures in the United States has increased as well as the direct
medical costs required to treat osteoporosis (Ref. 2). The petitioner
stated that in 2002 the National Osteoporosis Foundation estimated that
approximately 44 million men and women in the United States had low
bone density or osteoporosis and that this value was projected to
increase to more than 61 million by 2020 (Ref. 3). White and Asian
women are the most susceptible to chronic bone disease, but the
petitioner noted that the condition was also prevalent among African
Americans (Ref. 3). Five percent of the African American U.S.
population (more than 13 million people) are currently thought to have
osteoporosis compared to 20 percent for White and Asian women (Ref. 3).
The incidence of low bone mineral density in 2002 for African Americans
and White and Asian women was estimated to be 35 and 52 percent,
respectively (Ref. 3). The direct care expenditures resulting from
osteoporosis range from 12.2 to 17.9 billion dollars each year measured
in 2002 dollars (Ref. 4).
FDA agrees with the petitioner that, as required in Sec.
101.14(b)(1), osteoporosis is a disease for which the U.S. population
is at risk.
2. The Substances are Components of Food
A health claim characterizes the relationship between a substance
and a disease or a health-related condition (Sec. 101.14(a)(1)). A
substance means a specific food or a component of food, regardless of
whether the food is in conventional food form or a dietary supplement
(Sec. 101.14(a)(2)). The petition identified calcium and vitamin D as
a new substance for consideration in the calcium and osteoporosis
health claim. Calcium, one of the essential nutrients for humans, is a
component of milk and milk products (approximately 300 mg per serving),
as well as other food sources (e.g., Chinese cabbage, kale, and
broccoli) (Ref. 5). Vitamin D is naturally present in a small number of
foods, such as some fish liver oils, the flesh of fatty fish, the liver
and fat from aquatic mammals such as polar bears and seals, and eggs
from hens that have been fed vitamin D (Ref. 6). Therefore, the agency
concludes that calcium and vitamin D, are components of food and meet
the definition of a substance in the health claim regulation.
Health claim general requirements provide that where a substance is
to be consumed at ``other than decreased dietary levels'' the substance
must contribute taste, aroma, or nutritive value, or any other
technical effect listed in 21 CFR 170.3(o), and must retain that
attribute when consumed at levels necessary to justify the claim (Sec.
101.14(b)(3)(i)). Nutritive value as defined in Sec. 101.14(a)(3)
means a value in sustaining human existence by such processes as
promoting growth, replacing loss of essential nutrients, or providing
energy. Calcium and vitamin D are essential nutrients and thus provide
nutritive value to the diet (Refs. 5 and 6) and retain that attribute
when consumed at levels necessary to justify the claim. Therefore, FDA
concludes that the requirement of Sec. 101.14(b)(3)(i) is satisfied.
3. The Substances are Safe and Lawful
Under Sec. 101.14(b)(3)(ii), if the substance is to be consumed at
other than decreased dietary levels, the substance must be a food or a
food ingredient whose use at levels necessary to justify a claim has
been demonstrated by the proponent of the claim, to FDA's satisfaction,
to be safe and lawful under the applicable food safety provisions of
the act.
FDA evaluates whether the substance is ``safe and lawful'' under
the applicable food safety provisions of the act. For conventional
foods, this evaluation involves considering whether the ingredient that
is the source of the substance is generally recognized as safe (GRAS),
approved as a food additive, or authorized by a prior sanction issued
by FDA. (See Sec. 101.70(f).)
Dietary ingredients in dietary supplements are not subject to the
food additive provisions of the act (see section 201(s)(6) of the act
(21 U.S.C. 321(s)(6)). Rather, they are subject to the adulteration
provisions in section 402 of the act (21 U.S.C. 342) and, if
applicable, the new dietary ingredient provisions in section 413 of the
act (21 U.S.C. 350b), which pertain to dietary ingredients that were
not marketed in the United States before October 15, 1994. The term
``dietary supplement'' is defined in section 201(ff)(1) of the act and
includes vitamins; minerals; herbs
[[Page 500]]
and other botanicals; dietary substances for use by man to supplement
the diet by increasing total daily intake; and concentrates,
metabolites, constituents, extracts, and combinations of the preceding
types of ingredients.
For dietary supplements, the applicable safety provisions require,
among other things, that the dietary ingredient not present a
significant or unreasonable risk of illness or injury under conditions
of use recommended or suggested in labeling or, if no conditions of use
are suggested or recommended in the labeling, under ordinary conditions
of use (section 402(f)(1)(A) of the act). Further, a dietary supplement
must not contain a poisonous or deleterious substance which may render
the supplement injurious to health under the conditions of use
recommended or suggested in the labeling (section 402(f)(1)(D) of the
act).
The use of a health claim for calcium, or calcium and vitamin D,
and osteoporosis is being evaluated for use on the labels and in the
labeling of both conventional foods and dietary supplements. Thus, the
agency is evaluating the safety and lawfulness of both calcium and
vitamin D under the relevant provisions of the act for both
conventional foods and for dietary supplements.
a.Vitamin D
The petitioner asserts that vitamin D2 (ergocalciferol)
and vitamin D3 (cholecalciferol) have been affirmed as GRAS
when used as a source of this nutrient for breakfast cereals, grain
products and pastas, milk, and milk products according to Sec.
184.1950(c)(1) (21 CFR 184.1950(c)(1)). Vitamin D may also be added to
infant formula in accordance with section 412(a)(2) of the act (21
U.S.C. 350a(a)(2)), and as an optional ingredient in margarine
according to Sec. 166.110 (21 CFR 166.110). The petitioner also
asserts that FDA recently approved vitamin D3 as a food
additive that may be added in amounts up to 100 International Units
(IU) per serving to 100 percent fruit juices (excluding those
specifically formulated for infants) that are fortified with greater
than 33 percent of the Reference Daily Intake (RDI) of calcium per
reference amount customarily consumed (RACC) and to fruit drinks
(excluding those specifically formulated for infants) that are
fortified with greater than 10 percent of the RDI of calcium per RACC
(68 FR 9000; February 27, 2003). As part of that rulemaking, FDA
determined that persons 1 year of age or older would not be exposed to
amounts of vitamin D greater than the Tolerable Upper Intake Levels
(UL) after fortification of eligible juice products (68 FR 9000 at
9002). However, the agency did not allow vitamin D fortification of
juice products specifically formulated for infants (id.). Thus, FDA
concluded that the addition of vitamin D3 to calcium-
fortified fruit juices and juice drinks, excluding fruit juices and
juice drinks specifically formulated or processed for infants, at
levels not to exceed 100 IU per RACC is safe (68 FR 9000 at 9002).
FDA acknowledges that vitamin D2 and vitamin
D3 have been affirmed as GRAS when used in breakfast
cereals, grain products, pastas, milk and milk products at the intended
levels (Sec. 184.1950) and that vitamin D3 has been
approved as a food additive to calcium-fortified 100 percent fruit
juice and fruit drinks not intended for infants ((Sec. 172.380) (21
CFR 172.380)). FDA also acknowledges that vitamin D may be added to
infant formulas in accordance with section 412(a)(2) of the act and to
margarine as an optional ingredient (Sec. 166.110). Thus, the agency
is satisfied that the petitioner has demonstrated that vitamin D may be
lawfully used in conventional foods for the specific uses cited.
UL, as defined by the Institute of Medicine (IOM), are the highest
levels of daily nutrient intake that are likely to pose no risks of
adverse effects to almost all individuals in the general population
(Ref. 7). The IOM has established a UL for vitamin D by life stage,
gender, and age (Ref. 6). The IOM concluded that the most biologically
important possible adverse effect of excessive vitamin D is
hypercalcemia (i.e., an abnormally high concentration of calcium
compounds in the circulating blood) due to hypervitaminosis D.
Hypervitaminosis D is a condition resulting from the ingestion of an
excessive amount of the fat-soluble vitamin D. Using hypercalcemia as
the clinically defined endpoint, the IOM identified a no-observed-
adverse-effect level (NOAEL) at 2,400 IU per day for adults. The IOM
established 2,000 IU of vitamin D as the UL for individuals older than
18 years by dividing the NOAEL by an uncertainty factor of 1.2 to be
conservative to account for uncertainties in the data set. The UL for
individuals 1 through 18 years and pregnant and lactating women is
specified as 2,000 IU per day (Ref. 6).
The most recent nationally representative data, 1988-1994 National
Health and Nutrition Examination Survey (NHANES), found that the median
intake vitamin D intake from foods, excluding dietary supplements, to
be 164 IU/day for all individuals aged 2 months and older, excluding
nursing infants (Ref. 8). Vitamin D can be obtained from dietary
supplement sources as well as other food sources. Results from the
NHANES 1988-1994 survey indicate that approximately 40 percent of the
U.S. population, ages 2 months or older take dietary supplements and
that the most frequent amount of vitamin D taken as a dietary
supplement is 400 IU/day (Ref. 9).
Supplemental vitamin D can be obtained from multiple vitamin and
mineral products, products where calcium and vitamin D are the only
ingredients, or products where vitamin D is the sole ingredient (Ref.
9). Supplemental vitamin D can also be obtained from fish liver oils,
such as cod liver oil (Ref. 10). Multiple vitamin and mineral
supplement products generally contain 200 or 400 IU of vitamin D per
RACC and recommend consumption of 1 serving per day. The RACC for
dietary supplements is the maximum amount recommended as appropriate on
the label for consumption per eating occasion, or in the absence of
recommendations, one unit (i.e., one tablet, one capsule, one packet,
one teaspoon etc. (see Sec. 101.12(b) (21 CFR 101.12(b)) Table 2.--
Reference Amounts Customarily Consumed Per Eating Occasion: General
Food Supply \1, 2, 3, 4\ (Table 2)). Calcium and vitamin D only
products generally contain between 100 to 600 IU of vitamin D per RACC
(Ref. 11). Calcium and vitamin D only products with a RACC of less than
400 IU of vitamin D recommend consumption of one to three servings per
day and the recommended vitamin D intake does not exceed 600 IU per
day. Calcium and vitamin D only products with an RACC of 400 IU of
vitamin D or more recommend consumption of 1 serving per day and the
recommended vitamin D intake does not exceed 1,000 IU per day (id.).
Supplements that contain only vitamin D generally contain 400 to 1,000
IU per RACC, and recommend consumption of 1 serving per day (id). Cod
liver oil products contain between 100 to 540 IU of vitamin D per RACC
and the recommended vitamin D intake does not exceed 1,000 IU per day
in these products (id.). Thus, the range of vitamin D intake from the
various types of dietary supplement products generally varies from 100
to 1,000 IU/day. Only 7 percent of the products surveyed recommend
consumption of 1,000 IU of vitamin D per day (id).
FDA has also considered the intake of vitamin D from food and
dietary supplements among consumers of fruit juices and juice drinks,
as part of its rulemaking in response to a food additive petition for
vitamin D3 (68 FR 9000). Relying on data submitted by the
[[Page 501]]
petitioner for consumers of fruit juices and juice drinks 2 years of
age and older, it was estimated that the average and 90th percentile
dietary intakes from currently regulated uses in conventional foods
(including naturally occurring sources) and proposed food uses of
vitamin D, were 306 IU per person per day (IU/p/d) and 519 IU/p/d,
respectively (68 FR 9000 at 9001). Taking into account that the most
frequent level of vitamin D taken as a dietary supplement is 400 IU/
day, FDA estimated the mean and 90th percentile dietary intakes for
consumers of fruit juices and juice drinks 2 years of age and older
from current and proposed food uses and dietary supplement uses were
706 IU/p/d and 919 IU/p/d, respectively (id.). Thus, the mean and 90th
percentile vitamin D intake for this population of consumers is also
well below the UL of 2,000 IU/day.
The petitioner is proposing that for a food to be eligible for the
additional calcium and vitamin D and osteoporosis health claim that the
food meet or exceed the requirements for a ``high'' level of calcium
and a ``high'' level for vitamin D, as ``high'' is defined in Sec.
101.54 (21 CFR 101.54), as the levels necessary to justify the health
claim. For a food to be labelled as ``high'' in vitamin D, it must
contain 20 percent or more of the RDI per RACC for the specified
nutrient. The RDI for vitamin D is 400 IU. Twenty percent of the RDI
for vitamin D per day is 80 IU.
FDA notes that certain prepared foods are subject to food additive
regulations that limit the amount of vitamin D that can be added to
such foods. As noted previously, Sec. 184.1950 allows the addition of
vitamin D to breakfast cereals (350 IU/100 g), grain products and
pastas (90 IU/100 g), milk (42 IU/100g) and milk products (89 IU/100
g). In addition, Sec. 166.110 permits fortification of margarine (330
IU/100 g) and the newly issued Sec. 172.380 permits the addition of
vitamin D3 to calcium-fortified 100 percent fruit juice and
fruit drinks not intended for infants (100 IU/serving). Of these foods,
those that are ``high'' in calcium (i.e., milk, certain milk products,
fortified breakfast cereals and juices) are permitted to add enough
vitamin D to be ``high'' in vitamin D to qualify for the additional
claim. Foods that are not ``high'' in calcium (e.g., margarine,
enriched grain products and pastas) would not be permitted to bear the
calcium only claim. Likewise, these foods would not be permitted to
bear the calcium and vitamin D and osteoporosis claim because both
calcium and vitamin D must each be present at ``high'' levels to be
eligible to bear the claim.
The amounts of vitamin D that are allowed in flavored milk and milk
drinks (89 IU/100 g) and certain fruit juices and drinks (100 IU/
serving) are similar to the amount that is needed to be eligible for
the calcium and vitamin D and osteoporosis health claim (at least 80 IU
per RACC). The amounts of vitamin D in certain fortified cereals (350
IU/ 100 g) would provide a higher amount of vitamin D. For example, a
serving of a ready-to-eat biscuit-type breakfast cereal with a RACC of
55 g (see Table 2 in Sec. 101.12(b)) with the maximum amount of
vitamin D added would contain 192 IU of vitamin D/RACC.
The agency usually assumes that food consumption patterns generally
reflect 3 meals a day and a snack, with about 25 percent daily intake
for each (58 FR 2303 at 2379; January 6, 1993). Using this approach,
considering 4 servings a day from either the lowest (42 IU) or the
highest (350 IU) vitamin D containing categories that could be eligible
for a vitamin D and calcium and osteoporosis health claim, one could
consume from approximately 170 to 1,400 IU of vitamin D. Thus,
consumers who choose foods that bear the calcium and vitamin D and
osteoporosis health claim would be able to incorporate such foods into
the diet in a manner that would likely keep their total intake of
vitamin D well below the UL of 2,000 IU per day. For example, a serving
of a biscuit-type cereal with the maximum amount of vitamin D added
(192 IU) prepared with 1/2 cup of skim milk, which also has the maximum
amount of vitamin D added (51 IU), for breakfast would provide 243 IU
of vitamin D. A glass of orange juice with the maximum amount of
vitamin D added for lunch and as an afternoon snack would provide 200
IU of vitamin D. At dinner a serving of low-fat yogurt, to which
vitamin D has been added as an optional ingredient, would provide 92 IU
of vitamin D. The total vitamin D intake from these foods would provide
535 IU of vitamin D in a day. Furthermore, FDA believes it reasonable
to consider that consumers who supplement their diets with vitamin D
would likely be consuming the most frequent level of vitamin D
containing supplements (400 IU) per day. Thus, consumers who choose
foods that bear the calcium and vitamin D and osteoporosis health claim
and that consume a vitamin D supplement would likely keep their total
intake of vitamin D below the UL of 2,000 IU/day. The agency believes
it is unlikely that consumers would be consuming total amounts of
vitamin D, from both conventional foods and dietary supplements that
can bear the claim, at levels that would pose a safety concern.
Therefore, FDA tentatively concludes, that the use of vitamin D in
conventional foods, at levels necessary to justify the claim, as
described in section IV.A.2 of this document, and in accordance with
the GRAS affirmation (Sec. 184.1950) or the food additive regulation
(Sec. 172.380), is safe and lawful under the applicable food safety
provisions of the act. Further, FDA tentatively concludes that use of
vitamin D as a dietary ingredient or dietary supplement, at levels
necessary to justify the claim, as described in section IV.A.2 of this
document is safe and lawful under the applicable food safety provisions
of the act. Thus, FDA tentatively concludes that the preliminary
requirements in 21 CFR 101.14(b)(3)(ii) are satisfied.
b. Calcium
The petitioner stated the preliminary requirements for a health
claim for calcium and osteoporosis, including the requirement that the
substance is safe and lawful at the level necessary to justify a claim,
have already been established, as evidenced by the currently authorized
claim. In the 1993 calcium and osteoporosis health claim final rule,
FDA concluded that calcium's use at the levels necessary to justify the
claim was safe and lawful under the applicable food safety provisions
of the act (58 FR 2665 at 2670). At the time the calcium and
osteoporosis health claim was authorized, in order for a food or
dietary supplement to carry the claim, it had to meet or exceed the
requirements for a ``high'' level of calcium as defined in Sec.
101.54(c). A ``high'' level of calcium is at least 20 percent of the
RDI of calcium per RACC. The RDI for calcium is 1,000 mg/day. Twenty
percent of the RDI for calcium (200 mg) is well below the UL of 2,500
mg for calcium.
In the final rule for the authorized health claim about calcium and
osteoporosis (21 CFR 101.72) (58 FR 2665 at 2670), FDA identified 10
specific calcium compounds that are deemed to be safe and lawful for
use in a dietary supplement or as a nutrient supplement (i.e., added to
food) that may bear the calcium and osteoporosis health claim. The 10
compounds (calcium carbonate, calcium citrate, calcium
glycerophosphate, calcium oxide, calcium pantothenate, calcium
phosphate, calcium pyrophosphate, calcium chloride, calcium lactate,
and calcium sulfate) are either approved as food additives (21 CFR part
172), GRAS substances (21 CFR part 182), or affirmed as GRAS substances
(21 CFR part 184).
[[Page 502]]
At the time FDA published the final rule authorizing the health
claim about calcium and osteoporosis (January 6, 1993), ingredients
used in dietary supplements were subject to the premarket safety
evaluations required for new food ingredients and for new uses of food
ingredients. That is, such ingredients were required to be approved as
food additives, determined as GRAS substances, or affirmed as GRAS
substances before they could be used in food, including dietary
supplements. With passage of the Dietary Supplement Health and
Education Act in 1994 (DSHEA) (Public Law 103-417), Congress amended
the act to provide that ingredients for dietary supplements are exempt
from premarket safety evaluations for food additives or GRAS
substances. Instead, Congress provided that dietary ingredients are
subject to the adulteration provisions in section 402 of the act
(excluding the food additive adulteration provision), and, if
applicable, the new dietary ingredient provisions in section 413 of the
act, which pertain to dietary ingredients that were not marketed in the
United States before October 15, 1994. Therefore, the uses of these
sources of calcium are subject to review under different provisions of
the act, depending upon their use in or as a conventional food, or
alternatively, as a dietary ingredient or dietary supplement. Since
authorization of the calcium and osteoporosis health claim, no other
calcium compound, other than the 10 discussed previously, has been
demonstrated to FDA's satisfaction to be safe and lawful for use in a
dietary supplement or as a nutrient supplement in conventional food.
Subsequent to the publication of the final rule authorizing the
calcium and osteoporosis health claim, the IOM established a UL for
calcium based on life stages, gender, and age in 1997 (Ref. 5).
Although calcium is known to be an essential nutrient, it can also
cause adverse effects. The IOM noted that the adverse effects of excess
calcium intake in humans concern calcium intake from ``nutrient
supplements'' i.e., calcium taken as a dietary supplement, and that the
most widely studied and biologically important possible adverse effects
of excessive calcium intake are kidney stone formation, the syndrome of
hypercalcemia and renal insufficiency (milk alkali syndrome), and the
interaction of calcium with the absorption of other essential minerals
(Ref. 5). Using milk alkali syndrome as the clinically defined critical
endpoint, the IOM identified the lowest-observed-adverse-effect level
(LOAEL) of calcium intake in the range of 4,000 to 5,000 mg/day. The
IOM established 2,500 mg/day of calcium as the UL for individuals over
12 months old by dividing a LOAEL of 5,000 mg/day by an uncertainty
factor of 2 to take into account the relatively high prevalence of
renal stones in the U.S. population, which is 12 percent, and potential
increased risk of hypercalciuria and depletion of other minerals among
susceptible individuals.
The most recent nationally representative data, 1999-2000 NHANES,
found the median calcium intake from foods, excluding dietary
supplements, to be 735 mg/day for all individuals, excluding nursing
infants and children (Ref. 12). Calcium can be obtained from dietary
supplement sources as well as food sources.
Calcium is often contained in multiple vitamin and mineral
supplement products. Most of these products contain about 100 to 200 mg
of calcium per RACC and recommended consumption of the dietary
supplement once per day (Ref. 11). Some of these products contain 250
to 500 mg calcium with a recommendation of once per day, and 1 product
surveyed contained up to 1,000 mg calcium with a recommended serving of
once per day (id.). Calcium is also often contained in products where
calcium is the sole ingredient or where calcium and vitamin D are the
only ingredients. These types of products generally contain between 500
to 1,000 mg of calcium per RACC (id.). Calcium and vitamin D only
products with a RACC of 500 mg of calcium recommend consumption of 1 to
3 servings per day and the recommended calcium intake does not exceed
1,500 mg per day (id.). Calcium and vitamin D only products with a RACC
of 600 mg of calcium recommend consumption of 1 or 2 servings per day
(id.). Products with a RACC greater than 600 mg of calcium recommend
consumption of only 1 serving per day (id.). The daily intake level of
calcium suggested in calcium and vitamin D only products is between 300
to 1,500 mg/day. Thus, the range of calcium intake from the various
types of calcium containing dietary supplement products generally
varies from 100 to 1,500 mg calcium per day, which when added to the
median level of calcium intake from food (735 mg/day) is 835 to 2,235
mg calcium. This range includes amounts that are below the UL of 2,500
mg/day for calcium.
FDA also considered the amount of calcium that may be added to food
in order for foods to be eligible to bear the claim. Foods that are
eligible to bear the calcium or the vitamin D and calcium and
osteoporosis health claim must contain at least 200 mg calcium per
RACC. To estimate the daily intake of calcium from foods, the agency
assumed the same food consumption patterns as considered for vitamin D,
since the foods that provide enough calcium to be eligible for the
claim or the proposed additional claim, also contain vitamin D. Thus,
four servings of foods eligible to bear the health claim would provide
at least 800 mg calcium. Such an amount is well below the UL of 2,500
mg calcium. Thus, consumers who choose foods that bear the calcium, or
the calcium and vitamin D, and osteoporosis health claim would be able
to incorporate such foods into the diet in a manner that would likely
keep their total intake of calcium well below the UL of 2,500 mg per
day. Furthermore, consumers who choose conventional foods that bear the
calcium or the additional calcium and vitamin D claim and that consume
up to 1,500 mg of calcium per day from supplements would also likely
keep their total intake of calcium below the UL of 2,500 mg per day.
Therefore, FDA tentatively concludes, under the preliminary
requirements of Sec. 101.14(b)(3)(ii), that the use of calcium in
foods, including dietary supplements, at levels necessary to justify
the health claim (20 percent or more of the RDI for calcium) is safe
and lawful under the applicable provisions of the act.
III. Review of Scientific Evidence of the Substance-Disease
Relationship
A. Basis for Evaluating the Relationship Between Calcium and Vitamin D
and Osteoporosis
1. Background of the Relationship Between Calcium and Osteoporosis
FDA authorized the calcium and osteoporosis health claim in
response to NLEA, after conducting a review of the scientific
literature on calcium and osteoporosis. The current petitioner is
requesting, among other things, that the existing health claim for
calcium and osteoporosis (Sec. 101.72) be amended to allow additional
language for calcium and vitamin D and osteoporosis. FDA conducted its
review of the effects of calcium and vitamin D on osteoporosis
consistent with how the agency conducted its review for calcium and the
osteoporosis health claim. Thus, the agency examined the effects of
calcium and vitamin D on direct measures of bone status (i.e. bone
mineral density (BMD) and bone mineral content (BMC)).
According to the National Institutes of Health (NIH) Consensus
Statement ``Osteoporosis, Prevention, Diagnosis,
[[Page 503]]
and Therapy'' (hereinafter, the 2000 NIH Consensus Statement),''
osteoporosis is a skeletal disorder characterized by compromised bone
strength predisposing to an increased risk of fracture (Ref. 2). Bone
strength is dependent upon bone density and bone quality. Bone density
is determined by peak bone mass and amount of bone loss (Ref. 2). Bone
quality is a function of architecture, turnover, damage accumulation
(e.g., micro fractures) and mineralization (Ref. 2). A fracture occurs
when a failure-inducing force (e.g., trauma) is applied to osteoporotic
bone (Ref. 2). Thus, osteoporosis is a significant risk factor for
fractures, which are commonly described as osteoporotic fractures. The
most common osteoporotic fractures are in the vertebrae, hip, and
wrist-forearm.
The most common measures of overall bone strength are those for
bone mass, namely, BMD and BMC. Bone mineral content is the amount of
mineral at a particular skeletal site such as the femoral neck, lumbar
spine, or total body; whereas BMD is BMC divided by the area of the
scanned region (Ref. 5). As in the 1991 review, FDA has identified bone
mass (i.e., BMD, BMC) as a surrogate endpoint for osteoporosis. Thus,
FDA used bone mass to identify osteoporosis risk reduction for the
purpose of evaluating the scientific evidence for a health claim about
calcium, vitamin D, and osteoporosis (Ref. 2).
2. Physiological Role of Vitamin D in Maintaining Calcium Homeostasis
In humans and other mammals, vitamin D3 is
photosynthesized in the skin by the actions of solar ultraviolet B (UV-
B) radiation followed by isomerization, and is the normal dietary form
of vitamin D (Ref. 6). Vitamin D2 is synthesized from
ergosterol, a yeast and plant sterol (Ref. 6). Both vitamin
D2 and vitamin D3 are used as ingredients in
conventional food and as dietary ingredients in dietary supplements.
Vitamin D2 and vitamin D3 are biologically inert,
but serve equally as substrates for the production of the biologically
active 1,25-dihydroxy-vitamin D3 (calcitriol) (Ref. 6).
Vitamin D2 or D3 is hydroxylated at the 25
position in the liver to produce 25-hydroxy-vitamin D3 (25-
hydroxycholecalciferol), which is then further hydroxylated in the
kidney to form 1,25-dihydroxy-vitamin D3 (Ref. 6).
The predominant biological role of vitamin D is to maintain serum
calcium and phosphorus concentrations within their normal ranges (Ref.
6). 1,25-dihydroxy-vitamin D3 acts directly on intestinal
mucosal cells to increase absorption of calcium and on bone to further
release calcium (Refs. 6 and 13). If dietary calcium intake is
inadequate and serum calcium concentration starts to drop below
required levels, the parathyroid produces parathyroid hormone (PTH),
which then stimulates increased production of 1,25-dihydroxy-vitamin
D3 in the kidney. Together, PTH and 1,25-dihydroxy-vitamin
D3 mobilize calcium from bone and stimulate calcium
reabsorption in the kidney (Refs. 6, 13 and 14). To prevent
hypercalcemia, the elevated 1,25-dihydroxy-vitamin D3 acts
as a negative feedback regulator on the parathyroid gland to reduce PTH
secretion (Ref. 13). In addition, elevated serum calcium concentrations
stimulate thyroid production of calcitonin, which lowers the
circulating calcium levels by preventing bone resorption and increasing
renal calcium excretion (Ref. 15). Thus, 1,25-dihydroxy-vitamin
D3 first acts by increasing intestinal calcium absorption
and then, if dietary calcium is not adequate and serum calcium
concentration remains low, PTH increases 1,25-dihydroxy-vitamin
D3 levels to increase calcium reabsorption from urine and
ultimately liberate calcium stores from bone (Ref. 14).
B. Review of the Scientific Evidence of the Substance-Disease
Relationship
The petitioner requested, among other things, that the existing
health claim for calcium and osteoporosis (Sec. 101.72) be amended to
allow additional language for calcium and vitamin D intake and reduced
risk of osteoporosis. The petitioner also requested other amendments,
in addition to including calcium and vitamin D as a substance of the
claim, and the agency will discuss the scientific evidence about these
other proposed amendments in sections IV. B through F of this proposed
rule.
FDA has previously concluded that there is significant scientific
agreement among qualified experts to support the relationship between
calcium intake and reduced risk of osteoporosis (58 FR 2665 at 2672).
FDA is not changing this conclusion. There is still significant
scientific agreement for such a relationship (Refs. 2, 4, and 16).
Since the petitioner has requested that the agency authorize an
additional claim for calcium and vitamin D intake and osteoporosis, FDA
focused its review on studies that examined the effects of calcium and
vitamin D intake on osteoporosis risk. In order to authorize a health
claim relating calcium and vitamin D intake to reduced risk of
osteoporosis, FDA will consider whether there is significant scientific
agreement among qualified experts to support the relationship between
calcium and vitamin D intake and reduced risk of osteoporosis. FDA's
review of the evidence to support an amendment to include calcium and
vitamin D as a substance of the calcium and osteoporosis health claim
was conducted consistent with FDA published guidance on significant
scientific agreement in the review of health claims (Ref. 17).
The petition cited 221 references that summarized 3 bodies of
evidence in support of the health claim for calcium and vitamin D
intake and risk of osteoporosis. These included studies on the
relationship between: (1) Calcium intake and risk of osteoporosis, (2)
vitamin D intake and risk of osteoporosis, and, (3) calcium and vitamin
D intake and risk of osteoporosis. Scientific conclusions about the
substance-disease relationship cannot be drawn from studies that did
not analyze whether calcium plus vitamin D, together, were associated
with risk factors for osteoporosis (BMD or BMC).
1. Assessment of Intervention Studies
FDA identified a total of 13 intervention studies in the petition
on calcium and vitamin D intake and risk of osteoporosis for its review
of the proposed calcium and vitamin D and osteoporosis health claim
(Refs. 18 through 30). Scientific conclusions about the substance-
disease relationship could not be drawn from three of these studies.
Specifically, Aloia et al. (1994) (Ref. 18) and Prestwood et al. (1999)
(Ref. 28) did not include appropriate control groups that would allow
assigning any observed effects to calcium and vitamin D supplementation
(Ref. 31). Therefore, it could not be determined whether changes in the
endpoint of interest were due to calcium or vitamin D intake or to
unrelated and uncontrolled extraneous factors (Ref. 31). In addition,
Prestwood et al. (1999) measured outcomes (biochemical markers of bone
formation and resorption) that are not recognized as valid surrogate
endpoints for osteoporosis. The only validated surrogate endpoints for
osteoporosis are BMD and BMC. Grados et al. (2003) (Ref. 25) studied
women with vitamin D deficiency and the results could not be
extrapolated to the general population. Nutrient status and metabolism
can be severely altered when an individual is malnourished. Vitamin D
deficiency causes abnormalities in calcium and bone metabolism (Ref.
6). Vitamin D deficiency will cause a decrease in ionized blood
calcium, which will lead
[[Page 504]]
to an increase in the production of secretion of parathyroid hormone
(Ref. 6). The effect of vitamin D on calcium and bone metabolism can be
different than the effect of the same nutrient on healthy, well-
nourished individuals. Therefore, scientific conclusions cannot be
drawn from this study.
Thus, FDA identified 10 reports of 8 intervention studies, which
included 2 followup studies (Refs. 21 and 24), from which scientific
conclusions could be drawn about the effects of calcium and vitamin D
intake on reduced risk of osteoporosis (Refs. 19 through 24 and Refs.
26, 27, 29, and 30).
Orwoll et al. (1990) (Ref. 27) was a 3-year, randomized, double-
blind placebo-controlled study that provided U.S. men (n=36 control
group; n=41 treatment group; mean of 58 years for both groups) a
supplement containing 1,000 mg/day calcium and 1,000 IU/day vitamin D
or a placebo. IU is equivalent to the specific biological activity of
0.025 microgram ([micro]g) of vitamin D3 (i.e., 1 mcg equals
40 IU; 1 milligram (mg) equals 40,000 IU). There was no effect of
calcium and vitamin D supplementation on BMC (radius, vertebrae) when
compared to men receiving a placebo (Ref. 27).
Chapuy et al. (1992, 1994) reported the results from 1 1/2 years
(Ref. 20) and 3 years (Ref. 21) supplementation of French women
(n=1,634/group; 84 years mean) with 1,200 mg/day calcium and 800 IU/day
vitamin D or a placebo. In this randomized, double-blind placebo-
controlled study, calcium and vitamin D supplementation resulted in
significantly fewer hip and non-vertebral osteoporotic fractures (Refs.
20 and 21) and improved proximal femur BMD (Ref. 21), compared with the
placebo group.
Dawson-Hughes et al. (1997) (Ref. 23) provided a placebo or a
supplement containing 500 mg/day calcium and 700 IU/day vitamin D to
U.S. men and women (n=187-202/group; approximately 70 years mean) in a
3-year randomized, double-blind placebo-controlled study. For all
subjects, calcium and vitamin D produced a benefit in BMD (femoral
neck, spine, total body) and reduced non-vertebral fracture incidence
compared with subjects given placebo. When the BMD results for men
(n=86) and women (n=101) were analyzed separately, men had significant
effects at all three sites; whereas only total body bone loss was
significantly reduced in women. Two years following withdrawal of the
calcium and vitamin D supplements, BMD returned to levels observed in
the placebo group, with the exception of total body BMD in men, which
remained significantly higher in men previously given calcium and
vitamin D (Ref. 24).
Kreig et al. (1999) (Ref. 26) was a 2-year randomized, controlled
study in which French women (n=50-53/group; 84 years mean) were given a
supplement containing 1,000 mg/day calcium and 880 IU/day vitamin D or
left untreated. Bone density was significantly higher in the
supplemented group compared to the untreated group (Ref. 26).
Baeksgaard et al. (1998) (Ref. 19) was a 2-year, randomized,
double-blind placebo-controlled study in which Danish women (n=63-69/
group; 62.5 years mean) were given a placebo or a supplement containing
1,000 mg/day calcium and 560 IU/day vitamin D. A significant increase
in lumbar spine BMD was observed in the supplemented group compared to
the placebo group (Ref. 19).
Sosa et al. (2000) (Ref. 29) provided either a supplement
containing 1,000 mg/day calcium or 1,000 mg/day calcium and 1,520 IU/
day vitamin D to Spanish women (n=28-30/group; 78 years mean) in a 1-
year randomized, active controlled study. Calcium and vitamin D
supplementation significantly increased femoral neck BMD compared to
the calcium only group. No differences between the groups were observed
for fracture incidence (Ref. 29).
Dawson-Hughes et al. (1991) (Ref. 22) provided a supplement
containing 377 mg/day calcium or 377 mg/day calcium and 400 IU/day
vitamin D to U.S. women (n=124-125/group; 61 years mean) for 1 year in
a randomized, double-blind active-controlled study. Spine BMD was
significantly higher in the women that received calcium and vitamin D
compared to women who received calcium alone (Ref. 22).
Jackson et al. (2006) (Ref. 30) provided a supplement containing
1,000 mg/day calcium and 400 IU/day vitamin D3 to
postmenopausal women (n=16,936; 62 years mean) for 7 years who were
already enrolled in a Women's Health Initiative (WHI) clinical trial.
This was a randomized, double-blind placebo controlled study. Total hip
BMD was significantly higher in women who received calcium and vitamin
D compared to women in the placebo group. Spine and whole-body BMD were
not significantly different between the groups (Ref. 30).
2. Assessment of Observational Studies
The petition identified 8 observational studies on calcium and
vitamin D intake, consisting of 1 prospective cohort (Ref. 32), 2
prospective sub-cohorts (Ref. 33 and 34), and 5 cross-sectional studies
(Refs. 35 through 39). The eight observational studies either
calculated calcium and/or vitamin D intake from estimates of dietary
intake and/or dietary supplements.
When calcium or vitamin D intake is calculated from estimates of
intake of calcium or vitamin D containing foods or dietary supplements,
human and measurement error can occur, affecting the accuracy of the
calculation. In observational studies that calculate nutrient intake
from conventional foods or dietary supplements, measure of calcium and/
or vitamin D intake is based on recorded dietary intake methods, such
as food frequency questionnaires, diet recalls, or diet records, in
which the type and amount of foods and dietary supplements consumed are
estimated. Calcium and vitamin D levels in conventional foods are then
estimated using typical calcium and vitamin D concentration values for
the food product category, based on a source such as the U.S.
Department of Agriculture National Nutrient Database for Standard
Reference. A common weakness of observational studies is the limited
ability to ascertain the actual food, dietary supplement or nutrient
intake for the population studied as a result of poor memory, over-, or
underestimation of portion sizes and recall bias (Ref. 40). Thus, it is
difficult to ascertain an accurate amount of the nutrient consumed
based on reports of dietary intake from conventional foods and dietary
supplement use. Furthermore, the bioavailability of calcium from foods
can vary due to food processing and cooking procedures that are not
indicated in a recorded dietary intake method or not indicated nor
available for foods that have an assigned calcium concentration value
(Ref. 41).
In addition, conventional foods and multivitamin and multi-
ingredient supplements contain not only calcium and vitamin D, but also
other nutrients that may be associated with the metabolism of calcium
and vitamin D on bone health. Thus, it is not possible to attribute any
observed associations to calcium and vitamin D intake alone from
conventional foods and/or multivitamin and multi-ingredient supplements
because of the potential confounding effects from the other components
contained in the conventional foods and dietary supplements. Because
conventional foods and dietary supplements consist of many nutrients
and substances, it is difficult to study the nutrient or food
components in isolation (Ref. 42). For instance, bone health requires
more than just calcium and vitamin D (Refs. 4 to 6). Most notably,
phosphorus and
[[Page 505]]
magnesium make up more than half of bone mineral density (Refs. 4 and
5). Insufficient levels of magnesium may interfere with the ability to
metabolize calcium (Ref. 4).
As discussed previously, when evaluating the relationship between
vitamin D and calcium and a reduced risk of osteoporosis, there are
inherent problems associated with an observational study design in
assessing vitamin D and calcium intake from conventional food and/or
dietary supplements and in controlling for the intake of other
nutrients that may affect vitamin D and calcium metabolism. Based on
the problems associated with the use of an observational study design
to assess a relationship between calcium and vitamin D intake and a
reduced risk of osteoporosis, none of the eight observational studies
provided, nor could they provide, a sufficient assessment of the intake
of calcium and vitamin D from foods and/or dietary supplements in order
to evaluate such a relationship. In addition, none of the eight
observational studies controlled for, nor could they control for, the
intake from other components in foods and dietary supplements that are
associated with the metabolism of calcium and vitamin D, which control
is necessary in order to evaluate the relationship between calcium and
vitamin D and a reduced risk of osteoporosis. Further, two of these
studies (Refs. 34 and 36) measured serum vitamin D levels, which are
not a valid biomarker of dietary vitamin D intake because serum levels
reflect the cumulative effect of both exposure to sunlight and dietary
intake (Ref. 6). For the previously stated reasons, FDA concludes that
no scientific conclusions about the relationship between calcium and
vitamin D intake and the risk of osteoporosis can be drawn from the
eight observational studies on conventional foods or dietary
supplements.
3. Authoritative Statements
In its review of the scientific evidence, FDA also considered
conclusions from the 2000 NIH Consensus Statement, which was submitted
with the petition, and the Surgeon General Report ``Bone Health and
Osteoporosis'' (hereafter, the 2004 Surgeon General Report) (Refs. 2
and 4). The 2000 NIH Consensus Statement concluded that ``adequate
calcium and vitamin D intake are crucial to develop optimal peak bone
mass and to preserve bone mass throughout life'' and further,
``osteoporosis occurs in all populations and at all ages'' (Ref. 2).
Similarly, the 2004 Surgeon General Report states that ``calcium and
vitamin D intake and physical activity are now known to be major
contributors to bone health for individuals of all ages, and while bone
disease often strikes late in life, the importance of beginning
prevention at a very young age and continuing it throughout life is now
well understood'' (Ref. 4). These results extend the scientific
conclusions that not only calcium reduces the risk of osteoporosis but
that calcium and vitamin D also reduce the risk of osteoporosis.
IV. Decision to Amend the Calcium and Osteoporosis Health Claim
A. Addition of Vitamin D
The majority of the intervention studies FDA evaluated and
submitted with the petition established that calcium and vitamin D
significantly reduces the risk of osteoporosis (Refs. 18 through 29).
One intervention study (Ref. 29), which compared calcium
supplementation to supplementation with calcium and vitamin D showed no
difference in fracture incidence but did demonstrate significantly
increased femoral neck BMD with calcium and vitamin D. Another study
(Ref. 22) showed a significantly higher spine BMD in women with calcium
and vitamin D supplementation compared to calcium supplementation
alone. Therefore, the two studies (Refs. 22 and 29) that compared
supplementation with calcium to calcium and vitamin D suggest that the
combination of calcium and vitamin D may enhance the effects of
reduction in risk of osteoporosis when compared to calcium alone. The
role of vitamin D in enhancing the bioavailability of calcium through
increased intestinal absorption of dietary calcium, and increased renal
reabsorption of urinary calcium is well established. Based on its
review of the publicly available evidence pertaining to calcium,
vitamin D, and osteoporosis, FDA tentatively concludes that there is
sufficient evidence to amend Sec. 101.72 to include vitamin D so that,
in addition to claims for calcium and osteoporosis, additional claims
can be made for calcium and vitamin D and osteoporosis. Accordingly,
FDA is proposing to amend Sec. 101.72 to authorize an additional
health claim for calcium and vitamin D and reduced risk of
osteoporosis.
1. Nature of the Food Eligible to Bear the Calcium and Osteoporosis
Claim
The agency is not making any changes to the nature of the food,
including dietary supplements, labeled with the calcium and
osteoporosis health claim (Sec. 101.72(c)(2)(ii)). Those requirements
are that: (1) The food shall meet or exceed the requirements for a
``high'' level of calcium as defined in Sec. 101.54(b), i.e., the food
must contain 20 percent or more of the RDI for calcium per RACC; (2)
the calcium content of the product shall be assimilable; (3) dietary
supplements shall meet the United States Pharmacopeia (U.S.P.)
standards for disintegration and dissolution applicable to their
component calcium salts, except that dietary supplements for which no
U.S.P. standards exist shall exhibit appropriate assimilability under
the conditions of use stated on the product label; and (4) the food or
total daily recommended supplement intake shall not contain more
phosphorus than calcium on a weight per weight basis.
2. Nature of the Food Eligible to Bear the Calcium and Vitamin D and
Osteoporosis Claim
The general requirements for health claims (21 CFR
101.14(d)(2)(vii)) provide that, if the claim is about the effects of
consuming the substance at other than decreased dietary levels, the
level of the substance must be sufficiently high and in an appropriate
form to justify the claim. If a definition for the use of the term
``high'' for the substance has been established, the substance must be
present at a level that meets the requirements for the use of that
term. A ``high'' claim about the level of a nutrient in a food in
relation to the RDI established for that nutrient requires that the
food contain 20 percent or more of the RDI per RACC (see Sec.
101.54(b)). The RDI for vitamin D is 400 IU. Thus, a conventional food
must contain 20 percent or more of the RDI for vitamin D per RACC
(i.e., at least 80 IU) to be eligible for the additional calcium,
vitamin D and osteoporosis health claim. A dietary supplement must
contain 20 percent or more of the RDI for vitamin D per RACC (see Table
2 of Sec. 101.12(b)).
Accordingly, FDA is proposing that, in order for a food to be
eligible for the additional calcium and vitamin D and osteoporosis
health clam the food must: (1) Be eligible to bear a claim for the
calcium and osteoporosis health claim in Sec. 101.72, (2) meet or
exceed the requirements for a ``high'' level of vitamin D as defined in
Sec. 101.54(b), and (3) meet all of the general health claim
requirements set forth in Sec. 101.14.
B. Amendments to the Calcium and Osteoporosis Health Claim Other Than
the Inclusion of Vitamin D
As noted in the section I of this proposed rule, FDA published a
proposed rule entitled ``Food Labeling:
[[Page 506]]
Nutrient Content Claims, General Principles; Health Claims, General
Requirements and Other Specific Requirements for Individual Health
Claims'' (the 1995 proposal), to amend several provisions of the
regulations on nutrient content claims and health claims to increase
the flexibility in the use of nutrient content claims and health claims
on food products (60 FR 66206). The agency either extended or reopened
the comment period four times for the 1995 proposal, in response to
request from stakeholders (61 FR 11793, March 22, 1996; 62 FR 3635,
January 24, 1997; 62 FR 11129, March 11, 1997; and 69 FR 24541, May 4,
2004). The agency received approximately 160 comments in response to
the proposed rule. The comments specific to the requirements for the
calcium and osteoporosis health claim generally supported the agency's
tentative proposals. Specific comments are discussed below as they
pertain to the appropriate sections.
C. Elimination of the Requirement to List Race, Age and Sex as Risk
Factors for the Development of Osteoporosis
1. The 1995 Proposal
In the 1995 proposal, FDA proposed to amend several specific
requirements to the nature of the claim for the calcium and
osteoporosis health claim (60 FR 66206). The first required element for
the calcium and osteoporosis health claim is contained in Sec.
101.72(c)(2)(i)(A) and provides that: ``The claim makes clear that
adequate calcium intake throughout life is not the only recognized risk
factor in this multifactorial bone disease by listing specific factors,
including sex, race, and age that place persons at risk of developing
osteoporosis and stating that an adequate level of exercise and a
healthful diet are also needed.'' The original intent of presenting the
information as specified in Sec. 101.72(c)(2)(i)(A) was to convey the
message that for any individual several factors define disease risk.
FDA's tentative decision to amend Sec. 101.72(c)(2)(i)(A) in the
1995 proposal was based, in part, on the 1994 NIH Consensus Statement
on optimal calcium intake, which was published after authorization of
the calcium and osteoporosis final rule. The first of several
significant conclusions from the 1994 NIH Consensus Statement was that
a large percentage of Americans did not meet the currently recommended
guidelines for optimal calcium intake (Ref. 43). Because of the need to
correct this public shortfall and to improve bone health, which would
reduce the risk of osteoporosis, FDA tentatively concluded that a
singular focus on achieving and maintaining adequate calcium intake as
a required element of the claim was important (60 FR 66206 at 66216).
In the 1995 proposal, FDA also acknowledged, that the number of food
products bearing health claims, during this time, was not as great as
the agency had anticipated and FDA was concerned that manufacturers may
have been disinclined to use such lengthy health claims on food labels.
(id.) These concerns coupled with the fact that most Americans,
regardless of sex, race, or age, were not meeting the recommended
guidelines for optimal calcium intake led the agency to reevaluate the
requirement in Sec. 101.72(c)(2)(i)(A). Accordingly, FDA proposed to
simplify Sec. 101.72(c)(2)(i)(A) by limiting the requirement to a
balanced statement that reflects the importance of the nutrient calcium
over a lifetime in a healthful diet to reduce osteoporosis risk, but
that does not imply that calcium is the only risk factor for the
development of osteoporosis. FDA also proposed to replace the provision
in Sec. 101.72(c)(2)(i)(A) that the specific risk factors and the need
for an adequate level of exercise be stated in the claim, with the more
simple requirement that the claim not imply that adequate dietary
calcium intake is the only recognized risk factor for a reduced risk of
osteoporosis (60 FR 66206 at 66216 and 66217). In concert with these
proposed changes to Sec. 101.72(c)(2)(i)(A), FDA provided that the
claim may list the sex, age, or race of populations at risk for
osteoporosis, or the need for an adequate level of exercise as optional
information (60 FR 66206 at 66217).
The agency did not receive any comments opposing these proposed
amendments. Rather, several comments that addressed this issue
supported the agency's tentative amendments to Sec.
101.72(c)(2)(i)(A). The agency considered these comments when
responding to the health claim petition submitted by The Beverage
Institute for Health and Wellness.
2. The Beverage Institute for Health and Wellness Petition
The petitioner requested that the agency amend Sec.
101.72(c)(2)(i)(A) to eliminate reference to age, sex, race, and the
need for an adequate level of exercise. The petitioner did not include
the provision in Sec. 101.72(c)(2)(i)(A) concerning calcium's role in
a `healthful diet' and did not state why such provision was not
included in their proposed amendment. The petitioner stated that their
request for eliminating reference to age, sex, and race in the claim
was supported by scientific evidence establishing that calcium or
calcium and vitamin D reduces the risk of osteoporosis in all age
groups of both sexes and in all races. The petitioner stated that their
request for eliminating reference to the need for an adequate level of
exercise from the claim was supported by scientific evidence, submitted
with the petition, showing that calcium or calcium and vitamin D can
reduce the risk osteoporosis regardless of the level of physical
activity.
3. Agency's Proposed Amendments to the Calcium and Osteoporosis Health
Claim
The agency agrees with the petitioner that the claim no longer
needs to list specific risk factors for the development of
osteoporosis, including sex, race, and age. However, the agency also
tentatively concludes that a reference to a ``healthful diet'' and to
adequate physical activity is still a necessary part of the claim, as
well as the importance of adequate calcium or adequate calcium and
vitamin D intake throughout life.
Sex, Age, and Race Categories
The 2000 NIH Consensus Statement concluded that ``osteoporosis
occurs in all populations and at all ages'' and that ``adequate calcium
and vitamin D intake are crucial to develop optimal peak bone mass and
to preserve bone mass throughout life'' (Ref. 2). Furthermore, evidence
provided in the 2004 Surgeon General's Report as well as the 2000 NIH
Consensus Statement establishes that the benefits of calcium or calcium
and vitamin D on prevention of bone diseases, including osteoporosis,
are not dependent on age and not specific to any subpopulation in the
United States (Refs. 2 and 4).
Osteoporosis occurs in all populations at all ages (Ref. 4).
Osteoporosis is the major cause of fractures in the elderly, both men
and women. It begins later in men than women (Ref. 2). In women it
often follows menopause, especially in white women. Osteoporosis is a
disease that takes many years to develop and most often is not
discovered until the later years. For every 10 white women, 4 by age 50
or older in the United States will experience a hip, spine, or wrist
fracture sometime during the remainder of their lives and for white men
the number is 13 percent (Ref. 44). Though the lifetime risk for types
of fractures is less in men and nonwhite women, it does represent a
significant risk and may be increasing in certain populations, such as
Hispanic women (Ref. 45). Because of the mistaken view
[[Page 507]]
that osteoporosis is a disease that affects postmenopausal white women,
it often goes undetected in men and racial and ethnic minorities (Ref.
4). Risk of developing osteoporosis is likely to increase for all
ethnic groups as people's lifespan increases (Ref. 4).
Achieving and maintaining optimal bone health is a process that
occurs in both men and women throughout the lifespan (Ref. 2). Bone
mineral density declines with age in both men and women. Peak bone mass
is achieved at an early age and is a life-long determinant of skeletal
health. Calcium is the most important nutrient for achieving and
maintaining good skeletal health and vitamin D is required for optimal
absorption and utilization of calcium (Refs. 2 and 4). Thus, specific
reference to sex, race, and age is not necessary since the benefits of
dietary intake of calcium, or calcium and vitamin D would apply to both
sexes and all age and race categories.
Healthful Diet
Studies have shown that a well-balanced diet is important for bone
health throughout life (Ref. 4). Calcium and vitamin D remain the
primary nutrients required for good bone health and consuming diets
that include foods that contain these nutrients is critical. In
addition, other nutrients such as vitamin K, vitamin C, copper,
manganese, zinc, potassium, iron, and others may also play a role in
optimal bone health (Ref. 4). Thus, since many nutrients are involved
in bone health, it is important to consume a well-balanced diet that
consists of a variety of foods, including grains, fruits, vegetables,
nonfat or low-fat dairy products or other calcium-rich foods, meat or
beans.
In the 1995 proposal, FDA stated that it included a reference to a
``healthful diet'' in Sec. 101.72(c)(2)(i)(A) for consistency with the
general requirement in Sec. 101.14(d)(2)(v) that ``the claim enable
the public ***to understand the relative significance of such
information in the context of a total daily diet'' (60 FR 66206 at
66216). Similar to what the agency concluded in the 1995 proposed rule
for the effect of adequate calcium intake, the effect of calcium and
vitamin D can only be realized if the calcium and vitamin D is a part
of a healthy, well-balanced diet that provides all essential and other
nutrients to optimize nutritional health status. Thus, the agency is
retaining the requirement in Sec. 101.72(c)(2)(i)(A) that the claim
make clear the importance of adequate calcium intake, or when
appropriate, adequate calcium and vitamin D intake over a lifetime in a
healthful diet is essential to reduce osteoporosis risk.
Physical Activity
Physical activity, along with intake of calcium and vitamin D, is
known to be a major contributor to bone health for people of all ages
(Ref. 4). In order to reduce the risk of osteoporosis, it is important
to begin physical activity at an early age and continue throughout
life. Physical activity needs to be maintained for optimal bone health.
Physical activity helps to increase or preserve bone mass and reduces
the risk of falls (Ref. 4). Studies have shown that physical activity,
as well as diet, are responsible for 10 to 50 percent of bone mass and
structure (Ref. 4). Physical activity plays an important role in
skeletal health. Thus, physical activity has a significant impact on
one's risk for developing osteoporosis.
Two studies have shown that physical activity can have a more
beneficial effect in infants or young children if these groups have
adequate calcium intakes (Refs. 46 and 47). As with children, the
positive effects of physical activity and calcium in older adults on
bone health has also been shown (Ref. 4). Thus, there is a synergistic
effect between intake of calcium and physical activity.
Both the more current 2004 Surgeon General's Report (Ref. 4), and
the 2000 NIH Consensus Statement continue to emphasize the importance
of physical activity on bone health (Ref. 2). Thus, because physical
activity is integral to bone health, along with the need for adequate
calcium, and, as applicable, calcium and vitamin D, the agency is
requiring a reference to the need for physical activity as part of the
health claim.
In summary, FDA tentatively concludes that specific reference to
sex, race, age in the claim is no longer necessary since the benefits
of calcium or calcium and vitamin D apply to both sexes at all ages and
race categories. FDA also tentatively concludes, however, that the
nutritional status of the diet and physical activity have a significant
impact on bone health, and thus, one's risk of developing osteoporosis.
Accordingly, FDA, is proposing to eliminate the provision in Sec.
101.72(c)(2)(i)(A) that specific risk factors including sex, race, and
age be listed in the claim, but to retain the provisions concerning a
healthful diet and exercise. Thus, the proposed revision to Sec.
101.72(c)(2)(i)(A) reads as follows: ``The claim makes clear the
importance of adequate calcium intake or when appropriate, adequate
calcium and vitamin D intake throughout life, in a healthful diet along
with physical activity are essential to reduce osteoporosis risk. The
claim does not imply that adequate calcium intake or when appropriate,
adequate calcium and vitamin D intake is the only recognized risk
factor for the development of osteoporosis.''
FDA is requesting comments on whether the provision to specify sex,
race, or age in the claim language should be retained and why.
D. Elimination of the Requirement that the Claim Not State or Imply
that the Risk of Osteoporosis is Equally Applicable to the General
Population, and that the Claim Identify the Populations at Particular
Risk for the Development of Osteoporosis
1. The 1995 Proposal
The second element for the calcium and osteoporosis claim is
contained in Sec. 101.72(c)(i)(2)(B) and provides that: ``The claim
does state or imply that the risk of osteoporosis is equally applicable
to the general United States population. The claim shall identify the
populations at particular risk for the development of osteoporosis.
These populations include White (or the term (``Caucasian'') women and
Asian women in their bone forming years (approximately 11 to 35 years
of age or the phase ``during teen or early adult years'' may be used).
The claim may also identify menopausal (or the term ``Middle-aged'')
women, persons with a family history of the disease, and elderly (or
``older'') men and women as being at risk.''
FDA's tentative decision to amend Sec. 101.72(c)(2)(i)(B) in the
1995 proposed rule was based on the 1994 NIH Consensus Statement and an
FDA report published in 1995 on consumer understanding of health claims
(hereinafter referred to as the 1995 FDA health claims report (Ref.
48)).
The 1994 NIH Consensus Statement concluded that the two most
important factors that influence the occurrence of osteoporosis are
optimal bone mass attained in the first two or three decades of life
and the rate at which bone loss occurs in later years (Ref. 43). Thus,
the 1994 NIH Consensus Statement did not ascribe the relative risk of
osteoporosis on the basis of race or ethnicity.
As part of the 1995 FDA health claims report, FDA tested
participants understanding of a model calcium and osteoporosis health
claim, such as the following: ``Regular exercise and a healthy diet
with enough calcium helps teen and young adult white and Asian women
maintain good bone health and may reduce their high risk of
osteoporosis later in life.''
Results from this study (Ref. 48) showed that minority women were
unanimous in objecting to the inference
[[Page 508]]
that black American women do not need calcium and questioned the
accuracy of the information contained in the claim. All of the survey
participants recognized that calcium is essential for everyone.
Although there was some recognition based on prior knowledge that
younger women need to be concerned about osteoporosis, no participant
thought the model claim communicated that concept very well.
The agency did not intend that the calcium and osteoporosis health
claim imply that calcium is not needed by any individual or specific
population. Given that calcium is essential for every person, the
agency attempted to present this disease claim in a truthful,
nonmisleading, and scientifically valid manner. Likewise, the agency
tentatively concluded in the 1995 proposal that greater use in food
labeling of the calcium and osteoporosis health claim, articulated in a
manner that will be accepted and followed by consumers, could help
support significant strides in improving calcium intake in all segments
of the U.S. population. Thus, the agency proposed to revise Sec.
101.72(c)(2)(i)(B) by removing the provision that the claim identify by
race and ethnicity those populations at particular risk for the
development of osteoporosis, but to retain identification of teen and
young adult women, irrespective of race as the focus of the claim (60
FR 66206 at 66218).
All comments received from the 1995 proposal regarding
identification of the at-risk population by race and ethnicity agreed
with FDA's tentative decision to remove that requirement from Sec.
101.72(c)(2)(i)(B). However, most of the same comments disagreed with
the tentative decision to retain a focus on teen and young adult women.
One comment stated that, if the agency were to rely on the 1994 NIH
Consensus Statement (Ref. 43) in making its decision, the health claim
would also have to cite older people as a second group for whom calcium
intake is important, which would lengthen the claim sufficiently to
discourage its use on food labels. It said that requiring the claim to
emphasize the calcium needs of young adults and teenagers might lead
other consumers to conclude that calcium is not important for them. The
comment stated that nearly all teens and adults will need encouragement
to reach the high levels of calcium, 1,000 to 1,500 mg per day,
recommended by the 1994 NIH Consensus Statement. Several comments urged
the agency to allow calcium and osteoporosis claims to express the
lifelong need for adequate dietary calcium without requiring the
identification of any particular population segment as being at a
higher than average risk for the disease. The comments stated that a
claim such as ``adequate calcium in a healthful diet throughout life
may reduce the risk of osteoporosis'' would be appropriate. The agency
considered these comments when responding to the health claim petition
submitted by The Beverage Institute for Health and Wellness.
2. The Beverage Institute for Health and Wellness Petition
The petitioner included, in proposed language for Sec.
101.72(c)(2)(i)(B), that the claim not state or imply that the risk of
osteoporosis is equally applicable to the general U.S. population. In
addition, the petition included, as optional, a statement that
identifies other populations at risk for developing osteoporosis,
including women in their bone forming years from approximately 11 to 35
years of age. The petitioner provided scientific evidence that calcium
and calcium and vitamin D reduce the risk of osteoporosis in both men
and women in all age groups regardless of race or ethnicity.
3. Agency's Proposed Amendments to the Calcium and Osteoporosis Health
Claim
Scientific evidence from both the Surgeon General's Report on Bone
Health and Osteoporosis and the 2000 NIH Consensus Statement shows that
osteoporosis occurs in both sexes at all ages and that adequate calcium
and vitamin D are essential to the development of peak bone mass and
the preservation of bone mass throughout life (Refs. 2 and 4).
Osteoporosis does not affect everyone to the same degree (Ref. 4).
Osteoporosis is most prevalent in postmenopausal women (Ref. 4), and
white postmenopausal women experience almost 75 percent of hip
fractures and have the highest age adjusted fracture incidence (Ref.
2). Both men and women experience an age-related decline in BMD
starting in midlife, and men, especially older men do develop
osteoporosis (Ref. 4).
Based on the Surgeon General's Report on Bone Health and
Osteoporosis and the 2000 NIH Consensus Statement, specifically that
osteoporosis is most prevalent in White postmenopausal women (Refs. 2
and 4), FDA tentatively concludes that the provision in Sec.
101.72(c)(2)(i)(B) that the claim must identify certain populations for
particular risk for osteoporosis as White or Asian women between the
ages of 11 and 35 is no longer correct.
FDA also tentatively concludes that the provision in Sec.
101.72(c)(2)(i)(B) providing that the claim not state or imply that the
risk of osteoporosis is equally applicable to the general population is
no longer appropriate. While the risk of osteoporosis is not equally
applicable to the general population, in the sense that there may be
some subpopulations that are at a greater risk for developing
osteoporosis than others, osteoporosis still occurs in all populations
at all ages (Refs. 2 and 4). Since osteoporosis is most prevalent and
thus more associated with White postmenopausal women, it often has gone
unrecognized in men and other age and ethnic populations (Refs. 2 and
4). Thus, FDA tentatively concludes that it is no longer necessary to
limit the wording of the claim to targeted subgroups, even though such
subgroups may be at a relatively greater risk than others in the
general population. Accordingly, FDA is proposing to eliminate the
requirement in Sec. 101.72(c)(2)(i)(B).
FDA is requesting comments about whether the identification of any
population or populations at particular risk of osteoporosis should be
required or optional in the claim language and why.
E. Elimination of the Requirement that the Claim Identify the Mechanism
by Which Calcium Reduces the Risk of Osteoporosis
1. The 1995 Proposal
Section 101.72(c)(2)(i)(C) of the calcium and osteoporosis health
claim established a requirement for identifying the mechanism whereby
adequate dietary calcium over a lifetime reduces the risk of
osteoporosis as described below: ``The claim states that adequate
calcium intake throughout life is linked to reduced risk of
osteoporosis through the mechanism of optimizing peak bone mass during
adolescence and early adulthood. The phrase ``build and maintain good
bone health'' may be used to convey the concept of optimizing peak bone
mass. When reference is made to persons with a family history of the
disease, menopausal women, and elderly men and women, the claim may
also state that adequate calcium intake is linked to reduced risk of
osteoporosis through the mechanism of slowing the rate of bone loss.''
The agency concluded in developing this requirement, for the calcium
and osteoporosis health claim, that it was important for consumers to
have a basic understanding of the biological and physiological
mechanisms by which adequate dietary intake of calcium achieves a
reduced
[[Page 509]]
risk of osteoporosis (60 FR 66206 at 66218).
In the 1995 proposal, FDA proposed to make the statement of the
mechanism by which calcium intake affects the risk of osteoporosis
optional information (60 FR 66206 at 66218). This tentative conclusion
was based on information contained in the 1995 FDA health claims
report, which focused on consumer understanding of health claims (Ref.
48). The 1995 FDA health claims report found that because participants
had learned elsewhere that calcium intake is related to general bone
health, they thought the food label was not the right means for
conveying this information. The awareness by consumers that calcium's
ability to ``build and maintain good bone health'' is the mechanism
whereby risk of osteoporosis is reduced raised the question as to
whether there was a need to state that fact in a health claim. Thus, in
the interest of streamlining the claim, FDA proposed to make the
statement of the mechanism by which calcium intake affects the risk of
osteoporosis optional information (60 FR 66206 at 66218). No comments
were received objecting to this aspect of the 1995 proposal.
2. The Beverage Institute for Health and Wellness Petition
The petitioner requested that the agency allow information on the
mechanism by which calcium reduces the risk of osteoporosis to be
optional instead of required, and to extend this optional information
to the additional calcium and vitamin D and osteoporosis claim.
3. Agency's Proposed Amendments to the Calcium and Osteoporosis Health
Claim
Based on the petitioner's request and FDA's tentative conclusions
in the 1995 proposal that many consumers were aware that calcium was
necessary for good bone health, FDA is proposing to eliminate the
requirement in Sec. 101.72(c)(2)(i)(C) that the claim state the
mechanism by which calcium reduces osteoporosis risk. FDA is also
proposing that information of the mechanism by which calcium reduces
the risk of osteoporosis may be optional, for either the calcium or the
newly proposed calcium and vitamin D and osteoporosis claim. FDA
requests comments on the proposed amendments to Sec.
101.72(c)(2)(i)(C).
F. Elimination of the Requirement in Sec. 101.72(c)(2)(i)(E) that
Certain Products Bearing the Claim Include a Statement that Reflects
the Limits on the Benefits from Calcium
1. The 1995 Proposal
Section 101.72(c)(2)(i)(E) contains a conditional requirement that
a calcium and osteoporosis health claim include a statement that
reflects the limit on the benefit derived from dietary calcium intake
when the food contains 40 percent or more of the RDI of 1,000 mg of
calcium per day or 400 mg or more of calcium per RACC as defined in
Sec. 101.12(b).
In the 1995 proposal, FDA proposed to amend this requirement by
increasing the amount of calcium present in a food that would trigger
the conditional requirement in Sec. 101.72(c)(2)(i)(E), from 400 mg
per RACC to 1,500 mg per day (60 FR 66206 at 66219). FDA based this
proposal on conclusions from the NIH 1994 Consensus Statement regarding
methods to achieve optimal calcium intake and the absence of reported
adverse effects with moderate supplementation up to 1500 mg/day (60 FR
66206 at 66219). FDA's proposal to increase the threshold level in
Sec. 101.72(c)(2)(i)(E) was also based on several Congressional
findings in the Dietary Supplement Health and Education Act of 1994
(Public Law 103-417) (60 FR 66206 at 66218). One of those findings
identified a link between ingestion of certain nutrients or dietary
supplements and reduced risk of several chronic diseases, including
osteoporosis, and stated that the Federal government should not take
any actions to impose unreasonable regulatory barriers that limit or
slow the flow of safe products and accurate information to consumers.
One comment did not support FDA's tentative decision to amend Sec.
101.72(c)(2)(i)(E) to change the threshold from 400 mg of calcium per
RACC to 1,500 mg per day. The comment stated that a statement that
reflects the limit on the benefit derived from dietary calcium intake
is needed to protect consumers from over consumption of this nutrient.
The comment stated that 400 mg of calcium per RACC should be retained
as the threshold since most calcium-rich conventional foods do not
contain more than that amount and would not have to bear this type of
statement as part of a calcium and osteoporosis health claim. The
comment maintained that this approach is appropriate because such a
statement on conventional foods would appear to run at cross purposes
with the goal to increase calcium consumption and would be inconsistent
with the conclusion in the 1994 NIH consensus statement that ``the
preferred source of calcium is through calcium-rich foods such as dairy
products.''
The comment maintained that, because calcium supplements provide
calcium in addition to the calcium that consumers get from conventional
foods, it is important for consumers to know the maximum recommended
safe dose, and cited a second conclusion from the 1994 NIH consensus
statement that ``practices that might encourage total calcium intake to
approach or exceed 2,000 mg per day seem more likely to produce adverse
effects and should be monitored carefully.'' The comment suggested that
consumers should be made aware that a total daily intake of 2,000 mg of
calcium from conventional foods and dietary supplements appears to be
safe, but that higher intakes provide no further benefit. The comment
maintained that a lower threshold for a statement of the limits of
benefit on calcium supplements would not limit the flow of these
supplements to those who need them but would provide information to
help prevent their overuse by consumers.
The comment stated further that if FDA did raise the 400 mg calcium
per RACC threshold, several issues should be addressed. The comment
stated that FDA's proposal to require that the statement of limited
benefit apply to foods that provide more than 1,500 mg of calcium per
day means that the requirement pertains only to supplements and not to
foods since, for conventional foods, the requirement must be on a per
reference amount basis. The comment stated that the per day basis could
only apply to supplements.
Noting that the highest recommendation for calcium intake in the
1994 NIH consensus statement was 1,500 mg calcium per day, the comment
maintained that this level represents total dietary calcium intake from
conventional foods and dietary supplements. The comment stated that
1,500 mg should not be the threshold level for a limited benefit
statement. The comment argued that setting the threshold higher than
1,000 mg per day would encourage supplementation to an inappropriately
high level. The comment pointed out that the Food and Nutrition Board's
text, ``Eat for Life,'' advises consumers to avoid taking vitamin or
mineral dietary supplements in excess of the U.S. Recommended Dietary
Allowance (currently, the Reference Dietary Intake) in any one day--for
calcium, that amount is 1,000 mg per day. Accordingly, the comment
[[Page 510]]
recommended that the requirement for the limited benefit statement
apply only to dietary supplements of calcium whose recommended total
daily intake is 1,000 mg or more per day. The agency considered these
comments when responding to the health claim petition submitted by The
Beverage Institute for Health and Wellness.
2. The Beverage Institute for Health and Wellness Petition
The petitioner proposed to adopt the amendments to Sec.
101.72(c)(2)(i)(E) exactly as proposed in the 1995 proposal. The
petitioner also requested that FDA not extend a conditional requirement
for vitamin D in the proposed additional health claim for calcium and
vitamin D and osteoporosis.
3. Agency's Proposed Amendments to the Calcium and Osteoporosis Health
Claim
FDA has been persuaded to reevaluate the conditional requirement in
Sec. 101.72(c)(2)(i)(E) due to the Dietary Reference Intakes (DRIs)
established for calcium by the IOM (Ref. 5). DRIs for calcium were
established after FDA proposed amendments to the calcium and
osteoporosis health claim in the 1995 proposal and after FDA's receipt
of the comment opposing FDA's proposed changes to the conditional
requirement in Sec. 101.72(c)(2)(i)(E).
In 1997 the IOM conducted a major review of bone-related nutrients
(Ref. 4). A goal of the DRI effort was to determine the level of
nutrient intake for normal, healthy individuals that would prevent the
development of a chronic condition associated with that nutrient (Ref.
5). The DRIs for calcium, which were based on life stages and gender,
were set at intake levels of calcium to achieve adequate calcium
balance in the body (i.e., AI) and intake levels of calcium that pose
no risk of adverse health effects (i.e., UL). The AI for infants up to
6 months of age is 210 mg/day, for infants ages 7 months through 12
months it is 270 mg/day, for children ages 1 through 3 it is 500 mg/
day, for children ages 4 through 8 years it is 800 mg/day, for young
adults ages 9 through 18 it is 1,300 mg/day, for individuals aged 19
through 50 it is 1,000 mg/day, for individuals ages 51 and above it is
1,200 mg/day, for pregnant and lactating women ages 14 through 18 it is
1,300 mg/day, and for pregnant and lactating women aged 19 and older it
is 1,000 mg/day. The UL for all individuals ages 1 and above is 2,500
mg/day (Ref. 5).
The concept of a threshold level of calcium beyond which no further
bone benefit occurs is not presented in either the 2004 Surgeon
General's Report or the 2000 NIH Consensus Statement (Refs. 2 and 4).
Instead these reports discuss the level of calcium at which calcium
poses no risk of adverse health effects (i.e., UL).
When the calcium and osteoporosis health claim was initially
proposed the scientific evidence supported the concept that a threshold
nutrient intake level existed for calcium, below which bone health was
jeopardized, and above which no further benefit to bone health occurred
(56 FR 60689 at 60692 and 60695). Based on two observational studies
that reflected findings that calcium intakes of 800 to 1,000 mg of
calcium a day appear to be the upper level of calcium intake beyond
which no benefit to bone status has been observed and the observation
that higher amounts of calcium are needed in old age, FDA proposed to
require that a calcium and osteoporosis claim state that a total
dietary intake of calcium greater than 200 percent of the RDI has no
known additional benefit (56 FR 60689 at 60698). At the time of the
1991 proposal, the proposed RDI for calcium was 950 mg; 200 percent of
the RDI was 1,800 mg.
The agency's current thinking is that a statement reflecting the
limit on the benefit derived from dietary calcium intake, as derived in
the 1991 proposed rule, is no longer the appropriate approach.
Thus, FDA has tentatively concluded not to require a statement
about no known further benefit for foods containing 40 percent or more
of the RDI of 1,000 mg or 400 mg calcium per RACC. Accordingly, FDA is
proposing to eliminate the requirement in Sec. 101.72(c)(2)(i)(E). The
agency requests comments on the proposed amendment to eliminate the
requirement in Sec. 101.72(c)(2)(i)(E).
V. Description of Modifications to Sec. 101.72
A. Title of the Regulation
FDA is proposing to revise the title of the regulation to: ``Health
claims: calcium, vitamin D, and osteoporosis.'' This proposed amendment
is necessary to reflect the additional claim for calcium and vitamin D
and osteoporosis.
B. General Requirements
1. General requirements
Current Sec. 101.72(a) is entitled ``Relationship between calcium
and osteoporosis.'' FDA is proposing to revise Sec. 101.72 to permit
additional claims for calcium and vitamin D and osteoporosis. Thus,
proposed Sec. 101.72(a) includes information describing the effects of
vitamin D on calcium in reducing the risk of osteoporosis, including
the scientific evidence that establishes the role of vitamin D in
enhancing the effects of calcium in terms of bone health. As a result,
FDA is proposing to revise the title for Sec. 101.72(a) to
``Relationship between calcium, vitamin D, and osteoporosis.''
Current Sec. 101.72(b) sets out the significance of calcium on
osteoporosis, describes the various factors that play a role in the
development of osteoporosis, a multifactorial bone disease, and
stipulates that adequate calcium intake is not the only recognized risk
factor for osteoporosis. Since FDA is proposing to amend Sec. 101.72
so that additional claims can be made for calcium and vitamin D and
osteoporosis, Sec. 101.72 (b) will need to address the significance of
calcium as well as the significance of calcium and vitamin D on
osteoporosis. Therefore, FDA is proposing to: (1) Revise the title of
Sec. 101.72(b) to ``Significance of calcium or calcium and vitamin D''
and (2) make it clear that adequate calcium intake or adequate calcium
and vitamin D intake are not the only recognized risk factors in the
development of osteoporosis.
Current Sec. 101.72(b)(1) sets out key factors of heredity and
being female for identifying those individuals most at risk for
developing osteoporosis, and includes information on peak bone mass for
Caucasian, Asian women, and American women of African heritage. FDA is
proposing to remove Sec. 101.72(b)(1).
Current Sec. 101.72(b)(2) discusses the importance of maintenance
of an adequate intake of calcium throughout life for the target
subpopulation of adolescent and young adult Caucasian and Asian women.
If FDA eliminates, as proposed, the requirement that the claim identify
adolescent and young adult Caucasian and Asian women between the ages
of 11 and 35, as the populations at particular risk for the development
of osteoporosis, Sec. 101.72(b)(2) would no longer be appropriate.
Therefore, FDA is proposing to update the information in Sec.
101.72(b)(2) and include it in proposed Sec. 101.72(b). Thus, proposed
Sec. 101.72(b) will include information about the importance of
maintenance of adequate calcium or adequate calcium and vitamin D
throughout life and will read as follows: ``Significance of calcium or
calcium and vitamin D. Adequate calcium intake, or adequate calcium and
vitamin D intake, is not the only recognized risk factor in the
development of osteoporosis, which is a
[[Page 511]]
multifactorial bone disease. Maintenance of adequate calcium and
vitamin D intakes throughout life is necessary to achieve optimal peak
bone mass and to reduce the risk of osteoporosis in later life.
However, vitamin D is most effective in this regard when calcium
intakes are adequate. Increasing intake of calcium has been shown to
have beneficial effects on bone health independent of dietary vitamin
D.``
2. Requirements on the Nature of the Claim
Section 101.72(c)(2)(i) contains requirements for the nature of the
claim. FDA is proposing to revise Sec. 101.72(c)(2)(i) to read as
follows: ``Nature of the claim. A health claim associating calcium, or
when appropriate, calcium and vitamin D, with a reduced risk of
osteoporosis may be made on the label or labeling of a food described
in paragraphs (c)(2)(ii) and (d)(1) of this section, provided that:''
Current Sec. 101.72(c)(2)(i)(A) contains the specific requirement
that the claim makes clear that adequate calcium intake throughout life
is not the only recognized risk factor in this multifactorial bone
disease by listing specific factors, including sex, race, and age that
place persons at risk of developing osteoporosis and stating that an
adequate level of exercise and a healthful diet are also needed. The
agency is proposing to revise Sec. 101.72(c)(2)(i)(A) to read as
follows: ``The claim makes clear the importance of adequate calcium
intake, or when appropriate, adequate calcium and vitamin D intake,
throughout life, in a healthful diet along with physical activity, are
essential to reduce osteoporosis risk. The claim does not imply that
adequate calcium intake, or when appropriate, adequate calcium and
vitamin D intake, is the only recognized risk factor for the
development of osteoporosis;''
Current Sec. 101.72(c)(2)(i)(B) contains the specific requirement
that the claim does not state or imply that the risk of osteoporosis is
equally applicable to the general U.S. population. Furthermore, the
claim shall identify the populations at particular risk for the
development of osteoporosis. These populations include white (or the
term ``Caucasian'') women and Asian women in their bone forming years
(approximately 11 to 35 years of age or the phrase ``during teen or
early adult years'' may be used). The claim may also identify
menopausal (or the term ``middle-aged'') women, persons with a family
history of the disease, and elderly (or ``older'') men and women as
being at risk. The agency is proposing to remove these specific
requirements in Sec. 101.72(c)(2)(i)(B).
Current Sec. 101.72(c)(2)(i)(C) contains the specific requirement
that the claim identify the mechanism by which calcium reduces the risk
of osteoporosis. The agency is proposing to eliminate this specific
requirement and is providing in new Sec. 101.72(d)(4) that information
about the mechanism by which calcium, or when appropriate, calcium and
vitamin D, reduces the risk of osteoporosis is optional.
Current Sec. 101.72(c)(2)(i)(D) contains the specific requirement
that the claim does not attribute any degree of reduction in risk of
osteoporosis to maintaining an adequate calcium intake throughout life.
The agency is proposing to revise this specific requirement to include
information about calcium and vitamin D. Since the agency is proposing
to remove the specific requirements in Sec. 101.72(c)(2)(i)(B) and
(c)(2)(i)(C), the agency will redesignate newly revised Sec.
101.72(c)(2)(i)(D) as Sec. 101.72 (c)(2)(i)(B). Thus, Sec.
101.72(c)(2)(i)(B) will read as follows: ``The claim does not attribute
any degree of reduction in risk of osteoporosis to maintaining an
adequate dietary calcium intake, or when appropriate, an adequate
dietary calcium and vitamin D intake, throughout life.''
Current Sec. 101.72(c)(2)(i)(E) contains the specific requirement
that a calcium and osteoporosis health claim include a statement that
reflects the limit on the benefit derived from a total dietary calcium
intake of greater than 200 percent of the recommended daily intake of
calcium (2,000 mg of calcium). The agency is proposing to remove this
specific requirement.
Current Sec. 101.72(d)(1) and (d)(2) set out the optional
information that may be included in the claim. FDA is proposing to add
a new paragraph (d)(1) to include as optional the term ``vitamin D'' if
the food meets or exceeds the requirements for a ``high'' level of
vitamin D as defined in Sec. 101.54(b). Thus, proposed Sec.
101.72(d)(1) will read as follows: `` Optional information. The claim
may include the term ``vitamin D'' if the food meets or exceeds the
requirements for a ``high'' level of vitamin D as defined in Sec.
101.54(b);''
Since FDA is proposing to add new paragraph (d)(1) to Sec. 101.72,
the agency is proposing to redesignate current Sec. 101.72(d)(1) and
(d)(2) as Sec. 101.72(d)(2) and (d)(3), respectively. The agency is
also proposing to revise newly redesignated Sec. 101.72(d)(3) by
removing reference to the publication ``Dietary Guidelines for
Americans.'' FDA is proposing to take this action since the ``Dietary
Guidelines for Americans,'' may not necessarily contain information on
the number of people in the United States who have osteoporosis. Thus,
proposed Sec. 101.72(d)(3) will read as follows: ``The claim may
include information on the number of people in the United States who
have osteoporosis or low bone density. The sources of this information
must be identified, and it must be current information from the
National Center for Health Statistics, the National Institutes of
Health, or the National Osteoporosis Foundation.''
The agency is proposing to add new paragraph (d)(4) to Sec.
101.72, which will provide that the mechanism by which calcium, or when
appropriate, calcium and vitamin D, reduces the risk of osteoporosis
may be optional information in the claim. Thus, new paragraph (d)(4)
would read as follows: ``The claim may state that the role of adequate
calcium intake, or when appropriate, the role of adequate calcium and
vitamin D intake, throughout life is linked to reduced risk of
osteoporosis through the mechanism of optimizing peak bone mass during
adolescence and early adulthood. The phrase ``build and maintain good
bone health'' may be used to convey the concept of optimizing peak bone
mass. When reference is made to persons with a family history of the
disease, menopausal women, and elderly men and women, the claim may
also state that adequate intake of calcium, or adequate intake of
calcium and vitamin D, if applicable, is linked to reduced risk of
osteoporosis through the mechanism of slowing the rate of bone loss.''
Since many of the amendments FDA is proposing will alter language
used in the calcium and osteoporosis or the additional calcium and
vitamin D and osteoporosis health claim, FDA is proposing to revise
Sec. 101.72(e) to provide model health claims for the calcium and
osteoporosis health claim and to add new paragraph (f) to Sec. 101.72
to provide model health claims for the additional calcium and vitamin D
and osteoporosis health claim.
The agency invites comments to any or all of the proposed
amendments to Sec. 101.72.
VI. Analysis of Economic Impacts
A. Preliminary Regulatory Impact Analysis
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded
[[Page 512]]
Mandates Reform Act of 1995 (Public Law 104-4). Executive Order 12866
directs agencies to assess all costs and benefits of available
regulatory alternatives and, when regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). The agency believes that
this proposed rule is not a significant regulatory action as defined by
the Executive order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant economic impact
of a rule on small entities. The proposed rule, if finalized, amends
the current calcium and osteoporosis health claim language and would
require changes to the claim language on products currently bearing the
health claim. Thus, the only mandatory costs of this proposed rule, if
finalized, would be the costs to update the current wording of the
calcium and osteoporosis health claim on those products that currently
bear the claim. Based on FDA's 2001 Food Labeling and Product Survey
(FLAPS) (see discussion in section VI.A.2 ``Background'' of this
document), very few products bear the calcium and osteoporosis health
claim. Therefore, because of the limited use of the current calcium and
osteoporosis health claim, the agency certifies that the proposed rule
will not have a significant economic impact on a substantial number of
small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $122 million, using the most current (2005) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
proposed rule to result in any 1-year expenditure that would meet or
exceed this amount and has determined that this proposed rule does not
constitute a significant rule under the Unfunded Mandates Reform Act.
1. Need for This Regulation
Current regulations do not permit food producers to claim health
benefits for products by linking the intake of vitamin D, when combined
with the intake of calcium, with a reduced risk of osteoporosis.
However, current regulations do permit food producers to claim health
benefits for products by linking calcium intake with a reduced risk of
osteoporosis only if they also list the specific risk factors and at-
risk subpopulations for osteoporosis, the mechanism by which calcium
reduces the risk of osteoporosis, and the limit of the benefits of
dietary calcium at certain levels.
Health claims can inform consumers about diet-disease relationships
and encourage producers to produce more healthful foods. This proposed
rule would allow producers to make more nutrition information related
to osteoporosis available to consumers (linking the intake of calcium
and vitamin D to the risk of osteoporosis), while eliminating other
information currently required to be given to consumers when claiming
health benefits relating to the link between calcium intake and the
risk of osteoporosis.
2. Background
Osteoporosis represents a major public health problem in the United
States. This disease affects more than 10 million individuals and
causes approximately 1.5 million fractures annually. Every year, these
lead to 2.6 million physician office visits, 800,000 emergency room
visits, and more than 500,000 hospitalizations, and the placement of
nearly 180,000 people into nursing homes. The direct care expenditures
for osteoporotic fractures alone range from $12 to $18 billion each
year (measured in 2002 dollars) (Ref. 4). The indirect health costs,
such as pain, suffering, and lost mobility, of osteoporosis are also
large. Average calcium and vitamin D intakes are below recommended
levels for many consumers (Refs. 4, 49, and 50). Even though many
consumers are not achieving recommended intakes of calcium, producers
have rarely placed the calcium-osteoporosis health claim on products
that qualified for the claim. FDA's 2001 FLAPS (the most recently
available data) showed only 1 out of the 87 shelf-stable juice products
surveyed, a fortified orange juice, bearing the calcium osteoporosis
health claim. None of the 10 milk products surveyed bore the claim
(Ref. 51).
3. Regulatory Options
FDA has identified four regulatory options for this proposed rule:
(1) Take no new regulatory action; (2) reduce the required language in
the existing calcium-osteoporosis health claim; (3) expand the existing
calcium-osteoporosis health claim to include vitamin D; or (4) reduce
the required language in the existing calcium osteoporosis health claim
and include vitamin D as an option to the claim, as described in this
proposed rule.
4. Changes in Market Behavior in Response to Options
This proposed rule, if finalized as proposed, would require that
any food manufacturers wishing their products' labels to make the
calcium, or calcium and vitamin D, and osteoporosis health claim be
redesigned. Labels must be redesigned in order for a food to carry the
health claim since information on populations at particular risk for
osteoporosis would no longer be required or allowed for the claim (see
Sec. 101.72(c)(2)(A) and (c)(2)(B)).
Products that wish to continue making a calcium health claim would
not need to reformulate their products under the proposed rule. The
nature of the food eligible to make a calcium health claim remains food
that meets or exceeds a ``high'' level of calcium (as defined in Sec.
101.54(b)). Manufacturers wishing to take advantage of the expanded
calcium and vitamin D claim may voluntarily choose to reformulate their
products. If some producers choose to reformulate their products to
take advantage of the calcium and vitamin D health claim, they reveal
that they expect the private benefit that the claims give them to
exceed the expense of making the claims. If this is not the case, no
producer will voluntarily choose to use the claims. Likewise, consumers
who choose to purchase the products with the amended health claims
reveal that they value the products more highly than other
alternatives, including not purchasing the products.
We consider five potential effects in estimating the relative
public health benefits of the options: (1) The extent to which the
option encourages producers to use the health claims on their food
labels; (2) the extent to which the option encourages producers to
reformulate their products to make the health claims; (3) the extent to
which the option provides information to consumers; (4) potential risk-
risk tradeoffs (where the action taken to reduce the risk posed by one
hazard causes an increase in the risk posed by another hazard) with
each option; and (5) the availability of information on the
relationship between osteoporosis and calcium and vitamin D to
consumers who do not consume dairy products.
Producer responses
There are four likely responses to this proposal from producers:
(1) Make no
[[Page 513]]
changes (i.e., continue not making the calcium or calcium and vitamin D
health claim; (2) create new product labels to continue making the
calcium health claim (for products already making the existing claim);
(3) add the health claims to their products that qualify for the health
claims (increase usage of the claim due to the new required wording);
and (4) reformulate their products (by fortifying with calcium or
vitamin D, for example) to qualify for the health claims.
Several factors affect whether producers choose to use health
claims, including the flexibility of the health claims and how
appealing the health claims are to consumers. Revising the existing
calcium osteoporosis health claim language to make it shorter will make
it more appealing to put the health claims on labels. Package space is
limited, so more flexible and shorter claims are easier to use. Also,
Wansink, et al. (2004) found that shorter health claims on the front of
the package led to more favorable beliefs about the product and a more
positive image of the product among consumers (Ref. 52).
Approving a calcium, vitamin D, and osteoporosis health claim
should encourage the manufacturers of foods that are eligible for
fortification with vitamin D to do so because they will be able to
publicize the relationship between vitamin D, calcium, and osteoporosis
on their labels. If producers fortify more products with vitamin D,
consumers can get more vitamin D in their diet without making changes
in their dietary choices.
Consumer responses
Providing information about the relationship between calcium,
vitamin D, and osteoporosis on food packages provides a number of
benefits to consumers, including: (1) Informing them about the
nutrient-disease relationship; (2) helping them identify products that
are high in calcium and vitamin D; and (3) helping them make dietary
choices that reduce their risk of osteoporosis. The extent to which
consumers realize these benefits will depend on the consumers knowledge
of the relationship between calcium, vitamin D, and bone health; how
many products bear the calcium or calcium and vitamin D health claims;
how many consumers read the health claims; and how much they change
their behavior to include such products in their diets. There is
evidence that consumers who read nutrition information on packages eat
healthier diets (Refs. 53 and 54). However, there is a great deal of
uncertainty about how much consumers change their behavior in response
to label information.
Risk-risk tradeoffs
A potential concern is that allowing these osteoporosis health
claims on juice drinks will result in consumers switching away from
milk to juice drinks, which are higher in calories, for dietary sources
of calcium and vitamin D. Table 1 of this document presents the caloric
and nutrient profile of non-fat and low-fat milk products and an orange
juice drink product as reported in the USDA National Nutrient Database
for Standard Reference. Orange juice drinks are higher in calories and
contain less of some important nutrients than either non-fat or low-fat
milk (table 1 of this document).
Table 1: Profiles of Selected Nutrients in Non-fat and Low-fat Milk and
Orange Juice Drink (per 8-ounce serving)
------------------------------------------------------------------------
(2) Non- (3) Low
fat Fat
(1) Milk Milk
Orange (Skim), (1%),
Nutrient juice with with
drink added added
vitamin vitamin
A A
------------------------------------------------------------------------
Energy, kcal 134 83 102
------------------------------------------------------------------------
Protein, g 0.5 8.25 8.22
------------------------------------------------------------------------
Total Fat, g 0 0.2 2.37
------------------------------------------------------------------------
Saturated Fat, g 0 0.286 1.545
------------------------------------------------------------------------
Carbohydrate, g 33.36 12.14 12.18
------------------------------------------------------------------------
Total Dietary Fiber, g 0.5 0 0
------------------------------------------------------------------------
Total Sugars, g 23.29 12.46 12.69
------------------------------------------------------------------------
Calcium, mg 5 306 290
------------------------------------------------------------------------
Iron, mg 0.27 0.07 0.07
------------------------------------------------------------------------
Magnesium, mg 7 27 27
------------------------------------------------------------------------
Phosphorus, mg 10 247 232
------------------------------------------------------------------------
Potassium, mg 104 382 366
------------------------------------------------------------------------
Sodium, mg 5 103 107
------------------------------------------------------------------------
Zinc, mg 0.05 1.03 1.02
------------------------------------------------------------------------
Copper, mg 0.045 0.032 0.024
------------------------------------------------------------------------
Manganese, mg 0.017 0.007 0.007
------------------------------------------------------------------------
Selenium, mcg 0 7.6 8.1
------------------------------------------------------------------------
Vitamin C, mg 37.3 0 0
------------------------------------------------------------------------
Thiamin, mg 0.945 0.11 0.049
------------------------------------------------------------------------
[[Page 514]]
Riboflavin, mg 1.07 0.446 0.451
------------------------------------------------------------------------
Niacin, mg 12.44 0.23 0.227
------------------------------------------------------------------------
Pantothenic acid, mg 0.149 0.874 0.881
------------------------------------------------------------------------
Vitamin B-6, mg 1.244 0.091 0.09
------------------------------------------------------------------------
Folate, mcg 10 12 12
------------------------------------------------------------------------
Vitamin B-12, mcg 0 1.3 1.07
------------------------------------------------------------------------
Vitamin A, IU 109 499 478
------------------------------------------------------------------------
Vitamin D, IU 0 101.46 126.77
------------------------------------------------------------------------
Cholesterol, mg 0 5 12
------------------------------------------------------------------------
The likelihood of consumers switching from non-fat or low-fat milk
or to higher caloric juice drinks because of this rule is expected to
be small because non-fat and low-fat milk and juice drinks that are
eligible can already make the existing calcium and osteoporosis health
claim. Permitting the same set of products to make the proposed,
simpler calcium and osteoporosis health claim should not change the
relative appeal of the claim to producers of one type of beverage over
another. The allowance of the new calcium and vitamin D osteoporosis
health claim could expand the set of products making an osteoporosis
claim; however, the relative appeal of the new claim (calcium and
vitamin D) to producers of non-fat and low-fat milk and juice drinks
should be similar to the appeal of the existing calcium osteoporosis
claim.
There is little evidence to support that consumers would switch
from non-fat or low-fat milk to juice drinks as a result of this
proposed rule. As stated in the Surgeon General's report on bone health
and osteoporosis, consuming adequate levels of calcium and vitamin D
throughout life are critically important to an individual's bone
health. However, the report's review of national surveys suggests that
the average calcium intake of individuals is far below the levels
recommended for optimal bone health. One reason cited by the report for
these low levels of calcium intake relates to current lifestyle and
food preferences, which have resulted in reduced intake of dairy
products and other naturally occurring calcium-rich foods. The report
also posits that for some individuals lactose intolerance\3\ may also
play a role in not consuming adequate levels of calcium. Given this
information on the current preference and tolerance for dairy products,
expanding the calcium and osteoporosis health claim to include vitamin
D as a result of this proposed rule should only lead to an increase in
the overall consumption of these essential, under consumed nutrients.
---------------------------------------------------------------------------
\3\Lactose intolerance is a condition in which individuals
cannot metabolize lactose, the main sugar found in milk and other
calcium-rich dairy products. Information in the Surgeon General's
report on bone health and osteoporosis indicates that an estimated
30 to 50 million Americans are affected by lactose intolerance,
although to varying degrees.
---------------------------------------------------------------------------
In addition, according to the American Beverage Association, U.S.
sales of calcium-fortified orange juice has grown dramatically over
recent years, reaching nearly $1 billion in 2003 (Ref. 55), while
overall sales of juice have not grown. Therefore, FDA expects that the
nutritional profile of diets would most likely improve as a consequence
of changes in consumption resulting from this proposed rule. Switching
from unfortified to fortified juices would increase needed consumption
of calcium and vitamin D.
5. Benefits and Costs of Regulatory Options
The simplification of the current health claim for calcium and
osteoporosis, along with the additional proposed health claim for
calcium, vitamin D, and osteoporosis should increase and expand the
current usage of the health claim and therefore improve the U.S.
population's intake of these two important nutrients. Therefore, all of
the options considered below would improve public health relative to
the baseline of taking no new regulatory action. In our analysis of the
benefits and costs of the options, we compare the benefits and costs of
each option with each other option based on their relative effects on
consumer and producer behavior.
Option 1: Take no new regulatory action
This option would result in no change to the current situation.
This is the baseline for comparison of options and entails no costs or
benefits.
Option 2: Reduce the required language in the existing calcium
osteoporosis health claim.
Compared with Option 1, this option would increase the appeal of
the claim for producers, increase the use of the claim on products, and
thereby provide consumers with more information on the calcium and
osteoporosis diet-disease relationship. It could encourage more
reformulation of products to fortify with calcium than has occurred
with the existing claim. Like Option 1, this option provides consumers
with no information about the relationship of vitamin D to
osteoporosis.
With this option, manufacturers of some products making the current
calcium and osteoporosis health claim may have to re-label their
products to reflect the updated wording provided by the proposed claim.
The potential costs associated with a required label change will vary
depending on when the new effective compliance date is established.
Table 2 of this document shows the possible range of costs by product
type of having to re-label to be in compliance with the revised calcium
and osteoporosis health claim. The product re-labeling costs were
estimated using the FDA Labeling Cost Model (Ref. 56). The costs of re-
labeling included are administrative, graphic, prepress,
[[Page 515]]
engraving, and inventory costs. Re-labeling costs are shown for both a
12 month and 24 month compliance period.
Table 2: Cost of Label Changes for Option 2
----------------------------------------------------------------------------------------------------------------
12 months to comply, cost per label 24 months to comply, cost per label
----------------------------------- SKU SKU
-----------------------------------------------------------------------------
NAICS Codes Product Low Cost Med Cost High Cost Low Cost Med Cost High Cost
----------------------------------------------------------------------------------------------------------------
311421 Fruit Juices $7,478 $10,186 $15,282 $5,455 $7,595 $11,897
311411
----------------------------------------------------------------------------------------------------------------
311514 Non-fat and Low-fat $11,216 $14,086 $20,437 $7,127 $9,236 $14,327
311511 Milk, fluid, dry,
powered,
condensed,
flavored
----------------------------------------------------------------------------------------------------------------
311513 Low-fat Cheese, $6,611 $8,759 $13,758 $5,106 $6,999 $11,489
multiple types
----------------------------------------------------------------------------------------------------------------
311511 Yogurt-like $4,554 $6,490 $10,857 $4,140 $5,900 $9,880
products
----------------------------------------------------------------------------------------------------------------
325412 Dietary Supplements $9,728 $13,345 $22,834 $8,540 $11,739 $20,266
----------------------------------------------------------------------------------------------------------------
Average cost of label change $7,917 $10,573 $16,633 $6,074 $8,294 $13,572
regardless of product type
----------------------------------------------------------------------------------------------------------------
Option 3: Expand the existing calcium and osteoporosis health claim to
include vitamin D
Failing to shorten the existing calcium and osteoporosis health
claim will not make the health claim as appealing to producers and
consumers as Option 2, leading to less claim use and reformulation and
less information provided to consumers than Option 2. This option would
provide consumers with more information on vitamin D than Option 2,
should producers decide to voluntarily re-label and/or reformulate
their products to make use of the added vitamin D language.
Option 4: Reduce the required language in the existing calcium and
osteoporosis health claim and include vitamin D as an option to the
claim, as described in this proposed rule
Like Option 2, this option would increase the appeal of the calcium
and osteoporosis health claim for producers and thereby provide
consumers with more information on the calcium and osteoporosis diet-
disease relationship. Also like Option 2, producers of products with
existing calcium and osteoporosis health claim labeling will have to
revise their labeling in order to comply with the revised claim
language. Like Option 3, this option would provide consumers with more
information on vitamin D than Option 2 because the new, simplified
calcium and osteoporosis health claim can now contain information about
vitamin D as well. It could also encourage more reformulation of
products to fortify with vitamin D than would Option 2 and as many
products to fortify with calcium as Option 2.
Summary
FDA is unable to quantify the benefits of this proposed rule due to
uncertainty about the degrees of changes in consumer and producer
behavior. However according to information compiled in the Surgeon
General's report on bone health and osteoporosis, there are about 1.5
million osteoporotic fractures in the United States each year that
carry annual direct care expenditures of $12 to $18 billion per year
(2002 dollars). These fractures cause more than half a million
hospitalizations, over 800,000 emergency room encounters, more than 2.6
million physician office visits, and the placement of nearly 180,000
individuals into nursing homes annually (Ref. 4). The direct costs of
other complications from osteoporosis, and the indirect costs of these
fractures and other osteoporotic ailments (e.g., the value of
functional disability to the patient, the value of the pain and
suffering to the patient, the costs experienced by the care giver) if
calculated, would add substantially to the annual costs of this
disease. Any increase in calcium and vitamin D intake by consumers
insufficient in these nutrients as a result of this proposed rule could
possibly lower the incidence of osteoporosis and therefore the annual
costs associated with the disease.
Table 3 of this document provides a summary of the effects of the
rule, and which options create the smallest and largest behavior
changes for consumers and producers. All options should produce
positive net benefits, with the largest net benefit arising from Option
4, the proposed rule. With Option 4, the largest number of products and
labels would change, leading to the largest reduction in the risk of
osteoporosis.
Table 3: Summary of effects of options
------------------------------------------------------------------------
Effect Largest effect Smallest effect
------------------------------------------------------------------------
Encouraging producer use of the Option 4 Option 1
claims
------------------------------------------------------------------------
Encouraging fortification Option 4 Option 1
------------------------------------------------------------------------
Informing consumers Option 4 Option 1
------------------------------------------------------------------------
Informing consumers who do not Option 4 Option 1
buy dairy products about
alternative food sources for
vitamin D
------------------------------------------------------------------------
B. Small Entity Analysis (or Initial Regulatory Flexibility Analysis)
FDA has examined the economic implications of this proposed rule as
required by the Regulatory Flexibility Act (5 U.S.C. 601-612). If a
rule has a significant economic impact on a substantial number of small
entities, the Regulatory Flexibility Act requires agencies to analyze
regulatory options that would lessen the economic effect of the rule on
small entities consistent with statutory objectives. FDA does not
believe that this proposed rule will have a significant economic impact
on a substantial number of small entities because the only mandatory
costs of this rule are the costs to update the current wording of the
calcium osteoporosis
[[Page 516]]
health claim for manufacturers of products that currently make the
claim and wish to continue doing so. Also previously mentioned, FDA's
2001 Food Labeling and Product Survey showed only 1 out of 87 shelf-
stable juice products surveyed bore the current calcium and
osteoporosis health claim while none of the 10 milk products surveyed
bore the claim. This implies that not many products eligible to bear
the current claim would need to be re-labeled as a result of this
proposed rule.
In addition, FDA establishes uniform compliance dates for final
food labeling regulations in 2-year intervals. Therefore, companies
whose products currently make the calcium and osteoporosis health claim
and wish to continue doing so will have between 1 and 2 years to use
existing label inventory and expense the costs of designing revised
labeling. FDA estimates that on average, the cost to re-label a product
according to the revised health claim language will be $7,900 to
$16,600 per product if the compliance period is 12 months; and $6,100
to $13,600 per product if the compliance period is 24 months. FDA
requests comment on whether this rule will have a significant impact on
a substantial number of small entities. Manufacturers that wish to
begin using the revised calcium and osteoporosis health claim or the
new calcium, vitamin D, and osteoporosis health claim will only do so
if the benefits of labeling their products to inform consumers of the
claim outweigh the costs of doing so.
VII. Environmental Impact
The agency has determined under 21 CFR 25.32(p) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
VIII. Paperwork Reduction Act
FDA concludes that the labeling provisions of this proposed rule
are not subject to review by the Office of Management and Budget
because they do not constitute a ``collection of information'' under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). Rather the
food labeling health claim on the association between calcium only, or
calcium and vitamin D, and reduced risk osteoporosis is a ``public
disclosure of information originally supplied by the Federal government
to the recipient for the purpose of disclosure to the public'' (5 CFR
1320.3(c)(2)).
IX. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed rule, if finalized as proposed, has a preemptive effect on
State law. Section 4(a) of the Executive order requires agencies to
``construe * * * a Federal Statute to preempt State law only where the
statute contains an express preemption provision or there is some other
clear evidence that the Congress intended preemption of State law, or
where the exercise of State authority conflicts with the exercise of
Federal authority under the Federal statute.'' Section 403A of the act
(21 U.S.C. 343-1) is an express preemption provision. Section
403A(a)(5) of the act (21 U.S.C. 343-1(a)(5)) provides that: ``***no
State or political subdivision of a State may directly or indirectly
establish under any authority or continue in effect as to any food in
interstate commerce--***(5) any requirement respecting any claim of the
type described in section 403(r)(1) of the act made in the label or
labeling of food that is not identical to the requirement of section
403(r) * * *.'' Currently, this provision operates to preempt States
from imposing health claim labeling requirements concerning calcium and
vitamin D and reduced risk of osteoporosis because no such requirements
had been imposed by FDA under section 403(r) of the act. This proposed
rule, if finalized as proposed, would amend existing food labeling
regulations to add vitamin D to the authorized health claim for calcium
and a reduced risk of osteoporosis and would simplify the claim
language. Although any final rule would have a preemptive effect in
that it would preclude States from promulgating any health claim
labeling requirements for calcium or calcium and vitamin D and a
reduced risk of osteoporosis that are not identical to those that would
be required by a final rule, this preemptive effect is consistent with
what Congress set forth in section 403A of the act. Section 403A(a)(5)
of the act displaces both state legislative requirements and state
common law duties. Medtronic v. Lohr, 518 U.S. 470, 503 (1996) (Breyer,
J., concurring in part and concurring in judgment); id. at 510
(O'Connor, J., joined by Rehnquist, C.J., Scalia, J., and Thomas, J.,
concurring in part and dissenting in part); Cipollone v. Liggett Group,
Inc., 505 U.S. 504, 521 (1992) (plurality opinion); id. at 548-49
(Scalia, J., joined by Thomas, J., concurring in judgment in part and
dissenting in part).
FDA believes that the preemptive effect of this proposed rule, if
finalized as proposed, is consistent with Executive Order 13132.
Section 4(e) of the Executive order provides that ``when an agency
proposes to act through adjudication or rulemaking to preempt State
law, the agency shall provide all affected State and local officials
notice and an opportunity for appropriate participation in the
proceedings.'' FDA provided the States with an opportunity for
appropriate participation in this rulemaking when it sought input from
all stakeholders on February 17, 2006, when FDA's Division of Federal
and State Relations provided notice via fax and e-mail transmission to
State health commissioners, State agriculture commissioners, food
program directors, and drug program directors as well as FDA field
personnel of FDA's potential amendment to the health claim regulation
authorizing health claims for calcium and osteoporosis (Sec. 101.72).
The notice provided the States with further opportunity for input on
the rule. It advised the States of FDA's possible action and encouraged
the States and local governments to review the notice and to provide
any comments to the docket (Docket No. 2004P-0294), until March 2,
2006. FDA received no comments in response to the notice. FDA is also
providing an opportunity for State and local officials to comment on
this proposed rule.
In conclusion, the agency has determined that the preemptive
effects of this proposed rule are consistent with Executive Order
13132.
X. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper 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
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
XI. References
The following references have been placed on display in the
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20857, and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
(FDA has verified the Web site addresses, but FDA is not responsible
for any subsequent changes
[[Page 517]]
to the Web sites after this document publishes in the Federal
Register.)
1. The Beverage Institute for Health and Wellness, ``Petition
for Vitamin D, Calcium and Osteoporosis,'' (Docket No. 2004P-0464,
CP1), July 12, 2004.
2. Osteoporosis, Prevention, Diagnosis, and Therapy, National
Institutes of Health Consensus Statement, 17(1):1-45, March 27-19,
2000.
3. National Osteoporosis Foundation, America's Bone Health: The
State of Osteoporosis and Low Bone Mass, 2002, http://www.nof.org/advocacy/prevelence/index.htm.
4. Bone Health and Osteoporosis: A Report of the Surgeon
General, Rockville, MD: United States Department of Health and Human
Services, Office of the Surgeon General, 2004.
5. Standing Committee on the Scientific Evaluation of Dietary
Reference Intakes, Food and Nutrition Board, Institute of Medicine,
``Dietary Reference Intakes for Calcium, Phosphorus, Magnesium,
Vitamin D and Fluoride,'' Chapter 4, National Academy Press,
Washington, DC, 1997.
6. Standing Committee on the Scientific Evaluation of Dietary
Reference Intakes, Food and Nutrition Board, Institute of Medicine,
``Dietary Reference Intakes for Calcium, Phosphorus, Magnesium,
Vitamin D and Fluoride,'' Chapter 7, National Academy Press,
Washington, DC, 1997.
7. Standing Committee on the Scientific Evaluation of Dietary
Reference Intakes, Food and Nutrition Board, Institute of Medicine,
``Dietary Reference Intakes for Calcium, Phosphorus, Magnesium,
Vitamin D and Fluoride,'' Chapter 3, National Academy Press,
Washington, DC, 1997.
8. Bialostosky, K., J. Wright, J. Kennedy-Stephenson, et al.,
``Dietary Intake of Macronutrients Micronutrients and Other Dietary
Constituents: United States 1988-1994,'' National Center for Health
Statistics, Vital Health Statistics 11(245), Tables 93 and 94, 2002.
9. Erwin, R. E., J. D. Wright, and D. Read-Gillette,
``Prevalence of Leading Types of Dietary Supplements Used in the
Third National Health and Nutrition Examination Survey, 1988-1994,''
National Center for Health Statistics, Advance Data from Vital and
Health Statistics; no. 349, Hyattsville, MD: 2004.
10. Rajakumar, K., ``Vitamin D, Cod Liver Oil, Sunlight and
Rickets: A Historical Perspective,'' Pediatrics, 112:132-135, 2003.
11. Memorandum to the record, Determination of Amounts of
Vitamin D and Calcium in Common Dietary Supplement Products,
prepared by Jillonne H. Kevala, FDA, February 22, 2006.
12. Ervin, R. B., C. Y. Wang, J. D. Wright, et al., ``Dietary
Intake of Selected Minerals for the United States Population: 1999-
2000,'' National Center for Heath Statistics, Advance Data from
Vital and Health Statistics; no. 341 Hyattsville, MD: 2004.
13. Prentice, A., J-P. Bonjour, F. Branca, et al., ``PASSCLAIM--
Bone Health and Osteoporosis,'' European Journal of Nutrition,
42(Suppl 1):1/28-1/49, 2003.
14. H. F. DeLuca, ``Overview of General Physiologic Features and
Functions of Vitamin D,'' American Journal of Clinical Nutrition,
80(suppl):1689S-1696S, 2004.
15. William F. Ganong, ``Hormonal Control of Calcium Metabolism
and the Physiology of Bone,'' Chapter 21 in Review of Medical
Physiology, 21st ed., New York, McGraw-Hill Companies, 2003.
16. R. P. Heaney, ``The Importance of Calcium, Intake for
Lifelong Skeletal Health,'' Calcified Tissue International, 70:70-
73, 2002.
17. ``Guidance for Industry: Significant Scientific Agreement in
the Review of Health Claims for Conventional Foods and Dietary
Supplements,'' Rockville, MD: (http://www.cfsan.fda.gov/~dms/
ssaguide.html), December 1999.
18. Aloia, J.F., A. Vaswani, J. D. Yeh, et al., ``Calcium
Supplementation With and Without Hormone Replacement Therapy to
Prevent Postmenopausal Bone Loss,'' Annals of Internal Medicine,
120:97-103, 1994.
19. Baeksgaard, L., K. P. Andersen, and L. Hyldstrup, ``Calcium
and Vitamin D Supplementation Increases Spinal BMD in Healthy,
Postmenopausal Women,'' Osteoporosis International, 8:255-260, 1998.
20. Chapuy, M. C., M. E. Arlot, F. Duboeuf, et al., ``Vitamin
D3 and Calcium to Prevent Hip Fractures in Elderly
Women'', The New England Journal of Medicine,'' 327:1637-1642, 1992.
21. Chapuy, M. C., M.E. Arlot, P. D. Delmas, et al., ``Effect of
Calcium and Cholecalciferol Treatment for Three Years on Hip
Fractures in Elderly Women,'' British Medical Journal, 308:1081-
1082, 1994.
22. Dawson-Hughes, B., G. E. Dallal, G.E., Krall, E.A., Harris,
S., Sokoll, L.J., and G. Falconer, ``Effect of Vitamin D
Supplementation on Wintertime and Overall Bone Loss in Healthy
Postmenopausal Women,'' Annuals of Internal Medicine, 115:505-512,
1991.
23. Dawson-Hughes, B., S. S. Harris, E. A. Krall, et al.,
``Effect of Calcium and Vitamin D Supplementation on Bone Density in
Men and Women 65 Years of Age or Older,'' The New England Journal of
Medicine, 337:670-676, 1997.
24. Dawson-Hughs, B., S. S. Harris, E. A. Krall, et al., 2000
``Effect of Withdrawal of Calcium and Vitamin D Supplements on Bone
Mass in Elderly Men and Women,'' American Journal of Clinical
Nutrition, 72:745-750, 2000.
25. Grados, F., M. Brazier, S. Kamel, et al., ``Effects on Bone
Mineral Density of Calcium and Vitamin D Supplementation in Elderly
Women With Vitamin D Deficiency,'' Joint Bone Spine, 70:203-208,
2003.
26. Krieg, M. A., A. F. Jacquet, M. Bremgartner, et al.,
``Effect of Supplementation with Vitamin D3 and Calcium
on Quantitative Ultrasound of Bone in Elderly Institutionalized
Women: A Longitudinal Study,'' Osteoporosis International, 9:483-
488, 1999.
27. Orwoll, E. S., S. K. Oviatt, M. R. McClung, et al., ``The
Rate of Bone Mineral Loss in Normal Men and the Effects of Calcium
and Cholecalciferol Supplementation,'' Annuals of Internal Medicine,
112:29-34, 1990.
28. Prestwood, K. M., D. L. Thompson, A. M. Kenny, et al., ``Low
Dose Estrogen and Calcium Have an Additive Effect on Bone Resorption
in Older Women,'' Journal of Clinical Endocrinology Metabolism,
84:179-183, 1999.
29. Sosa, M., P. L[aacute]inez, A. Arbelo, et al., ``The Effect
of 25-dihydroxyvitamin D on the Bone Mineral Metabolism of Elderly
Women with Hip Fracture,'' Rheumatology, 39:1263-1268, 2000.
30. Jackson, R. D., et al., ``Calcium Plus Vitamin D
Supplementation and the Risk of Fractures, The Women's Health
Initiative,'' The New England Journal of Medicine, 354:669-683,
2006.
31. Spilker, B. in Guide to Clinical Trials, Philadelphia, PA:
Lippincott Williams & Wilkins, 2000, p. 59-64.
32. Cumming, R. G., and M. C. Nveitt, ``Calcium for Prevention
of Osteoporotic Fractures in Postmenopausal Women,'' Journal of Bone
Mineral Research, 12:1321-1329, 1997.
33. Ensrud, K. R., T. Duong, J. A. Cauley, et al., ``Low
Fractional Calcium Absorption Increases the Risk for Hip Fracture in
Women with Low Calcium Intake,'' Annuals of Internal Medicine,
132:345-353, 2000.
34. Hannan, M. T., D. T. Felson, B. Dawson-Hughes, et al.,
``Risk Factors for Longitudinal Bone Loss in Elderly Men and Women:
The Framingham Osteoporosis Study,'' Journal of Bone Mineral
Research, 15:710-720, 2000.
35. Ilich, J. Z., M. Skugor, T. Hangartner, et al., ``Relation
of Nutrition, Body Composition and Physical Activity to Skeletal
Development: A Cross-Sectional Study in Preadolescent Females,''
Journal of the American College of Nutrition, 17:136-147,1998.
36. Kardinaal, A. F. M., A. Ando, P. Charles, et al., ``Dietary
Calcium and Bone Density in Adolescent Girls and Young Women in
Europe,'' Journal of Bone Mineral Research, 14:583-592, 1999.
37. Kristinsson, J. [Ouml]., [Ouml]. Valdimarsson, G.
Sigurdsson, et al., ``Serum 25-hydorxyvitamin D Levels and Bone
Mineral Density in 16-20-Year-Old Girls: Lack of Association,''
Journal of Internal Medicine, 243:381-388, 1998.
38. Lamberg-Allardt, C. J. E., T. A. Outila, M. U. M.
K[auml]rkk[auml]inen, et al., ``Vitamin D Deficiency and Bone Health
in Healthy Adults in Finland: Could this be a Concern in Other Parts
of Europe?,'' Journal of Bone Mineral Research, 16:2066-2073, 2001.
39. Oliveri, M. B., A. Wittich, C. Mautalen, et al.,
``Peripheral Bone Mass is Not Affected by Winter Vitamin D
Deficiency in Children and Young Adults from Ushuaia,'' Calcified
Tissue International, 67:220-224, 2000.
40. Flegal, K. M., ``Evaluating Epidemiologic Evidence of the
Effects of Food and Nutrient Exposures,'' American Journal of
Clinical Nutrition, 69:1339S-1344S, 1999.
41. Reddy, M. B. and M. Love, ``The Impact of Food Processing on
the Nutritional Quality of Vitamins and Minerals,'' Advances in
Experimental Medicine and Biology, 459:99-106, 1999.
42. Sempos, C. T., K. Liu, and N.D. Ernst, ``Food and Nutrient
Exposures: What to Consider When Evaluating Epidemiologic
Evidence,'' American Journal of Clinical Nutrition, 69:1330S-1338S,
1999.
[[Page 518]]
43. National Institutes of Health, Office of the Director, ``NIH
Consensus Statement, Optimal Calcium Intake,'' vol. 12, No. 4, June
6-8, 1994.
44. Cummings, S. R. and L. J. Melton, III, ``Epidemiology and
Outcomes of Osteoporotic Fractures,'' The Lancet, 359:1761-1767,
2002.
45. Zingmond, D. S. and L. J. Melton, 3rd, and S. L. Silverman.
``Increasing Hip Fracture Incidence in California Hispanics, 1983 to
2000,'' Osteoporosis International, 8:603-610, 2004.
46. Specker B. L., L. Mulligan, and M. L. Ho, ``Longitudinal
Study of Calcium Intake, Physical Activity, and Bone Mineral Content
in Infants 6-18 Months of Age,'' Journal of Bone Mineral Research,
4:569-576, 1999.
47. Specker B., and T. Binkley, ``Randomized Trial of Physical
Activity and Calcium Supplementation on Bone Mineral Content in 3-
to 5-Year-Old Children,'' Journal of Bone Mineral Research, 18:885-
892, 2003.
48. Levy, A., Food and Drug Administration, Center for Food
Safety and Applied Nutrition, Division of Market Studies, ``Summary
Report on Health Claims Focus Groups,'' June 15, 1995.
49. Calvo, M. S., S. J. Whiting, and C. N. Barton, ``Vitamin D
Fortification in the United States and Canada: Current Status and
Data Needs,'' American Journal of Clinical Nutrition,
80(suppl):1710S-1716S, 2004.
50. Moore, C., M. M. Murphy, D. R. Keast, et al., ``Vitamin D
Intake in the United States,'' Journal of the American Dietetic
Association, 104(6):980-983, 2004.
51. U.S. Food and Drug Administration, Center for Food Safety
and Applied Nutrition, Office of Nutritional Products, Labeling, and
Dietary Supplements, ``Food Label and Package Survey 2000-2001,''
(http://www.cfsan.fda.gov/~dms/lab-flap.html), August 2004.
52. Wansink B., Sonka, S.T. and C.M. Hasler, ``Front-Label
Health Claims: When Less is More,'' Food Policy, 29(6):659-667,
2004.
53. Kim, S., R. M. Nayga, Jr., and O. Capps Jr., ``The Effect of
Food Label Use on Nutrient Intakes: An Endogenous Switching
Regression Analysis,'' Journal of Agricultural and Resource
Economics, 25(1):215-231, 2000.
54. Neuhouser, M. L., A. R. Kristal, and R. E. Patterson, ``Use
of Food Nutrition Labels Associated With Lower Fat Intake,'' Journal
of the American Dietetic Association, 99(1):45-50, 53, 1999.
55. American Beverage Association, Press Release, September 17,
2004, (http://www.ameribev.org/news-detail/index.aspx?nid=32).
56. ``Food and Drug Administration Labeling Cost Model,''
Health, Social, and Economics Research, Research Triangle Park, NC,
January 2003.
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
the authority delegated to the Commissioner of the Food and Drugs, and
redelegated to the Deputy Director for Regulatory Affairs, it is
proposed that 21 CFR part 101 be amended as follows:
PART 101--FOOD LABELING
1. The authority citation for 21 CFR part 101 continues to read as
follows:
Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342,
343, 348, 371; 42 U.S.C. 243, 264, 271.
2. Section 101.72 is revised to read as follows:
Sec. 101.72 Health claims: calcium, vitamin D, and osteoporosis.
(a) Relationship between calcium, vitamin D, and osteoporosis. An
inadequate intake of calcium or calcium and vitamin D contributes to
low peak bone mass, which has been identified as one of many risk
factors in the development of osteoporosis. Peak bone mass is the total
quantity of bone present at maturity, and experts believe that it has
the greatest bearing on whether a person will be at risk of developing
osteoporosis and related bone fractures later in life. Another factor
that influences total bone mass and susceptibility to osteoporosis is
the rate of bone loss after skeletal maturity. Vitamin D is required
for normal absorption of calcium and to prevent the occurrence of high
serum parathyroid hormone (PTH) concentration, which stimulates
mobilization of calcium from the skeleton and can lower bone mass.
Calcium, along with vitamin D and several other nutrients, is required
for normal bone mineralization. While vitamin D is required for optimal
bone mineralization, it is more effective when calcium intake is
adequate. An adequate intake of calcium and vitamin D is thought to
exert a positive effect during adolescence and early adulthood in
optimizing the amount of bone that is laid down. However, the upper
limit of peak bone mass is genetically determined. The mechanism
through which adequate intakes of calcium and vitamin D and optimal
peak bone mass reduce the risk of osteoporosis is thought to be as
follows. All persons lose bone with age. Hence, those with higher bone
mass at maturity take longer to reach the critically reduced mass at
which bones can fracture easily. The rate of bone loss after skeletal
maturity also influences the amount of bone present at old age and can
influence an individual's risk of developing osteoporosis. Maintenance
of adequate intakes of calcium and vitamin D later in life is thought
to be important in reducing the rate of bone loss particularly in the
elderly and in women during the first decade following menopause, but a
significant protective effect is also seen among men and younger women.
(b) Significance of calcium or calcium and vitamin D. Adequate
calcium intake, or adequate calcium and vitamin D intake, is not the
only recognized risk factor in the development of osteoporosis, which
is a multifactorial bone disease. Maintenance of adequate calcium and
vitamin D intakes throughout life is necessary to achieve optimal peak
bone mass and to reduce the risk of osteoporosis in later life.
However, vitamin D is most effective in this regard when calcium intake
is adequate. Increasing intake of calcium has been shown to have
beneficial effects on bone health independent of dietary vitamin D.
(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 calcium or, when appropriate, calcium and vitamin D with a
reduced risk of osteoporosis may be made on the label or labeling of a
food described in paragraphs (c)(2)(ii) and, (d)(1) of this section,
provided that:
(A) The claim makes clear the importance of adequate calcium
intake, or when appropriate, adequate calcium and vitamin D intake,
throughout life, in a healthful diet along with physical activity, are
essential to reduce osteoporosis risk. The claim does not imply that
adequate calcium intake, or when appropriate, adequate calcium and
vitamin D intake, is the only recognized risk factor for the
development of osteoporosis;
(B) The claim does not attribute any degree of reduction in risk of
osteoporosis to maintaining an adequate dietary calcium intake, or when
appropriate, an adequate dietary calcium and vitamin D intake,
throughout life.
(ii) Nature of the food. (A) The food shall meet or exceed the
requirements for a ``high'' level of calcium as defined in Sec.
101.54(b);
(B) The calcium content of the product shall be assimilable;
(C) Dietary supplements shall meet the United States Pharmacopeia
(U.S.P.) standards for disintegration and dissolution applicable to
their component calcium salts, except that dietary supplements for
which no U.S.P. standards exist shall exhibit appropriate
assimilability under the conditions of use stated on the product label;
(D) A food or total daily recommended supplement intake shall not
contain more phosphorus than calcium on a weight per weight basis.
[[Page 519]]
(d) Optional information. (1) The claim may include the term
``vitamin D'' if the food meets or exceeds the requirements for a
``high'' level of vitamin D as defined in Sec. 101.54(b);
(2) The claim may include information from paragraphs (a) and (b)
of this section.
(3) The claim may include information on the number of people in
the United States who have osteoporosis or low bone density. The
sources of this information must be identified, and it must be current
information from the National Center for Health Statistics, the
National Institutes of Health, or the National Osteoporosis Foundation.
(4) The claim may state that the role of adequate calcium intake,
or when appropriate, the role of adequate calcium and vitamin D intake,
throughout life is linked to reduced risk of osteoporosis through the
mechanism of optimizing peak bone mass during adolescence and early
adulthood. The phrase ``build and maintain good bone health'' may be
used to convey the concept of optimizing peak bone mass. When reference
is made to persons with a family history of the disease, menopausal
women, and elderly men and women, the claim may also state that
adequate intake of calcium or adequate intake of calcium and vitamin D,
if applicable, is linked to reduced risk of osteoporosis through the
mechanism of slowing the rate of bone loss.
(e) Model health claims. The following model health claims may be
used in food labeling to describe the relationship between calcium and
osteoporosis:
Physical activity and adequate calcium throughout life, as part of a
well-balanced diet, may reduce the risk of osteoporosis.
Adequate calcium as part of a healthful diet, along with physical
activity, may reduce the risk of osteoporosis in later life.
(f) Model additional health claims for calcium and vitamin D. The
following model health claims may be used in food labeling to describe
the relationship between calcium, vitamin D, and osteoporosis:
Physical activity and adequate calcium and vitamin D throughout
life, as part of a well-balanced diet, may reduce the risk of
osteoporosis.
Adequate calcium and vitamin D as part of a healthful diet,
throughout life along with physical activity, may reduce the risk of
osteoporosis in later life.
Dated: December 18, 2006.
Michael M. Landa,
Deputy Director, Regulatory Affairs, Center for Food Safety and Applied
Nutrition.
[FR Doc. E6-22573 Filed 1-4-07; 8:45 am]
BILLING CODE 4160-01-S