Food Labeling: Health Claims; Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis, 497-519 [E6-22573]
Download as PDF
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
DATE OF PUBLICATION IN THE
FEDERAL REGISTER].
Issued in Washington, DC, on December
27, 2006.
James Ballough,
Director, Flight Standards Service.
[FR Doc. 06–9989 Filed 1–4–07; 8:45 am]
BILLING CODE 4910–13–P
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.
cprice-sewell on PROD1PC66 with PROPOSALS
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 § 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
§ 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 § 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
§ 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)
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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: https://
www.regulations.gov. Follow the
instructions for submitting comments.
• Agency Web site: https://
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 email. 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 https://
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 https://
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:
PO 00000
Frm 00027
Fmt 4702
Sfmt 4702
497
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
§ 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
§ 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,
E:\FR\FM\05JAP1.SGM
05JAP1
cprice-sewell on PROD1PC66 with PROPOSALS
498
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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)).
The regulations require the evidence
supporting a health claim to be
presented to FDA for review before the
claim may appear in labeling
(§§ 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 (§ 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
1FDA 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).
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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 § 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
§ 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
PO 00000
Frm 00028
Fmt 4702
Sfmt 4702
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 (§ 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).
Specifically, the petitioner’s proposed
amendments to § 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 § 101.72(c)(2)(i)(A)
regarding race, age, gender, and the
need for physical activity; (3) eliminate
the requirement in § 101.72(c)(2)(i)(B)
that the claim identify the population at
particular risk for osteoporosis; (4)
eliminate the requirement in
§ 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
2Although 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 § 101.72,
which applies to both conventional food and
dietary supplements.
E:\FR\FM\05JAP1.SGM
05JAP1
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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 § 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).
cprice-sewell on PROD1PC66 with PROPOSALS
B. Nature of the Substance
The petition requested, among other
things, that FDA amend the calcium and
osteoporosis health claim (§ 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.
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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 § 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
(§ 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 (§ 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
PO 00000
Frm 00029
Fmt 4702
Sfmt 4702
499
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
(§ 101.14(b)(3)(i)). Nutritive value as
defined in § 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 § 101.14(b)(3)(i)
is satisfied.
3. The Substances are Safe and Lawful
Under § 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
§ 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
E:\FR\FM\05JAP1.SGM
05JAP1
cprice-sewell on PROD1PC66 with PROPOSALS
500
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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 § 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 § 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
(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
(§ 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
((§ 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
(§ 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 noobserved-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
PO 00000
Frm 00030
Fmt 4702
Sfmt 4702
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 § 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
E:\FR\FM\05JAP1.SGM
05JAP1
cprice-sewell on PROD1PC66 with PROPOSALS
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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
§ 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, § 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, § 166.110 permits
fortification of margarine (330 IU/100 g)
and the newly issued § 172.380 permits
the addition of vitamin D3 to calciumfortified 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.
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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 § 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
PO 00000
Frm 00031
Fmt 4702
Sfmt 4702
501
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
(§ 184.1950) or the food additive
regulation (§ 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
§ 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).
E:\FR\FM\05JAP1.SGM
05JAP1
cprice-sewell on PROD1PC66 with PROPOSALS
502
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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-
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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
PO 00000
Frm 00032
Fmt 4702
Sfmt 4702
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
§ 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 (§ 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,
E:\FR\FM\05JAP1.SGM
05JAP1
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
cprice-sewell on PROD1PC66 with PROPOSALS
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 1,25dihydroxy-vitamin D3 (calcitriol) (Ref.
6). Vitamin D2 or D3 is hydroxylated at
the 25 position in the liver to produce
25-hydroxy-vitamin D3 (25hydroxycholecalciferol), 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). 1,25dihydroxy-vitamin D3 acts directly on
intestinal mucosal cells to increase
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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-dihydroxyvitamin 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 1,25dihydroxy-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 (§ 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
PO 00000
Frm 00033
Fmt 4702
Sfmt 4702
503
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
E:\FR\FM\05JAP1.SGM
05JAP1
cprice-sewell on PROD1PC66 with PROPOSALS
504
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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 3year, randomized, double-blind placebocontrolled 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 (µg) 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 placebocontrolled study, calcium and vitamin D
supplementation resulted in
significantly fewer hip and nonvertebral 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 3year randomized, double-blind placebocontrolled 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
remained significantly higher in men
previously given calcium and vitamin D
(Ref. 24).
Kreig et al. (1999) (Ref. 26) was a 2year 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.
PO 00000
Frm 00034
Fmt 4702
Sfmt 4702
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
E:\FR\FM\05JAP1.SGM
05JAP1
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
cprice-sewell on PROD1PC66 with PROPOSALS
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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
‘‘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 § 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 § 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
(§ 101.72(c)(2)(ii)). Those requirements
PO 00000
Frm 00035
Fmt 4702
Sfmt 4702
505
are that: (1) The food shall meet or
exceed the requirements for a ‘‘high’’
level of calcium as defined in
§ 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
§ 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 § 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 § 101.72, (2) meet or exceed the
requirements for a ‘‘high’’ level of
vitamin D as defined in § 101.54(b), and
(3) meet all of the general health claim
requirements set forth in § 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:
E:\FR\FM\05JAP1.SGM
05JAP1
506
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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.
cprice-sewell on PROD1PC66 with PROPOSALS
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 § 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
§ 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
§ 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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
§ 101.72(c)(2)(i)(A). Accordingly, FDA
proposed to simplify § 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
§ 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 § 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
§ 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 § 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 § 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
PO 00000
Frm 00036
Fmt 4702
Sfmt 4702
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
E:\FR\FM\05JAP1.SGM
05JAP1
cprice-sewell on PROD1PC66 with PROPOSALS
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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 wellbalanced 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 § 101.72(c)(2)(i)(A) for
consistency with the general
requirement in § 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 § 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.
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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
§ 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 § 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
PO 00000
Frm 00037
Fmt 4702
Sfmt 4702
507
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
§ 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
§ 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
E:\FR\FM\05JAP1.SGM
05JAP1
cprice-sewell on PROD1PC66 with PROPOSALS
508
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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 § 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
§ 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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 § 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
§ 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 § 101.72(c)(2)(i)(B)
PO 00000
Frm 00038
Fmt 4702
Sfmt 4702
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
§ 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
E:\FR\FM\05JAP1.SGM
05JAP1
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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.
cprice-sewell on PROD1PC66 with PROPOSALS
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
§ 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 § 101.72(c)(2)(i)(C).
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
F. Elimination of the Requirement in
§ 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
§ 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 § 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
§ 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
§ 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
PO 00000
Frm 00039
Fmt 4702
Sfmt 4702
509
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
E:\FR\FM\05JAP1.SGM
05JAP1
510
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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.
cprice-sewell on PROD1PC66 with PROPOSALS
2. The Beverage Institute for Health and
Wellness Petition
The petitioner proposed to adopt the
amendments to § 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
§ 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 § 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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
§ 101.72(c)(2)(i)(E). The agency requests
comments on the proposed amendment
to eliminate the requirement in
§ 101.72(c)(2)(i)(E).
V. Description of Modifications to
§ 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 § 101.72(a) is entitled
‘‘Relationship between calcium and
osteoporosis.’’ FDA is proposing to
revise § 101.72 to permit additional
claims for calcium and vitamin D and
PO 00000
Frm 00040
Fmt 4702
Sfmt 4702
osteoporosis. Thus, proposed § 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
§ 101.72(a) to ‘‘Relationship between
calcium, vitamin D, and osteoporosis.’’
Current § 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 § 101.72 so that additional
claims can be made for calcium and
vitamin D and osteoporosis, § 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 § 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 § 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
§ 101.72(b)(1).
Current § 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,
§ 101.72(b)(2) would no longer be
appropriate. Therefore, FDA is
proposing to update the information in
§ 101.72(b)(2) and include it in
proposed § 101.72(b). Thus, proposed
§ 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
E:\FR\FM\05JAP1.SGM
05JAP1
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
cprice-sewell on PROD1PC66 with PROPOSALS
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
§ 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 § 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
§ 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 § 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
being at risk. The agency is proposing to
remove these specific requirements in
§ 101.72(c)(2)(i)(B).
Current § 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 § 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 § 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 § 101.72(c)(2)(i)(B) and
(c)(2)(i)(C), the agency will redesignate
newly revised § 101.72(c)(2)(i)(D) as
§ 101.72 (c)(2)(i)(B). Thus,
§ 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 § 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 § 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 § 101.54(b). Thus, proposed
§ 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
§ 101.54(b);’’
Since FDA is proposing to add new
paragraph (d)(1) to § 101.72, the agency
is proposing to redesignate current
§ 101.72(d)(1) and (d)(2) as
§ 101.72(d)(2) and (d)(3), respectively.
The agency is also proposing to revise
newly redesignated § 101.72(d)(3) by
removing reference to the publication
‘‘Dietary Guidelines for Americans.’’
PO 00000
Frm 00041
Fmt 4702
Sfmt 4702
511
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
§ 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 § 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 § 101.72(e) to
provide model health claims for the
calcium and osteoporosis health claim
and to add new paragraph (f) to § 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
§ 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
E:\FR\FM\05JAP1.SGM
05JAP1
cprice-sewell on PROD1PC66 with PROPOSALS
512
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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 1year 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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-
PO 00000
Frm 00042
Fmt 4702
Sfmt 4702
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
§ 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 § 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
E:\FR\FM\05JAP1.SGM
05JAP1
513
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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)
Nutrient
(2) Non-fat Milk (Skim),
with added vitamin A
(1) Orange juice drink
Energy, kcal
134
(3) Low Fat Milk (1%),
with added vitamin A
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
Total Dietary Fiber, g
12.14
0.5
Total Sugars, g
12.18
0
23.29
0
12.46
12.69
5
Iron, mg
0.27
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
cprice-sewell on PROD1PC66 with PROPOSALS
Calcium, 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
0.11
0.049
Thiamin, mg
VerDate Aug<31>2005
306
0.07
0.945
15:47 Jan 04, 2007
Jkt 211001
PO 00000
Frm 00043
Fmt 4702
290
Sfmt 4702
E:\FR\FM\05JAP1.SGM
0.07
05JAP1
514
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
TABLE 1: PROFILES OF SELECTED NUTRIENTS IN NON-FAT AND LOW-FAT MILK AND ORANGE JUICE DRINK (PER 8-OUNCE
SERVING)—Continued
Nutrient
(2) Non-fat Milk (Skim),
with added vitamin A
(1) Orange juice drink
Riboflavin, mg
(3) Low Fat Milk (1%),
with added vitamin A
1.07
0.451
12.44
Niacin, mg
0.446
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
Vitamin B–12, mcg
0
Vitamin A, IU
Cholesterol, mg
1.07
15:47 Jan 04, 2007
478
101.46
126.77
0
Jkt 211001
499
0
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
VerDate Aug<31>2005
12
1.3
109
Vitamin D, IU
cprice-sewell on PROD1PC66 with PROPOSALS
12
5
intolerance3 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.
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
3Lactose 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.
PO 00000
Frm 00044
Fmt 4702
Sfmt 4702
12
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 dietdisease 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,
E:\FR\FM\05JAP1.SGM
05JAP1
515
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
engraving, and inventory costs. Relabeling 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 SKU
NAICS Codes
Product
311421
311411
Fruit Juices
311514
311511
Low Cost
Med Cost
24 months to comply, cost per label SKU
High Cost
Low Cost
Med Cost
High Cost
$7,478
$10,186
$15,282
$5,455
$7,595
$11,897
Non-fat and Low-fat Milk, fluid,
dry, powered, condensed, flavored
$11,216
$14,086
$20,437
$7,127
$9,236
$14,327
311513
Low-fat Cheese, multiple types
$6,611
$8,759
$13,758
$5,106
$6,999
$11,489
311511
Yogurt-like products
$4,554
$6,490
$10,857
$4,140
$5,900
$9,880
325412
Dietary Supplements
$9,728
$13,345
$22,834
$8,540
$11,739
$20,266
$7,917
$10,573
$16,633
$6,074
$8,294
$13,572
cprice-sewell on PROD1PC66 with PROPOSALS
Average cost of label change 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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
PO 00000
Frm 00045
Fmt 4702
Sfmt 4702
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
claims
Option 4
Option 1
Encouraging fortification
Option 4
Option 1
Informing consumers
Option 4
Option 1
Informing consumers who do
not buy dairy
products about
alternative food
sources for vitamin D
Option 4
Option 1
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
E:\FR\FM\05JAP1.SGM
05JAP1
516
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
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 relabeled 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 relabel 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.
cprice-sewell on PROD1PC66 with PROPOSALS
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)).
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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).
PO 00000
Frm 00046
Fmt 4702
Sfmt 4702
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 (§ 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
E:\FR\FM\05JAP1.SGM
05JAP1
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
cprice-sewell on PROD1PC66 with PROPOSALS
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,
https://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. KennedyStephenson, 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. ReadGillette, ‘‘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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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: (https://
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
PO 00000
Frm 00047
Fmt 4702
Sfmt 4702
517
Calcium Have an Additive Effect on Bone
Resorption in Older Women,’’ Journal of
Clinical Endocrinology Metabolism, 84:179–
183, 1999.
´
29. Sosa, M., P. Lainez, 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. O., O. Valdimarsson, G.
Sigurdsson, et al., ‘‘Serum 25hydorxyvitamin 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. Karkkainen, 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.
E:\FR\FM\05JAP1.SGM
05JAP1
518
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
cprice-sewell on PROD1PC66 with PROPOSALS
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,’’
(https://www.cfsan.fda.gov/~dms/labflap.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, (https://
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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
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:
§ 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
PO 00000
Frm 00048
Fmt 4702
Sfmt 4702
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 § 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 § 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.
E:\FR\FM\05JAP1.SGM
05JAP1
Federal Register / Vol. 72, No. 3 / Friday, January 5, 2007 / Proposed Rules
(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 § 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.
cprice-sewell on PROD1PC66 with PROPOSALS
(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 wellbalanced 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
VerDate Aug<31>2005
15:47 Jan 04, 2007
Jkt 211001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 101
[Docket Nos. 1994P–0390 (formerly 94P–
0390) and 1995P–0241 (formerly 95P–0241)]
Food Labeling: Nutrient Content
Claims, General Principles; Health
Claims, General Requirements and
Other Specific Requirements for
Individual Health Claims; Withdrawal in
Part
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Proposed rule; withdrawal in
part.
SUMMARY: The Food and Drug
Administration (FDA) is announcing
that it is withdrawing certain proposed
amendments of a proposed rule that
published in the Federal Register of
December 21, 1995 (60 FR 66206),
related to the calcium and osteoporosis
health claim (21 CFR 101.72). FDA is
taking action in response to a health
claim petition submitted by The
Beverage Institute for Health and
Wellness to amend the calcium and
osteoporosis claim. Elsewhere in this
issue of the Federal Register, FDA is
publishing a proposed rule to amend the
calcium and osteoporosis claim.
DATES: The proposed rule that
published on December 21, 1995 (60 FR
66206) is withdrawn in part for
§ 101.72(c)(2)(i)(A), (B), and (E) as of
January 5, 2007.
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:
I. Background
In the Federal Register of December
21, 1995, FDA published a proposed
rule entitled ‘‘Nutrient Content Claims,
General Principles; Health Claims,
General Requirements and Other
Specific Requirements for Individual
Health Claims’’ (60 FR 66206), the 1995
proposal, to amend its regulations on
health claims and nutrient content
claims to provide more flexibility in the
use of these claims on food products,
and to amend specific requirements to
certain individual health claims. FDA
took this action in response to citizen
petitions submitted by the National
Food Processors Association (NFPA)
(Docket No. 1994P–0390) and the
PO 00000
Frm 00049
Fmt 4702
Sfmt 4702
519
American Bakers Association (ABA)
(Docket No. 1995P–0241). The agency
has extended or reopened the comment
period for the 1995 proposal four times
in response to requests by stakeholders
and other FDA initiatives and
developments. The most recent
reopening of the comment period was
announced in the Federal Register of
May 4, 2004 (69 FR 24541), and the
comment period was open until July 6,
2004.
On July 12, 2004, the agency received
a health claim petition submitted by
The Beverage Institute for Health and
Wellness requesting that the agency
amend the calcium and osteoporosis
health claim to, among other things,
simplify the language used in the claim.
In response to this health claim petition,
FDA is publishing elsewhere in this
issue of the Federal Register a proposed
rule to, among other things, simplify the
language used in the calcium and
osteoporosis health claim. Accordingly,
the agency is withdrawing certain
proposed amendments to the specific
requirements in the calcium and
osteoporosis health claim.
II. Withdrawn Proposed Amendments
to § 101.72(c)(2)(i)(A), (B), and (E) of the
1995 Proposal
In the 1995 proposal, FDA proposed
to simplify § 101.72(c)(2)(i)(A) by
limiting the requirement to a balanced
statement that reflects the importance of
the essential 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, and to eliminate the
provision in § 101.72(c)(2)(i)(A) that the
specific risk factors, including sex, race,
age, and the need for an adequate level
of exercise be stated in any claim.
Elsewhere in this issue of the Federal
Register, FDA is proposing alternative
amendments to § 101.72(c)(2)(i)(A).
Therefore, FDA is withdrawing this
proposed amendment of the 1995
proposal.
In the 1995 proposal, FDA proposed
to revise § 101.72(c)(2)(i)(B) by removing
the requirement to identify by race or
ethnicity those populations at particular
risk for the development of
osteoporosis, but to retain identification
of teen and young women, irrespective
of race or ethnicity, as the focus of the
claim. Elsewhere in this issue of the
Federal Register, FDA is proposing
alternative amendments to
§ 101.72(c)(2)(i)(B). Therefore, FDA is
withdrawing this proposed amendment
of the 1995 proposal.
In the 1995 proposal, FDA proposed
to increase the amount of calcium
E:\FR\FM\05JAP1.SGM
05JAP1
Agencies
[Federal Register Volume 72, Number 3 (Friday, January 5, 2007)]
[Proposed Rules]
[Pages 497-519]
From the Federal Register Online via the Government Printing 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: https://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: https://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 https://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 https://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, addit