[Code of Federal Regulations]
[Title 21, Volume 2]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR101.79]
[Page 137-140]
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES--CONTINUED
PART 101--FOOD LABELING--Table of Contents
Subpart E--Specific Requirements for Health Claims
Sec. 101.79 Health claims: Folate and neural tube defects.
(a) Relationship between folate and neural tube defects--(1)
Definition. Neural tube defects are serious birth defects of the brain
or spinal cord that can result in infant mortality or serious
disability. The birth defects anencephaly and spina bifida are the most
common forms of neural tube defects and account for about 90 percent of
these defects. These defects result from failure of closure of the
covering of the brain or spinal cord during early embryonic development.
Because the neural tube forms and closes during early pregnancy, the
defect may occur before a woman realizes that she is pregnant.
(2) Relationship. The available data show that diets adequate in
folate may reduce the risk of neural tube defects. The strongest
evidence for this relationship comes from an intervention study by the
Medical Research Council of the United Kingdom that showed that women at
risk of recurrence of a neural tube defect pregnancy who consumed a
supplement containing 4 milligrams (mg)(4,000 micrograms (mcg)) folic
acid daily before conception and continuing into early pregnancy had a
reduced risk of having a child with a neural tube defect. (Products
containing this level of folic acid are drugs). In addition, based on
its review of a Hungarian intervention trial that reported
periconceptional use of a multivitamin and multimineral preparation
containing 800 mcg (0.8 mg) of
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folic acid, and its review of the observational studies that reported
periconceptional use of multivitamins containing 0 to 1,000 mcg of folic
acid, the Food and Drug Administration concluded that most of these
studies had results consistent with the conclusion that folate, at
levels attainable in usual diets, may reduce the risk of neural tube
defects.
(b) Significance of folate--(1) Public health concern. Neural tube
defects occur in approximately 0.6 of 1,000 live births in the United
States (i.e., approximately 6 of 10,000 live births; about 2,500 cases
among 4 million live births annually). Neural tube defects are believed
to be caused by many factors. The single greatest risk factor for a
neural tube defect-affected pregnancy is a personal or family history of
a pregnancy affected with a such a defect. However, about 90 percent of
infants with a neural tube defect are born to women who do not have a
family history of these defects. The available evidence shows that diets
adequate in folate may reduce the risk of neural tube defects but not of
other birth defects.
(2) Populations at risk. Prevalence rates for neural tube defects
have been reported to vary with a wide range of factors including
genetics, geography, socioeconomic status, maternal birth cohort, month
of conception, race, nutrition, and maternal health, including maternal
age and reproductive history. Women with a close relative (i.e.,
sibling, niece, nephew) with a neural tube defect, those with insulin-
dependent diabetes mellitus, and women with seizure disorders who are
being treated with valproic acid or carbamazepine are at significantly
increased risk compared with women without these characteristics. Rates
for neural tube defects vary within the United States, with lower rates
observed on the west coast than on the east coast.
(3) Those who may benefit. Based on a synthesis of information from
several studies, including those which used multivitamins containing
folic acid at a daily dose level of 400 mcg (0.4
mg), the Public Health Service has inferred that folate alone at levels
of 400 mcg (0.4 mg) per day may reduce the risk of neural tube defects.
The protective effect found in studies of lower dose folate measured by
the reduction in neural tube defect incidence, ranges from none to
substantial; a reasonable estimate of the expected reduction in the
United States is 50 percent. It is expected that consumption of adequate
folate will avert some, but not all, neural tube defects. The underlying
causes of neural tube defects are not known. Thus, it is not known what
proportion of neural tube defects will be averted by adequate folate
consumption. From the available evidence, the Public Health Service
estimates that there is the potential for averting 50 percent of cases
that now occur (i.e., about 1,250 cases annually). However, until
further research is done, no firm estimate of this proportion will be
available.
(c) Requirements. The label or labeling of food may contain a
folate/neural tube defect health claim provided that:
(1) General requirements. The health claim for a food meets all of
the general requirements of Sec. 101.14 for health claims, except that a
food may qualify to bear the health claim if it meets the definition of
the term ``good source.''
(2) Specific requirements--(i) Nature of the claim--(A)
Relationship. A health claim that women who are capable of becoming
pregnant and who consume adequate amounts of folate daily during their
childbearing years may reduce their risk of having a pregnancy affected
by spina bifida or other neural tube defects may be made on the label or
labeling of food provided that:
(B) Specifying the nutrient. In specifying the nutrient, the claim
shall use the terms ``folate,'' ``folic acid,'' ``folacin,'' ``folate, a
B vitamin,'' ``folic acid, a B vitamin,'' or ``folacin, a B vitamin.''
(C) Specifying the condition. In specifying the health- related
condition, the claim shall identify the birth defects as ``neural tube
defects,'' ``birth defects spina bifida or anencephaly,'' ``birth
defects of the brain or spinal cord anencephaly or spina bifida,''
``spina bifida and anencephaly, birth defects of the brain or spinal
cord,'' ``birth defects of the brain or spinal cord;'' or ``brain or
spinal cord birth defects.''
(D) Multifactorial nature. The claim shall not imply that folate
intake is
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the only recognized risk factor for neural tube defects.
(E) Reduction in risk. The claim shall not attribute any specific
degree of reduction in risk of neural tube defects from maintaining an
adequate folate intake throughout the childbearing years. The claim
shall state that some women may reduce their risk of a neural tube
defect pregnancy by maintaining adequate intakes of folate during their
childbearing years. Optional statements about population-based estimates
of risk reduction may be made in accordance with paragraph (c)(3)(vi) of
this section.
(F) Safe upper limit of daily intake. Claims on foods that contain
more than 100 percent of the Daily Value (DV) (400 mcg) when labeled for
use by adults and children 4 or more years of age, or 800 mcg when
labeled for use by pregnant or lactating women) shall identify the safe
upper limit of daily intake with respect to the DV. The safe upper limit
of daily intake value of 1,000 mcg (1 mg) may be included in
parentheses.
(G) The claim shall state that folate needs to be consumed as part
of a healthful diet.
(ii) Nature of the food--(A) Requirements. The food shall meet or
exceed the requirements for a ``good source'' of folate as defined in
Sec. 101.54;
(B) Dietary supplements. Dietary supplements shall meet the United
States Pharmacopeia (USP) standards for disintegration and dissolution,
except that if there are no applicable USP standards, the folate in the
dietary supplement shall be shown to be bioavailable under the
conditions of use stated on the product label.
(iii) Limitation. The claim shall not be made on foods that contain
more than 100 percent of the RDI for vitamin A as retinol or preformed
vitamin A or vitamin D per serving or per unit.
(iv) Nutrition labeling. The nutrition label shall include
information about the amount of folate in the food. This information
shall be declared after the declaration for iron if only the levels of
vitamin A, vitamin C, calcium, and iron are provided, or in accordance
with Sec. 101.9 (c)(8) and (c)(9) if other optional vitamins or minerals
are declared.
(3) Optional information--(i) Risk factors. The claim may
specifically identify risk factors for neural tube defects. Where such
information is provided, it may consist of statements from
Sec. 101.79(b)(1) or (b)(2) (e.g., Women at increased risk include those
with a personal history of a neural tube defect-affected pregnancy,
those with a close relative (i.e., sibling, niece, nephew) with a neural
tube defect; those with insulin-dependent diabetes mellitus; those with
seizure disorders who are being treated with valproic acid or
carbamazepine) or from other parts of this paragraph (c)(3)(i).
(ii) Relationship between folate and neural tube defects. The claim
may include statements from paragraphs (a) and (b) of this section that
summarize the relationship between folate and neural tube defects and
the significance of the relationship except for information specifically
prohibited from the claim.
(iii) Personal history of a neural tube defect-affected pregnancy.
The claim may state that women with a history of a neural tube defect
pregnancy should consult their physicians or health care providers
before becoming pregnant. If such a statement is provided, the claim
shall also state that all women should consult a health care provider
when planning a pregnancy.
(iv) Daily value. The claim may identify 100 percent of the DV (100%
DV; 400 mcg) for folate as the target intake goal.
(v) Prevalence. The claim may provide estimates, expressed on an
annual basis, of the number of neural tube defect-affected births among
live births in the United States. Current estimates are provided in
Sec. 101.79(b)(1), and are approximately 6 of 10,000 live births
annually (i.e., about 2,500 cases among 4 million live births annually).
Data provided in Sec. 101.79(b)(1) shall be used, unless more current
estimates from the U.S. Public Health Service are available, in which
case the latter may be cited.
(vi) Reduction in risk. An estimate of the reduction in the number
of neural tube defect-affected births that might occur in the United
States if all women consumed adequate folate throughout
[[Page 140]]
their childbearing years may be included in the claim. Information
contained in paragraph (b)(3) of this section may be used. If such an
estimate (i.e., 50 percent) is provided, the estimate shall be
accompanied by additional information that states that the estimate is
population-based and that it does not reflect risk reduction that may be
experienced by individual women.
(vii) Diets adequate in folate. The claim may identify diets
adequate in folate by using phrases such as ``Sources of folate include
fruits, vegetables, whole grain products, fortified cereals, and dietary
supplements.'' or ``Adequate amounts of folate can be obtained from
diets rich in fruits, dark green leafy vegetables, legumes, whole grain
products, fortified cereals, or dietary supplements.'' or ``Adequate
amounts of folate can be obtained from diets rich in fruits, including
citrus fruits and juices, vegetables, including dark green leafy
vegetables, legumes, whole grain products, including breads, rice, and
pasta, fortified cereals, or a dietary supplement.''
(d) Model health claims. The following are examples of model health
claims that may be used in food labeling to describe the relationship
between folate and neural tube defects:
(1) Examples 1 and 2. Model health claims appropriate for foods
containing 100 percent or less of the DV for folate per serving or per
unit (general population). The examples contain only the required
elements:
(i) Healthful diets with adequate folate may reduce a woman's risk
of having a child with a brain or spinal cord birth defect.
(ii) Adequate folate in healthful diets may reduce a woman's risk of
having a child with a brain or spinal cord birth defect.
(2) Example 3. Model health claim appropriate for foods containing
100 percent or less of the DV for folate per serving or per unit. The
example contains all required elements plus optional information: Women
who consume healthful diets with adequate folate throughout their
childbearing years may reduce their risk of having a child with a birth
defect of the brain or spinal cord. Sources of folate include fruits,
vegetables, whole grain products, fortified cereals, and dietary
supplements.
(3) Example 4. Model health claim appropriate for foods intended for
use by the general population and containing more than 100 percent of
the DV of folate per serving or per unit: Women who consume healthful
diets with adequate folate may reduce their risk of having a child with
birth defects of the brain or spinal cord. Folate intake should not
exceed 250% of the DV (1,000 mcg).
[61 FR 8779, Mar. 5, 1996; 61 FR 48529, Sept. 13, 1996, as amended at 65
FR 58918, Oct. 3, 2000]