21 CFR 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 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 § 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 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 § 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 § 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 § 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 § 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 § 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 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).
Title 21 published on 2015-04-01
The following are ALL rules, proposed rules, and notices (chronologically) published in the Federal Register relating to 21 CFR Part 101 after this date.