Background logic for FDA’s arguments to mandate folic acid fortification

SOURCE: Extract on my website | original FDA URL

1. Background

In September 1992. following an open meeting sponsored by the Centers for Disease Control (CDC) in Atlanta, GA (57 FR 29323) and based on reviews of the relevant scientific data, PHS recommended that all women of childbearing age in the United States consume 0.4 mg (400µg) of folate daily to reduce their risk of having a pregnancy affected with spina bifida or other neural tube defects (Ref. 1). In discussing this recommendation, PHS raised several issues that directly bear on FDA’s responsibilities under the Federal Food. Drug, and Cosmetic Act (the act). One of these issues was to identify the best approach for increasing intake of folate by women during their childbearing years. [Sanjeev: THIS IS THE LIVESTOCK MODEL OF PUBLIC HEALTH, NAMELY COMMUNISM, IN WHICH WOMEN HAVE THE EFFECTIVE STATUS OF SHEEP BELONGING TO THE STATE] PHS identified several possible approaches by which folate intake by the target population might be increased. These approaches included: (1) Improvement of dietary habits. (2) fortification of the U.S. food supply, and (3) daily use of folate supplements by women throughout their childbearing years. The PHS recommendation also cautioned against the effects of higher intakes of folate. The recommendation stated that a widely recognized adverse effect of high intakes of folate is masking the anemia of vitamin B12 deficiency and thus allowing the neurologic damage to progress untreated. PHS said that care should be taken to keep total folate consumption at less than 1 mg (1,000 µg)/day, except under the supervision of a physician (Ref, 1).

After the PHS recommendation was issued. FDA convened a subcommittee on folate of its Food Advisory Committee (hereinafter referred to as the “Folic Acid Subcommittee”) to consider some of the issues raised by the recommendation. At a meeting in November 1992. the Folic Acid Subcommittee discussed approaches for ensuring that the folate intakes of women would be increased. [Sanjeev: At every step FDA discloses its LIVESTOCK APPROACH TOWARDS WOMEN] It identified several approaches. These included: (1) Development of a fortification scheme such that 90 percent of women of childbearing age could receive at least 400 µg of folate per day from all sources, while preventing excessively high folate intakes by nontarget groups; (2) appropriate labeling of foods, including dietary supplements; and (3) implementation of an educational program directed primarily at women of childbearing age that emphasizes the importance of folate intake before, during, and after conception and its effect on the incidence of neural tube defects. The Folic Acid Subcommittee also recommended that a surveillance and monitoring system be established to provide baseline data on vitamin B12 status in subgroups of the population that might potentially be at greatest risk as a result of increased intakes of folate.

These issues and the Folic Acid Subcommittee’s recommendations are fully discussed elsewhere in this issue of the Federal Register in a proposed rule entitled “Food Labeling; Health Claims and Label Statements: Folic Acid and Neural Tube Defects” (hereinafter referred to as the health claims proposal).

1. The Proposal

In this document, the agency is proposing to implement its tentative conclusion, discussed at length in the health claims proposal, that food fortification should be limited to cereal-grain products. Specifically, FDA is proposing to establish a fortification scheme that will assist women in the target population in increasing their daily intake of folate. [Sanjeev: “ASSIST” IS FINE, but MANDATORY FORTIFICATION IS NOT ASSISTANCE: IT IS FORCE] This document also responds to a citizen petition (Docket No. 92P-0132), submitted by Glenn Scott, that requested that the agency amend the standards of identity for enriched cereal-grain products to include a requirement for the addition of folic acid, although the levels of addition suggested by the petitioner were lower than those that FDA is proposing to require in this document.

FDA is proposing to amend the following standards of identity to require the addition of folic acid: Enriched bread, rolls and buns (5136.115 (21 CFR 136.115)); enriched flour (5137.165 (21 CFR 137.165)); enriched self-rising flour (5 137.185 (21 CFR 137.185)); enriched corn grits (5 137.235 (21 CFR 137.235)); enriched corn meals (5137.260 (21 CFR 137.260)); enriched farina (5137.305 (21 CFR 137.305)); enriched rice (5137.350 (21 CFR 137.350)); enriched macaroni products (5 139.115 (21 CFR 139.115)); enriched nonfat milk macaroni products (5139.122 (21 CFR 139.122)); and enriched noodle products (5 139.155 (21 CFR 139.155)). FDA notes that the standards of identity for enriched bromated flour (5137.160 (21 CFR 137.160)), enriched vegetable macaroni products (5139.135 (21 CFR 139.135)), and enriched vegetable noodle products (5 139.165 (21 CFR 139.165)) cross-reference the standards of identity for enriched flour, enriched macaroni products. and enriched noodle products, respectively, and will thus also be amended by this proposal. FDA also points out that the standard for enriched macaroni products fortified with protein is stayed and thus will not be addressed in this rulemaking.

As fully discussed in the health claims proposal published elsewhere in this issue of the Federal Register, FDA has tentatively decided that the fortification of the food supply is an appropriate approach for increasing the intake of folate by women in the target population. [Sanjeev: NOT A STEP PASSES WITHOUT THE LIVESTOCK MODEL IN THE MIND OF FDA] As noted by the Folic Acid Subcommittee and expert speakers who testified before the Folic Acid Subcommittee, food fortification has the advantage of reaching a great number of women in the target population before conception and during early pregnancy, when the risk of neural tube defects is greatest. [Sanjeev: FDA conveniently didn’t mention that the NON-TARGET POPULATION WOULD ALSO BE FORCED TO CONSUME FOLIC ACID] It also has the advantage of providing folate in a continuous and passive manner and, thus, represents an effective means for improving the folate nutriture of women in their childbearing years.

In determining what foods would be appropriate for fortification with folic acid and at what levels, the agency used the U.S. Department of Agriculture (USDA) 1987-1988 national food consumption data (Ref. 2) to estimate daily intake of folate for the target population, as well as the general population, with fortification at different levels for cereal grains. dairy products, and juices. The agency estimated the effects of fortification using three values – 0.070, 0.140, and 0.350 mg of folic acid/100 g of cereal-grain products. As discussed in the health claims proposal, the value of 0.070 mg/100 g (0.3 mg/lb) is the amount, recommended in 1974 by the Food and Nutrition Board, National Research Council, National Academy of Sciences, that would restore folate lost in the milling of cereal-grain products and represents about a four-fold increase in the level of folate that ordinarily occurs in wheat floor (Ref. 3).  [Sanjeev: Restoration is a LEGITIMATE objective, but folic acid is not natural, hence problematic] The value of 0.140 mg,/100 g is twice that amount, and 0.350 mg/100 g is five times that amount. [Sanjeev: Since 0.070 mg is FOUR TIMES NATURAL LEVEL, 0.14 mg is EIGHT TIMES]

The different approaches that FDA used in estimating the effects of fortification of food with these levels of folic acid are fully discussed in the health claims proposal, published elsewhere in this issue of the Federal Register. in arriving at these estimates, FDA made provision for consumption of ready-to-eat cereals fortified with folic acid as well as dietary supplements containing folic acid.

In its analysis, FDA assumed likely underreporting biases in food intakes. The agency did so because national food consumption surveys generally underestimate the food intake of survey respondents. This fact is supported, in part, by the observation that when consumer-reported dietary intakes are used as a basis for designing intervention diets (not necessarily for weight reduction), subjects that follow the intervention diet frequently lose weight (Ref. 4). Further, calorie intakes that were estimated based on the survey respondents’ daily reported food intake fell below the current average calorie intakes recommended by the Food and Nutrition Board. For example, in the 1987-1988 USDA Nationwide Food Consumption Survey (Ref. 2) used for these estimates, calculated median energy intakes of women 19 to 50 years of age were only about 1,500 calories, whereas the most recent recommended average energy intake for this gender/ age group is 2,200 calories (Ref. 5).

FDA also took into account in performing its analysis that underestimation of folate contents of foods was likely in the analysis that had been done. Comparison of newer methods of sample preparation with older methods for determining the folate content of foods has revealed underestimates in the range of 20 percent for vegetables such as spinach and cauliflower and 50 percent for canned tuna. Thus, commonly used methods for folate analysis may significantly underestimate the folate content of foods.

As fully discussed in the health claims proposal published elsewhere in this issue of the Federal Register, results of FDA’s analysis show that when fortification included fruit juices and dairy products in addition to cereal grain and dietary supplements, folate intakes of some nontarget group consumers exceeded 1 mg/day regardless of the fortification level examined. However, when fortification was limited to cereal-grain products at levels of 70 µg/100 g or 140 µg/100 g, daily intake levels remained below 1 mg/100 g. At fortification levels of 350 µg/100 g, the estimated daily intake could reach levels of 1,220 µg/100 g, which exceeds the recommended safe upper limit.

The agency also estimated the daily intake of folate for consumers who follow Federal government dietary guidance, such as the U.S. Dietary Guidelines and the Department of Health and Human Services (DHHS)/ USDA Food Guide Pyramid, and consume cereal-grain products fortified with folic acid, to determine whether these consumers will have daily intakes in excess of the recommended safe upper limit of approximately 1 mg/day.

These estimates, as shown in Table 7 in the health claims proposal, indicate that consumers who followed even the low end of recommendations from the DRHS/USDA Food Guide Pyramid could, without supplement use, easily consume 420µg or more of folate per day from cereal-grain products fortified with 70 µg folic acid/100 g. Further. such consumers’ daily intake could triple if such products were fortified with 350 µg folic acid/100 g.

As a result of its analysis of fortification of several cereal-grain, dairy, and juice products, FDA has tentatively concluded that fortification should be limited to cereal-grain products and not extended to dairy products and fruit juices. (The agency notes that results of its analysis are presented in Tables 4 through 7 in the health claims proposal published elsewhere in this issue of the Federal Register.) The agency found that intakes by very large segments of the general population would reach several milligrams per day if all of these foods were fortified with folic acid.

The agency has also tentatively decided that the appropriate fortification level for cereal-grain products is 140 µg/l00 g. Based on the results of its analysis, fortification of cereal-grain products with 140 µg/100 g will provide daily intakes for the nontarget population that remain within the recommended safe upper limit of approximately 1 mg/day, while providing increased intakes of folate for women in their childbearing years. The agency notes that with supplement use, 95th percentile intakes by adults 51+ years of age could reach 840 to 860 µg/ day if these enriched cereal-grain products are fortified with 140 µg/100 g. While the agency recognizes that this level approaches the recommended safe upper limit and does not take into account likely underreporting biases regarding food intakes and underestimation of folate content of foods, it tentatively concludes that fortification of cereal-grain products with 140 µg/100 g folic acid is he most appropriate fortification level of the three levels analyzed to ensure that folate intakes by the target population will increase. Fortification at a lower level of 70 µg/100 g may not provide sufficient folate levels to that portion of the target population that have lower daily food intakes or that consume minimal amounts of cereal-grain products. For example folate intake estimates for the 25th percentile of the target population if cereal-grain products were supplemented with 70 µg/100 g of folic acid showed levels of 160 to 180 µg/day without supplement use and 200 µg/day with supplement use.

In this document, the agency is proposing to provide for folic acid fortification of the individual enriched cereal-grain products discussed below, which are subject to standards of identity.