FDA ESTABLISHMENT OF SAFE MAXIMUM INTAKE LEVELS FOR VITAMIN/MINERALS

Executive Summary

FDA ESTABLISHMENT OF SAFE MAXIMUM INTAKE LEVELS FOR VITAMIN/MINERALS is recommended in the final report of FDA's Task Force on Dietary Supplements, the agency noted in a June 18 advanced notice of proposed rulemaking. The task force suggested that "FDA use notice and comment rulemaking to establish safe levels of use for vitamins and essential minerals in dietary supplements," and that these levels "be the maximum daily safe supplemental intake for a given vitamin or essential mineral, called a 'dietary supplement limit' (DSL)," the agency said. The June 18 notice calls for comment on the recommendation. The task force recommended that FDA adopt a dietary supplement limit (DSL) "for each vitamin and essential mineral." The task force suggested establishing a DSL for amino acid supplements as well (see story, p. 8). The dietary supplements task force, an internal agency group, was established in 1991 to examine FDA's options for regulating various types of dietary supplements. Also called the "Dykstra Report" after Deputy Associate Commissioner for Regulatory Affairs Gary Dykstra, the task force's final report was submitted to FDA in May 1992, but is only now being released with the agency's proposed regs for dietary supplements (see following stories). Although the task force acknowledged that "most vitamins and minerals are generally safe when their intake is limited to small multiples" of the recommended daily allowance (RDA), FDA said that "the task force identified certain health risks at higher levels of intake." The final report observes that FDA "generally has not been willing to pursue enforcement actions unless it could demonstrate some degree of toxicity or potential toxicity." According to the notice, the task force found that FDA has not set "safe levels for nutrients in dietary supplements because the industry has shown that setting such levels provides it with a cutoff point just below which FDA will not take action, even though such levels are high. Such levels then become the industry norm." As an alternative to devising DSLs for vitamins and minerals, the task force suggested that FDA "could call for the submission of food additive or GRAS [generally recognized as safe] affirmation petitions on the use of vitamins and essential minerals in dietary supplements," according to the notice. One approach suggested by the task force would be for FDA to "propose to affirm as GRAS" the "highest RDA levels listed by the National Academy of Sciences." This approach would shift the burden to "those commenting," who would have to "submit evidence that would justify a higher level that represents safe use," FDA noted. Such an action "would facilitate the prompt publication of a proposal and focus the work of agency scientists on preparing the final rules based on the evidence submitted," FDA explained. The task force recommended this approach, FDA said, "because it believed that it is appropriate for the agency to distinguish between those vitamin and essential mineral potencies in dietary supplements whose use is safe, and those whose use creates public health concern." In its notice, FDA requested comments on "the appropriate procedures, both scientific and administrative, and types of data for establishing the safety of vitamins and essential minerals intended for consumption in dietary supplements in quantities significantly in excess of the amounts necessary to meet the known nutrient needs of practically all healthy people." FDA also listed five questions that interested parties could comment on, such as how to satisfy the requirement that the "tolerance limitation not be set higher than the level necessary to accomplish the additive's intended physical or other technical effect." The agency also asked: "What safety factor or margin of safety is appropriate?"; How should "adverse effects be identified" against the safety factor or margin of safety?; "Under what circumstances and how can data from nonexperimental adverse reaction reports and other sources be utilized?"; and is it necessary to establish good manufacturing practices to assure the safety of vitamins/minerals? FDA called for similar comments on herbal and other dietary supplement products. "As a secondary issue," FDA said it is inviting opinions on "what assumptions consumers make about the safety of ingredients in dietary supplement products, and on what information consumers should have on the label or in labeling to make informed choices about the safety of these products." Outlining reasons why FDA is concerned about vitamins and minerals, the agency said it has "identified certain public health issues related to dietary supplements." For example, FDA echoed the recommendations of the task force report in citing the need for a "comprehensive science-based evaluation of the potential toxicity of vitamins and minerals at various intake levels" and the need to "establish the levels of intake of vitamins and essential minerals that are safe." Certain vitamins and minerals, such as vitamin A, "may have adverse effects when consumed daily at higher levels," FDA explained. Consumption of 25,000 international units (IUs) per day of vitamin A for several months or more, for instance, "can produce multiple adverse effects including hepatic cirrhosis, increased intracranial pressure and possibly birth defects," the agency said. The RDA for vitamin A is 5,000 IUs. Other vitamins that have been associated with adverse effects at higher intake levels include vitamin B[6], niacin and selenium, according to FDA. Another concern about dietary supplements voiced by the agency is that there "apparently are no generally adopted good manufacturing practices that address how supplement products are to be manufactured to ensure that they have the claimed potency, appropriate purity and other quality performance attributes that help to ensure safety." The 1986 National Health Interview Survey, FDA pointed out, showed that "the labeled potencies of vitamin and mineral-containing supplements varied widely." Vitamins and minerals represented one section of the June 18 notice, which deals with amino acids, herbs and "other components of dietary supplements" in separate sections. Compartmentalizing dietary supplements adheres to a distinction made by FDA Deputy Commissioner for Policy Michael Taylor during a speech in April outlining the agency's position. Taylor complained that the term "dietary supplement" was "unfortunately" being used to "refer to a very diverse spectrum of products that pose widely varying concerns" and may be subject to different regulatory approaches ("The Tan Sheet" April 5, p. 1). In the June 18 notice, FDA characterized dietary supplements as "vitamins, essential minerals, protein, amino acids, herbs, animal and plant extracts (e.g., garlic extracts and inert glandulars), fats and lipid substances (e.g., fish oils, sterols and essential fatty acids), dietary fibers, and chemical compounds that may have biological activity but that are generally not recognized as nutrients under the traditional definition of that term (e.g., bioflavanoids, enzymes, nucleic acids, para- aminobenzoic acid and rutin)."