# Food Labeling: Trans Fatty Acids in Nutrition Labeling, Nutrient Content Claims, and Health Claims > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/fr%3A03-17525 ## Record - **Collection:** Federal Register - **Document type:** Rule - **Published:** July 11, 2003 - **Citation:** 68 FR 41434 ## Text DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 101 [Docket No. 94P-0036] RIN 0910-AB66 Food Labeling: Trans Fatty Acids in Nutrition Labeling, Nutrient Content Claims, and Health Claims AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending its regulations on nutrition labeling to require that trans fatty acids be declared in the nutrition label of conventional foods and dietary supplements on a separate line immediately under the line for the declaration of saturated fatty acids. This action responds, in part, to a citizen petition from the Center for Science in the Public Interest (CSPI). This rule is intended to provide information to assist consumers in maintaining healthy dietary practices. Those sections of the proposed rule pertaining to the definition of nutrient content claims for the “free” level of trans fatty acids and to limits on the amounts of trans fatty acids wherever saturated fatty acid limits are placed on nutrient content claims, health claims, and disclosure and disqualifying levels are being withdrawn. Further, the agency is withdrawing the proposed requirement to include a footnote stating: “Intake of trans fat should be as low as possible.” Issues related to the possible use of a footnote statement in conjunction with the trans fat label declaration or in the context of certain nutrient content and health claims that contain messages about cholesterol-raising fats in the diet are now the subject of an advance notice of proposed rulemaking (ANPRM) which is published elsewhere in this issue of the Federal Register . DATES: This rule is effective January 1, 2006. FOR FURTHER INFORMATION CONTACT: Julie Schrimpf, Center for Food Safety and Applied Nutrition (HFS-832), Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-2373. SUPPLEMENTARY INFORMATION: Table of Contents I. Background A. Nutrition Labeling B. Nutrient Content and Health Claims C. Comments II. Highlights of the Final Rule III. Legal Authority A. Statutory Authority B. The First Amendment IV. Review of the Science A. Reviews by the Federal Government and the Institute of Medicine (IOM/National Academy of Science (NAS) B. Published Studies V. Nutrition Labeling of Trans Fat A. Voluntary v. Mandatory Declaration of Trans Fatty Acids in Nutrition Labeling B. Format, Including Percent of Daily Value (% DV), for Nutrition Labeling of Trans Fat C. Definition of Trans Fatty Acids D. Methodology VI. Nutrient Content Claims, Health Claims, Disclosure and Disqualifying Levels VII. Other Issues VIII. Effective Date IX. Final Regulatory Impact Analysis A. The Current Situation and the Need for This Regulation B. Regulatory Alternatives C. Changes Resulting From This Rule X. Final Regulatory Flexibility Analysis A. Introduction B. Economic Effects on Small Entities C. Regulatory Options D. Recordkeeping and Reporting Requirements E. Summary XI. Unfunded Mandates A. Future Costs B. Particular Regions, Communities, or Industrial Sectors C. National Productivity and Economic Growth D. Full Employment and Job Creation E. Exports XII. Environmental Impact XIII. Paperwork Reduction Act XIV. Federalism XV. References I. Background A. Nutrition Labeling The Nutrition Labeling and Education Act of 1990 (the 1990 amendments) (Public Law 101-535) amended the Federal Food, Drug, and Cosmetic Act (the act) to provide, among other things, that certain nutrients and food components be included in nutrition labeling. Section 403(q)(2)(A) and (q)(2)(B) (21 U.S.C. 343(q)(2)(A) and (q)(2)(B)) of the act state that the Secretary of Health and Human Services (the Secretary) (and, by delegation, FDA) can, by regulation, add or delete nutrients included in the food label or labeling if he or she finds such action necessary to assist consumers in maintaining healthy dietary practices. In response to these provisions, in the Federal Register of November 27, 1991 (56 FR 60366), FDA published a proposed rule entitled “Food Labeling; Reference Daily Intakes and Daily Reference Values; Mandatory Status of Nutrition Labeling and Nutrient Content Revision.” In that document, the agency proposed to require that foods bear nutrition labeling listing certain nutrients and the amount of those nutrients in a serving of the food. Given the scientific knowledge about trans fatty acids at the time, FDA did not propose to require that trans fatty acids be listed. However, FDA requested comments on whether the listing of trans fatty acids should be voluntary (56 FR 60366 at 60371). (Note: throughout this preamble, FDA has used the term “ trans fatty acids” and “ trans fat” interchangeably; likewise, for the terms “saturated fatty acids,” and “saturated fat”). In the Federal Register of January 6, 1993 (58 FR 2079), FDA issued a final rule implementing the 1990 amendments entitled “Food Labeling; Mandatory Status of Nutrition Labeling and Nutrient Content Revision, Format for Nutrition Label” that prescribes how nutrition labeling is to be provided on foods that are regulated by the agency. In that document, the agency required the declaration of total fat and saturated fat in the nutrition label, with the declaration of both monounsaturated fat and polyunsaturated fat (both defined as the cis isomers only) required, when claims are made about fatty acids and cholesterol. Based on its review of the comments, the agency stated that it was premature to include trans fatty acids in nutrition labeling because of a lack of agreement on the dietary implications of trans fatty acid intake. However, the agency acknowledged that it might be necessary to revisit the labeling of trans fatty acids in the future (58 FR 2079 at 2090-2092). FDA received a citizen petition, dated February 14, 1994, from CSPI (docket number 94P-0036/CP1) stating that an increasing body of evidence suggests that dietary trans fatty acids raise blood cholesterol levels, thereby increasing the risk of coronary heart disease (CHD). The petitioner argued that the 1993 final rules implementing the 1990 amendments do not adequately reflect the effect of dietary trans fatty acids on CHD and that label values for saturated fat underestimate the total amount of “heart-unhealthy” fats because trans fatty acids are not declared. CSPI requested that FDA amend the definition of saturated fat in § 101.9(c)(2)(i) (21 CFR 101.9(c)(2)(i)) to include trans fatty acids so that the declaration of saturated fat on the nutrition label would provide consumers with complete information on all “heart-unhealthy” fatty acids. In addition, the petitioner requested that all saturated fat claims in § 101.62(c) (21 CFR 101.62(c)), the saturated fat threshold on all cholesterol claims in § 101.62(d), the claims for “lean” and “extra lean” in § 101.62(e), and disqualification and disclosure levels for health and nutrient content claims be amended to reflect the combined levels of saturated and trans fatty acids. Further, CSPI requested that FDA: (1) Limit “vegetable oil” claims (e.g., “made with vegetable oil”) to foods that are low in both saturated and trans fatty acids, and (2) require that “partially hydrogenated” fat be listed on food labels as “partially saturated.” On July 13, 1998, CSPI amended its petition in a way that would maintain the definition of saturated fat in § 101.9(c)(2)(i), yet provide consumers with information on the trans fatty acid content of the food. Specifically, CSPI suggested that FDA either: (1) Disclose the sum of trans and saturated fats next to the term “saturated fat*” with an asterisk at the bottom of the label that states “contains ___ grams of trans fat,” or (2) disclose the sum of trans and saturated fats next to the term “saturated + trans fat” when trans fat was present. In response to CSPI's petition, FDA issued a proposed rule in the Federal Register of November 17, 1999 (64 FR 62746), entitled “Food Labeling: Trans Fatty Acids in Nutrition Labeling, Nutrient Content Claims, and Health Claims” (hereinafter identified as “the November 1999 proposal”). In that document, FDA proposed to amend its nutrition labeling regulations to require that the amount of trans fatty acids in a food, including dietary supplements, be included in the amount and percent Daily Value (%DV) declared for saturated fatty acids, with a footnote indicating the amount of trans fatty acids in a serving of the product, when the product contains 0.5 or more grams (g) trans fatty acids per serving. FDA reviewed recent research that showed that consumption of diets containing trans fatty acids, like diets containing saturated fats, results in increased serum low-density lipoprotein cholesterol (LDL-C), a major risk factor for CHD. The proposed rule was issued to assist consumers in maintaining healthy dietary practices (64 FR 62746 at 62754). B. Nutrient Content and Health Claims In the Federal Register of November 27, 1991 ( 56 FR 60478), FDA also published a proposed rule entitled “Food Labeling: Definitions of Nutrient Content Claims for the Fat, Fatty Acid, and Cholesterol Content of Food.” Although the agency proposed definitions for fat, fatty acid, and cholesterol nutrient content claims, it did not propose a definition for the nutrient content claim “saturated fat free.” However, the comments in response to that proposal recommended that FDA define the claim “saturated fat free.” In the Federal Register of January 6, 1993 (58 FR 2302), FDA issued a final rule entitled “Food Labeling: Nutrient Content Claims, General Principles, Petitions, Definition of Terms; Definition of Nutrient Content Claims for the Fat, Fatty Acid, and Cholesterol Content of Food,” (hereinafter the “nutrient content claims final rule”). In that rule, the agency stated that it did not set a trans fat criterion for most claims because the evidence suggesting that trans fatty acids raise serum cholesterol was inconclusive at that time (58 FR 2302 at 2332 and 2340). However, FDA did set a trans fat criterion for the “saturated fat free” claim stating that “because of the uncertainty regarding this issue, the fact that consumers would expect a food bearing a ‘saturated fat free’ claim to be free of saturated fat and other components that significantly raise serum cholesterol, and the potential importance of a saturated fat free claim, the agency believes that it would be misleading for products that contain measurable amounts of trans fatty acids to bear a ‘saturated fat free’ claim” (58 FR 2302 at 2332). The trans fat criterion for the claim “saturated fat free” was set at a level not to exceed 1 percent of total fat in the food (58 FR 2302 at 2419). The agency stated that 1 percent was the appropriate threshold because analytical methods for measuring trans fatty acids below that level were not reliable (58 FR 2302 at 2332). This action was taken under the authority of section 403(r)(2)(A)(vi) of the act, which prohibits a claim if it is misleading in light of the level of another nutrient in the food. Some comments that FDA received after publication of the nutrient content claims final rule objected to the 1 percent criterion for trans fatty acids in the definition of “saturated fat free.” One comment pointed out that a cookie containing 1.5 g of total fat would be allowed to have only 0.015 g of trans fatty acids, an amount that could not be accurately measured. In response to these comments, in the Federal Register of August 18, 1993 (58 FR 44020 at 44032), the agency amended the definition of “saturated fat free” to require that a food contain less than 0.5 g of trans fatty acids in addition to less than 0.5 g of saturated fat per reference amount customarily consumed (hereinafter referred to as “reference amount”) and per labeled serving to be eligible to bear the claim. In the November 1999 proposal, FDA concluded that dietary trans fatty acids have adverse effects on blood cholesterol measures that are predictive of CHD risk (64 FR 62746 at 62754). Consequently, to avoid misleading claims, the agency proposed that the amount of trans fatty acids be limited wherever saturated fat limits are placed on nutrient content claims, health claims, or disclosure and disqualifying levels. In the November 1999 proposal, the agency did not propose to take action requested by CSPI to amend § 101.65(c)(3) (21 CFR 101.65(c)(3)) to state that “made with vegetable oil” is an implied claim that the product is low in saturated fat and trans fats combined (64 FR 62746 at 62762) because the agency proposed to amend nutrient content claims for saturated fat to include a trans fatty acid criterion. The agency stated that the proposed amendments to nutrient content claims and the requirements for implied nutrient content claims in § 101.65(c)(3) adequately addressed the petitioner's request. In addition, in the November 1999 proposal, FDA requested comment on whether “ trans fat free” claims would help consumers maintain healthy dietary practices and whether they would provide incentive to the food industry to reduce the amount of trans fat in the food supply (64 FR 62746 at 62759). FDA proposed a definition for the trans fat free claim. FDA concluded that there was no basis for defining “low trans fat” without quantitative recommendations for daily intake of trans fat. Further, FDA did not define a “reduced trans fat” claim because it was concerned that a reduced trans fat claim would detract from educational messages that emphasize lower intakes of saturated fat. Persons who believed that a “reduced trans fat” claim would be useful were advised to submit a petition under § 101.69 (21 CFR 101.69). In the November 1999 proposal, FDA proposed to deny CSPI's request that the agency require that “partially hydrogenated” fat be listed as “partially saturated” fat (64 FR 62746 at 62762). Among other reasons, the agency stated that “hydrogenated” and “partially hydrogenated” are not intended to describe the nutritional properties of the fat or oil. It explained that the purpose of the ingredient statement is to identify the ingredients in a food by listing the common or usual names of each ingredient (64 FR 62746 at 62762-62763). Comments to the November 1999 proposal requested that the final rule define the nutrient content claim “reduced trans fat.” Other comments suggested a “reduced saturated fat” claim that would be defined as a reduction of saturated and trans fats combined. The agency considered these comments and determined that all interested parties should have an opportunity to comment on whether the final rule should define claims that address reduced levels of trans fat. Therefore, FDA reopened the comment period for the November 1999 proposal on December 5, 2000, for a period of 45 days (65 FR 75887) stating that it would consider only comments that addressed “reduced trans fat” and “reduced saturated and trans fat” claims. Subsequent to FDA's November 1999 proposal, the Institute of Medicine of the National Academy of Sciences (IOM/NAS) issued a report entitled “Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids” (the IOM/NAS macronutrient report) (Ref. 140) and found, similar to the effect of saturated fat, “a positive linear trend” between trans fatty acid intake and total and LDL-C concentrations, and therefore increased risk of CHD. Because trans fats are unavoidable in ordinary diets, the IOM/NAS report recommended that “ trans fat consumption be as low as possible while consuming a nutritionally adequate diet.” Likewise, the conclusions in two other scientific reports, which became available subsequent to the November 1999 proposal, i.e., the Dietary Guidelines for Americans, 2000 (Ref. 88) and guidelines from the National Cholesterol Education Program (NCEP) (Ref. 89), were similar with recommendations to limit trans fat intake in the diet. Although the IOM/NAS report (Ref. 140) underscored the relationship between the intake of trans fat and the increased risk for heart disease and emphasized that consumers need to limit trans fat in their diets, it did not provide a Dietary Reference Intake (DRI) value for trans fat or information that FDA believes is sufficient to support the agency's establishing a Daily Reference Value (DRV) or other information on the label, such as a %DV, for trans fat. In response to the recommendations of the new scientific reports to limit the intake of trans fat and to provide consumers with label information that may better assist them in understanding the quantitative declaration of trans fat in the context of a total daily diet, FDA reopened the comment period of the November 1999 proposal for a period of 30 days (67 FR 69171, November 15, 2002). In that document the agency proposed to require an asterisk (or other symbol) in the %DV column for trans fat, when it is listed, that is tied to a similar symbol at the bottom of the Nutrition Facts box that is followed by the statement “Intake of trans fat should be as low as possible.” The agency stated that the statement is taken from the IOM/NAS macronutrient report and is consistent with the dietary guidance in the other recent scientific reports identified in that document (67 FR 69171 at 69172). In the November 15, 2002, Federal Register document to reopen the comment period the agency also stated that it would consider the exercise of its enforcement discretion for those manufacturers who wanted to begin labeling the trans fat content of food products prior to publication of the final rule (67 FR 69171 at 69172). The agency cautioned manufacturers that the trans fat final rule may differ from what was being proposed in the November 15, 2002, document to reopen the comment period and that manufacturers would then be required to change their labels to conform to the final rule. C. Comments FDA received over 1,650 letters in response to the November 1999 proposal, over 45 letters in response to the December 5, 2000, notice reopening the comment period, and over 25 letters in response to the November 15, 2002, proposal and notice to reopen the comment period. Each of these letters contained one or more comments. Responses were received from industry, trade associations, consumers, consumer advocacy organizations, academia, health care professionals, professional societies, city and State governments, other Federal agencies, and other countries. Some of the comments supported the proposal generally or supported aspects of the proposal. Other comments objected to specific provisions and requested revisions. Some comments requested that the proposal be withdrawn or reproposed. A few comments addressed issues outside the scope of the proposal and will not be discussed here. On September 18, 2001, the Office of Information and Regulatory Affairs (OIRA), Office of Management and Budget, sent to the Secretary of the Health and Human Services (the Secretary) a letter requesting that the Secretary and FDA consider giving greater priority to the November 1999 proposal (Ref. 156) in light of the growing body of scientific evidence suggesting that consumption of trans fatty acids in foods increases the consumer's risk of developing CHD. The estimated public health benefits from increased consumer awareness of trans fat content in foods that were described in FDA's preliminary Regulatory Impact Analysis in the November 1999 proposal, and the subsequent evidence found in more recent studies, strongly support the interests of the Government to lower the incidence of and economic burden of CHD in the United States. This final rule summarizes the relevant comments that were received in response to the November 1999 proposal and provides the agency's conclusions regarding the labeling of trans fat on the Nutrition Facts panel. A summary of the relevant comments that pertain to nutrition labeling of trans fat, the agency's responses to the comments, and a discussion of the agency's conclusions follow. II. Highlights of the Final Rule In this final rule and given the current state of scientific knowledge, FDA is requiring the mandatory declaration in the nutrition label of the amount of trans fatty acids present in foods, including dietary supplements. The declaration of this nutrient must be on a separate line immediately under the declaration for saturated fat but it will not include a %DV that is required for some of the other mandatory nutrients, such as saturated fat. In addition, the agency is withdrawing those sections of the proposed rule pertaining to the definition of nutrient content claims for “free” and for “reduced” levels of trans fatty acids, and limits on the amounts of trans fatty acids, wherever saturated fatty acid limits are placed on nutrient content claims, health claims, and disclosure and disqualifying levels. Further, the agency is withdrawing the proposed requirement to include a footnote stating: “Intake of trans fat should be as low as possible.” The action the agency is taking in this final rule is based on its evaluation of comments received in response to the November 1999 proposal, the reopening of the comment period on November 15, 2002, and on scientific evidence that shows that consumption of trans fatty acids increases LDL-C, a primary risk factor for CHD. The scientific evidence includes current authoritative reports, such as Dietary Guidelines 2000 (Ref. 87), that recommend that Americans cut back on trans fats when reducing fat intake. The agency concludes that the declaration of this nutrient on a separate line, will help consumers understand that trans fat is chemically distinct from saturated fat and will assist them in maintaining healthy dietary practices. The agency intends to promote consumer awareness and understanding of the health effects of trans fat as part of an educational program. FDA is issuing an ANPRM elsewhere in this issue of the Federal Register that will solicit comment and additional consumer research that potentially could be used to establish new nutrient content claims about trans fat, to establish qualifying criteria for trans fat in certain nutrient content claims and health claims, and to establish disclosure and disqualifying criteria for trans fat. In addition, the ANPRM is soliciting comment on whether it should consider statements about trans fat, either alone or in combination with saturated fat and cholesterol, as a footnote in the Nutrition Facts panel or as a disclosure statement in conjunction with claims to enhance consumer's understanding about cholesterol-raising lipids. III. Legal Authority General Comments FDA received a number of comments from trade associations and others in industry asserting that FDA did not meet its burden under the first amendment in proposing to mandate nutrition labeling of trans fat. Further, the comments asserted that FDA did not meet its first amendment burden for establishing restrictions on specific claims by virtue of how FDA defined nutrient content claims or established disqualifying and disclosure levels, including the effects that those actions would have on restricting certain health claims on food. In addition, comments raised questions about whether the agency's proposed action was consistent with the Administrative Procedure Act (APA) and whether the agency was acting consistent with its authority under the act. As stated in section VI of this document, FDA is withdrawing those sections of the rule pertaining to the definition for nutrient content claims that were proposed, and to limits on the amounts of trans fatty acids wherever saturated fatty acid limits are placed on nutrient content claims, health claims, and disclosure and disqualifying levels. Further, the agency is withdrawing the proposed requirement to include a footnote stating “Intake of trans fat should be as low as possible.” The agency provides an overview of comments received on these withdrawn sections in section VI of this document, and therefore, is not addressing those comments here. Thus, the agency is addressing only those comments that pertain to legal issues about the agency's action to require mandatory trans fat labeling. A. Statutory Authority Several comments question whether the agency's proposed requirement for mandatory trans fat labeling would prevent consumer deception or would assist consumers in maintaining healthy dietary practices. The comments suggest that the data do not support mandatory trans fat labeling, unless the label contains a nutrient content or health claim related to fat or cholesterol or unless polyunsaturated fat or monounsaturated fat is voluntarily declared on the label. Specifically, the comments assert that mandatory trans fat labeling in the absence of claims, or statements about other fats, would not assist consumers in following healthy dietary practices or would not prevent consumer deception. A few comments suggest that there was no basis for concluding any health benefit can be expected from disclosure of trans fat levels on foods when present in amounts that have not been clinically shown to have a material impact on human health or disclosure on foods with a trivial contribution of fat. Another comment argues that the agency could only require mandatory labeling of trans fat under the statute where the absence of such labeling constitutes the omission of a material fact under section 201(n) of the act (21 U.S.C. 321(n)), such as when nutrient content claims are made about cholesterol or fatty acids, or when polyunsaturated and monounsaturated fats are voluntary listed. A related comment suggests that trans fat labeling would be appropriate where the declaration of “total fat” and “saturated fat,” that did not explicitly include trans fat, were established as misleading under section 201(n) of the act (without trans fat listed). The comment seems to suggest that the declaration of “total fat” and “saturated fat” in that situation would be misleading if the actual nutrition contribution from trans fat that such products make to the diet was greater in comparison to other products. In addition, one comment suggests that mandatory nutrition labeling of trans fat can only be “material” where there is sufficient trans fat present in the food to significantly impact the overall fatty acid contribution that the food makes to the diet, such that only having total fat and saturated fat on the label would misrepresent the nutritional value of the product in a material way. FDA believes it has adequate authority to adopt this rule. FDA's authority under the act to require trans fat labeling includes sections 201(n), 403(a)(1) and (q), and 701(a) of the act (21 U.S.C. 371(a)). FDA has authority under section 701(a) of the act to issue regulations for the efficient enforcement of the act. FDA can require labeling of certain facts that are material in light of representations made in the labeling or with respect to consequences which may result from the use of the article in order for a product not to be misbranded under sections 201(n) and 403(a) of the act. Further, under section 403(q)(2)(A) of the act, the Secretary (and FDA, by delegation) may require that information relating to a nutrient be in the labeling of food for the purpose of “providing information regarding the nutritional value of such food that will assist consumers in maintaining healthy dietary practices.” The agency believes that the data in the record supports mandatory trans fat labeling to ensure that consumers are not misled and are adequately informed about the product's attributes. Accordingly, FDA believes that mandatory trans fat labeling is necessary for foods not to be misbranded under section 403(a) of the act. The absence of information about the content of trans fat in foods that are subject to mandatory labeling would constitute an omission of a material fact under section 201(n) of the act. Under the act, the agency has the mandate to ensure that labeling provides truthful and nonmisleading information to consumers. Thus, the law provides the agency with authority to require specific label statements when needed for reasons other than to ensure the safe use of food. Under section 403(a)(1) of the act, a food is misbranded if its labeling is false or misleading in any particular. Section 201(n) of the act amplifies what is meant by “misleading” in section 403(a)(1) of the act. Section 201(n) of the act states that, in determining whether labeling is misleading, the agency shall take into account not only representations made about the product, but also the extent to which the labeling fails to reveal facts material in light of such representations made or suggested in the labeling or material with respect to consequences which may result from use of the article to which the labeling relates under the conditions of use prescribed in the labeling or under such conditions of use as are customary or usual (see § 1.21 (21 CFR 1.21)). Thus, the omission of certain material facts from the label or labeling of a food causes the product to be misbranded within the meaning of 21 U.S.C. 343(a)(1) and 321(n). In general, the agency believes the concept of “material fact” is one that must be applied on a case-by-case basis. The agency has required special labeling in cases where information is necessary to ensure that consumers are aware of special health risks associated with consumption of a particular product. For example, although protein products intended for use in weight reduction are not inherently unsafe, FDA requires a warning statement for such products that states, in part, that very low calorie protein diets may cause serious illness or death. Another example of required information is the use of the term “milk derivative” following the ingredient declaration of sodium caseinate when used in a product labeled “non dairy” (21 CFR 101.4(d)). 1 1 FDA's regulation regarding the failure to reveal material facts (§ 1.21) states that “affirmative disclosure of material facts * * * may be required, among other appropriate regulatory procedures, by * * * regulations in this chapter promulgated pursuant to section 701(a) of the act; or direct court enforcement action (emphasis added).” Thus, establishing a requirement for mandatory trans fat labeling is consistent with § 1.21. Consumption of trans fat results in consequences to the consumer. Consumers may increase or decrease their risk of CHD based on the level of trans fat in their diets. Thus, the presence or absence of trans fat in a food product is a material fact under section 201(n) of the act. Consumers must know—and the agency believes is material information that the reasonable consumer should know—the amount of trans fat in food products that they select as part of their total daily diet to choose products that would allow them to reduce their intake of trans fat, and thus, reduce the risk of CHD. Section IV of this document discusses the scientific evidence for why trans fat consumption places consumers at risk for CHD. Absent mandatory labeling, consumers would not be able to understand the relative contribution that foods make to their total daily intake of trans fat. First, because polyunsaturated and monounsaturated fats are not subject to mandatory labeling, simply including trans fat as part of the total fat contribution would not allow consumers to calculate the trans fat content by finding the difference between the sum total of all the mandatory fats listed on the label and the total fat content. Second, even if all component fats were required to be listed, it would not be realistic to expect consumers to do such calculations on each product to compare the relative trans fat contribution of each. Further, the fact that an individual food product may contain zero gram trans fat is still a “material fact” for that food. In the context of mandatory labeling of nutrients in a nutrition facts panel, the relative contribution of various food products to the total day's consumption of a heart unhealthy fat is important for consumers “to readily observe and comprehend the information and to understand the relative significance of that information in the context of the total daily diet” (section 2(b)(1)(A) of Public Law 101-535). Further, foods in which trans fat has replaced saturated fat would appear to be heart healthy based on the saturated fat grams listed on the nutrition facts panel, when, in fact, such foods may not be heart healthy due to the large contribution of trans fat to the total fat content. Consumers would be misled without having trans fat information available on the label. Thus, for the reasons set forth previously, FDA concludes that it is acting within its statutory authority under the act to require trans fat labeling. Moreover, Congress provided the agency with the express authority to add to the list of nutrients on the label under section 403(q)(2)(A) of the act. As stated in section V.A of this document, section 403(q)(2)(A) gives FDA the authority to require that information on additional nutrients be included in nutrition labels if FDA determines that providing such information will assist consumers to maintain healthy dietary practices. Section IV of this document provides ample evidence of the heart unhealthy effects from consumption of trans fat over a range of intakes, information the agency believes is material information that the reasonable consumer should know. When scientific evidence supports such labeling, the agency has discretion to determine whether to require the addition of a particular nutrient to the label of food products. Thus, the agency is well within its statutory authority for requiring mandatory labeling of trans fat and is not limited to requiring such information only when certain claims are made or only when other fats are listed on the label. Further, the agency disagrees with the comments that assert that mandatory trans fat labeling would not assist consumers to maintain healthy dietary practices, unless the label also carries a nutrient content or health claim or information about other fats. The agency also disagrees with comments suggesting that there is no basis for concluding any health benefit can be expected from disclosure of trans fat if foods contain a trivial amount of trans fat or if trans fat is not present in amounts that have not been clinically shown to adversely affect human health. The agency is exercising the discretion that Congress gave it in the 1990 amendments to include trans fat as a mandatory nutrient in food labeling, based on the state of the scientific evidence on the increased LDL-C levels from intake of trans fat (see section IV of this document). The scheme that Congress established would require all mandatory nutrients be listed on the food label, including those that the agency determines are necessary under section 403(q)(2)(A) of the act. Congress wanted one uniform statutory scheme for food labeling and discussed the importance of maintaining consistency in the format and content of the food label to “help all consumers to better understand and improve their eating habits by providing uniform information in a coherent and understandable format.” (136 Cong. Rec. S 16607 at 16609 (statement of Senator Metzenbaum)). The statute does not require other mandatory nutrients to be listed, for example, saturated fat, only when monounsaturated and polyunsaturated fat are voluntarily listed. Mandatory nutrients are listed for each food that bears a nutrition facts panel. Food that bears a nutrition label must contain certain required nutrients as part of that label to not be misbranded. Further, section 403(q)(2)(A) provides that mandatory labeling would be appropriate when information about a nutrient would assist consumers to maintain healthy dietary practices. Information on the trans fat content of food would assist consumers in this way. Consumers need the information on trans fat content of all foods that they consume so that they can reduce their intake of trans fat. The fact that a food may have no trans fat or a small amount of trans fat is useful information to the consumer so that food choices can be made and the consumer can put that product, along with many other products consumed as part of the daily diet, into the context of the total daily diet to maintain healthy dietary practices. Consumers would have information on the amount of trans fat in a product, along with other information about the amount of saturated fat and cholesterol. Consumers could use information about all three fats, not just saturated fat and cholesterol, to incorporate nutrition education information about recommended contributions for all three fats to the diet when making healthier food choices. There is ample discussion in section IV of this document about the heart unhealthy effects of consuming trans fat and there is a new and strong consensus among the scientific community for reducing trans fat intake. Thus, the agency believes it is within the bounds of its statutory authority under section 403(q)(2)(A) of the act to require the listing of trans fat on the food label, which listing is not dependent on the presence of claims or other voluntary fat information. B. The First Amendment Several general comments were received asserting that the agency's action to mandate labeling is subject to review under the first amendment. The comments assert that mandatory labeling of trans fat is commercial speech, and thus, such speech is entitled to the full range of first amendment protections as all commercial speech (citing to Pearson v. Shalala , 164 F.3d 650 (D.C. Cir. 1999)). The comments further assert that “compelled speech” is entitled to the same protections as speech “bans,” (citing to Central Hudson Gas & Elec. Corp. v. Public Service Comm'n of New York , 477 U.S. 557 at 566 (1980)). One comment explained that the court in Pearson emphasized that the first amendment does not allow FDA to restrict truthful, nonmisleading information as a “paternalistic” means of directing consumer food choices (164 F.3d at 656 (citing Bates v. State Bar of Arizona , 433 U.S. 350 at 377(1977) (“[W]e view as dubious any justification that is based on the benefits of public ignorance.”)); 44 Liquormart, Inc. v. Rhode Island , 517 U.S. 484, 503 (1996) (opinion of Stevens, J. joined by Kennedy, J., and Ginsburg, J.) (“The First Amendment directs us to be especially skeptical of regulations that seek to keep people in the dark for what the government perceives to be their own good.”). The comment further cited several cases for the proposition that the government cannot compel speech when disclosures are not necessary to materially alleviate real consumer harm (citing to IDFA v. Amestoy , 92 F.3d 67, 73 (2nd Cir. 1996); Ibanez v. Florida Dep't of Business and Prof'l Regulation , 512 U.S. 136 (1994); and Edenfield v. Fane , 507 U.S. 761 (1993)). Another comment suggests that the agency needed to consider the limitations imposed by the first amendment to avoid unjustified burdens and costs on food labeling where there is no genuine public health benefit from a rule that does not materially alleviate a genuine harm of potential consumer deception. Some comments assert that FDA's proposal to mandate trans fat labeling does not remedy a concrete harm as required by the first amendment. One comment suggests that a trans fat labeling rule could be supported if carefully crafted to remedy consumer deception but not where risk of consumer deception cannot be established as a genuine harm. Other comments state that FDA did not tailor its approach to labeling and would be requiring mandatory labeling of trans fat for foods containing as little as 0.5 g trans fat, which would not alleviate a genuine harm. The comment seems to further suggest that including trans fat in the total fat content on the label would be sufficiently tailored to alleviate a genuine harm. Another comment states that there is mere speculation in the record that providing information on trans fat would assist consumers to maintain healthy dietary practices, and thus, is not narrowly tailored to materially alleviate a genuine harm. A few comments state that treating trans fats the same as saturated fat on labeling would be the same as proposing to require false information on labels. Such an outcome, the comments state, would be indefensible on Constitutional grounds. One comment states that mandatory declaration of trans fat can only be justified under constitutional provisions when the absence of such declaration would constitute an omission of a material fact. FDA believes that this regulation is consistent with the first amendment. As noted previously, the failure to disclose the amount of trans fat in a product is an omission of material fact. When a manufacturer makes explicit or implicit health claims, the failure to provide trans fat information is likely to mislead the consumer. Moreover, the reasonable consumer would expect that the information on the label would give them the most important nutrition information relative to the healthfulness of a product. Yet the omission of trans fat runs counter to that expectation, impeding rational consumer choice. As the agency has explained earlier, consumers need information about trans fat on all foods, not just those that contain a certain threshold level of trans fat, to reduce overall intake of trans fat in the diet. Consumers can use that information to compare products and make selections that can reduce their risk of CHD. Accordingly, FDA believes that this final rule passes muster under the four-part test in Central Hudson primarily because, as discussed previously, requiring the factual information on the amount of trans fat in labeling ensures that the label is not false or misleading. Under the first prong of Central Hudson , commercial speech must be related to lawful activity and not be misleading. Speech that is false or misleading is not protected and may be prohibited ( Central Hudson , 447 U.S. 557 at 563-564). 2 2 The agency does not need to address the comments that asserted that proposing to treat trans fat the same as saturated fat in the November 1999 proposal would be the same as requiring false labeling. Since the agency is requiring separate line labeling in this final rule, those comments are moot. Given this determination, arguably the agency need not address the other three parts of the Central Hudson test at all. Nonetheless, and particularly in light of FDA's showing that such information is important to ensuring that consumers are adequately informed about the products they are buying, the proposed requirement satisfies the next three prongs. Turning to the second prong, the asserted governmental interest must be substantial. FDA's interest is clearly substantial, for at least two reasons. As noted previously, the FDA has a substantial interest in protecting and promoting public health and in preventing consumer deception by ensuring the accuracy and completeness of trans fat information in labeling. (See Pearson , 164 F.3d at 656.) The food labeling regulations seek to ensure that consumers have access to information about food that is scientifically valid, truthful, reliable, and not misleading. (58 Fed. Reg. 2478, 2526 (1993)). Consumers have a first amendment interest in obtaining information on which to base a decision, particularly one that has health consequences, regarding whether to buy a product, and this interest is “served by insuring that the information is not false or deceptive.” ( National Comm'n on Egg Nutrition v. FTC , 570 F.2d 157, 162 (7th Cir. 1977), cert. denied , 439 U.S. 821 (1978)). Moreover, FDA has a substantial governmental interest in assisting consumers to maintain healthy dietary practices. Such interest is consistent with the purpose of section 403(q)(2)(A) of the act; to provide information to consumers on nutrients ( trans fat content of food) when such information is of public health importance. The government is not confined to asserting a substantial government interest in preventing consumer deception for a regulation before that regulation can sustain a first amendment review ( Rubin v. Coors Brewing Co. , 514 U.S.476, 484- 85 (1995) (finding that the protection of the health, safety, and welfare of citizens is a substantial government interest)). In fact, FDA's interest in this rule includes an interest in ensuring consumers have information they need to help them maintain healthy dietary practices by providing factual information to consumers on food labels so that they can reduce CHD risk. Under the third prong of Central Hudson , the regulation must directly advance the government's interest asserted ( Central Hudson 447 U.S. 557 at 566). Requiring mandatory trans fat labeling on food products directly advances the government interest. As stated in section V.A of this document, analyses of survey data show that consumers rely on the Nutrition Facts label as a guide to choosing foods that meet their dietary objectives. The most frequently reported label use and the one that increased the most following the implementation of the 1990 amendments was to see how high the food was in nutrients such as fat. Mandatory trans fat labeling would help consumers maintain healthy dietary practices because it would provide needed information about the amount of trans fat in a given product so that consumers could plan a daily diet in a way that would reduce their intake of trans fat. Further, as stated in section V.A of this document, consumers need to be able to see the trans fat content of all foods subject to mandatory labeling so that they can compare the relative contribution of trans fat from each and make purchasing decisions accordingly. Finally, under the fourth prong of Central Hudson , the regulation must be no more extensive than necessary to serve the government interest ( Central Hudson 447 U.S. 557 at 566). That is the case here. Given, as stated in section V.A, that consumers need to understand the relative contribution of trans fat from all foods subject to mandatory labeling to make choices among products that will reduce their intake of trans fat, there are not “numerous and obvious less-burdensome alternatives” ( Cincinnati v. Discovery Network , 507 U.S. 410, 418 n.13 (1993)) than the requirement imposed here. Imparting truthful, factual, noncontroversial information about the presence or absence and amount of trans fat in food products on the label will provide consumers with information to help them to reduce their risk of CHD. Thus, the agency's action to require factual information be imparted to consumers about trans fat content of foods by requiring such information in labeling is sufficiently narrowly tailored to meet the fourth prong of Central Hudson . The “government is not required to employ the least restrictive means conceivable” rather it is required to have “‘a fit that is not necessarily perfect, but reasonable; that represents not necessarily the single best disposition but one whose scope is in proportion to the interest served’” ( Greater New Orleans Broadcasting Ass'n, Inc. v. U.S. , 527 U.S. 173 at 177 (citing Board of Trustees of State Univ. of N.Y. v. Fox , 492 U.S. 469, 480 (1989))). Requiring disclosure of trans fat content would assist consumers to maintain healthy dietary practices, provide complete, factual information on a food label to help them to reduce trans fat intake and thereby reduce their risk of CHD. Further, it would prevent them from being misled by providing information on trans fat that can help them make product comparisons and choose products that are heart healthy. The agency disagrees with the suggestion that narrow tailoring under the fourth prong of Central Hudson requires that trans fat content be included in the figure for total fat content. Such an approach would not provide consumers with labeling information on the amount of trans fat in a product. To provide consumers with a way to calculate the amount of trans fat in a product, all other fats (including monounsaturated and polyunsaturated fats) would be required to be on the label. The comment provided no basis for why monounsaturated fat and polyunsaturated fat should be made mandatory, why it would make sense for consumers to have to calculate the value for trans fat content from each label under the statutory scheme in section 403(q)(2)(A) of the act, and why such an approach would be less burdensome under the fourth prong of Central Hudson to support its assertion. Moreover, there is a substantial argument that the agency need not satisfy the Central Hudson test because that test applies to prohibitions on speech, and not compelled commercial speech, which is at issue here. Although consumer curiosity alone is an insufficient interest to compel factual speech ( International Dairy Foods Ass'n v. Amestoy , 92 F. 3d 67, 74 (2nd Cir. 1996)), the government can compel manufacturers to disclose information that “bears on a reasonable concern for human health or safety or some other sufficiently substantial government concern.” Id. FDA's rule to require mandatory trans fat labeling is one that would require manufacturers to disclose such information. Further, the U.S. Court of Appeals for the second circuit upheld a regulation compelling speech where the goal of the statute was to reduce the amount of mercury released into the environment; a goal that was “inextricably intertwined with the goal of increasing consumer awareness of the presence of mercury in a variety of products” ( National Electrical Manufacturer's Ass'n v. Sorrell , 272 F. 3d 104, 115 (2d Cir. 2001)). FDA is providing information that will assist consumers to maintain healthy dietary practices and prevent consumers from being misled if incomplete nutrition information on trans fat were provided on the food label, i.e., information that did not include the presence or amount of trans fat in foods. Similar to the goal the State of Vermont has in increasing awareness of consumers to prevent the harmful consequences of mercury containing products entering the environment, FDA wants to prevent the harmful consequences (increased risk of CHD) to consumers from trans fats. Thus, the agency's action to require trans fat labeling in this rule comports with similar actions in other compelled commercial speech cases which have been upheld under the first amendment. For all of the foregoing reasons, the agency believes it has complied with its burdens under the first amendment to support mandatory disclosure of the amount of trans fat in food labeling. The information that FDA is requiring in food labeling for trans fat, i.e., the amount of trans fat listed in grams or an optional footnote stating “Not a significant source of trans fat” if zero grams are present, is purely factual information. FDA's action to compel trans fat labeling does not “prescribe what shall be orthodox in politics, nationalism, religion, or other matters of opinion or force citizens to confess by word or act their faith therein.” Rather, it simply provides for factual and uncontroversial information that can be supported if such labeling is reasonably related to FDA's government interests ( Zauderer , 471 U.S. at 650-51 (distinguishing between the level of review necessary under the first amendment where factual and uncontroversial information is required and recognizing that the constitutionally protected interest in not providing such information is minimal); see also Glickman v. Wileman Brothers & Elliott, Inc. , 521 U.S. 457, 472 (1997) (distinguishing compelled financial contributions that promote speech to encourage consumer purchases from speech in which the content of the message focuses on political or ideological differences). FDA's interests in requiring mandatory trans fat labeling is to protect the public health by providing consumers with information that will assist them in maintaining healthy dietary practices and by preventing misleading labeling by providing factual, truthful, and noncontroversial information. Providing information to consumers about the trans fat content of foods on food labeling is reasonably related to the agency's interest of assisting consumers to maintain healthy dietary practices. As explained in section IV of this document, there is a relationship between the level of trans fat in the diet and risk of CHD. To reduce this risk, consumers need information about the level of trans fat in food products. The agency has evidence that consumers refer to product labels when purchasing food products and use labels to determine how much fat is in a product (Ref. 96). Thus, by requiring that trans fat information be on a food label, the agency will be assisting consumers in making food purchasing decisions that can result in a reduction in trans fat intake so that they can reduce their risk of CHD. Moreover, because the presence or absence of trans fat is a material fact under section 201(n) of the act, as explained earlier, mandatory labeling that provides information about the presence or absence of trans fat, and if present, at what levels, is a reasonable means for imparting full, factual information to consumers so that they will not be misled in purchasing decisions because they have no information about trans fat content and may not even be able to calculate it based on information on other fats on the label. The agency has carefully considered the limitations imposed by the first amendment to avoid unjustified burdens and costs of food labeling where there is no genuine public health benefit from the rule that does not alleviate a harm of potential consumer deception. The agency did carefully calculate the costs and benefits of food labeling (see section IX of this document) and determined that the scope of mandatory trans fat labeling was in proportion to the government interest served. Cincinnati v. Discovery Network, Inc. , 507 U.S. 410 (1993) (stating that a regulation “should indicate that its proponent ‘carefully calculated’ the costs and benefits associated with the burden on speech imposed by its prohibition” (quoting Fox , 492 U.S. at 480)). Moreover, the agency has documented that there is a public health benefit to the final rule. To the extent that those who commented “believe that their money is not being well spent, ‘does not mean that they have first amendment complaint.’” Glickman , 521 U.S. at 472. Administrative Procedure Act One comment asserts that FDA must adopt regulations that are supported by the rulemaking record and that are not otherwise arbitrary and capricious in light of the statutory limitations on the agency's authority. This comment and another assert that the data do not support a basis for treating trans fat and saturated fat the same either chemically or for purposes of one's health, and that therefore, FDA is proposing to require food labels that provide false information. One comment said that to equate trans fat and saturated fat on the existing body of evidence would be arbitrary and capricious in violation of the APA. Another comment asserts that FDA did not account for legal and policy considerations that are necessary to construct an appropriate trans fat regulatory framework and thus, does not have a rulemaking record that satisfies the agency's burden of proof under the APA. The comment seemed to relate deficiencies in the record necessary to satisfy first amendment requirements to a failure to satisfy APA requirements. One comment asserts that the rulemaking record for FDA's proposal does not support the expansive scope of the mandatory trans fat labeling proposal, and therefore, fails to satisfy the requirements of the APA. The comment states that the body of scientific evidence did not establish a genuine “harm” from trans fat consumed at ordinary intake levels from foods that would be subject to the mandatory labeling requirements. To the extent that comments were raising concerns about the agency going to a final rule based on including trans fat in the amount and % DV for saturated fat and that doing so would be the same as requiring false information on labels, those comments are now moot since the agency is requiring a separate line for labeling trans fat. FDA disagrees with the comment that suggests that FDA did not account for legal and policy considerations necessary to construct an appropriate trans fat regulatory framework, and that the rulemaking record does not support the scope of this rule. As stated previously, the agency is using the statutory framework that Congress provided in section 403(q)(2)(A) of the act to require mandatory trans fat labeling. Further, the agency has explained its rationale, based on the science, for why it believes that it is necessary for consumers to have information on the trans fat content of foods to maintain healthy dietary practices. To the extent that the comments assert that the body of scientific evidence did not establish a “harm” from trans fat consumed at ordinary intake levels from foods, and thus, would preclude the agency from requiring mandatory trans fat labeling under the APA, the agency disagrees. The science supports adverse health effects from consumption of trans fat among a range of intakes that includes intakes at average intake levels among the U.S. population (see section IV of this document). That said, mandating the disclosure of this information does not require FDA to find that trans fatty acids actually cause CHD. In mandating the disclosure of this information, FDA need not meet the standard of proof required to establish causation in a private tort action ( Glastetter v. Novartis Pharmaceutical Corp. , 252 F.3d 986, 991 (8th Cir. 2001)). “The distinction between avoidance of risk through regulation and compensation for injuries after the fact is a fundamental one. In the former, risk assessments may lead to control of a toxic substance even though the probability of harm to any individual is small and the studies necessary to assess the risk are incomplete; society as a whole is willing to pay the price as a matter of policy. In the latter, a far higher probability (greater than 50 percent) is required since the law believes it is unfair to require an individual to pay for another's tragedy unless it is shown that it is more likely than not that he caused it * * *.” In re “Agent Orange” Product Liability Litigation , 597 F. Supp. 740, 781 (E.D.N.Y.) 1984), aff'd 818 F. 2d 145 (2d. Cir. 1987). In making its decision, the agency follows “the preventive perspective that agencies adopt in order to reduce public exposure to harmful substances.” Glastetter , 252 F. 3d at 991, quoting Hollander v. Sandoz Pharmaceuticals Corp. , 95 F. Supp. 2d 1230, 1234 n.9 (W.D. Okla. 2000). Accordingly, so long as we conclude that the consumer would reasonably expect this information to be disclosed and that it is scientifically justifiable to require its disclosure, we are justified in taking this action. The agency has determined, based on this scientific evidence, that consumers need this information to maintain healthy dietary practices. Thus, the agency is not precluded under the APA, as the comment suggests, from issuing this final rule. In addition, the agency has discussed why it believes that this final rule comports with the first amendment, and thus, disagrees with the comment that suggests that because it did not meet its burdens under the first amendment, it did not satisfy the APA requirements. IV. Review of the Science A. Reviews by the Federal Government and the Institute of Medicine (IOM)/National Academy of Sciences (NAS) In the November 1999 proposal, FDA reviewed reports published by the U.S. Federal government and the IOM/NAS. These reports, which were published between 1988 and 1995, showed that conclusions about the role of trans fat in raising LDL-C, the primary risk factor for CHD, and dietary recommendations were evolving as results from new studies became available (64 FR 62746 at 62749). For example, the 1988 Surgeon General's Report (Ref. 2) and the 1989 IOM/NAS Report (Ref. 4) found no adverse effects of trans fat. Later, the 1993 publication from the NCEP stated that “ trans fatty acids raise LDL-C levels nearly as much as do cholesterol-raising saturated fatty acids” (Ref. 5). The fourth edition of Dietary Guidelines for Americans, a joint 1995 publication from the U.S. Department of Health and Human Services and the U.S. Department of Agriculture (USDA) stated that, “Partially hydrogenated vegetable oils, such as those used in many margarines and shortenings, contain a particular form of unsaturated fat known as trans -fatty acids that may raise blood cholesterol levels, although not as much as saturated fat” (Ref. 6). Subsequent to the November 1999 proposal, new expert panels have been convened to update, in light of new scientific evidence, the conclusions and recommendations in the reports discussed previously. FDA has reviewed these new reports to evaluate whether their updated conclusions reversed or significantly altered its earlier conclusions. The Dietary Guidelines 2000 (Ref. 87) makes the following statements regarding trans fatty acids and food sources of trans fat: Foods high in trans fatty acids tend to raise blood cholesterol. These foods include those high in partially hydrogenated vegetable oils, such as many hard margarines and shortenings. Foods with a high amount of these ingredients include some commercially fried foods and some bakery goods. (Ref. 87, p. 28); Aim for a total fat intake of no more than 30 percent of calories, as recommended in previous editions of the Guidelines. If you need to reduce your fat intake to achieve this level, do so primarily by cutting back on saturated and trans fats. (Ref. 87, p. 30); Limit use of solid fats, such as ... hard margarines, ... and partially hydrogenated shortenings. Use vegetable oil as a substitute. (Ref. 87, p. 30). In the report describing the basis for its recommendations, the Advisory Committee on Dietary Guidelines 2000 (Ref. 88) suggested that information be provided to help the reader of the Dietary Guidelines 2000 distinguish among the different kinds of fats—saturated, trans , and unsaturated. The advisory committee summarized the scientific evidence on trans fatty acids as follows: Trans fatty acids are included because a definitive body of recent experimental evidence indicates that trans fatty acids raise the concentration of the most dangerous form of serum cholesterol (LDL-cholesterol). The advisory committee further states: Trans fatty acids also tend to lower a protective form of serum cholesterol (HDL-cholesterol). Prospective epidemiological studies further note that higher intakes of trans fatty acids are associated with a higher incidence of coronary heart disease. (Ref. 88, p. 37). Recent guidelines from the National Cholesterol Education Program (NCEP) (Ref. 89) provide an update to the 1993 NCEP report (Ref. 5). The 2001 NCEP report is an evidence-based report that extensively references the scientific literature. The expert panel concluded that: Trans fatty acids raise serum LDL-cholesterol levels. Through this mechanism, higher intakes of trans fatty acids thus should increase risk for CHD. Prospective studies support an association between higher intakes of trans fatty acids and CHD incidence. (Ref. 89, p. V-15). Based on these conclusions, the Expert Panel recommended for individuals at increased risk for CHD that: Intakes of trans fatty acids should be kept low. The use of liquid vegetable oil, soft margarine, and trans fatty acid-free margarine are encouraged instead of butter, stick margarine, and shortening. (Ref. 89, p. V-15). Lastly, a recent report of the IOM/NAS found “a positive linear trend between trans fatty acid intake and LDL cholesterol concentration, and therefore increased risk of CHD” (Ref. 140). The report summarized that this would suggest a Tolerable Upper Intake Level (UL) of zero, but because trans fats are unavoidable in ordinary diets and achieving such a UL would require extraordinary changes in dietary intake patterns that might introduce other undesirable effects and unknown health risks, a UL was not proposed. Instead, the report recommended “that trans fat consumption be as low as possible while consuming a nutritionally adequate diet.” In summary, the recently updated Dietary Guidelines (Ref. 87 ), NCEP (Ref. 89), and IOM/NAS (Ref. 140) reports, based on current scientific evidence, consistently find that trans fatty acids are associated with increased LDL-C levels and, therefore, that lower intakes of both saturated and trans fatty acids are important dietary factors in reducing the risk of CHD in the general population and for those at increased risk for CHD. In addition, these new reports (Refs. 87, 89, and 140) either reversed previous scientific conclusions of no deleterious effects of trans fatty acids (Refs. 2 and 4), or strengthened previous scientific conclusions of an adverse effect of trans fat intakes on CHD risk (Refs. 5 and 6). Thus, based on the current body of scientific evidence, there is strong agreement among the expert panels that the available evidence is sufficiently compelling to conclude that trans fat intakes increase CHD risk. Accordingly, these expert panels recommended, in addition to their longstanding recommendations that Americans consume diets limited in saturated fat, that consumers also select food products that are low in trans fat. Although the expert panels' primary emphases remain on limiting intakes of saturated fat (which contributes on average about 11-12 percent of calories in U.S. diets), they also have recommended limiting intakes of trans fats (which contribute, on average, about 3 percent of calories in U.S. diets). These recommendations are made for the general population (Refs. 87 and 140) and persons at increased risk for CHD whose LDL-C is above goal levels (Ref. 89). (Comment 1) Several comments on the November 1999 proposal questioned whether the conclusions regarding trans fat would be supported by pending scientific reviews. Some of these comments recommended that FDA not issue a final rule until after publication of Dietary Guidelines 2000. Other comments recommended waiting until the IOM/NAS completes work on a review of dietary reference values for macronutrients. The Dietary Guidelines 2000 have been published (Refs. 87 and 88). While they do not mention trans fat in its broad guideline, “Choose a diet that is low in saturated fat and cholesterol and moderate in total fat,” the recommendations from the Dietary Guidelines 2000 and the accompanying advisory committee review clearly state that foods high in trans fatty acids tend to raise blood LDL-C which increases the risk of CHD. Reductions in intakes of both saturated and trans fats are suggested for maintaining total fat to no more than 30 percent of calories. Substitutions of foods low in trans and saturated fatty acids (e.g., vegetable oils) for foods with higher levels of trans fatty acids (e.g., hard margarines, partially hydrogenated shortenings) are also recommended. Thus, in the Dietary Guidelines 2000, the recommendations to reduce trans fat intake are definitive, not tentative. Additionally, the recommendations in the Dietary Guidelines 2000 are reinforced by similar findings and recommendations from other recent expert panels (Refs. 89 through 91, and 140), including those of the IOM/NAS report on macronutrients (Ref. 140), which has also been published. The IOM/NAS report recommends that “ trans fat consumption be as low as possible while consuming a nutritionally adequate diet.” (Comment 2) One comment suggested that trans fat is a healthier choice than saturated fat, quoting 1994 and 1998 statements that it attributed to the American Heart Association (AHA) recommending that margarine be used instead of butter and that trans fats displace saturated fats in the diet. The comment suggested that, if AHA or others in the scientific community recommend margarine be used instead of butter, this establishes that hydrogenated vegetable oils and trans fat have health benefits, at least in comparison to saturated fatty acids. Several other comments stated that trans fats displace saturated fats in the diet, thus implying that they are healthful alternatives to saturated fats. FDA disagrees with the comments' conclusions that the recommendations of the AHA and other scientific bodies that margarine be substituted for butter provides a basis for concluding that trans fat has health benefits or is a healthier choice than saturated fats. The recently updated 2000 AHA Guidelines (Ref. 91) recommend that intakes of foods with a high content of cholesterol-raising fatty acids (i.e., trans and saturated fats) be limited because both raise serum LDL-C levels, and consequently, increase CHD risk. Specifically, the AHA recommends limiting the intake of: (1) Foods rich in saturated fatty acids (e.g., full-fat dairy products, fatty meats, tropical oils), and (2) trans -fatty acids, the major contributor of which is hydrogenated fat (Ref. 91). Relative to trans fat, the 2000 AHA guidelines state that, “It has been established that dietary trans -unsaturated fatty acids can increase LDL cholesterol and reduce HDL cholesterol” (Ref. 91). Moreover, the AHA recommendations are consistent with the recommendations of the other scientific bodies described earlier in this document. All of these reports recommend substituting vegetable oils for animal fats; and, within the vegetable oil category, recommend selecting those products that are lower in or free of trans fat (e.g., liquid vegetable oils, soft margarines, and trans -free margarines) in place of more hydrogenated oil products (e.g., stick margarines and shortenings). More recently, the IOM/NAS concluded that there is no evidence of health benefits associated with trans fat intakes, but that trans fat does increase LDL-C and, therefore, the risk of CHD (Ref. 140). Thus, the comment's premise that the current recommendations of the AHA and other scientific bodies support the conclusion that trans fat is a healthful alternative to butter and animal fats is not consistent with, nor supported by, the full context and intent of recommendations by the AHA and other scientific bodies. Those comments that said trans fat is a healthful alternative to saturated fat also are not consistent with the recommendations of the AHA and other scientific bodies. These expert bodies all concluded that both trans and saturated fatty acids increase the risk of CHD by increasing serum LDL-C levels and, therefore, they recommended limiting intakes of both trans and saturated fatty acids. It should be noted that recommendations to consume margarine instead of butter are based on the fact that the combined amount of cholesterol-raising lipids ( trans and saturated fats) are lower in margarines than in butter (Ref. 92). Additionally, butter, unlike margarine, contains dietary cholesterol which also has cholesterol-raising effects (Ref. 139). B. Published Studies To evaluate the evidence that dietary trans fat increases the risk of CHD, FDA reviewed the scientific evidence cited in the petition and recent human studies from its own literature search. In the November 1999 proposal, FDA summarized its review of the findings of intervention and observational studies on the relationship between intakes of trans fatty acids and CHD (64 FR 62746 at 62749-62754). FDA considered the findings from human studies to constitute evidence that is more directly relevant and persuasive than findings from animal studies. FDA gave greater weight to results from dietary intervention studies than to observational (epidemiological) studies because of an intervention study's ability to provide evidence for a cause-effect relationship. FDA regarded results from observational studies as indirect evidence for a relationship between trans fatty acid intake and CHD risk. FDA also reviewed estimates of dietary intakes of trans fatty acids in the U.S. population (64 FR 62746 at 62752-62753). In the November 1999 proposal, FDA evaluated results of 12 dietary intervention studies (Refs. 7 through 15, 34, 36, and 82). FDA focused on the physiological measures of serum and plasma LDL-C concentrations to evaluate whether trans fatty acid intakes influence the risk of CHD because such measures are recognized as valid predictors of increased risk for CHD (Ref. 5). FDA concluded that controlled intervention studies, in different population groups in the United States and other countries, consistently indicate that consumption of diets containing trans fatty acids, like diets containing saturated fats, results in increased serum LDL-C (a major risk factor for CHD) compared with consumption of diets containing cis -monounsaturated or cis -polyunsaturated fat sources (64 FR 62746 at 62753). The agency also compiled reports of changes in serum total and high density lipoprotein cholesterol (HDL-C) and serum lipoproteins to present a more complete picture of serum lipid changes (64 FR 62746 at 62799-62821). In the November 1999 proposal, FDA also reviewed nine publications that examined associations between trans fatty acids, serum lipids and CHD endpoints: Four publications describing three prospective cohort studies (Refs. 19 through 21 and 38), one publication describing an inter-cohort study (Ref. 22), three publications describing case control studies (Refs. 16 through 18), and one publication describing a cross-sectional study (Ref. 23). FDA stated that these epidemiological investigations of associations between dietary trans fatty acids and risk of CHD must be interpreted cautiously because of the imprecision associated with the dietary collection methodologies used, the difficulty of eliminating confounding factors, and because no dose-response relationship has been demonstrated in the studies (64 FR 62746 at 62752). FDA also stated that despite these generally recognized deficiencies in the observational studies, the repeated and consistent findings from these studies show that consumption of trans fatty acids is associated with adverse effects on CHD risk in humans, which supports the findings from intervention studies (64 FR 62746 at 62752). Thus, in the November 1999 proposal, FDA concluded that controlled intervention studies in different population groups in the United States and other countries consistently indicate that consumption of diets containing trans fatty acids, like diets containing saturated fats, results in increased serum LDL-C compared with consumption of diets containing cis -monounsaturated or cis -polyunsaturated fat sources (64 FR 62746 at 62753). FDA also concluded that these findings are consonant with findings from observational studies among free-living persons in the United States and other countries (64 FR 62746 at 62753). In the November 1999 proposal, FDA also summarized the results of estimates of dietary intake of trans fatty acids in the U.S. population (64 FR 62746 at 62752). FDA noted that estimates of mean consumption of trans fatty acids in the United States ranged from about 3 g/day to about 13 g/day. Based on national food disappearance data, estimated mean values for the daily per capita consumption of total trans fatty acids were variable: 12.8 g/day (Ref. 24), 10.2 g/day (Ref. 39), and 8.1 g/day (Ref. 25). Based on a nationally representative sample of the U.S. population, the estimated mean intake of trans fatty acids was 5.3 g/day (2.6 percent of calories) and the 90th percentile intake was 9.4 g/day for individuals 3 years of age and older in the U.S. population (Ref. 12). Estimates of mean trans fatty acids intake were 4.4 g/day for men and 3.6 g/day for women in one observational study in the United States (Ref. 18) and 3.4 g/day for men in another (Ref. 23). Some studies presented mean or median intakes for quintiles of the population studied. Median intakes were 3.1 g/day for men and 3.0 g/day for women in the lowest quintile and 6.7 g/day for men and 6.8 g/day for women in the highest quintile (Ref. 18). Another study reported intakes of 1.5 g/day and 5.3 g/day, respectively, for the lowest and highest quintiles of male health professionals (Ref. 19). For female nurses in the United States, mean energy-adjusted intakes of trans fatty acids were 2.4 and 5.7 g/day, respectively for the lowest and highest quintiles of trans fatty acid intakes (Ref. 21). FDA concluded that, overall, the estimates of mean trans fatty acids intakes are similar to intakes of trans fatty acids in the U.S. intervention studies (the selected intervention studies used in this comparison were those in which trans fatty acid contents were determined by chemical analysis of duplicate portions of the diets and for which statistically significant increases in serum LDL-C were reported compared to diets containing cis -polyunsaturated fatty acids (Refs. 13, 34, and 82) or cis -monounsaturated fatty acids (Ref. 12)). The intakes of trans fatty acids for which the increases in serum LDL-C were statistically significant in the intervention studies ranged from 7.6 g/day to 13 g/day (Refs. 12, 13, 34, and 82). FDA stated that these levels are very similar to the estimated intakes of the many individuals in the United States whose trans fatty acid intake is greater than the mean of 5.3 g/day (64 FR 62746 at 62753). Subsequent to the November 1999 proposal, additional studies on the topic of trans fatty acid intakes and CHD risk have been published (Refs. 98 through 102). FDA reviewed the findings from these new studies to evaluate whether they differ significantly from the findings of studies included in the proposed rule. In general, the results from these recently published intervention and prospective studies are consistent with the results from the studies included in the November 1999 proposal in that they also found that diets containing trans fat increased LDL-C, and therefore, CHD risk (Refs. 98 to 101) and that, in free-living populations, consumption of trans fat was associated with increased risk of heart attack and death from CHD (Ref. 102). In addition, a cross-sectional observational study has been published (Ref. 93). This study, which was the subject of several comments, suggests no relationship between current intakes of trans fat in European countries and CHD risk. FDA has addressed this study in Comment 4 of this document. (Comment 3) Many comments discussed the strength of the scientific evidence for establishing whether trans fatty acids adversely affect CHD risk by raising LDL-C levels. A number of comments found the evidence to be strong and supportive of trans fatty acid labeling on foods. Other comments questioned whether there was sufficient evidence to warrant labeling of trans fat content. Several comments stated that the health impact of the intake levels reported in population-based surveys and observational studies was minimal. A few comments to the November 15, 2002, proposal to reopen the trans fat comment period questioned the scientific validity of the IOM/NAS report based on the underlying science and regression equations relied upon. The comments argued that one of the articles relied upon (Ref. 83) was an opinion essay and was not peer-reviewed by the New England Journal of Medicine (NEJM) where it was published. Based on an evaluation of the scientific evidence, FDA concludes that the scientific evidence is sufficient to require nutrition labeling of trans fat. In the November 1999 proposal, FDA systematically summarized and reviewed the available individual human studies (64 FR at 62749-62754 and 62798 to 62821). In re-examining this review in light of the comments, FDA finds no basis to alter its earlier conclusion that, in general, there is consistency in finding adverse effects of trans fat on CHD risk. Controlled intervention studies in different population groups in the United States and other countries consistently indicated that consumption of diets containing trans fat results in elevations of LDL-C, and therefore, increased risk of CHD (Refs. 7 to 15, 34, 36, and 82). In addition, positive statistical associations are consistently reported in observational studies between estimated trans fat intake in free-living populations and incidence of CHD manifested as heart attack or death from CHD (Refs. 16 to 22, and 38) or increased risk of CHD as assessed by higher levels of LDL-C (Ref. 23) (64 FR 62751 to 62753). Thus, FDA continues to find that a large body of the most persuasive types of evidence (i.e., intervention trials and prospective cohort observational studies) consistently show that trans fat intakes adversely affect CHD risk under both controlled trial conditions and in free-living populations following their usual dietary patterns. This consistency was seen across studies done: (1) In the United States and several European countries, (2) using a variety of test and control products and study designs, (3) using a range of intake levels for trans fatty acids (less than (<) 1 percent to 7 percent of calories), (4) by different investigators and research groups, (5) with different populations and selection/exclusion criteria, and (6) within different total dietary contexts. This relationship was also consistently found in comparisons of high vs. low consumers of trans fats in free-living U.S. populations consuming their normal diets. Thus, whether controlled intervention trials or among free-living U.S. populations consuming their usual diets, the adverse effects of trans fat intakes on CHD risk were consistently observed. Moreover, FDA's conclusions were consistent with those of independent Federal Government expert panels that published dietary recommendations for U.S. population groups subsequent to publication of the November 1999 proposal (Refs. 87 and 89 through 91) that were cited in the Federal Register to reopen the comment period on November 15, 2002. These expert panels, reviewing the same scientific evidence as FDA described in the proposed rule, and given their knowledge of U.S. dietary patterns, consistently concluded that trans fat intakes are associated with increased CHD risk and recommended that U.S. consumers and those who need to lower their LDL-C level minimize their intakes of trans fat to reduce their risk of CHD. For example, the IOM/NAS noted “a positive linear trend between trans fatty acid intake and total and LDL-C concentrations, and therefore, increased risk of CHD, thus suggesting an upper limit of zero” (Ref. 90). However, they further stated that, because trans fatty acids are unavoidable in ordinary diets, a complete avoidance of these fats is not possible without extraordinary changes in patterns of dietary intake. Such extraordinary adjustments may introduce other undesirable effects (e.g., elimination of foods such as diary products and meats that contain trans fatty acids may result in inadequate intakes of protein and certain micronutrients). For these reasons, the IOM/NAS recommended that trans fatty acid consumption be as low as possible while consuming a nutritionally adequate diet. In response to the comments about the scientific validity of an article used in the IOM/NAS report, FDA notes that the paper by Ascherio and coworkers (Ref. 83) is not the only information that the IOM/NAS relied on to conclude that trans fatty acid consumption should be as low as possible relative to CHD risk. Moreover, FDA did not find the LDL/HDL cholesterol ratio used in the Ascherio et al. analysis to be a useful endpoint for purposes of the trans fatty acid rule-making (see Comment 10). Additionally, FDA's independent evaluation of the scientific evidence concluded that there is consistency in finding adverse effects of trans fat on risk of CHD. Therefore, even though the independent reviews of FDA and the other expert panels differed to some degree in how they used the available scientific evidence, the resultant consistency of the conclusions across these reviews provides strong credence to the finding that trans fatty acid consumption increases CHD risk via increases in LDL-C. In summary, based on the consistent results across a number of the most persuasive types of study designs (i.e., intervention trials and prospective cohort studies) that were conducted using a range of test conditions and across different geographical regions and populations, the agency now agrees with the comments that stated that the available evidence for an adverse relationship between trans fat intakes and CHD risk is strong. FDA also finds the results from the large prospective cohort studies among free-living U.S. population groups to be persuasive evidence that the trans fat intakes associated with U.S. dietary patterns can have a significant adverse effect on CHD risk for U.S. consumers. The scientific agreement for this relationship among the various expert groups and consensus among these expert groups in recommending that U.S. consumers limit their intakes of saturated and trans fats now provide further evidence of the strength of the science and the public health importance of lowering trans fat intakes for U.S. consumers. Therefore, the comments do not persuade FDA to change its position in the proposed rule that labeling of trans fatty acids is warranted based on: (1) The scientific evidence; and (2) the public health importance of the guidelines recommending that consumers limit their intakes of both of the LDL-C-raising fats: trans and saturated fats. Thus, FDA concludes that its tentative conclusion in the proposed rule that “under conditions of use in the United States, consumption of trans fatty acids contributes to increased serum LDL-C levels, which increases the risk of CHD” (64 FR 62746 at 62754) is no longer tentative. FDA continues to find the overall weight of scientific evidence in support of this conclusion to be sufficiently compelling to now warrant trans fatty acid labeling. (Comment 4) Several comments stated that a new observational study by van de Vijver et al., “Association between trans fatty acid intake and cardiovascular risk factors in Europe: The trans FAIR Study” (Ref. 93) showed no association between average total trans fat intake in Europe and LDL-C or HDL-C so that average trans fat intake in the United States is probably not detrimental to human health. FDA disagrees with the comments. The trans FAIR study had a cross-sectional design, measuring trans fatty acid intake and serum lipids in 327 men and 299 women, ages 50 to 65 years, in 8 European countries from approximately 1997 to 1999. The study reported no statistically significant association between total trans fat intake and serum LDL-C. The habitual intake of trans fat was estimated to be about 2 g/day (e.g., approximately 1 percent of calories). FDA notes that cross-sectional designs, such as the one used by van de Vijver et al., are relatively weak designs for showing associations between diet and serum lipids (Ref. 93). As an observational study, they are generally considered to be less persuasive than intervention trials. Moreover, compared with other types of observational studies (e.g., prospective (cohort) observational studies and retrospective (case-control) studies), they are considered particularly weak. Considering the weaknesses of the cross-sectional design used in the trans FAIR study compared with the much larger body of evidence from more persuasive types of studies (i.e., intervention trials and prospective observational studies) that consistently demonstrate an adverse effect of trans fat intakes on LDL-C, FDA does not find the trans FAIR study to be sufficiently compelling to override the overall weight of the scientific evidence reviewed in the November 1999 proposal or to override the independent conclusions of recent expert panels convened by the Federal Government (Refs. 87 and 89), the IOM/NAS (Ref. 90), and the AHA (Ref. 91). For the reasons cited previously, FDA disagrees with the comments that a lack of association between trans fat intake and serum lipids in the European trans FAIR study indicates that average trans fat intake in the United States is probably not detrimental to human health. (Comment 5) Many comments emphasized the inadequacies in the assessment of intakes of trans fatty acids by the U.S. population and noted that the current data are insufficient in regard to the trans fatty acid content of foods. One comment noted that USDA's data for the trans fatty acid content of foods are limited to a few foods with a small number of samples. Thus, the comment concluded that extrapolation of trans fatty acid content from a few foods must be used to estimate the content of trans fat in the large number of foods that make up the total diets of the U.S. population. This extrapolation results in intake estimate errors with unknown effects. Some comments assert that the data are an over-estimate of the U.S. population's trans fatty acid intake and other comments assert that the data are an under-estimate. FDA agrees that estimates of dietary intakes of trans fat, as with all intake estimates based on participant reports and limitations in compositional data bases, are subject to multiple sources of error. In the November 1999 proposal, the agency reviewed intake estimates from three different types of data: (1) National food consumption survey, (2) national disappearance data, and (3) observational studies done in U.S. population groups. By examining results from multiple methods of estimating intakes, the agency was able to assess some, but not all, of the uncertainties in current intake estimates. In discussing these data, FDA noted the very limited composition data available for the trans fatty acid composition of foods and the difficulties in determining the accuracy of reported trans intakes with current knowledge and methods (64 FR at 62752-62753). In the November 1999 proposal, FDA reviewed an analysis that used the results of the 1989-1991 Continuing Survey of Food Intakes by Individuals (CSFII), a national food consumption survey of the U.S. population conducted by the USDA (Ref. 26). This study reported a mean trans fatty acid intake of 5.3 g/day (2.6 percent of calories) for persons 3 years and older. One way to evaluate the accuracy of survey intake estimates is to compare the reported caloric intakes to known requirements, or to levels from intervention trials that have been shown to maintain body weight for some period of time. The authors of this study stated that these reported caloric intakes were 20-40 percent below known physiologic requirements, suggesting significant under-reporting of intakes (Ref. 26). The reported caloric intakes in the CSFII were also approximately 265 to 1,000 calories/day below levels required to maintain body weights for U.S. subjects in intervention trials (Ref. 26). Therefore, the estimates of intakes from the CSFII survey data are likely significantly under-reported, particularly when expressed on a gram per day basis. The second type of trans fatty acid intake estimate considered in the November 1999 proposal was derived from estimates of trans fatty acids available in the U.S. food supply calculated from USDA-Economic Research Service fats and oils production figures and food disappearance data for fats and oils. Three studies provided daily per capita estimates of trans fatty intakes of 12.8 g, 10.2 g, and 8.1 g. (Refs. 24, 39, and 25, respectively). Although all three estimates were “corrected” for losses due to waste in processing and use, per capita intake estimates based on disappearance data generally overestimate intakes (Ref. 4). Finally, observational studies conducted in U.S. populations also can provide intake estimates. In the November 1999 proposal, FDA reviewed several observational studies, including several prospective cohort studies conducted in U.S. populations who were healthy at the time of enrollment (Refs. 19, 21, and 38). Estimates of daily trans intakes ranged from 1.3 to 3.2 percent of calories and from 1.5 to 6.4 g/day for adult participants in these studies. These ranges of intake estimates are somewhat lower than those in the CSFII survey so are therefore also likely underestimated. However, even with these relatively low intake estimates, these studies found that among free-living adults, those adults consuming trans fatty acids at the highest quintiles of intake had increased relative risk of CHD as compared to adults consuming trans fatty acids at the lowest quintiles of intake. In summary, the different types of studies, and different studies within a study type, estimated different intake levels for the U.S. population. The estimates from the food disappearance data are likely overestimated. The estimates from the observational studies and the national food consumption survey are likely underestimated. All estimates used the same compositional data base which, as noted above, has very limited data on the trans fat content of foods. Although we have no external “gold standard” against which to determine which estimate is most accurate, the available intake estimates suggest that average intakes of U.S. consumers probably fall within the range of 1.3 g to 12.8 g/day. Because of the multiple sources of uncertainty in intake estimates, caution must be exercised to avoid over-interpretation of the available dietary intake estimates and their relationship to the trans fat levels used in the intervention trials. It is important to note, however, that the agency's determination of the scientific basis for and public health importance of trans fat labeling was based on the totality of the scientific evidence. In this evaluation, FDA weighted the results of the intervention trials most heavily. The intervention trials clearly demonstrate, in a cause and effect manner, an adverse effect of trans fat intakes on LDL-C levels, and therefore on CHD risk, across a broad range of intakes (less than 1 percent to 7 percent of calories), dietary patterns, and population groups. For the purposes of determining that the scientific evidence was sufficient to conclude that trans fat labeling was warranted from a public health perspective, FDA finds that the intervention and observational studies provided strong evidence of both a causal relationship between trans fat intake and risk of CHD and applicability to the general U.S. population. Therefore, FDA does not need to rely solely on dietary intake estimates to make this determination. Because of the serious public health consequences of CHD in the U.S. population, prudent public health dictates that we help consumers control those risk factors which they can alter directly through their own behavior. Heart-healthy diets that limit the intakes of both saturated and trans fats can serve this purpose as is evidenced by recommendations in the recent expert panel reports (Refs. 87, 89 through 91, and 140). (Comment 6) Many comments addressed the issue of the relevance of intervention study intakes to usual conditions of use in the United States. Some comments expressed concern that FDA's conclusions relied on intervention studies in which the intakes of trans fatty acids were very high and not representative of U.S. intakes of about 5.3 g/day (3 percent of calories). FDA disagrees with the comments that it relied heavily on intervention trials with high trans fat intake. A range of fatty acid intakes was included in the dietary intervention assessments. For example, the four U.S. research investigations with chemical analyses of the diets included a total of 15 study diets (Refs. 12, 13, 34, and 82). These studies included diets with little or no trans fat (e.g., 0.4 to 0.6 percent of calories), diets that contained moderate levels of trans fat (e.g., 3 to 4 percent of calories), as well as diets with a higher intake of trans fat (e.g., 6 to 7 percent of calories). FDA relied on the totality of the evidence, i.e., intervention studies that had trans fat intakes that ranged from very low levels (less than 1 percent of calories) to intakes up to 6 to 7 percent of calories and on findings from observational studies that showed an adverse relationship between trans fat intakes and CHD risk among U.S. population groups consuming their usual diets. Thus, in the aggregate, the U.S. intervention studies included an assessment of the effect of a wide range of trans fatty acid levels that overlap the range of intake estimates for the U.S. population. As noted in FDA's response to Comment 5, the relevance of the findings from the intervention studies for the U.S. population are shown by the consistent findings of an adverse relationship between trans fat and CHD risk in the prospective studies of free-living U.S. population groups. Thus, the relevance of the trans intakes used in the intervention studies for the U.S. population was confirmed by the consistent findings in the prospective studies that showed an adverse association between trans intake and CHD risk among free-living U.S. population groups. The recommendations of recent expert panels that Americans limit their intakes of trans fat shows that a broad-based scientific agreement exists as to the public health merits of trans fat labeling for the U.S. population within the context of current dietary intakes. (Comment 7) Other comments suggested that the study populations were not representative of the U.S. population. For example, one comment said that the intervention studies included individuals at high risk with serum cholesterol levels greater than (>) 320 milligrams (mg)/deciliter (dL) or LDL-C > 130 mg/dL. Another comment stated that the agency failed to reflect that relative risk will depend on the base risk of the population used for comparisons with the U.S. general population. FDA disagrees with these comments. Of the 512 subjects included in the dietary intervention studies cited in the November 1999 proposal, 48 percent of the dietary intervention population had an LDL-C level of 100 to 120 mg/dL that is categorized as near or above optimal level according to the NCEP lipid classification scheme (Ref. 89). Thirty-eight percent had an LDL-C of 130 to 159 mg/dL, categorized as borderline high; and 14 percent had a LDL-C of greater than or equal to (≥)160 mg/dL, categorized as high. Only 5 percent of the participants had a low HDL-C level, < 40 mg/dL; and another 7 percent had a high HDL-C level, ≥60 mg/dL. Most (88 percent) had mean HDL-C levels in the range of 41 to 59 mg/dL. Also, 73 percent of the population was in the age group where the CHD risk is lower, e.g., men <45 years of age and women <55 years of age. The study populations were described as participants who had normal cardiac, kidney and liver function, and were not taking medications that affect lipid levels. Many participants had near or optimal LDL-C levels and most had HDL-C levels that were neither high nor low by the NCEP criteria. The data that FDA relied on included a dietary intervention population that is representative of the U.S. general population. (Comment 8) Some comments suggested that the test products were not representative of available commercial products in the U.S. marketplace. One comment suggested that several studies were designed to study the effects of different food oil sources and not designed to specifically study the effect of trans fat on blood lipid levels. FDA disagrees with these comments. In general, the test products used in studies done by U.S. research groups were either commercially available products or were produced specifically for a study by U.S. manufacturers using oil sources commonly used in the U.S. market (Refs. 12 through 15, 34, and 82). However, regardless of whether studies used products typical of those commercially available in other countries, products commercially available in the United States, or products developed specifically for the study at hand, results were generally consistent across all these studies and consistent with the larger body of evidence that included studies done in Europe and with European oils. That is, there was consistency across studies in finding that higher intakes of trans fat resulted in increased levels of LDL-C and, therefore, in increased risk of CHD. Moreover, the observational studies in U.S. populations, where participants were consuming products commercially available in the U.S. marketplace, also consistently showed that higher intakes of trans fat were associated with adverse effects on CHD risk (Refs. 19, 21, and 38). FDA also recognizes that the intervention studies were designed with a variety of objectives in mind. Some were designed to compare two different sources of hydrogenated oils (e.g., Refs. 9, 14, 15, and 36). Many were designed to compare the effects of different types of fatty acids by varying the source oils to achieve the desired fatty acid types and levels (e.g., Refs. 7, 8, 10, 11 through 13, and 34). The study designs also varied significantly in how they identified controls for the comparisons of interest. Despite these differences in objectives and study design, the general consistency across studies in finding that trans intakes are adversely related to CHD risk provides evidence that the relationship is likely real and not simply an artifact of a particular type of study design (Ref. 94). Thus, most of the intervention trials provide enough information about test products, study population, and study diets to evaluate their relevance to the U.S. general population. The wide range of trans fatty acid intakes, products, and population characteristics in these studies overlaps with those found for U.S. consumers in the general population. Important, however, is that there is remarkable consistency across the intervention studies, regardless of population, products and diets used, in finding that higher intakes of trans fatty acids are associated with increased levels of serum LDL-C, a major risk factor for CHD. Thus, the available intervention studies show consistent results across a broad range of use conditions and population characteristics. FDA, therefore, disagrees with comments that suggest that the test products used in intervention studies are not applicable to the U.S. marketplace, or the study designs are not applicable to evaluating the relationship of trans fat to CHD risk in the U.S. population. (Comment 9) Many comments questioned whether the scientific evidence shows that the physiological effects of trans fat on CHD risk are equivalent to, greater than, or less than those of saturated fat on a gram-for-gram basis. Some comments noted that the intervention studies show that the increase in LDL-C levels associated with trans fat is greater than that from unsaturated fats but less than that from saturated fat. Some comments noted that in the review of science for the November 1999 proposal, FDA concluded that the available studies do not provide a definitive answer to the question of whether trans fatty acids have an effect on LDL-C and CHD risk equivalent to saturated fats on a gram-for-gram basis, but in the preliminary regulatory impact analysis, FDA estimated that the effects of saturated and trans fatty acids on LDL-C levels are about equivalent. FDA notes that the intervention studies demonstrate that the net physiologic effect of a particular fatty acid or category of fatty acids is dependent upon the composition of both the intervention diet and the comparison diet. In the dietary intervention research reviewed, the study investigators used a variety of study designs to assess the effect of a defined quantity of trans fatty acids (provided by food sources of hydrogenated oil) on levels of serum or plasma lipids. The best study designs controlled the variation in the ranges of protein, fat, cholesterol, and carbohydrate with particular attention given to the fatty acids. The effect of trans fat study diets were compared by replacement with food sources of: (1) Cis -unsaturated fatty acids, (2) monounsaturated (oleic) fatty acids, and (3) saturated fatty acids. As FDA stated in the November 1999 proposal (64 FR 62745 at 62750), the intervention study data showed the following: (1) Trans fatty acids increased LDL-C in comparison with cis -polyunsaturated fatty acids (Refs. 8, 13, 15, and 82); (2) trans fatty acids increased LDL-C levels in comparison with cis -monounsaturated fatty acids (Refs. 7, 11 and 12); and (3) trans fatty acids increased LDL-C, or there was no significant difference, in comparison with saturated fatty acids (Refs. 7 through 12). Based on these results, FDA concluded in the science review section of the November 1999 proposal that the available studies do not provide a definitive answer to the question of whether trans fatty acids have an effect on LDL-C and CHD risk equivalent to saturated fats on a gram-for-gram basis. However, FDA also stated that the studies that compared a saturated fat diet with a diet in which some of the saturated fat was replaced with trans fat showed that trans fat, like saturated fat, increases LDL-C. For purposes of its regulatory impact analysis in the proposal, FDA needed a basis for quantifying its estimates of the compliance costs and benefits associated with given changes in trans fat intakes and the associated changes in CHD risk. The available evidence always presents some uncertainty for these types of analyses, as there is with other inputs into regulatory decisions. Given these caveats, FDA, in order to develop the tools required for a quantitative evaluation of benefits and costs, reviewed a meta analysis of five intervention trials that included six levels of trans fat intakes (Refs. 62 and 69). Using multiple regression to statistically control for differences in other fatty acids between trans -enriched diets and reference diets, the authors projected linear increases in LDL-C as a function of level of increasing trans fat intake. According to the regression equations, each additional percent of energy from trans fat, when substituted for the same percent of calories from cis -monounsaturated fatty acids, was predicted to increase LDL-C by 1.5 mg/dL. This relationship was then used as the basis for estimating the benefits and costs of the proposed rule and not for purposes of establishing whether there is a gram-for-gram relationship between trans and saturated fatty acids on LDL-C levels and CHD risk. FDA notes that, in rulemaking to implement the 1990 amendments, the agency also found it necessary to use coefficients derived from regression equations to estimate the benefits and costs of various regulations (56 FR 60856, November 27, 1991; 58 FR 2927, January 6, 1993). In one such analysis, FDA used the equation of Hegsted and Keys to predict how changes in total serum cholesterol would be affected by projected changes in saturated fat intake (56 FR 60856 at 60869, November 27, 1991). Because the Hegsted and Keys equations did not include coefficients for trans fat or information on components of total cholesterol (e.g., LDL-C), FDA found it necessary to find regression equations that included trans fat intakes and LDL-C levels. The equations of Katan et al. and Zock et al. (Refs. 62 and 69), together with the equations of Mensink and Katan (Ref. 65), which summarized the results of 27 clinical trials, were available to meet this need for a quantitative basis on which to estimate the benefits and costs of the proposed rule. In estimating the benefits and costs, FDA also recognized that the type of macronutrient substituted for trans fat in the diet would affect the magnitude and nature of the changes in LDL-C in response to decreases in trans fatty acid intakes. Thus, FDA also estimated how the benefits and costs would be altered if saturated fat, cis -polyunsaturated fat or carbohydrate, rather than cis -monounsaturated fat, were used to replace some of the trans fat in the diet. In this analysis an intermediate step in the calculation showed that when saturated fat was substituted for cis -monounsaturated fat, LDL-C was raised by 1.52 mg/dL, an amount similar to that found when trans fat was substituted for cis -monounsaturated fat (1.50 mg/dL). Regardless of whether FDA reviewed the effects of saturated fat and trans fat on LDL-C and CHD risk for the science section or the regulatory impact section, the conclusion about those effects is the same. That is, both trans fatty acids and saturated fatty acids raise LDL-C levels, a major risk factor for CHD risk. Consumers need to minimize their intakes of both types of fatty acids within a moderate fat intake to implement dietary guidelines for healthful diets. These conclusions are consistent with those reached independently by expert panels (Refs. 87, 89, 90 and 91). (Comment 10) Many comments addressed the issue of the potential adverse effects of trans fat on HDL-C levels. Some comments suggested that trans fat has more adverse health effects than saturated fat because trans fat, in addition to raising LDL-C, also lowers HDL-C, the so-called “good” cholesterol, whereas saturated fat raises HDL-C. Some comments noted that trans fat raises the LDL/HDL ratio approximately twice as much as saturated fat. Other comments stated that, in the prospective studies, the risk of CHD associated with trans fat intake was much greater than the risk associated with saturated fat, and much greater than would be predicted based on the effect on serum lipids. In contrast, one comment stated that it is premature to conclude that trans fat intake lowers HDL-C because many intervention studies showed that trans fat intake causes only a small decrease or has no effect on HDL-C. Based on the recommendations of the 1993 NCEP Expert Panel (Ref. 5), in the November 1999 proposal, FDA concluded that an examination of the effects of trans fatty acids on serum LDL-C would provide the strongest evidence, and should be the primary criterion, to evaluate whether trans fatty acids influence CHD risk. In the November 1999 proposal, FDA tentatively concluded that the available evidence demonstrated that under conditions of use in the United States, consumption of trans fatty acids contributes to increased serum LDL-C levels, which increases the risk of CHD. The evidence for this relationship alone was sufficient for the agency to tentatively conclude that addressing trans fatty acids in nutrition labeling is important to public health. FDA's review of the intervention trials showed that HDL-C decreased when trans fats replaced saturated fats. Further, Federal Government advisory groups (Refs. 88 through 90, and 140) and an advisory group of health professionals (Ref. 91) have stated that substitution of trans fat for saturated fat lowers HDL-C. To date, lowered HDL-C levels have been shown to be a useful predictor of heart disease risk because of its correlation with CHD risk. However, it is not known whether lowering HDL-C is related to CHD risk in a cause and effect manner. Until this relationship is confirmed by appropriate study designs, the use of HDL-C as a surrogate biomarker for CHD risk must be done with caution and clear recognition of the uncertainty surrounding this use. For example, FDA notes that the NCEP 2001 Report (Ref. 89) makes several statements that both recognize and qualify the relationship between trans fatty acids, HDL-C, and CHD risk. While the NCEP Report states that a low HDL-C level is strongly and inversely associated with risk for CHD, the NCEP Report also states that, because of the association of low HDL levels with other atherogenic factors, a low HDL-C is not as strongly independent in its prediction as suggested by usual multivariate analysis. Therefore, while FDA did not place primary reliance upon the relationships among trans fat intakes and adverse effects on HDL-C and CHD risk in deciding that nutrition labeling was warranted, FDA also recognizes this possible relationship, so concerns about possible adverse effects cannot be ignored (64 FR 62746 at 62798 to 62821). For this reason, FDA included information on the effects of trans fatty acids on HDL-C levels when reviewing the available human studies in the science review section. Additionally, because of the possibility of an adverse effect on HDL-C levels from trans fat intake and a correlation between such an effect with CHD risk, the possible impact on HDL-C levels from trans fat intake was used in the regulatory impact section as one of several possible approaches for determining cost benefit ratios of trans fat labeling. The agency would have been remiss in evaluating the full range of possible cost/benefit relationships if it had failed to include this potential adverse effect from trans fatty acid intakes to CHD risk in these analyses. The question of interpretation of LDL/HDL ratios is more difficult. For example, concurrent small changes in both LDL-C and HDL-C could result in a similar LDL/HDL ratio as would concurrent large changes in both LDL-C and HDL-C assuming the changes are in the same direction. Or, large changes in HDL-C with moderate changes in LDL-C could give similar LDL/HDL ratios as would moderate changes in HDL and small changes in LDL. However, it is likely that the magnitude of the change in the individual blood cholesterol levels is as, or more, important than is a change in the ratio of the two. Thus, interpretation of the LDL/HDL ratio is unclear and until there is evidence by which its meaning can be more precisely defined, use of this ratio requires considerable caution. However, even with these caveats, regardless of whether results are expressed as increased levels of LDL-C or as increases in LDL/HDL ratios, the conclusion is the same: trans fat intakes increase CHD risk. (Comment 11) A number of comments emphasized that, in addition to HDL-C, trans fat has other adverse effects that may contribute to CHD risk but saturated fat does not. The comments mentioned that trans fat has adverse effects on various CHD risk factors including serum lipoprotein(a), serum triglycerides, insulin resistance and diabetes risk. These comments also stated that trans fat has adverse effects on aspects of lipid metabolism that may cause increased CHD risk, such as interference with metabolism of omega-3 fatty acids, interference with enzymes such as delta-6-desaturase, promotion of essential fatty acid insufficiency, and increase in free radical formation. Several of the comments argued that some of these CHD risk factors represent additional biological mechanisms related to trans fat that could account for the amount of CHD risk observed in prospective studies beyond that explained by changes in LDL-C and HDL-C. Some comments stated that trans fat may have adverse effects on other health conditions, besides CHD. One of these comments requested that, in order to provide the full picture of health issues involved with trans fats, FDA review trans fat effects on cancer, obesity, immunity, reproduction, development, and diabetes when publishing the final rule. Another comment characterized trans fatty acids as being atypical fatty acids with an insidious nature in disrupting lipid metabolism. Some comments identified potential adverse effects of trans fat on lowered birth weights and decreased visual acuity in infants exposed to high levels of trans fatty acids in utero or via breast milk. The comments suggested that FDA advise pregnant and lactating women to limit their trans fat intake. FDA recognizes that the relationship of biomarkers, other than LDL-C, and to a lesser degree, HDL-C, with CHD risk is less well established and difficult to interpret. Moreover, at this time, the findings suggesting effects of trans fat on non-heart disease risks are preliminary. Therefore, FDA finds that its focus on LDL-C provides a sufficient basis for concluding that the labeling of trans fat levels in food products is warranted. V. Nutrition Labeling of Trans Fats In the November 1999 proposal, FDA proposed that when trans fats are present in a food, including dietary supplements, the declaration of saturated fat must include the combined quantitative amount by weight of both saturated and trans fats. Further, FDA proposed that when 0.5 or more grams per serving of trans fats are present, the declaration be followed by a symbol that refers to a footnote at the bottom of the nutrition label stating the number of grams of trans fat present in a serving of the product, i.e., “Includes ___ g trans fat.” The agency also had discussed, in addition to the one proposed, several other options for declaring trans fat in the Nutrition Facts panel. These included: (1) Declaring the combined amount of both saturated fat and trans fat as “Saturated fat” without identifying the amount of trans fat, (2) declaring the combined amount of both saturated fat and trans fat as “Saturated + trans fats” without identifying the amount of trans fat, (3) declaring the combined amount of both saturated fat and trans fat as “Saturated + trans fats'' with an explanatory footnote stating the amount of each fat separately, and (4) declaring the amount of trans fat as a separate line item under saturated fat. The agency proposed that with all of these options the term “ trans fatty acids'' and “ trans fat'' could be used interchangeably. A. Voluntary v. Mandatory Declaration of Trans Fatty Acids in Nutrition Labeling (Comment 12) The majority of the comments supported the November 1999 proposal, which required the mandatory declaration of trans fat in nutrition labeling when it is present in a food, including dietary supplements. An overwhelming majority of comments supporting the mandatory declaration of trans fat did so because of public health concerns. Some comments stated that the scientific evidence clearly demonstrates that consumption of trans fat contributes to increased LDL-C and, hence, increased risk of CHD. Several comments noted that consumers are increasingly aware of the relationship between dietary fat and chronic disease, especially CHD, and look to the nutrition label for information about “heart-unhealthy” fat. A few comments noted that another benefit of mandatory labeling of trans fat is that it may provide an incentive to manufacturers to reduce the trans fat content of their foods. A few comments stated that mandatory labeling of trans fat was not warranted because the scientific data linking trans fat to CHD is weak and because the average intake of trans fat, estimated as 2.91 percent of energy in the proposal, is minimal. Other comments also opposed mandatory labeling stating that the effect of trans fat on LDL-C or CHD risk was not sufficient to establish public health risk at ordinary levels of intake. Some comments stated that, although mandatory labeling of trans fat was not warranted, a requirement for label declaration of trans fat could be justified in certain circumstances. Several of these comments stated that required label declaration of trans fat was justified if it was needed to prevent the label from being misleading because of the level of trans fat in light of other information on the labe [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/fr%3A03-17525. Public record. Not legal advice.