Federal Register / Vol. 58, No. 3 / Wednesday, January 6, 1993 / Rules and Regulations DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 101 [Docket No. 91N - 0096] RIN 0905 - AB67 Food Labeling: Health Claims and Label Statements; Dietary Saturated Fat and Cholesterol and Coronary Heart Disease AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is announcing its decision to authorize the use on the label or labeling of certain foods of health claims relating to an association between dietary lipids (specifically, saturated fat and cholesterol) and cardiovascular disease (specifically, coronary heart disease (CHD)). The agency has concluded that, based on the totality of the scientific evidence, there is significant scientific agreement among qualified experts that diets low in saturated fat and cholesterol may reduce the risk of heart disease. Therefore, FDA has concluded that claims on foods relating the reduction in dietary saturated fat and cholesterol to reduced risk of CHD are justified. This action is in response to provisions of the Nutrition Labeling and Education Act of 1990 (the 1990 amendments) that bear on health claims and has been developed in accordance with the final rule on general requirements for health claims, which is published elsewhere in this issue of the Federal Register. EFFECTIVE DATE: May 8, 1993. FOR FURTHER INFORMATION CONTACT: Paddy Wiesenfeld, Center for Food Safety and Applied Nutrition (HFS - 465), Food and Drug Administration, 8301 Muirkirk Rd., Beltsville, MD 20708, 301 - 344 - 5825. SUPPLEMENTARY INFORMATION: I. Background In the Federal Register of November 27, 1991 (56 FR 60727), FDA proposed to authorize the use in food labeling of health claims relating diets low in saturated fat and cholesterol to decreased risk of CHD. The proposed rule was issued in response to provisions of the 1990 amendments (Pub. L. 101 - 535) that bear on health claims and in accordance with the proposed general requirements for health claims for food (56 FR 60537, November 27, 1991). As amended by the 1990 amendments, the Federal Food, Drug, and Cosmetic Act (the act) provides that a food is misbranded if it bears a claim that characterizes the relationship of a nutrient to a disease or health-related condition unless the claim is made in accordance with section 403(r)(3) or (r)(5)(D) of the act (21 U.S.C. 343(r)(3) or (r)(5)(D)). Section 3(b)(1)(A) of the 1990 amendments specifically requires that the agency determine whether claims respecting 10 nutrient/disease relationships meet the requirements of section 403(r)(3) or (r)(5)(D) of the act. The relationship between dietary lipids and cardiovascular disease is one of the claims required to be evaluated. In the Federal Register of March 28, 1991 (56 FR 12932), FDA published a notice requesting scientific data and information on the 10 specific topic areas identified.Relevant scientific studies and data received in response to this request were considered as part of the agency's review of the scientific literature on lipids and cardiovascular disease. Comments received in response to the notice and not specifically addressed in the proposed rule are summarized and addressed in this document. Because of the extremely large volume of scientific literature on this topic, FDA limited its scientific review to those aspects of the relationship for which the strongest scientific evidence and agreement already existed: dietary intakes of total savidence relating saturated fat and cholesterol to cardiovascular disease, the proposed rule identified qualifying and disqualifying criteria for foods, specified mandatory and optional information for health claims statements, and provided model health claims. FDA also discussed potential safety issues associated with reducing current dietary intakes of saturated fat, cholesterol, and total fat. FDA requested written comments in response to the proposed rule and solicited comments on several issues in particular. The agency asked how to restrict the use of these health claims to foods that are appropriately included as part of healthy diets, and whether there is a need for consumer summaries. On January 30 and 31, 1992, FDA held public hearings on all aspects of the proposed rules published in response to the 1990 amendments, including health claims for dietary saturated fat and cholesterol and heart disease (57 FR 239). In response to its proposed health claim on lipids and cardiovascular disease, the agency received approximately 100 comments from consumers, consumer advocacy groups, State health departments, organizations of health professionals, the food industry, and Government agencies. A number of comments were received that were more appropriately answered in other documents, and these were forwarded to the appropriate docket for response. II. Comments on the Relationship Between Dietary Saturated Fats and Cholesterol and CHD The majority of comments supported FDA's conclusion, noting that the scientific evidence that dietary saturated fat and cholesterol increase the risk of CHD is very strong and well accepted in the scientific community. Many of these comments provided little or no detail on their reasoning. One detailed comment that supported the saturated fat and cholesterol/heart disease relationship was the report of the Life Sciences Research Office (LSRO) of the Federation of American Societies for ExperimentalBiology (FASEB), which evaluated recent scientific publications on this topic. The FASEB draft report was summarized by FDA in the November 27, 1991, proposal (Ref. 78). The final report was submitted to the docket as a comment (Ref. 196). The conclusions of the final LSRO report concur with previous dietary guideline recommendations that reducing intakes of saturated fat and cholesterol would lower total blood and low-density lipoprotein-cholesterol (LDL-cholesterol) levels and, thus, lower risks of CHD in the U.S. population. A number of comments suggested modification and revision in various provisions of the proposal. A summary of the suggested changes and the agency's responses follows. 1. The agency received a number of comments focusing exclusively on dietary cholesterol as a risk factor for heart disease. Some comments suggested that the scientific evidence does not support a relationship between dietary cholesterol and blood cholesterol levels and suggested that the nutrient/disease linkage is primarily with saturated fat. The comments noted that most dietary cholesterol is not absorbed, and that individual responses to dietary cholesterol are highly variable. Conversely, manycomments noted the compelling nature of the scientific evidence linking dietary cholesterol to risk of heart disease. The 1992 LSRO review of the science on this topic (Ref. 196) not only strongly supported the relationship between dietary cholesterol and increased blood cholesterol levels but suggested that newer evidence increased the importance of dietary cholesterol as a risk factor for heart disease. FDA agrees with those comments that suggested that there is adequate scientific evidence and significant scientific agreement that diets high in cholesterol increase the risk of heart disease. This conclusion is consistent with current dietary guidancnk submitted either data or compelling logic to convince FDA that this conclusion is not correct. FDA recognize that there is some scientific disagreement about the relative importance of dietary cholesterol versus saturated fat intakes (56 FR 60730). However, there are strong and consistent data that support that saturated fat and cholesterol have independent effects on the risk of heart disease. Because the data support an independent effect for dietary cholesterol and for saturated fat, the relativeimportance of dietary cholesterol versus saturated fat on blood cholesterol levels and risk of heart disease really is irrelevant to the agency's conclusion that a health claim on both nutrients is appropriate. FDA recognizes that individual responses to dietary cholesterol are less consistent than to saturated fat. However, recent authoritative reviews (Refs. 20, 29, 31 through 36, 63, 71, 74, 98, 99, 129, 130, 136, 141, 150, 151, and 223) have concluded that the majority of persons in the United States will benefit from recommended dietary changes in cholesterol intake, even though the magnitude of the benefit varies among individuals. 2. Several comments stated that FDA did not address the issue of a beneficial role for dietary cis-monounsaturated fatty acids (MUFA's), a major source of dietary fat in the United States, in reducing the risk of heart disease. In this context, one comment noted that the Keys equation, which was used in several studies for predicting or explaining changes in blood total cholesterol based on dietary intakes of saturated and polyunsaturated fatty acids (PUFA's), was inadequate as a basis for evaluating the role of dietary lipids in reducing risk of heart disease, because it does not include a term for the amount of MUFA's. The comment further stated that, in light of newer data on possible beneficial effects of MUFA's, this equation may no longer adequately reflect the predictive value of changes in fat intakes to changes in blood cholesterol levels in the U.S. population. The LSRO report (Ref. 196) evaluated the potential usefulness of oleic acid, the major cis-monounsaturated fatty acid, as a replacement for saturated fat in the American diet. The report concluded that recent research results are consistent with the conclusions that substitution of oleic acid for saturated fatty acids (SFA's) in the diet is safe and without adverse effects on blood LDL-cholesterol levels. The report stated that substitution of cis-monounsaturated fats for saturated fatscan allow Americans to maintain customary intakes of total dietary fat without the negative effects of the more cholesterol-raising SFA's (i.e., lauric, myristic, and palmitic fatty acids). The LSRO report noted, however, that a diet high in monounsaturated fats (i.e., oleic acid) may contribute to development of obesity, a risk factor for heart disease. FDA is aware of the recent and ongoing research efforts on the possible beneficial role of cis-forms of MUFA's in helping Americans to find a practical means of reducing saturated fat intake without changing total dietary fat intakes (Refs. 6,37, 53, 57, 89, 93, 139, 144, 158, 159, 175, 180, 188, 192, 196, and 219). FDA, however, considers this issue outside the scope of this rule. In the proposed rule, the agency noted that, because of the extremely large volume of scientific research on lipids and cardiovascular disease and because of the extremely limited time constraints of the 1990 amendments, it had limited its science review to an evaluation of the relationship of saturated fat and cholesterol intakes to risk of CHD. Therefore, in both the proposed and final rules, FDA has limited the health claim to saturated fats and cholesterol. FDA notes that the rapidly expanding science base may now, or in the future, be adequate to support that cis-monounsaturated fatty acids have a beneficial role in reducing blood total and LDL-cholesterol levels. However, because the question ofr a health claim is outside the scope of this rulemaking, the question should be the subject of a petition for a health claim in accordance with the provisions of the final rule on general requirements for health claims published elsewhere in this issueof the Federal Register. 3. One comment suggested that novel fats that affect a surrogate marker for the disease, such as lowering of blood LDL-cholesterol, should be allowed to carry a health claim. FDA is aware that a large amount of research and development is being done on novel fats. Novel fats are those fats that are not commonly found in the food supply. Some examples of novel fats include those fats modified by rearrangement of fatty acids in triglyceride or by the addition of a cyclic or aromatic ring to a fatty acid. (The issue of ``bioavailability'' of novel fats is addressed elsewhere in this issue of the Federal Register in the final rules on mandatory nutrition labeling, nutrient content claims, and health claims.) FDA did not have any scientific evidence on the possible effects of specific novel fats on risk of heart disease, or on other validated surrogate markers for heart disease, in developing this final rule. Therefore, FDA has not dealt with this issue in this final rule. III. Qualifying Nutrients The qualifying levels for saturated fat, cholesterol, and total fat are the maximum level at which these nutrients may be present in a food if it is to qualify to bear a claim. The levels of saturated fat, cholesterol, and total fat in a food must be less than those specified in the qualifying levels for the food to be eligible. A. Saturated Fat and Cholesterol In the proposed rule, FDA tentatively provided that, to bear a claim associating a diet low in saturated fat and cholesterol with reduced rate of coronary heart disease, the food must be ``low saturated fat,'' ``low cholesterol,'' and ``low fat,'' as those terms are defined in new 101.62. FDA also proposed to require that the food contain 1 g or less of saturated fat per 100 g of food. 4. A number of comments recommended that claims include information about the amount of saturated fat and cholesterol beyond the information contained on the nutrition panel. Some comments recommended the use of an index or ``cholesterol-saturated fat index'' (CSI) that integrates known relative effects of saturated fat and cholesterol intakes in predicting increased changes in total and LDL-cholesterol levels (Refs. 202 and 203). These comments pointed out that the CSI consists of a single score or number by which it would be possible to determine the relative cholesterol-raising propensity of a given food. The comments suggested that the CSI for a given food would be calculated from the experimentally-derived formula: (1.01 x g saturated fat) + (0.05 x mg cholesterol). One comment included a detailed listing of CSI's for a wide variety of foods, including milk with 1-percent fat, which had a CSI of 2, and butter, which had a CSI of 37. FDA agrees with the concept that consumers should have label information presented in a manner that enables them to evaluate an individual food relative to total dietary goals. However, the agency has not included any requirement for use of a CSI index in the final rule. The comments did not provide data to show that consumers would find use of a CSI index more helpful than the nutrition information currently required on food labeling. FDA is concerned that consumers might place undue emphasis on the CSI index in purchasing decisions and not concentrate on consuming healthful diets, which include a variety of foods. FDA considers that a consistent approach to nutrition information on food labels will be less confusing to consumers than the use of a CSI index. FDA's general approach is to provide information that allows a consumer to construct a diet that is consibecause it would likely lead the consumer to place more emphasis on the specific food than on the entire diet. In addition, the larger scientific community has not generally agreed on a particular symbol or approach, such as the CSI index, for helping consumers to identify foods that will help lower their risk of heart disease. Thus, FDA is retaining its proposed approach with respect to the label information that must appear on foods that qualify for a health claim on lipids and heart disease. 5. A few comments suggested that foods that contain eggs or egg products should be eligible to bear the authorized health claim. The agency agrees that a food containing eggs or egg products should not be denied a health claim for saturated fat and cholesterol and heart disease, provided that the food is ``low saturated fat,'' ``low cholesterol,'' and ``low total fat'' and meets the other qualifying requirements for a health claim on this topic. The qualifying criterion for cholesterol is based on the final concentration of cholesterol in the food product and not on the cholesterol content of ingredients. Therefore, if eggs and egg products used as ingredients do not cause a food to exceed the definition of ``low cholesterol,'' the food may qualify for a health claim. 6. Other comments suggested that the qualifying level for the saturated fat and cholesterol content of a serving of food be made less restrictive so that a larger number of wholesome foods can qualify for a health claim. Some of the comments stated that the permissible level of 1 g of saturated fat for a serving of food should be increased to 2 g. A few comments proposed that ``foods that contain 20 milligrams or less of cholesterol per serving and 2 grams or less of saturated fat should be allowedto make a health claim.'' Other comments asserted that the saturated fat and cholesterol/heart disease health claims should be allowed on foods that qualify for the comparative claim, ``reduced cholesterol.'' Some comments also objected to the per 100 gdensity criterion for qualifying levels of saturated fat and cholesterol, suggesting that it unfairly discriminates against foods that have a useful dietary role in reducing the risk of heart disease but that, because their servings sizes are less than 100 g, exceed the qualifying criterion on a per 100-g density basis. Based on the large number of comments that the agency received, FDA has reassessed the qualifying levels for saturated fat, total fat, and cholesterol, including the density criterion. (See the final rule on general requirements for nutrient contentclaims published in this issue of the Federal Register for a more detailed discussion. FDA incorporates that discussion by cross reference. Based on this reanalysis and on the comments received, FDA has been persuaded that the second qualifying criterion based on per 100 g is too restrictive for ``low fat'' and ``low cholesterol'' claims. (The proposed definition for ``low cholesterol'' did not include a per 100-g criterion.) The agency has concluded that this criterion should be modified to moredirectly reflect the nutrient dence foods with small serving sizes that it was designed to address. Therefore, FDA has modified the density criterion from a per 100-g basis to a per 50-g basis for foods that have a reference amount customarily consumed of 30 g or of 2 tablespoons or less. With this modification, a larger number of wholesome foods may qualify for a health claim, including more brands of breakfast cereals and cereal grain products (Ref. 222). The agency disagrees that ``reduced cholesterol'' and other comparative claims should be the basis for qualifying levels of nutrients. Many foods, even after meeting the requirements for ``reduced'' claims, contain significant amounts of saturated fatg foods together within a total dietary context, the absolute amount of nutrient present in a food is important. 7. Some comments noted that FDA's proposed definition of saturated fat (i.e., the sum of lauric, myristic, palmitic, and stearic acids) is not consistent with the most recent evidence on cholesterol-raising fatty acids. The comments suggested that the cholesterol-raising characteristics of SFA's are due almost entirely to three SFA's: lauric, myristic and palmitic fatty acids. Conversely, stearic acid, which is a significant source of SFA's in the U.S. diet, has relatively little effect on blood cholesterol levels. The comments further note that this variability in cholesterol-raising potential opens new opportunities to replace cholesterol-raising saturates with other saturates that are not cholesterol-raisers (i.e., stearic acid). The agency agrees that specific SFA's vary in their potential for an adverse effect on blood cholesterol levels and on other atherosclerotic risk factors. In the proposed rule (56 FR 60727 at 60734), FDA acknowledged that lauric, myristic, and palmitic SFA's have the greatest effect on blood cholesterol levels, and that, in this respect, stearic acid is relatively neutral. FDA disagrees, however, that the definition of saturated fat should be limited only to the sum of lauric, myristic, and palmitic fatty acids. In the final rule on mandatory nutrition labeling published elsewhere in this issue of the Federal Register, and in response to comments, FDA has changed the definition of saturated fat to include the sum of all fatty acids containing no double bonds. This definition will apply to all references to saturated fat on the food label. Also, as noted in the preamble to the final rule on mandatory nutrition labeling published elsewhere in this issue of the Federal Register, this definition for saturated fat is consistent with dietary guidelines for diets to reduce risk of heart disease (i.e., consume less than 10 percent of calories as saturated fat; therefore, all four saturated fat (lauric, myristic, palmitic and stearic) plus less abundant saturated fats are included in the new definition.) Furthermore, FDA has noted that elevated blood cholesterol is not the only risk factor for cardiovascular disease (56 FR 60727 at 60734). Saturated fats have been implicated as possibly increasing the risk of cardiovascular disease through mechanisms other than adverse effects on blood total and LDL-cholesterol (Ref. 20). B. Total Dietary Fat as a Qualifying Criterion In the proposal (56 FR 60727 at 60739), FDA proposed to prohibit health claims relating diets low in saturated fat or cholesterol to lower blood cholesterol levels and reduced risk of CHD unless the food also meets requirements for a ``low'' claim relative to total fat content (i.e., 3 g or less of fat per label serving size, per reference amount customarily consumed, and per 100 g). FDA notes that, while total fat is not as strongly or directly linked to increased risk of CHD as it may have significant indirect effects. 8. A number of comments supported the agency's position that a food must not only be low in saturated fat and low in cholesterol but must also be low in total fat, and that decreasing total fat intakes will generally aid in decreasing intakes of saturated fat and cholesterol. However, several comments opposed the additional ``low fat'' qualifying criterion, suggesting that foods recommended by public health authorities (such as fish, chicken, and lean beef and vegetable oils that are low in saturated fat and cholesterol) would not qualify for a health claim and that this would appear inconsistent with efforts to encourage an overall healthful diet. FDA agrees that total fats are an appropriate qualifying criterion, and this provision is retained in new 101.75(c)(2)(ii). (In the November 1991 proposed rules, FDA combined the regulations for lipids and cardiovasuclar disease (proposed 101. In these final regulations, FDA has separated the two health claims into individual sections. New 101.75 covers dietary saturated fat and cholesterol and coronary heart disease. New 101.73 covers dietary fat and cancer.) FDA has retained this criterion because low fat foods generally help individuals in reducing their intake of saturated fat and cholesterol. In addition, excess calories, of which fat contributes more per g than the other energy nutrients, is associated with two health-related conditions (obesity and diabetes) that are risk factors for heart disease. These provisions now read in new 101.75(c)(2)(ii): ``The food shall meet all the requirements for a `low saturated fat,' `low cholesterol,' and `low fat' food; * * *.'' FDA agrees that lean meats, fish, and poultry, when eaten in moderation and prepared with little or no added fat, can play an important role in helping consumers to meet dietary guidelines. Meats, fish, and poultry play an important role in the U.S.dietary pattern, serving as entrees as well as rich sources of protein, bioavailable sources of many minerals, and rich sources of several vitamins. As proposed, the qualifying criteria virtually prohibit this category of foods from bearing health claims. As a result, the proposed criteria may inadvertantly interfere with the dietary guidance goals of encouraging consumption of a variety of foods and of increased use of lean meats, fish, and poultry instead of higher fat cuts. In the final rule on general requirements for nutrient content claims published elsewhere in this issue of the Federal Register, FDA is defining the term ``extra lean'' as a claim for game meats and fish. Although this definition is not as stringent as the definition for ``low fat,'' ``low saturated fat,'' and ``low cholesterol,'' it is consistent with the U.S. Department of Agriculture (USDA) definition for ``extra lean'' for meats and poultry. The agency is persuaded that, to be consistent with the dietary guidence goals discussed above, health claims should be allowed on ``extra lean'' cuts of meat, fish, and poultry. FDA is therefore providing for saturated fat and cholesterol/CHD claims on ``extra lean'' game meats and fish that meet these requirements. This provision is added in new 101.75(c)(2)(ii) which reads: ``* * * except that fish and game meats (i.e., deer, bison, rabbit, quail, geese, and ostrich) may meet the requirements for `extra lean' in 101.62.'' FDA disagrees with the comment suggesting that foods consisting entirely of fats and oils, but low in saturated fat and cholesterol, should qualify for heart disease health claims. Low fat diets are recommended in all Federal Government and NationalAcademy of Sciences' dietary guidelines for reducing the risk of heart disease. Labeling of foods that are 100-percent fat with a message implying they are ``heart healthy'' is clearly inconsistent with dietary guidelines. FDA believes that the use of content claims is a more appropriate method for helping consumers make purchasing decisions about those oil products that they choose to include in their total daily diet than allowing those foods to bear health claims. 9. One comment suggested that total fat should be the basis for both the cancer and the heart disease health claims because these two diseases generally are considered together under a single dietary guidance goal for moderation in intakes of total fat and saturated fat. The agency agrees that public health dietary guidelines generally focus on the reduction in total fat as a major, single goal when referring to both heart disease and cancer risks. However, health claims are specific for a nutrient-disease relationship. Heart disease and cancer relate to dietary factors through different mechanisms. In the instance of CHD, dietary saturated fat and cholesterol are the major dietary risk factors because they increase blood LDL-cholesterol levels, which increase the risk of heart disease. As noted in the proposed rule (56 FR 60727 at 60739) and discussed above, total fat consumption affects risk of heart disease indirectly, through its effects on obesity and on facilitating dietary reductions in saturated fat and cholesterol. In contrast to the association between dietary fat and heart disease, the observed association between dietary fat and cancer has not been attributed to a specific type of lipid but has generally been linked to total fat intakes (see the final rule on dietary lipids and cancer published else where in this issue of the Federal Register. Health claims must reflect current scientific understanding and agreement as to the basis of a diet-disease relationship. Thus, total fat is not listed as a causal dietary fat in the health claim. Instead, it is addressed as an additional criterion that must be met by a food before it may carry a health claim relating dietary saturated fat and cholesterol to risk of heart disease, because of the strong indirect effect of fat on heart disease risk. Of course, food labels may also include the claim ``low fat'' in addition to a health claim in accordance with the requirements for such claims, as discussed in the final rule on general requirements for nutrient content claims elsewhere in this issue of the Federal Register. C. Other Qualifying Criteria 10. Some comments recommended that consumption of foods that alter other risk factors for CHD be included as qualifying nutrients relative to the fat/heart disease claim. For example, because foods high in salt or excess calories from sugars may be related to hypertension or obesity, respectively, the comments requested that limits be placed on the amount of salt or sugars that a food bearing this health claim may contain. FDA recognizes that both hypertension and obesity are risk factors for heart disease and (see the final rule on sodium and hypertension, published elsewhere in this issue of the Federal Register. As stated in the dietary guidelines, salt and sugars should be used in moderation. However, FDA believes that the arguments for making sugars content a qualifying criterion are considerably less compelling than those for total fat. FDA has not established a Daily Reference Value for sugars because, other than dental caries, no public health concerns related to sugar have been substantiated (see final rule on Reference Daily Intakes and Daily Reference Values published elsewhere in this issue of the Federal Register). A cause-and-effect relationship between sugars intake and obesity is also not well established (Refs. 224 and 225). Conversely, the relationship of fat to obesity is based in part on the fact that fat is a more concentrated source of calories than sugars (9 calories per g versus 4 calories per g). Furthermore, new research suggests that, on a calorie-by-calorie comparison, fat calories may be more likely to be laid down as adipose (fat) tissue in the body than carbohydrate calories (including sugar) (Ref. 20). Additionally, since saturated fat and cholesterol constitute part of the total fat content of foods, most dietary guidelines suggest that it is generally easier to reduce the target nutrients if total fat also is reduced (Refs. 20, 29, 33, 35, 36, 136, 150, and 151). High total fat intakes are also associated with the risk of cancer (see the final rule on dietary lipids and cancer, published elsewhere in this issue of the Federal Register. For these reasons, all current dietary guidelines include reduction of total fat as well as saturated fat and cholesterol when recommending dietary changes to reduce the risk of heart disease. Similar recommendations are not made for sugars (Refs. 20, 35, 136, and 151). Thus, FDA concludes that the arguments to make sugars content a qualifying or disqualifying criterion are not convincing based on available data. FDA recognizes that all food nutrients, including sugars, have an appropriate role in the diet. In the case of salt (and sodium), the issue is more difficult. FDA has found that sodium is a risk factor for hypertension (see the final rule on health claims for sodium and hypertension published elsewhere in this issue of the Federal Register). Furthermore, hypertension is considered to be a risk factor for cardiovascular disease, particularly for strokes and, to a lesser degree, for heart disease (Refs. 20 and 30 through 36). In choosing qualifying criteria for authorized health claims, FDA has tried to limit the number of qualifying nutrients to those nutrients that are most strongly linked to the nutrient/disease relationship, based on the current science. In the case of total fat, FDA concluded that it is appropriate to include it as a qualifying criterion because saturated fat is a subcomponent of total fat and because dietary guidelines consistently recommend moderate intakes of saturated fat, cholesterol, and total fat. Sodium is a disqualifying nutrient for the dietary saturated fat and cholesterol/heart disease health claim, as for all health claims (i.e., as finalized, any health claim is prohibited on a food if the food contains 480 mg or more of sodium per reference amount customarily consumed, per label serving, or, if the reference amount is 30 g or less or 2 tablespoons or less per 50 g of food). The suggestion to make sodium a qualifying, rather than a disqualifying nutrient for this claim is less compelling than the argument for total fat. The link of salt to heart disease is not as direct as the link between saturated fat and cholesterol to heart disease. Dietary guidelines generally deal with sodium and fat separately. If sodium were changed from a disqualifying to a qualifying nutrient, that is, if foods were required to be low in sodium to be eligible for a saturated fat/cholesterol and heart disease claim, the number of foods that could bear such a claim would be greatly reduced. Foods excluded would include many foods in the following food categories that are generally found to be useful in meeting healthful diets: vegetable products, whole wheat breads, cereals, legume products, and some dairy products (Ref. 222). By retaining sodium as a disqualifying nutrient, not only will a much broader range of useful foods be allowed to qualify for a fat/heart disease claim, but foods in these and other food categories that contain large amounts of sodium will be disqualified. Examples of foods that willbe excluded because their sodium content exceeds the disqualifying levels are certain vegetable products such as sauerkraut and some juices, many soups, and some sauces. 11. Several comments recommended that the agency drop the qualifying requirement for saturated fat in proposed101.73(a)(3)(iii), in which FDA proposed that the saturated fat content of the food must be less than 1 g per 100 g of food. One comment suggested that the agency instead require that the food be low in saturated fat or have ``not more that 7 percent of calories from saturated fat.'' The agency was persuaded by the comments that the additional density requirement (per 100 g) for saturated fat is not necessary. The agency was originally concerned that if it used only the definition for ``low saturated fat'' in the nutrient content claim proposal; the claim could appear on certain fats and oils. However, the agency has recognized that the requirement that a food meet the ``low fat'' criteria will prohibit foods that are 100 percent fat, such as oils, from bearing that health claim. The agency therefore has dropped the additional qualifying requirement for saturated fat that was in proposed 101.73(a)(3)(iii). The agency has determined that the food or food product must meet the following qualifying criteria: ``low in saturated fat, low in cholesterol, and low in total fat,'' as described in the rule on nutrient content claims published elsewhere in this issue of the Federal Register and stated in new 101.75(c)(2)(ii). IV. Safety Issues In the proposed rule (56 FR 60727 at 60735), FDA noted that reductions in dietary intakes of saturated fat and cholesterol could result in higher intakes of other dietary components (e.g., monounsaturated and polyunsaturated fats, simple and complexcarbohydrates, and commercially generated fats), because calories lost from decreased intakes of saturated fats would likely be ``made up'' by other energy-yielding nutrients. The availability of saturated fat and cholesterol/heart disease health claimswill likely motivate manufacturers to alter the amount and type of fats added to foods, resulting in changes in composition of the U.S. food supply. As FDA discusses more thoroughly in the preamble of the final rule on general requirements for health claims, which appears elsewhere in this issue of the Federal Register, changes in consumption patterns may affect whether a food ingredient is safe and lawful under the act. Manufacturers should therefore assure themselves that such consumption changes will not affect the lawful status of the foods containing these ingredients. The agency, in its proposed rule (56 FR 60727 at 60735 to 60737), identified several areas of possible concern regarding changing American dietary patterns. A. Trans-fatty Acids One area of potential concern identified in the proposed rule is the potential for increased consumption of trans-fatty acids because of substitution of these fats for SFA's in foods. Trans-fatty acids (generally isomers of cis-monounsaturated fatty acids) are primarily constituents of commercially hydrogenated or hardened natural vegetable oils used in formulating margarine, shortenings, and salad and cooking oils. 12. A number of comments were received, some agreeing and some disagreeing, on the agency's public health concern that trans-fatty acids may have cholesterol-raising characteristics, and, therefore, may increase the risk of heart disease. These concerns were raised in response to the published results of the Mensink and Katan study (Ref. 95). This study assessed the effects of a diet enriched in trans-fatty acid on blood lipids in 34 healthy women and 25 healthy men. The study results suggested that compared to an isocaloric diet enriched in oleic acid (a monounsaturated fat), the trans-fatty acid diet significantly increased LDL-cholesterol and significantly decreased high-density lipoprotein cholesterol (HDL-cholesterol) levels(two risk factors for heart disease (Refs. 1, 31, 33, 35, 48, 49, 74, 84, 112, 113, and 187)). (An evaluation of study design, results, and public health implications is found in the proposed rule (56 FR 60727 at 60736)). In addition, the potential adverse health effects of trans-monounsaturated fatty acids were evaluated in the final version of the 1992 LSRO report on Lipids and Cardiovascular Disease (Ref. 196). This report states that: * * *until recently there was the general belief that trans-monounsaturates are ``neutral'' with respect to serum cholesterol levels. However, the recent findings of Mensink and Katan (1990) strongly suggest that these fatty acids have an adverse effect on serum lipoprotein levels, especially raising LDL-cholesterol levels. Still it hardly seems prudent to alter general dietary recommendations on the basis of a single study, albeit an excellent piece of investigation. Further carefully controlled studies thus appear to be in order before definitive recommendations can be made about trans-fatty acids for the American diet. Other comments stated that ``trans-fatty acids in foods may increase the risk of CHD equal to or greater than saturated fatty acids.'' Another comment suggested that ``trans-fatty acids may increase the risk of coronary heart disease by a mechanism other than by increasing blood cholesterol.'' Another comment referred to trans-fatty acids as ``deadly trans-fat pollution.'' Another comment suggested that the agency require a ``warning'' label for foods containing significant amy may have ``cholesterol-raising'' effects. One comment on trans-fatty acids provided data that suggested that the trans-fatty acid content of some foods such as French fries was much higher than reported in commonly used food composition tables (i.e., that a medium serving of French fries from a fast food restaurant contained 7 g of trans-fatty acids, the upper daily limit of consumption suggested in several authoritative reports). Another comment criticized these data suggesting that proper sampling of the class of analyzed food had not been done. One comment suggested that cis- and trans-monounsaturated fatty acids have similar metabolic actions. No data were provided in support of this comment, although it pointed out that the 1985 FASEB report on trans-fatty acid (Ref. 74) concluded that trans-fatty acids did not increase the risk of heart disease. One comment was concerned with the negative tone of the discussion on trans-fatty acids and suggested that the cited 1991 study by Mensink and Katan (Ref. 95) on adverse effects of trans-fatty acids was limited by its short duration (3 weeks), study population (healthy students), and processing techniques used to generate the hydrogenated trans-fatty acid isomers used in the test diets (varying catalyst and time) (Ref. 200). The comment expressed concern that the trans-fatty acids used in the test diets differed from those most commonly found in the U.S. food supply (i.e., different positional isomers), and that the trans-fatty acids may have been consumed in larger quantities in the test diets than they are generally consumed in the United States. The comment further suggested that a combination of these factors may have created a situation in which the study results suggesting that the consumption of diets enriched in trans-fatty acids increase blood LDL-cholesterol levels and decreased blood high density lipoprotein HDL-cholesterol; a blood cholesterol component for which low levels are associated with increased CHD risk (Refs. 1,47 through 49, 74, 75, 112, 113, and 187) were not necessarily applicable to the U.S. population. One comment referred to the report of Nestel (Ref. 177), which compared the effect of edible vegetable oil blends containing hydrogenated fatty acids on serum lipids. (The diets and study design are described in Table 1 of this document.) The results of this study showed that low saturated fat test diets containing trans-fatty acids from different oil sources lowered blood total cholesterol and LDL-cholesterol levels significantly as compared to control diets high in saturated fat. Among the other comments on the study by Mensink and Katan (Ref. 95, 56 FR 60737 at 60736), was a referral to a published article written by Mensink and Katan (Ref. 201) which addressed criticisms of their 1990 study by noting that another study of longer duration (16 weeks), conducted in the same laboratory, found a similar effect on blood cholesterol levels, even after only 2 weeks on the diets (Ref. 201). One comment suggested a need for further research in the area of trans-fatty acids and blood cholesterol levels before policy decisions are made. The agency agrees in general with the conclusions of the 1992 LSRO report that, while the available evidence to date is suggestive that trans-monounsaturated fatty acids may have LDL-cholesterol-raising characteristics, there is insufficient evidence upon which to make policy decisions at this time. FDA also notes that the requirement that foods be ``low'' in total fat before making a fat/heart disease health claim limits a manufacturer's ability to increase trans-fatty acid levels in foods, since any substitution of trans-fatty acids for SFA's must be done within the 3 g per reference serving size, or per 50 g, limit for total fat. This approach is unlikely to result in significantly increased levels of trans-fatty acids in relationship of trans-fatty acid to heart disease claims at a later date if new data become available to confirm and strengthen the initial findings of an adverse effect of trans-fatty acids on blood LDL- and HDL-cholesterol levels. Resultsfrom well-designed scientific studies on the effect of trans-fatty acids at, or, slightly above, current U.S. consumption levels on blood lipids levels and on other risk factors for cardiovascular disease will aid the agency in reaching future decisions. B. PUFA's In the proposed rule, FDA expressed concerns about possible safety problems associated with consumption of diets enriched in polyunsaturated fats because of the substitution of these fats for SFA's (56 FR 60737 at 60736). Among concerns that FDA raised were potential adverse effects on cell membrane fluidity (a possible risk factor for cardiovascular disease (Ref. 20); decreasing levels of blood HDL-cholesterol; increase in formation of lipid hydroperoxides (oxidized LDL-cholesterol has a high atherogenic potential, Ref. 132); increasing blood triglyceride levels (a possible risk factor for heart disease (Ref. 187); and increasing the risk of some types of cancer (see the proposed rule on dietary lipids and cancer at 56 FR 60764, November 27, 1991). 13. Many comments raised issues concerning the question of the safety of PUFA's in foods and supplements. Comments suggested that safety issues related to PUFA's included increased risk of cancer, coronary thrombosis, and osteoporosis in humans. A few comments also stated that PUFA's may adversely affect immune function. Conversely, others disagreed with the statement in the proposal that PUFA's may increase predisposition to or frequency of certain types of cancer because none of the dietary consensus documents of the Federal Government identified PUFA's as a risk factor for cancer in humans. One comment disagreed that diets enriched in PUFA's may decrease HDL-cholesterol levels but did agree with the description of results from the study by Wardlaw in Table 2 of the proposed rule (56 FR 60727 at 60764 (Ref. 144)) that, ``High concentrations of PUFA's may have pharmacological effects on lowering HDL-cholesterol, however, diets containing 35 percent of calories from fat and a polyunsaturated:saturated fatty acid (P:S) ratio of less than 1.5 are not likely to lower HDL-cholesterol significantly.'' One comment suggested that diets high in PUFA's (greater than 10 percent of calories) cannot be achieved by the American public, so the potential safety concerns were overly emphasized. The LSRO report on ``Lipids and Cardiovascular Disease,'' submitted as a comment to the record, separated the evaluation of PUFA's into two categories: omega-6 polyunsaturates and omega-3 polyunsaturates (Ref. 196). Relative to linoleic acid (one ofthe major types of omega-6 fatty acids in the U.S. diet and an essential fatty acid), the report noted that while: * * * higher intakes may slightly reduce LDL-cholesterol * * * a higher consumption may increase risk for some cancers, promote LDL oxidation with the arterial wall, and possibly raise the risk for coronary thrombosis * * *. A reasonable recommendation may be to avoid both excessively low intakes of linoleic acid (below 4 percent of calories) and higher intakes (above 7 percent of calories). Relative to the second type of PUFA's, the omega-3 fatty acids, the LSRO report noted that: Recommendations for increasing omega-3 fatty acids for the purpose of preventing common chronic diseases must be made with caution and only after more conclusive data are available * * *. Since these fatty acids are biologically active, they deserveintense investigation, but not premature recommendations for their consumption by the general public. FDA agrees with the concern that high levels of intake of PUFA's have the potential for adverse effects in some persons. However, when consumed in amounts similar to current intakes, little or no risk is anticipated (Refs. 20, 29, 31, 33, 35, 74, 78, 136, and 196). Indeed, adequate intakes of essential fatty acids are needed to prevent nutrient deficiencies. By requiring that a food be low in total fat as a qualifying criterion, FDA has made it unlikely that excessively high intakes of PUFA's will be encouraged through the use of a health claim, because there is little room for manipulation of different fats within this range for total fat. Given current levels of intake of essential fatty acids by the U.S. population, deficiencies are not anticipated (56 FR 60727 at 60738; also, see document on dietary lipids and cancer published elsewhere in this issue of the Federal Register. C. Other Safety Issues 14. One comment expressed concern about foods that qualify for a health claim for lipids and cardiovascular disease but that contain a nutrient that may increase the risk of cardiovascular disease or another disease or disorder. As an example, the comment suggested skim milk, which contains no or low fat and cholesterol but does contain casein. The comment suggested that casein has been reported to have atherosclerotic properties in some animals, but no data were provided to support this comment. The basic concept of this comment, that the use of foods bearing health claims should not unduly increase the risk of disease because of the level of nutrients other than the nutrient that is the subject of the claim, is mandated by section 403(r)(3)(A)(ii) of the act. The preamble of the final rule concerning the general requirements for health claims, which appears elsewhere in this issue of the Federal Register, contains an extensive discussion of the agency's implementation of that section of the act through disqualifying nutrient levels. FDA, however, disagrees with the specifics of this comment, i.e., that casein should be considered a negative component that would disqualify a food from bearing a fat/heart disease claim. FDA is aware of early research suggesting that casein has possible adverse effects on risk of heart disease (Ref. 20). However, these observations have never gained wide acceptance by the scientific community, and casein (a rich source of protein) is not considered to significantly contribute to the risk of heartdisease. V. Miscellaneous Issues The proposal contained a number of additional provisions addressing both mandatory and optional aspects of claims about lipids and cardiovascular disease in proposed 101.73(a)(4) and (a)(5). Proposed 101.73(a)(4)(i) provided that a claim must state that a diet low in saturated fat and cholesterol will reduce high blood cholesterol and, thus, the risk of coronary heart disease. Proposed 101.73(a)(4)(ii) provided that health claims must include the caveat that ``some but not all individuals'' would benefit from these dietary changes. Also the terminology for heart disease, blood lipid levels, and dietary fats were described in proposed 101.73(a)(4)(iii)(A), (a)(4)(iii)(B), and (a)(4)(iii)(C). Furthermore, information on the multifactorial nature of the disease and other risk factors was included as a specific requirement in proposed 101.73(a)(4)(iv), and optional information on the need for medical guidance and on the prevalence of heart disease in the U.S. population was provided in proposed 101.73(a)(5)(i) and (a)(5)(ii), respectively. Many of these provisions are addressed in the following comments. 15. Some comments questioned the applicability of a claim relating diets low in saturated fat and cholesterol to reduced risk of heart disease in the general U.S. population. These comments asserted that only about 25 percent of the population may be responsive to reduction in dietary cholesterol and saturated fat. Thus, the comments argued, it would be misleading to imply that all persons would benefit. Conversely, the LSRO report concluded that ``all people in the United States * * * will potentialnce of high intakes of dietary cholesterol for the whole population is prudent.'' Another comment suggested that the agency prescribe the term ``most'' individuals, persons, or people in referring to those people who may benefit from these dietary changes rather than ``most but not all people.'' As discussed in the proposed rule (56 FR 60727 at 60740), FDA recognizes that the beneficial effects from reduction of intakes of saturated fat and cholesterol are highly variable among individuals, particularly in terms of magnitude of effect. For this reason, FDA proposed to require that health claims make clear that the effects described in the claim are likely to be realized by ``some but not all persons'' (proposed 101.73(a)(4)(ii)). At the same time, FDA does not wish to imply that a health claim on dietary lipids and heart disease in accordance with this rule is not useful information for the general population. Current dietary guidelines and the LSRO report cited above conclude that, even if responses among individuals are variable in magnitude, the majority of the population, including persons with normal blood cholesterol levels, will benefit from these dietary goals (Refs. 20, 29 through 36, 74, 136, and 151). Given the strong scientific agreement that the majority of persons in the U.S. will benefit from a reduction in intake of saturated fat and cholesterol, FDA has concluded that the proposed term ``some persons but not all'' is too conservative. FDA has thus not included any requirement for indicating that the nutrient/diseaserelationship is limited to ``some persons but not all'' in the final rule. Therefore, new 101.75(c)(2)(i)(A) reads: ``The claim states that diets low in saturated fat and cholesterol `may' or `might' reduce the risk of heart disease;''. 16. Several comments recommended that the agency require that health claims include a statement on seeking medical advice for persons with multiple risk factors for heart disease. These comments suggested that the majority of the population at risk of cardiovascular disease may require medical advice and may need a combination of medication and diet and lifestyle changes. For these persons, adopting a diet low in saturated fat and cholesterol may not substitute for aggressive medical intervention. FDA agrees that persons with blood LDL-cholesterol levels in the moderate to high risk ranges and with multiple risk factors for heart disease should seek medical advice. However, as noted above, dietary goals for intakes of saturated fat and cholesterol have been recommended for the general population as well as for persons with elevated blood cholesterol levels because of findings of benefit across the entire range of blood cholesterol levels (Refs. 31 and 33). FDA is concerned, therefore, that to require a statement that persons seek medical advice and guidance as part of the health claim might give the erroneous impression to consumers that there is no benefit for them in making the recommended dietary changes unless they have been identified as high risk patients. For this reason, FDA is not persuaded to change the status of information on medical advice from an optional to a mandatory requirement. Thus, the agency is retaining this provision as an optional statement in new 101.75(d)(7),which states: The claim may state that individuals with elevated blood total- or LDL-cholesterol should consult their physicians for medical advice and treatment. If the claim defines high or normal blood total- or LDL-cholesterol levels, then the claim shall state that individuals with high blood cholesterol should consult their physicians for medical advice and treatment. 17. The agency proposed in 101.73(a)(4)(iv) that the health claim may state that CHD is a multifactorial disease and listed major risk factors for the disease that may be used in the claim. This provision was worded so as to suggest that providing01.73(a)(4). The agency received comments that both supported and opposed FDA requiring that any health claim describe CHD as a multifactorial disease. Several comments suggested that the multifactorial nature of the disease should be referred to indirectly, while other comments suggested that these multiple factors should be required to be identified in the health claim. Some comments identified a number of modifiable dietary risk factors for cardiovascular disease not included among those listed the proposed health claims such as: sodium (56 FR 60825), fiber (56 FR 60582), and antioxidant vitamins (56 FR 60624). Other comments recommended that the agency require that the most important risk factors for CHD, elevated LDL-cholesterol, high blood pressure, and cigarette smoking, be listed. FDA recognizes that its proposal was inadvertantly ambiguous about whether the fact that CHD is a multifactorial disease would be a required element of the health claim on dietary lipids and this disease. As pointed out in the proposal (56 FR 60726 at 60740), given the multiple dietary, genetic, and lifestyle risk factors for this disease, consumers would be misled if they were to think that dietary factors are the only risk factors. Given this fact, FDA has concluded that the multifactorial natureof the disease should be a required element (101.75(c)(2)(i)(E)). The issue that is raised as a result is how the significant risk factors should be presented. FDA is concerned that encouraging an unrestricted listing of risk factors for heart disease could result in the listing on food labels of risk factors withrelatively little importance or minimal scientific support or could be used to bypass other label requirements. For example, some comments listed several nutrient risk factors for heart disease, including sodium intake. While FDA is authorizing the use of sodium/hypertension health claims, the agency has not been presented with evidence that sodium intake is a risk factor for heart disease. A claim characterizing the relationship between sodium and heart disease is a health claim and would misbrand a food under section 403(r)(1)(B) of the act unless it is specifically authorized by the agency. Thus, the comments suggested that some would use a list of factors as a backdoor means of making unauthorized health claims. As a result, FDA concludes that only the significant risk factors should appear as part of a health claim. For example, those factors that identify the populations that are at risk, where the general population is not at risk, are appropriate for inclusion in the claim. Listing risk factors that are not significant would be false or misleading and could, as explained above, misbrand the food under section 403(r)(1)(B) of the act. While FDA has decided that the fact that coronary heart disease is multifactorial should be a mandatory element of nutrition labeling, it has also decided that the specific risk factors need not be. As discussed below in conjunction with model health claims, FDA has received numerous comments that the shorter health claims are, the more likely it is that they will be used and understood. Therefore, given the information that it is requiring, FDA has decided, that on balance, it is not necessary to include the significant risk factors as mandatory elements of a claim. The listing of risk factors provided in proposed 101.73(a)(4)(iv) represented scientific consensus as to the most significant factors for heart disease. In this final rule, FDA has redesignated the list of risk factors in proposed 101.73(a)(4)(iv) as new 101.75(d)(1). This section provides a list of the factors that, based on general scientific agreement, are the major factors for heart disease. The agency has also provided that any list of risk factors included as part of a health claim The claim may identify one or more of the following risk factors in addition to saturated fat and cholesterol about which there is general scientific agreement that they are major risk factors for this disease: a family history of coronary heart disease, elevated blood LDL-cholesterol, excess body weight, high blood pressure, cigarette smoking, and long-term physical inactivity. 18. Other comments pointed out that, while excessive intake of some nutrients such as fat may be harmful, there are also minimum intake levels which are essential. Some of the comments suggested that the agency identify minimum thresholds levels forSFA's, MUFA's, PUFA's, total fat, and other dietary nutrients below which intakes should not drop. The comments expressed concern that intakes below these levels would increase risk of nutrient deficiencies. FDA recognizes that there are intake levels for nutrients below which there may be a risk of nutrient deficiencies that could present a risk of adverse effects. FDA disagrees, however, that these levels should be included in the health claim on dietary saturated fat/cholesterol and heart disease. In the proposed rule for a health claim on lipids and cardiovascular disease and as stated in the proposed rule on dietary lipids and cancer, FDA noted that: The requirement of linoleic acid to avoid essential fatty acid deficiency is 1 to 2 percent of total calorie intake. Currently, the average linoleic acid consumption in the U.S. ranges between 5 and 10 percent of total calorie intake, and deficiencies of essential fatty acids are rare in the U.S. Thus, a reduction of total fat consumption from the current 36 to 37 percent of total calorie intake to about 30 percent is not likely to cause essential fatty acid deficiencies in the general population. (56 FR 60764 at 60712) Furthermore, as previously noted in the response to comment 14 of this document, the reduction of saturated fat intakes to meet dietary goals for reduction in risk of heart disease is likely to result in increased intakes of PUFA--the source of the essential fatty acid, linoleic acid. Thus, FDA concludes, as was also concluded in several authoritative reports (Refs. 20, 29, 35, 136, and 150), that there is little likelihood of nutritional deficiencies resulting from changes in U.S. dietary patterns in response to health claims relative to saturated fat/cholesterol and heart disease. 19. One comment suggested that health claims not be allowed on foods that have been modified to meet the ``low fat,'' ``low saturated fat'' or ``low cholesterol'' requirements unless the foods are nutritionally equivalent to the unmodified versions of those foods. FDA rejects this comment. The issue of the effects of a failure to maintain nutritional equivalency are fully addressed by 101.3(e) of FDA's regulations, and in the final rule on standardized foods named by use of a nutrient content claim and a traditional standardized term, published elsewhere in this issue of the Federal Register. As long as a food meets the requirements of those regulations, 101.14, and 101.75, it may bear a health claim on the relationship of saturated fat and cholesterol and coronary heart disease. 20. One comment asked the agency to reconsider its position that health claims are inappropriate for foods intended to be consumed by infants and toddlers of less than 2 years of age; second, to reconsider the amount of total fat, saturated fat and cholesterol that meet requirements for health for infants and toddlers; third, to reconsider the age when infants and toddlers should start to consume ``low fat'' diets. The comment recommended that low saturated fat, low cholesterol, and low fat diets should be extended to even earlier ages, and that the percent of calories from fat for infants and toddlers should be less than 30 percent to reduce obesity, a risk factor for heart disease. The comment did not submit scientific data to support the proposities) earlier than 2 years of age. FDA disagrees with the comment. In the 1990 amendments, Congress indicated that, if FDA's decision on a health claim petition deviated from recommendations of the Federal Government, those differences should be justified (section 403(r)(4)(C) of theact). The agency based its conclusions on the report from the National Cholesterol Education Program (NCEP) on population strategies for healthy children and adolescents (56 FR 60727 at 60731 (Ref. 34)). This report stated that general dietary recommendations for diets low in saturated fat, cholesterol, and total fat should be extended to cover toddlers and children 2 years and older. FDA has seen no compelling evidence to counter the conclusions of the NCEP report. 21. Several comments supported the agency's proposed limitation in proposed 101.73(a)(4)(iii) on interchangeable terms for the disease, for lipids levels, and for the nutrients involved. Another comment suggested that the term ``low density lipoprotein cholesterol'' or the term ``LDL-cholesterol'' be used in place of the term ``total blood cholesterol.'' FDA agrees that the term ``LDL-cholesterol'' is more precise than the term ``blood total cholesterol,'' but disagrees that it should be used in place of the term ``total blood cholesterol'' in 101.75(d)(2) of the final rule. FDA, in proposing the term ``total blood cholesterol'' was using language commonly used in dietary guidance materials at the time of the proposal. Since the publication of the proposal, the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) held a consensus conference on Triglycerides, High Density Lipoprotein, and Coronary Heart Disease in February 1992 (Ref. 187). As a result of that conference, a consensus panel draft report was published reconfirming that high levels of blood LDL-cholesterol are associated with high risk of CHD. The consensus conference panel draft report also concluded that low levels of another blood cholesterol component, HDL-cholesterol, in conjunction with high levels of LDL-cholesterol, were associated with a higher risk of heart disease. These two different cholesterol transport components of blood cholesterol when considered in combination are better predictors of risk than when considered independently. The agency believes that the term ``blood total cholesterol'' should be retained to minimize consumer confusion, since that term is used in dietary guidance materials and many consumers know their blood total cholesterol levels. However, the agency believes that consumers will eventually learn that high LDL-cholesterol levels are strongly associated with risk of heart disease and are reduced by diets low in saturated fat and cholesterol in most people. The agency has therefore specified in new 101.75(d)(2) that the term ``LDL-cholesterol'' may optionally be used in addition to the term ``blood cholesterol,'' and states: ``The claim may indicate that the relationship of saturated fat and cholesterol to heart disease is through the intermediate link of ``blood cholesterol'' or, ``blood total- and LDL-cholesterol.'' In other respects, the agency is carrying forward the terminology from the proposal in new 101.75(c)(2)(i)(B), the agency is limiting the terms used to specify the disease to heart disease or coronary heart disease. This provision is consistent with proposed 101.73(a)(4)(iii)(A). Furthermore, in new 101.75(c)(2)(i)(C), the agency retains the limitations on specifying the nutrient in proposed 101.73(a)(4)(iii)(C). However, 101.75(c)(2)(i)(C) states that: ``In specifying the nutrient, the claim uses the terms `saturated fat' and `cholesterol,' and lists both;''. 22. One comment requested that health claims relating to lipids and cardiovascular disease be allowed for fruits and vegetables, which are naturally low in saturated fat, total fat, and cholesterol. FDA agrees that fruits and vegetables should be allowed to bear appropriate health claims. The agency notes that because most fruits and vegetables are naturally low in saturated fat and do not contain cholesterol, they will meet the qualifying criterion of new 101.62 for ``low saturated fat,'' ``low cholesterol,'' and ``low total fat,'' and thus will qualify under 101.75(c) to bear this claim. FDA advises that it has made a couple of additional minor changes in 101.75. The agency has added 101.75(a)(1), which, consistent with other regulations that the agency is adopting that authorize health claims, defines some of the terms in the regulation. These definitions are consistent with generally accepted science and with the discussion in the proposal. In addition in 101.75(d)(5), FDA has added the National Institutes of Health and ``Nutrition and Your Health: Dietary Guidelinesfor Americans'' (Ref. 29) in recognition that both are sources of information on the number of Americans with heart disease. VI. Model Health Claims 23. Several comments suggested that the model health claims should be reduced in length. Some suggested that health claims should follow examples established by the Surgeon General's office, keeping the health claim in a precise, easily understandable text. One manufacturer submitted model health claims and examples of labeling. One comment submitted an example of a possible health claim: ``Eating a healthful diet low in fat, saturated fat and cholesterol can help reduce the risk of heart disease.'' Another comment suggested that the health claim should state: ``This ---------- can be part of a total diet low in saturated fat and cholesterol, which can reduce risk of heart disease. Use in place of more saturated fats as part of a diet low in total fat.Contains -------- grams of saturated fat, ---------- grams of total fat per serving.'' Another comment recommended an additional statement to be added to the health claim: ``In vitro and animal data are often useful for formulating research hypotheses, but can be inappropriate and unreliable for making public policy.'' FDA agrees with the comments that, to the extent possible, the model health claims should be shortened and made more understandable. They are more likely to be used by manufacturers if they take up as small an amount of label space as possible. Consumers will be more likely to read messages if they are stated simply and succinctly. However, section 403(r)(3)(B)(iii) of the act requires that health claim regulations ensure that claims accurately represent the nutrient/disease relationship and its significance and enable consumers to understand the information and its significance in the context of the total daily diet. Thus, there are constraints on FDA's authority to permit claims to be abbreviated. The issue of shorter health claims has been discussed in detail in the preamble to the final rule on general requirements for health claims published elsewhere in this issue of the Federal Register. As noted in comment 15 of this document, FDAhas dropped the phrase ``in some but not all.'' Additionally, FDA is making reference to the blood cholesterol linkage between dietary saturated fat and cholesterol and risk of heart disease optional. FDA reasons that this amount of detail is not necessary to motivate consumers to implement recommended dietary changes and contributes to wordiness. Thus, the minimum requirements can now be met with a statement as simple as ``While many factors affect heart disease, diets low in saturated fat and cholesterol may reduce the risk of this disease.'' Additional provisions that were included in the proposed rule have been deleted or made optional to simplify health claims. Other model health claims are provided in new 101.75(e). As discussed earlier in this preamble, FDA does, however, believe it is important for each model health claim to acknowledge that many factors affect heart disease. Other changes incorporated into the final regulation include reorganization of paragraphs and clarification of requirements. The final regulation requires claims to use the word ``may'' or ``might'' rather than ``can'' or other words when describingthe possible effect of a diet low in fat and cholesterol on risk of heart disease (101.75(c)(2)(i)(A)). Although FDA recognizes that it cannot require preclearance of claims, it considers this and other restrictions on word choices to be necessary so that claims will accurately reflect the state of the science. All changes in the final regulation are a logical outgrowth of the proposal. 24. A few comments suggested that the agency amend the language of the health claim to include ``very-low fat, low-cholesterol diets begin to reverse CHD in some patients.'' Accompanying the comments were six scientific publications describing six clinical trials. The comments thus suggested tighter criteria for the qualifying levels of fat and cholesterol, e.g., ``very low,'' and a replacement of ``may reduce the risk of'' with a stronger statement about a ``reversal'' of CHD. In addition, the suggested claim would target one segment of the general population which is at increased risk for heart disease. The comments submitted a number of publications to justify use of the term ``reversal'' of heart disease. FDA does not agree that the submitted publications justify the statement that heart disease may be reversed by very low fat, low saturated fat, and low cholesterol diets. Three of the randomized, controlled trials were previously reviewed (in Table 2 of the proposal) by the agency (56 FR 60727 at 60754 through 60755 and 60763) (Refs. 12, 14, and 106). The fourth was conducted in 1984 (Ref. 197) and therefore evaluated by Government and other public health authoritative reports, and the two remaining studies did not provide adequate information to be able to attribute beneficial results to specific dietary components (Refs. 198 and 199). Thus, while FDA finds these results very interesting and considers the studies to suggest a decrease in progression of heart disease from the combination of medical interventions used in these studies, FDA has concluded that these results are not applicable to health claims for several reasons. First, the treatment modality used to obtain results was primarily drugs that lower both blood lipids and blood pressure, in combination with dietary changes. Secondly, the treatment changes were quite severe, and their implementation in the general population is unlikely to be a reasonable goal. Finally, subjects were persons with serious preexisting CHD and under close medical supervision. 25. An association of medical professionals provided a number of references that suggest serum cholesterol goals for patients with noninsulin-dependent diabetes mellitus and patients with hyperlipidemia. The comment asked that the health claim be required to specifically identify and target this group of individuals as high-risk populations. FDA disagrees that specific dietary advice and goals for persons with diseases such as noninsulin-dependent diabetes mellitus and hyperlipidemia should be required to be included as part of health claim messages. These are serious health conditions and require medical supervision. Health claims are intended for the general population. Foods bearing claims for conditions requiring medical supervision are more appropriately regulated as foods for special dietary use, as medical foods, or as drugs, depending upon the specifics of the food and the claims made for it. VII. Consumer Summary FDA also proposed to make available consumer summaries to provide additional information on the health claim. Comments from consumers, health care professionals, public health associations, and the food industry supported the use and availability ofconsumer summaries. FDA did not receive any comments that did not support the use of consumer summaries for this health claim regulation. Comments were received, however, for other health claim regulations suggesting that there was no need for consumer su As discussed in the final rule on general requirements for health claims published elsewhere in this issue of the Federal Register, consumer summaries are not required, although their use remains an option. For this reason, the proposed consumer summary has not been included in this final rule. VIII. Summary of Updated Science Review To ensure that significant new evidence had not become available subsequent to the proposal, FDA updated its review of the scientific evidence with human studies that were directly relevant to the proposed rule or that became available after publication of its proposal (Table). A. Relationship of Dietary Saturated Fat and Cholesterol to Blood Cholesterol and, Therefore, to Risk of Heart Disease. 1. Saturated Fat In the proposed rule (56 FR 60727 at 60728), FDA accepted the conclusions of consensus documents that serum cholesterol levels are a valid intermediate predictor of risk of heart disease (Refs. 20, 29 through 36, 74, 136, 150, and 151). FDA limited its evaluation of the nutrient/disease relationship to diets low in saturated fat and cholesterol and reduced risk of CHD. FDA additionally proposed that health claims should be prohibited on foods that are not low in fat because of strong indirect linksbetween high fat diets and risk of heart disease. A recent study supports the applicability of dietary modifications to children. A longitudinal study in 108 healthy Hispanic preschool children (Ref. 183) compared children in the highest tertile (a tertile is a comparison based on thirds, i.e., highest, middle and lowest tertile) of total fat and saturated fat consumption (36.2 percent and 14.6 percent of calories as fat and saturated fat, respectively) to children in the lowest tertile (30 percent and 11 percent of calories as fat and saturated fat). Higher total fat and saturated fat intakes were associated with higher blood total and LDL- cholesterol levels (Table). Several new clinical trials provide additional support that reductions in intakes of dietary saturated fat and cholesterol reduce serum total and LDL-cholesterol levels, even though serum triglyceride and HDL-cholesterol levels do not change significantly. Deneke et al. (Ref. 162) compared the effects on blood cholesterol levels in 10 men, mean age 66, (Table) of isocaloric, liquid diets differing in type and amount of SFA. In the self controlled, cross-over study, the saturated fat was derived from either butter (25 percent SFA), beef (18 percent SFA), cocoa butter (23 percent SFA) or olive oil (8 percent SFA). These fat diets also differed in the amount of stearic acid: 4, 7.6, 13 and 1.2 percent, respectively. Diets enriched in saturated fat from butter, beef, or cocoa butter, significantly increased total cholesterol and LDL-cholesterol compared to diets containing less saturated fat. The higher concentration of stearic acid in both beef and cocoa butter diets did not negate the effect of saturated fat on blood cholesterol levels. Under the conditions of the study design, stearic acid was neutral in its ability to change blood cholesterol levels. This study should be repeated using more subjects, including healthy subjects, and with solid foodsto provide nutritional data that is more applicable to the general public. In another dietary intervention study, the effects of a low fat, low saturated fat, no cholesterol diet on serum cholesterol was reported (Ref. 184). Five familial hypercholesterolemic (FH) patients and four healthy control individuals consumed a diet that was very low fat (8.2 percent of calories), and high carbohydrate (90.5 percent of calories) for 1 month, following 1 month on a basal diet, and after 3 months on a wash-out diet (see Table). Both normal controls and FH patients responded similarly, with a significant decrease in total and LDL-cholesterol. HDL-cholesterol decreased nonsignificantly, but serum triglycerides increased significantly. One difference in response by FH patients and controls to the diets was observed in cholesterol syntho 4.8 mg/kg/day) in FH patients. Another dietary intervention study compared the effects of diets supplemented with saturated fat or linoleic acid on blood cholesterol levels (Ref. 180). This study of free-living subjects was conducted in 12 mildly hypercholesterolemic individuals (5 men and 7 women) ages 27 to 74 years, in a randomized, cross-over design that provided 2 weeks on the basal diet and 3 weeks on each of the test diets. Total fat composition of the diets is shown in the Table. The test diets contained an additional 17.3 percent SFA or 14.8 percent of PUFA (in the form of linoleic acid). The saturated fat-enriched diet significantly increased total cholesterol and LDL-cholesterol compared to the baseline diet. The linoleic-supplemented diet, which has a similar concentration of saturated fat as the basal diet, produced significantly lowered total cholesterol, 19 mg/decaliter (dL) (0.5 millimoles/Liter (mmol/L)) less compared to the basal diet and 39 mg/dL (1.0 mmol/L) less compared to the saturated fat-enriched diet.This study should be repeated using more subjects including healthy subjects and with solid foods to provide nutritional data that are more applicable to the general public. The study does suggest the possibility of more flexibility in dietary options available for the general public. The effect of a ``Western'' diet rich in saturated fat and cholesterol (total fat, saturated fat and cholesterol: 43 percent, 21 percent, of calories, 1,020 mg/day, respectively) on blood cholesterol levels was measured in free-living subjects who normally consume a low fat, low saturated fat, Tarahumara diet (less than 20 percent of calories from total fat, 7 percent from saturated fat and less than 50 mg/day) (Ref. 176). The study included 12 adults (5 women) and one 12-year-old boy. After consumption of the ``Western'' diet for 5 weeks, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides increased significantly in all subjects. Total cholesterol increased from 121 mg/dL at baseline to 159 mg/dL, and LDL-cholesterol went from 72 to 100 mg/dL. The ``Western'' diet as described by the study design contains a higher level of total fat, saturated fat, and cholesterol than consumed by the U.S. general population. 2. Dietary Cholesterol In another recent study, the effect of dietary cholesterol (in the form of eggs) on serum cholesterol levels was measured in seventy 18 to 19 year old, free-living, healthy males (Ref. 190). A baseline diet containing 3 eggs per week was consumed byall subjects for 3 months (diet composition contained in the Table: total fat was 40 percent of approximately 3,350 calories per day). The subjects were divided into three groups of approximately equal numbers: one group continued on the baseline diet, group 2 was supplemented with 7 eggs per week, and the third group was supplemented with 14 eggs per week for an additional 5 months. No significant differences were reported in total cholesterol, LDL-cholesterol, or triglycerides between groups. The authors proposed several suggestions to explain these results. They stated that the relatively high levels of total fat compounded with a low content PUFA compared to SFA content may have canceled the potential serum cholesterol-raising effects of dietary cholesterol. Secondly, they suggested that the subjects may have adapted to the diet by decreasing cholesterol synthesis or by increasing the rate of cholesterol eliminated from the body. Meta-analysis was used to examine the effects of dietary cholesterol on serum cholesterol from 76 studies that had reported completely controlled diets (Ref. 221). This meta-analysis, unlike previously reported studies, included baseline together with added dietary cholesterol data, PUFA and SFA content of the diet, and weighted the number of subjects in each trial. The diets used in the trials included formula diets, semipurified diets, and diets based on customary food. The baseline dietary cholest cholesterol than added dietary cholesterol. Thus when baseline dietary cholesterol was high, added dietary cholesterol resulted in diminished increases in total blood cholesterol. Therefore, when one to two eggs are added to a diet that already contain350 to 400 mg/day of cholesterol, little increase in blood cholesterol would be expected. B. Estimates of Change in Blood Cholesterol by Following Low Fat, Saturated Fat and Cholesterol Dietary Guidelines In the following group of studies, the effectiveness of diets reduced in total fat, SFA, and cholesterol to levels suggested by national nutritional guidelines and health organizations were evaluated. A diet referred to as ``US74'' (fat content was 38 percent of total calories, SFA 18 percent, MUFA's 14 percent, PUFA 4 percent, and cholesterol 600 mg/day) (Table, Ref. 168) was compared to the diet recommended by U.S. public health authorities (fat 30 percent and SFA, MUFA, and PUFA 10 percent of total calories, respectively, and cholesterol 300 mg/day and referred to as modified diet (``MOD'' diet)) on total blood cholesterol levels. The study included 5 free-living women of Chinese origin and 14 of Caucasian origin, in a cross-over, randomized order design with each test diet lasting 3 weeks. Throughout the intervention study, the Chinese women had consistently higher total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride levels than Caucasians, regardless of diet selected. Caucasian women showed a significant decrease in total cholesterol and LDL-cholesterol only when the US74 diet was compared to the MOD diet. Consumption of the US74 diet increased total cholesterol and very-low density lipoprotein-cholesterol (VLDL-cholesterol) in Chinese women compared to a self selected diet (in which fat was 34 percent of total calories and SFA was about 12 percent, MUFA was 13 percent (based on g of oleic acid/day), PUFA was 8 percent (based on g of linoleic acid/day), and cholesterol was 360 mg/day). The second study evaluated the effectiveness of the American Heart Association (AHA) Step-1 diet in lowering blood cholesterol in free-living subjects (Ref. 154). (The AHA Step-1 diet contains 10 percent or less saturated fat; 30 percent or less oftotal calories from fat; and less than 300 mg/day cholesterol.) Forty-nine men and 38 women completed the 18 week dietitian-instructed study (they were hypercholesterolemic, total cholesterol 243 mg/dL. and LDL-cholesterol 169 mg/dL; and mean age of 50 years, Table). Modest, but significant, decreases were observed in total-cholesterol and LDL-cholesterol after 6 weeks. No further reductions in total- or LDL-cholesterol were observed at 12 or 18 weeks, and there was a tendency to return to or exceed baseline cholesterol levels. The authors suggested that since most of the participants knew they were hypercholesterolemic before the study, they may have already been following a self-developed, low saturated fat, low fat, low cholesterol diet. This conclusion was derived from analysis of self-administered food frequency questionnaires and 4-day food records, including 1 weekend day collected on baseline diet and AHA Step-1 diets. The third study compared the effectiveness of the AHA Step-3 diet with a typical American diet. It pointed out additional considerations in implementing dietary changes to reduce blood cholesterol and CHD risk in women. In the study, 19 free-living premenopausal women consumed a typical American diet for 28 days prior to 5 months of the AHA Step-3 diet (Table, Ref. 161). In brief, self-reported dietary fat, saturated fat, and cholesterol for the American versus AHA Step-3 diet was 37 percent versus21 percent; 15.7 percent versus 4.7 percent; and 271 versus 96 mg/day, respectively. Total cholesterol, LDL-cholesterol, and HDL-cholesterol decreased in these women consuming the AHA Step-3 diet. However, only after subdividing the women by body mass indody mass index, had significant decreases in blood cholesterol, while moderate or grossly obese women did not. The authors suggest that results from this study with free-living individuals may imply that obese women may be more sensitive to dietary carbohydrates and therefore not as responsive to a diet low in total fat, saturated fat, and cholesterol and enriched in carbohydrate (43.8 versus 59.4 percent). Secondly, alternative diets that replace SFA by means other than carbohydrate exchange may be more effective in these individuals. In a fourth study, the effectiveness of intensive dietary instruction on reduction of serum cholesterol level was evaluated as part of the Heart Tune Program (Ref. 169). Hypercholesterolemic patients (30 women and 19 men) attended 4 consecutive classes on heart disease, properties and definitions of fat, healthy food selections, and meal preparations for 2 1/2 hours per week. At baseline, the total and LDL-cholesterol levels of participants in the study were 268 mg/dL (6.95 mmol/L) and 180 mg/dL (4.68 mmol/L), respectively. After 4 weeks of enrollment in the program, there was a significant reduction in both total cholesterol and LDL-cholesterol to 240 mg/dL (6.30 mmol/L) and 161 mg/dL (4.16 mmol/L), respectively. Additional confirmation and estimation of benefits associated with a reduction in serum cholesterol levels that are predictive of heart disease was provided using a computer model (Ref. 170). Subjects for the computer model system included both men and women with blood cholesterol levels ranging from 200 mg/dl (5.2 mol/L) to 300 mg/dL (7.8 mmol/L) at baseline. Data for the study incorporated updated estimates from both America (Framingham Heart Study) and Canada (Canadian Health Survey). Results suggested that, by reducing serum cholesterol levels by 5 to 33 percent, life expectancy could be lengthened by 0.03 to 3.16 years. In summary, the updated literature review was consistent with and generally supported the tentative conclusions reached in the proposed rule (56 FR 60727 at 60735). That is, diets low in saturated fat and cholesterol reduce blood cholesterol levels,particularly LDL-cholesterol levels. C. Safety Issues 1. Trans-fatty Acids One area identified in the proposed rule as a potential concern was the possibility of increased intake of trans-fatty acids as a result of changes in the fat composition of the U.S. food supply. One study that has been widely cited within thescientific community is the study by Mensink and Katan (Ref. 95). Studies that examined the effects of trans-fatty acids on serum cholesterol levels are limited and report conflicting results and conclusions. One trans-fatty acid study discussed and evaluated in Table 2 of the proposed rule (56 FR 60727 at 60761, Ref. 95), reported that consumption of a diet enriched in trans-fatty acids (11 percent of total calories or 33 g/day) significantly increased total cholesterol and LDL-cholesterol and significantly reduced HDL-cholesterol levels in healthy subjects. The level of trans-fatty acids used was much higher than the level reported available for consumption by the U.S. population (3 to 4 percent of calories or 7 to 10 g/day). In a recent study by Zock and Katan (Ref. 193), healthy, free-living, normolipidemic individuals (26 males and 30 females) consumed diets that compared the effect of C - 18 fatty acids (saturated, trans-monoene, and unsaturated form) on serum lipids. Each diet, which did not differ in nutrient content, lasted for 3 weeks and was eaten as solid foods. In this multiple, cross-over design study, the trans-fatty acid level was set at 7.7 percent of total calories or 24 g/day. Both stearate and trans-fatty acid-enriched diets increased total cholesterol and LDL-cholesterol levels significantly, relative to the linoleate diet (a polyunsaturated fat). In addition, both stearate and trans-fatty acids significantly reduced HDL-cholesterol rbserved in 46 of 56 subjects on the trans-fatty acid enriched diet. The authors concluded that, if the data from this study are combined with those from the previous study (Refs. 95 and 193), the results suggested that for every 1 percent of energy derived from trans-fatty acids, LDL-cholesterol would increase by 1.2 mg/dL and HDL-cholesterol would be lowered by 0.6 mg/dL relative to an equivalent amount of oleic or linoleate. The authors concluded that the current U.S. trans-fatty acid consumption level of about 3 to 4 percent of total calories may increase LDL-cholesterol by 4 mg/dL and decrease of HDL-cholesterol by 2 mg/dL. 2. Unsaturated Fatty Acids In the following group of studies, the effect of diets reduced in total fat, SFA, and cholesterol to levels suggested by national nutritional guidelines and health organizations was evaluated with respect to the possibility of increased intake of unsaturated fatty acids, especially PUFA's. This issue was raised in the proposal as a result of possible changes in the fat composition of the U.S. food supply (56 FR 60727 at 60735). In a randomized, blinded, controlled dietary intervention study, the effect of diets enriched in vegetable oils on serum cholesterol levels in 31 free-living mildly hypercholesterolemic men (Ref. 192) was reported. Two conditions were examined: Testdiets, in which the saturated fat content was 7 percent (test) versus 15 percent in the control diets, were enriched in either MUFA (22 percent MUFA-test versus 14 percent-control) or PUFA (22 percent PUFA-test versus 9 percent PUFA-control) (refer to the Table). Total and LDL-cholesterol levels were reduced significantly by consumption of diets reduced in saturated fat and enriched (22 percent of calories) in either MUFA or PUFA (total cholesterol: -15 (PUFA) and -12 (MUFA) percent, and LDL-cholesterol: -20 (PUFA) and -12 (MUFA) percent, respectively). 3. PUFA-Enriched Diets Versus MUFA-Enriched Diets A recent study by Mata et al. (Ref. 175) compared the long-term effects of PUFA-enriched diets versus MUFA-enriched diets, on blood cholesterol levels in 46 free-living, healthy men (mean age 33 years) and 32 women (mean age 42). The two diets were similar in all respects other than the content of the test unsaturated fatty acids (the PUFA-enriched diet content contained total fat 37 percent; SFA 12.5 percent; PUFA 13 percent; and MUFA 10 percent; while the MUFA-enriched diet had the same amount oftotal and saturated fat but 3.4 percent PUFA and 20 percent MUFA) (see Table). This controlled, solid food study, was conducted in two phases: phase 1, PUFA-enriched diets (for 16 weeks) followed by a second phase, the MUFA-enriched diet, which lasted for 28 weeks. The MUFA-enriched diet had no effect on blood total cholesterol in men but increased it in women. The MUFA-enriched diet increased HDL-cholesterol levels compared to the PUFA-enriched diet. HDL-cholesterol levels increased in both men (17 percent) and women (30 percent). No significant changes occurred in LDL-cholesterol or total triglycerides. In summary, the updated literature review reveals relatively few new studies pertaining to possible unintended safety effects from reducing dietary intakes of saturated fat and cholesterol. Possible adverse effects on LDL-cholesterol and HDL-cholesterol from the consumption of large quantities of trans-fatty acids are supported by recent scientific reports. Most results are consistent with those of earlier reviews (Refs. 20, 30 through 36, 136, 150, and 151) and with comments received in response to the proposed rule. Overall, the updated literature review provided no convincing evidence to suggest that the agency's tentative conclusions as to the relationship of saturated fat and cholesterol to risk of heart disease, as described in the proposal, required modifica IX. Conclusions FDA has responded to all comments received in response to the proposed saturated fat and cholesterol and CHD health claim regulation. In addition, the agency has reviewed all additional scientific studies received in comments or independently identified. The agency has determined that the new studies strengthen the tentative conclusions reached in the proposed regulation. After considering the comments and the new scientific studies, the agency concludes that there is significant scientific agreement based on the totality of publicly available scientific evidence that a claim that diets low in saturated fat and cholesterol may reduce the risk of CHD is supported by that evidence. Therefore, FDA is authorizing a claim. The agency has decided that the regulations for the authorized health claims are most useful if they follow a consistent format and require only information that the agency considers essential. Therefore, the agency has made a number of editorial changes in the proposed codified material of the saturated fat and cholesterol and CHD health claim to make it more consistent with other authorized claims. X. Environmental Impact The agency has determined under 21 CFR 25.24(a)(11) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required. XI. Economic Impact In its food labeling proposals of November 27, 1991 (56 FR 60366 et seq.), FDA stated that the food labeling reform initiative, taken as a whole, would have associated costs in excess of the $100 million threshold that defines a major rule. Thus, inaccordance with Executive Order 12291 and the Regulatory Flexibility Act (Pub. L. 96 - 354), FDA developed one comprehensive regulatory impact analysis (RIA) that presented the costs and benefits of all of the food labeling provisions taken together. That RIA was published in the Federal Register of November 27, 1991 (56 FR 60856), and along with the food labeling proposals, the agency requested comments on the RIA. FDA has evaluated more than 300 comments that it received in response to the November 1991 RIA. FDA's discussion of these comments is contained in the agency's final RIA published elsewhere in this issue of the Federal Register. In addition, FDA will prepare a final regulatory flexibility analysis (RFA) subsequent to the publication of the food labeling final rules. The final RFA will be placed on file with the Dockets Management Branch (HFA - 305), Food and Drug Administration, rm. 1 - 23, 12420 Parklawn Dr., Rockville, MD 20857, and a notice will be published in the Federal Register announcing its availability. In the final RIA, FDA has concluded, based on its review of available data and comments, that the overall food labeling reform initiative constitutes a major rule as defined by Executive Order 12291. Further, the agency has concluded that although the costs of complying with the new food labeling requirements are substantial, such costs are outweighed by the public health benefits that will be realized through the use of improved nutrition information provided by food labeling. XII. References The following references have been placed on display in the Dockets Management Branch (address above) and may be seen by interested persons between 9 a.m. and 4 p.m., Monday through Friday. 1. Abbott, R. D., P. W. Wilson, W. B. Kannel, W. P. 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Park, ``Evaluation of Health Aspects of Sugar Contained in Carbohydrate Sweeteners,'' Report on Sugar Task Force 1986, Executive Summary, pp. s1 - s16, 1986. List of Subjects in 21 CFR Part 101 Food Labeling, Reporting and recordkeeping requirements. Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, 21 CFR part 101 is amended as follows: PART 101--FOOD LABELING 1. The authority citation for 21 CFR part 101 continues to read as follows: Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act (15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342, 343, 348, 371). 2. New 101.75 is added to subpart E to read as follows: 101.75 Health claims: dietary saturated fat and cholesterol and risk of coronary heart disease. (a) Relationship between dietary saturated fat and cholesterol and risk of coronary heart disease. (1) Cardiovascular disease means diseases of the heart and circulatory system. Coronary heart disease is the most common and serious form of cardiovascular disease and refers to diseases of the heart muscle and supporting blood vessels. High blood total- and low density lipoprotein (LDL)- cholesterol levels are major modifiable risk factors in the development of coronary heart disease. High coronary heart disease rates occur among people with high blood cholesterol levels of 240 milligrams/decaliter (mg/dL) (6.21 millimoles per liter (mmol/L)) or above and LDL-cholesterol levels of 160 mg/dL (4.13 mmol/L) or above. Borderline high risk blood cholesterol levels range from 200 to 239 mg/dL (5.17 to 6.18 mmol/L) and 130 to 159 mg/dL (3.36 to 4.11 mmol/L) of LDL-cholesterol. Dietary lipids (fats) include fatty acids and cholesterol. Total fat, commonly referred to as fat, is composed of saturated fat (fatty acids containing no double bonds), and monounsaturated and polyunsaturated fat (fatty acids containing one or more double bonds). (2) The scientific evidence establishes that diets high in saturated fat and cholesterol are associated with increased levels of blood total- and LDL-cholesterol and, thus, with increased risk of coronary heart disease. Diets low in saturated fat and cholesterol are associated with decreased levels of blood total- and LDL-cholesterol, and thus, with decreased risk of developing coronary heart disease. (b) Significance of the relationship between dietary saturated fat and cholesterol and risk of coronary heart disease. (1) Coronary heart disease is a major public health concern in the United States, primarily because it accounts for more deaths than any other disease or group of diseases. Early management of risk factors for coronary heart disease is a major public health goal that can assist in reducing risk of coronary heart disease. There is a continuum of mortality risk from coronary heart disease that increases with increasing levels of blood LDL-cholesterol. Individuals with high blood LDL-cholesterol are at greatest risk. A larger number of individuals with more moderately elevated cholesterol also have increased risk of coronary events; such individuals comprise a substantial proportion of the adult U.S. population. The scientific evidence indicates that reducing saturated fat and cholesterol intakes lowers blood LDL-cholesterol and risk of heart disease in most individuals. Thereis also evidence that reducing saturated fat and cholesterol intakes in persons with blood cholesterol levels in the normal range also reduces risk of heart disease. (2) Other risk factors for coronary heart disease include a family history of heart disease, high blood pressure, diabetes, cigarette smoking, obesity (body weight 30 percent greater than ideal body weight), and lack of regular physical exercise. (3) Intakes of saturated fat exceed recommended levels in many people in the United States. Intakes of cholesterol are, on average, at or above recommended levels. One of the major public health recommendations relative to coronary heart disease risk is to consume less than 10 percent of calories from saturated fat, and an average of 30 percent or less of total calories from all fat. Recommended daily cholesterol intakes are 300 mg or less per day. (c) Requirements. (1) All requirements set forth in 101.14 shall be met. (2) Specific requirements. (i) Nature of the claim. A health claim associating diets low in saturated fat and cholesterol with reduced risk of coronary heart disease may be made on the label or labeling of a food described in paragraph (c)(2)(ii (A) The claim states that diets low in saturated fat and cholesterol ``may'' or ``might'' reduce the risk of heart disease; (B) In specifying the disease, the claim uses the terms ``heart disease'' or ``coronary heart disease;'' (C) In specifying the nutrient, the claim uses the terms ``saturated fat'' and ``cholesterol'' and lists both; (D) The claim does not attribute any degree of risk reduction for coronary heart disease to diets low in dietary saturated fat and cholesterol; and (E) The claim states that coronary heart disease risk depends on many factors. (ii) Nature of the food. The food shall meet all of the nutrient content requirements of 101.62 for a ``low saturated fat,'' ``low cholesterol,'' and ``low fat'' food; except that fish and game meats (i.e., deer, bison, rabbit, quail, wildturkey, geese, and ostrich) may meet the requirements for ``extra lean'' in 101.62. (d) Optional information. (1) The claim may identify one or more of the following risk factors in addition to saturated fat and cholesterol about which there is general scientific agreement that they are major risk factors for this disease: A family history of coronary heart disease, elevated blood total and LDL-cholesterol, excess body weight, high blood pressure, cigarette smoking, diabetes, and physical inactivity. (2) The claim may indicate that the relationship of saturated fat and cholesterol to heart disease is through the intermediate link of ``blood cholesterol'' or ``blood total- and LDL cholesterol.'' (3) The claim may include information from paragraphs (a) and (b) of this section, which summarize the relationship between dietary saturated fat and cholesterol and risk of coronary heart disease, and the significance of the relationship. (4) In specifying the nutrients, the claim may include the term ``total fat'' in addition to the terms ``saturated fat'' and ``cholesterol''. (5) The claim may include information on the number of people in the United States who have coronary heart disease. The sources of this information shall be identified, and it shall be current information from the National Center for Health Statistics, the National Institutes of Health, or ``Nutrition and Your Health: Dietary Guidelines for Americans,'' U.S. Department of Health and Human Services (DHHS) and U.S. Department of Agriculture (USDA), Government Printing Office. (6) The claim may indicate that it is consistent with ``Nutrition and Your Health: Dietary Guidelines for Americans,'' DHHS and USDA, Government Printing Office. (7) The claim may state that individuals with elevated blood total- or LDL-cholesterol should consult their physicians for medical advice and treatment. If the claim defines high or normal blood total- or LDL-cholesterol levels, then the claim shallstate that individuals with high blood cholesterol should consult their physicians for medical advice and treatment. (e) Model health claims.The following are model health claims that may be used in food labeling to describe the relationship between dietary saturated fat and cholesterol and risk of heart disease: (1) While many factors affect heart disease, diets low in saturated fat and cholesterol may reduce the risk of this disease; (2) Development of heart disease depends upon many factors, but its risk may be reduced by diets low in saturated fat and cholesterol and healthy lifestyles; (3) Development of heart disease depends upon many factors, including a family history of the disease, high blood LDL-cholesterol, diabetes, high blood pressure, being overweight, cigarette smoking, lack of exercise, and the type of dietary pattern.A healthful diet low in saturated fat, total fat, and cholesterol, as part of a healthy lifestyle, may lower blood cholesterol levels and may reduce the risk of heart disease; (4) Many factors, such as a family history of the disease, increased blood- and LDL-cholesterol levels, high blood pressure, cigarette smoking, diabetes, and being overweight, contribute to developing heart disease. A diet low in saturated fat, choles (5) Diets low in saturated fat, cholesterol, and total fat may reduce the risk of heart disease. Heart disease is dependent upon many factors, including diet, a family history of the disease, elevated blood LDL-cholesterol levels, and physical inactivity. Dated: November 3, 1992. David A. Kessler, Commissioner of Food and Drugs. Louis W. Sullivan, Secretary of Health and Human Services. Note: The following table will not appear in the annual Code of Federal Regulations. BILLING CODE 4160 - 01 - F [FR Doc. 92 - 31519 Filed 12 - 28 - 92; 8:45 am] BILLING CODE 4160 - 01 - C