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U.S. Department of Health and Human Services

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Qualified Health Claims: Letter of Enforcement Discretion - Corn Oil and Corn Oil-Containing Products and a Reduced Risk of Heart Disease (Docket No. 2006P-0243)

March 26, 2007

Richard O. Wood
The Wood Burditt Group, L.L.C.
1025 Everett Road
Suite 100
Lake Forest, Illinois 60045

RE: Qualified Health Claim Petition - Corn Oil and Corn Oil-Containing Products and a Reduced Risk of Heart Disease (Docket No. 2006P-0243)

Dear Mr. Wood:

This letter responds to a health claim petition dated April 28, 2006, submitted to the Food and Drug Administration (FDA or the agency) by ACH Food Companies, Inc. pursuant to section 403(r)(4) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 343(r)(4)). The petition requested that the agency authorize a qualified health claim characterizing the relationship between the consumption of corn oil and corn oil-containing products and a reduced risk of heart disease. This petition proposed as model qualified health claims:

"Substituting corn oil for solid fats may reduce your risk of heart disease."
"Substituting corn oil for fats high in saturated fat may reduce your risk of heart disease."
"Scientific evidence establishes that including corn oil-containing foods in your diet may reduce your risk of heart disease. To achieve such benefits, include slightly less than 1 tablespoon (12 grams) of corn oil per day in your diet while not increasing calories, saturated fat or cholesterol. One serving of this product contains x grams of corn oil. Although there is scientific evidence supporting the claim, the evidence is not conclusive."

FDA filed the petition on June 16, 2006 as a qualified health claim petition and posted the petition on the FDA website for a 60-day comment period, consistent with the agency's guidance on procedures for qualified health claims.(1) The agency received one comment on this petition. The comment supported the claims unconditionally. FDA considered the comment in its evaluation of this petition. By mutual agreement, the decision date for this petition was extended to March 28, 2007.

This letter sets forth the basis of FDA's determination that the current evidence for the proposed qualified health claims is appropriate for consideration of a qualified health claim on conventional foods. This letter also sets out the factors that FDA intends to consider in the exercise of its enforcement discretion for a qualified health claim with respect to consumption of corn oil and corn oil-containing products and a reduced risk of coronary heart disease (CHD).

I. Overview of Data and Eligibility for a Qualified Health Claim

A health claim characterizes the relationship between a substance and a disease or health-related condition (21 CFR 101.14(a)(1)). The substance must be associated with a disease or health-related condition for which the general U.S. population, or an identified U.S. population subgroup is at risk (21 CFR 101.14(b)(1)). Health claims characterize the relationship between the substance and a reduction in risk of contracting a particular disease or health-related condition.(2) In a review of a qualified health claim, the agency first identifies the substance and disease or health-related condition that is the subject of the proposed claim and the population to which the claim is targeted.(3) FDA considers the data and information provided in the petition, in addition to other written data and information available to the agency, to determine whether the data and information could support a relationship between the substance and the disease or health-related condition.(4)

The agency then separates individual reports of human studies from other types of data and information. FDA focuses its review on reports of human intervention and observational studies.(5)

In addition to individual reports of human studies, the agency also considers other types of data and information in its review, such as meta-analyses,(6) review articles,(7) and animal and in vitro studies. These other types of data and information may be useful to assist the agency in understanding the scientific issues about the substance, the disease, or both, but cannot by themselves support a health claim relationship. Reports that discuss a number of different studies, such as meta-analyses and review articles, do not provide sufficient information on the individual studies reviewed for FDA to determine critical elements such as the study population characteristics and the composition of the products used. Similarly, the lack of detailed information on studies summarized in meta-analyses and review articles prevents FDA from determining whether the studies are flawed in critical elements such as design, conduct of studies, and data analysis. FDA must be able to review the critical elements of a study to determine whether any scientific conclusions can be drawn from it. Therefore, FDA uses meta-analyses, review articles, and similar publications(8) to identify reports of additional studies that may be useful to the health claim review and as background about the substance-disease relationship. If additional studies are identified, the agency evaluates them individually.

FDA uses animal and in vitro studies as background information regarding mechanisms of action that might be involved in any relationship between the substance and the disease. The physiology of animals is different than that of humans. In vitro studies are conducted in an artificial environment and cannot account for a multitude of normal physiological processes such as digestion, absorption, distribution, and metabolism that affect how humans respond to the consumption of foods and dietary substances (IOM, 2005). Animal and in vitro studies can be used to generate hypotheses or to explore a mechanism of action but cannot adequately support a relationship between the substance and the disease.

FDA evaluates the individual reports of human studies to determine whether any scientific conclusions can be drawn from each study. The absence of critical factors such as a control group or a statistical analysis means that scientific conclusions cannot be drawn from the study (Spilker et al., 1991; Federal Judicial Center, 2000). Studies from which FDA cannot draw any scientific conclusions do not support the health claim relationship and these are eliminated from further review.

Because health claims involve reducing the risk of a disease in people who do not already have the disease that is the subject of the claim, FDA considers evidence from studies in individuals diagnosed with the disease that is the subject of the health claim only if it is scientifically appropriate to extrapolate to individuals who do not have the disease. That is, the available scientific evidence must demonstrate that: (1) the mechanism(s) for the mitigation or treatment effects measured in the diseased populations are the same as the mechanism(s) for risk reduction effects in non-diseased populations; and (2) the substance affects these mechanisms in the same way in both diseased people and healthy people. If such evidence is not available, the agency cannot draw any scientific conclusions from studies that use diseased subjects to evaluate the substance-disease relationship.

Next, FDA rates the remaining human intervention and observational studies for methodological quality. This quality rating is based on several criteria related to study design (e.g., use of a placebo control versus a non-placebo controlled group), data collection (e.g., type of dietary assessment method), the quality of the statistical analysis, the type of outcome measured (e.g., disease incidence versus validated surrogate endpoint), and study population characteristics other than relevance to the U.S. population (e.g., selection bias and whether important information about the study subjects - e.g., age, smoker vs. non-smoker - was gathered and reported). For example, if the scientific study adequately addressed all or most of the above criteria, it would receive a high methodological quality rating. Moderate or low quality ratings would be given based on the extent of the deficiencies or uncertainties in the quality criteria. Studies that are so deficient that scientific conclusions cannot be drawn from them cannot be used to support the health claim relationship, and these are eliminated from further review.

Finally, FDA evaluates the results of the remaining studies. The agency then ranks the strength of the total body of publicly available evidence.(9) The agency conducts this ranking process by considering the study type (e.g., intervention, prospective cohort, case-control, cross-sectional), the methodological quality rating previously assigned, the quantity of evidence (number of the various types of studies and sample sizes), whether the body of scientific evidence supports a health claim relationship for the U.S. population or target subgroup, whether study results supporting the proposed claim have been replicated,(10) and the overall consistency(11) of the total body of evidence.(12) Based on the totality of the scientific evidence, FDA determines whether such evidence is credible to support the substance/disease relationship, and, if so, determines the ranking that reflects the level of comfort among qualified scientists that such a relationship is scientifically valid.

A. Substance

A health claim characterizes the relationship between a substance and a disease or health-related condition (21 CFR 101.14(a)(1)). A substance means a specific food or component of food regardless of whether the food is in conventional form or a dietary supplement (21 CFR 101.14(a)(2)). The petition identified corn oil, rather than any specific component in the corn oil, as the substance of the proposed claims. However, the petition stated that "corn oil contains at least three major components that almost certainly play a role in its lowering effect on LDL and total cholesterol," i.e., polyunsaturated fatty acids, monounsaturated fatty acids, and phytosterols. Unsaturated fatty acids (UFAs) (i.e., polyunsaturated and monounsaturated fatty acids) are fat components that occur naturally in many foods. Therefore, the agency concludes that UFAs from corn oil are a component of food and thus meet the definition of substance in the health claim regulations (21 CFR 101.14(a)(2)).(13)

B. Disease or Health Related Condition

A disease or health-related condition means damage to an organ, part, structure, or system of the body such that it does not function properly or a state of health leading to such dysfunctioning (21 CFR 101.14(a)(5)). The petition identified heart disease as the disease that is the subject of the proposed qualified health claims.

The agency concludes that heart disease is a disease and therefore the petitioner has satisfied the requirement in 21 CFR 101.14(a)(5).

C. Safety

Under 21 CFR 101.14(b)(3)(ii), if the substance is to be consumed at other than decreased dietary levels, the substance must be a food or a food ingredient or a component of a food ingredient whose use at levels necessary to justify a claim must be demonstrated by the proponent of the claim, to FDA's satisfaction, to be safe and lawful under applicable food safety provisions of the Act. For conventional foods, this evaluation involves considering whether the ingredient that is the source of the substance is GRAS, approved as a food additive, or authorized by a prior sanction issued by FDA (see 21 CFR 101.70(f)).

The petition asserts that, under 21 CFR 101.14(b)(3)(i), corn oil provides taste, aroma and nutritive value as established by compositional data from the United States Department of Agriculture (USDA) National Nutrient Database, a monograph for corn oil from the Food Chemical Codex, and the presence of linoleic acid, an essential fatty acid. The petition further asserts that corn oil is GRAS because of its long history of widespread use.

In order to receive a possible benefit from consumption of UFAs from corn oil and a reduced risk of CHD, the scientific evidence suggests that the daily minimum amount of UFAs from corn oil that should be consumed in place of foods high in SFAs, while not increasing caloric intake, is approximately 13.3 g of UFAs, which corresponds to about 16 g of corn oil (see Section IV, paragraph F). An intake of 16 g of corn oil provides approximately 144 calories, but because the approved qualified health claim (see Section V) specifies that corn oil is to replace saturated fat in the diet while not increasing caloric intake, an individual's total fat intake should not increase based on the recommendations in the claim.

UFAs can be separated into two categories: monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Based on a lack of information on adverse effects, a Tolerable Upper Intake Level (UL) for MUFAs has not been set by the Institute of Medicine (IOM), and because of insufficient evidence relating low and high intakes of MUFAs and chronic disease, an Acceptable Macronutrient Distribution Range (AMDR) has not been set by the IOM. Median MUFA intake, however, ranges from approximately 25 to 39 g/day for men and 18 to 24 g/day for women (IOM, 2002). According to data from USDA (U.S. Department of Agriculture, 2006), 16 g of corn oil would provide 4.4 g of MUFAs.

The IOM has classified PUFAs into two categories: n-3 PUFAs and n-6 PUFAs. According to data from the USDA (U.S. Department of Agriculture, 2006), the PUFAs in corn oil consist primarily of n-6 PUFAs. Based on a lack of information on adverse effects, a UL for n-6 PUFAs has not been set by the IOM. Lacking safety data upon which to base a UL, the IOM has set an AMDR for n-6 PUFAs (linoleic acid) of five to ten percent of energy. The ten percent of energy "upper boundary" for the AMDR is based on the approximate highest intake levels for individuals in North America (IOM, 2002). The Continuing Survey of Food Intakes by Individuals, 1994-1996, 1998, which represents a wide range in the amount of foods consumed in the U.S., showed that the 99th percentile of n-6 PUFAs intake for all individuals (31.3 g/day) would exceed the sum of the median intake of PUFAs (12 g/day) plus the PUFAs from 16 g of corn oil (8.8 g/day). Because the 99th percentile of intake was used to set the upper boundary of the AMDR for n-6 PUFAs, consuming 16 g of corn oil per day falls well within the boundaries of the AMDR for n-6 PUFA intake.

UFAs are ubiquitous, natural components of the food supply that provide nutritive value to the diet; certain individual UFA components have been approved as direct food additives or authorized for use in foods; and the level of UFAs from corn oil necessary to justify the claim should not increase an individual's total fat intake due to the replacement of SFAs in the diet. Therefore, FDA concludes that under the preliminary requirements of 21 CFR 101.14(b)(3)(ii), the use of UFAs from corn oil at levels necessary to justify the claim is safe and lawful.

II. The Agency's Consideration of a Qualified Health Claim

FDA has identified the following disease endpoints to use in identifying CHD risk reduction for purposes of a health claim evaluation: the incidence of coronary events (myocardial infarction (MI), ischemia), cardiovascular death, coronary artery disease, and atherosclerosis. The following surrogate endpoints for identifying CHD risk reduction for purposes of a health claim evaluation were used: high blood pressure, blood (serum or plasma) total cholesterol, and blood (serum or plasma) low density lipoprotein (LDL)-cholesterol levels.(14) These disease and surrogate endpoints were used to evaluate the potential effects of UFAs from corn oil on CHD risk.

The petition cited 120 publications as evidence to substantiate the relationship for this claim. These publications consisted of: 6 review articles; 7 animal studies; 26 publications from FDA, USDA, National Academy of Sciences, National Institute of Health, World Health Organization and various trade associations; 4 websites; 29 studies that did not evaluate the substance and disease relationship; 1 meta-analysis; 1 speech and 46 articles on human intervention or observational studies that evaluated the substance/disease relationship.

A. Assessment of Background Materials

"Background materials" here refers to review articles, meta-analyses, speeches, and federal and non-profit association reports. Although useful for background information, these materials do not contain sufficient information on the individual studies that they reviewed and, therefore, FDA could not draw any scientific conclusions from this information. FDA could not determine factors such as the study population characteristics or the composition of the products used (e.g., food, dietary supplement). Similarly, the lack of detailed information on studies summarized in these materials prevents FDA from determining whether the studies are flawed in critical elements such as design, conduct of studies, and data analysis. FDA must be able to review the critical elements of a study to determine whether any scientific conclusions can be drawn from it. As a result, the background materials supplied by the petitioner do not provide information from which scientific conclusions can be drawn regarding the substance/disease relationship claimed by the petitioner.

B. Assessment of Animal Studies

FDA also uses animal studies as background information regarding mechanisms of action that might be involved in any relationship between the substance and the disease, and they can also be used to generate hypotheses or to explore a mechanism of action, but they cannot adequately support a relationship between the substance and the disease in humans. FDA did not consider the animal studies submitted with the petition as supportive information about the substance/disease relationship because such studies cannot mimic the normal human physiology that may be involved in the risk reduction of any type of food allergy, nor can the studies mimic the human body's response to the consumption of UFAs from corn oil. Therefore, FDA cannot draw any scientific conclusions from the animal studies regarding UFAs from corn oil and CHD risk reduction.

C. Assessment of the Intervention Studies

FDA identified 44 human intervention studies for its evaluation of the relationship between consumption of corn oil and risk of CHD. Scientific conclusions could not be drawn from 40 of the 44 studies regarding the substance/disease relationship for one or more of the following reasons.

  • Three studies did not measure a validated surrogate endpoint of CHD (i.e., serum total and LDL-cholesterol, blood pressure) (see Appendix 1). Because these studies did not measure a validated surrogate endpoint, scientific conclusions about the relationship between consumption of corn oil and risk of CHD could not be drawn.
  • Seventeen studies did not include a control group consuming SFAs for comparison to the relative effects of corn oil (see Appendix 1). Therefore, it could not be determined if the replacement of SFAs with corn oil reduced the risk of CHD. Hence, scientific conclusions could not be drawn from these studies.
  • In seventeen studies (see Appendix 1) the duration of the study intervention was too short (less than three weeks) to adequately determine if changes in serum total and LDL-cholesterol levels were reflective of the intervention treatment (Kris-Etherton and Dietschy, 1997.). Hence, scientific conclusions could not be drawn from these studies.
  • Two studies (see Appendix 1) did not provide enough information to evaluate the composition of the dietary intervention; therefore, the agency was unable to determine the study's methodological quality rating. Hence, scientific conclusions could not be drawn from these studies.
  • Six studies (see Appendix 1) did not perform statistical analysis between the intervention and control groups. Statistical analysis of the relationship is a critical factor because it provides the comparison between subjects consuming corn compared to those consuming saturated fat to determine whether there is a reduction in CHD risk. When statistics are not performed on the specific substance/disease relationship, it cannot be determined whether there is a difference between the two groups. As a result, because these studies provided no information about whether corn oil reduces the risk of CHD, no scientific conclusions could be drawn from them.

Seven studies (see Appendix 1) were a republication of another study and therefore these studies provided no new scientific evidence to support the substance and disease relationship.

Four articles (three intervention studies) evaluated the relationship between UFAs from corn oil and CHD risk by replacing SFAs with UFAs from corn oil (Ng et al., 1991; Lichtenstein et al., 1993; Lichtenstein et al., 1994; Sirtori et al., 1992). Lichtenstein et al., 1993, and Lichtenstein et al., 1994, outline the same intervention study and use the same subjects. Each of these two articles provides some distinctive details on the study groups which are useful in evaluating the substance/disease relationship; therefore, both publications are useful for the scientific review. All three intervention studies received high to moderate methodological quality ratings.

Lichtenstein et al. (1993 and 1994) conducted a randomized, crossover intervention study in 14 subjects (six males and eight females) from the United States. The study compared a diet high in SFAs from multiple food sources to a diet high in UFAs from corn oil. The subjects were on each diet for 32 days and all of the meals and snacks were provided. The consumption of UFAs from corn oil significantly (p<0.05) reduced serum total and LDL-cholesterol levels compared to the two diets containing high levels of SFAs.

Ng et al. (1991) conducted a randomized double-blind crossover intervention study in 27 subjects (20 males and 7 females) from Malaysia. The subjects received a diet high in SFAs predominantly from coconut oil or high in UFAs from corn oil for five weeks. All of the meals were provided to the subjects. The diet containing UFAs from corn oil significantly (p<0.05) reduced both serum total and LDL-cholesterol levels compared to the diet high in SFAs.

Sirtori et al. (1992) conducted a crossover study in 12 subjects with hypercholesterolemia in Italy. The subjects received a diet high in SFAs for more than one month, followed by a diet high in UFAs from corn oil for six weeks. There were no differences in the serum total and LDL-cholesterol levels between the diets containing SFAs and the UFAs from corn oil.

D. Assessment of the Observational Studies

There were two case-report studies available to the agency on the substance/disease relationship. One case report did not measure a validated surrogate endpoint of CHD (i.e., blood total and LDL-cholesterol, blood pressure) (Albutt and Chance, 1969). Because this study did not measure a validated surrogate endpoint, scientific conclusions about the relationship between consumption of UFAs from corn oil and risk of CHD could not be drawn. The other case report did not include a control group consuming SFAs for comparison to the relative effects of UFAs from corn oil (Carlson and Sterner, 1960). Therefore, it could not be determined if the replacement of SFAs with UFAs from corn oil reduced the risk of CHD. Hence, scientific conclusions could not be drawn from this study.

III. Strength of the Scientific Evidence

Below, the agency rates the strength of the total body of publicly available evidence. The agency conducts this rating evaluation by considering the study type (e.g., intervention, prospective cohort, case-control, cross-sectional), the methodological quality rating previously assigned, the quantity of evidence (number of various types of studies and sample sizes), whether the body of evidence supports a health claim relationship for the U.S. population or target subgroup, whether study results supporting the proposed claim have been replicated,(15) and the overall consistency (16) of the total body of evidence. Based on the totality of the scientific evidence, FDA determines whether such evidence is credible to support the substance/disease (or health-related condition) relationship, and if so, determines the ranking that reflects the level of comfort among qualified scientists that such a relationship is scientifically valid.

Based on the discussion in Section II above, the totality of the scientific evidence in this case includes four reports of three intervention studies (Ng et al., 1991; Lichtenstein et al., 1993; Lichtenstein et al., 1994; Sirtori et al., 1992). Two studies (Ng et al., 1991; Lichtenstein et al., 1993; Lichtenstein et al., 1994) reported that UFAs from corn oil reduced serum total and LDL-cholesterol levels compared to a diet high in SFAs. A study by Sirtori et al. (1992) found no effect of UFAs from corn oil on serum total and LDL-cholesterol levels compared to a diet high in SFAs. All three intervention studies contained small numbers of subjects (12-27 subjects per study).

Based on FDA's review of the strength of the total body of scientific evidence for the proposed claim, FDA concludes that the scientific evidence is credible and supports the substance/disease relationship.(17) However, due to the small number of subjects in the two intervention studies that showed a beneficial relationship and the fact that not all of the studies reported a benefit, FDA believes that the scientific evidence represents a very low level of comfort among qualified scientists that the claimed relationship is scientifically valid. Therefore, FDA intends to consider the exercise of its enforcement discretion for a qualified health claim about UFAs from corn oil on the label or in labeling of corn oil and corn oil products that include a truthful and non-misleading description of the strength of the body of scientific evidence, e.g., "very limited and preliminary scientific evidence suggests."

IV.       Other Enforcement Discretion Factors

Factors that FDA intends to consider in the exercise of its enforcement discretion for qualified health claims about UFAs from corn oil and reduced risk of CHD are discussed below.

For the purpose of this enforcement discretion letter, the following definitions will be used: (1) "corn oil" means products that are essentially pure corn oil and are labeled as such; (2) "vegetable oil blends" means a blend of two or more vegetable oils formulated to contain corn oil; (3) "vegetable oil spread" means margarine (21 CFR 166.110) and margarine-like products formulated to contain corn oil; (4) "dressings for salads" means dressings for salads formulated to contain corn oil; (5) "shortenings" means vegetable oil shortenings formulated to contain corn oil; and (6) "corn oil-containing foods" means all other foods, such as sauces or baked goods, formulated to contain corn oil, excluding corn oil, vegetable oil blends, vegetable oil spreads, dressings for salads, and shortenings. The term "corn oil products" refers to items 2 - 6 in the above list.

A. Total fat, Saturated Fat, and Cholesterol Criteria for CHD-related Health Claims

In regulations authorizing CHD-related health claims, FDA has generally required, with a few exceptions, that foods bearing the claims meet the "low fat" criterion defined by 21 CFR 101.62(b)(2), "low saturated fat" criterion defined by 21 CFR 101.62(c)(2), and the "low cholesterol" criterion defined by 21 CFR 101.62(d)(2) (see authorized claims in 21 CFR §§  101.75, 101.77, 101.81, 101.82, and 101.83). The agency will discuss below how it intends to consider these criteria as factors in deciding whether to exercise its enforcement discretion for a qualified health claim about UFAs from corn oil and CHD risk on corn oil, vegetable oil blends, vegetable oil spreads, dressings for salads, shortenings and corn oil-containing foods. Later in Section IV., B., FDA discusses total fat, saturated fat, and cholesterol content relative to the general requirements for health claims (21 CFR 101.14), specifically, disqualifying levels (21 CFR 101.14(a)(4)).

"Low fat" criterion

FDA has required in the past that foods bearing CHD-related health claims meet the requirement for "low fat" as defined by 21 CFR 101.62(b)(2) as foods that contain less than 3 g of fat per reference amount customarily consumed (RACC), or, for foods with a RACC of less than 30 g or less than 2 tablespoons, per 50 g. The requirement of the "low fat" criterion was first introduced in the dietary lipid and cardiovascular disease proposed rule (56 FR 60727 at 60739; November 27, 1991). FDA stated that, although total fat is not directly related to increased risk for CHD, it may have significant indirect effects. The agency stated that low fat diets facilitate reduction in the intake of saturated fat and cholesterol to recommended levels. Furthermore, the agency noted that obesity is a major risk factor for CHD, and dietary fats, which have more than twice as many calories per gram as proteins and carbohydrates, are major contributors to total caloric intakes. There have been several exceptions to this criterion in the past. Products derived from whole soybeans without added fat are exempted from the "low fat" criterion in the soy protein and CHD health claim (21 CFR 101.82(c)(2)(iii)(C)). In the plant sterol/stanol esters and CHD health claim, FDA does not require foods bearing the claim to meet the "low fat" criterion but requires that total fat level of foods not exceed the total fat disqualifying level (21 CFR 101.14(a)(4)) with an exception for spreads and dressings for salads on a per 50 g basis (21 CFR 101.83(c)(2)(iii)(C)). In not requiring the "low fat" criterion for that claim, FDA noted that the Dietary Guidelines for Americans, 2000 (USDA & DHHS, 2000) recommended choosing a diet that is low in saturated fat and cholesterol and moderate in total fat. Specifically, the Dietary Guidelines recommended moderate amounts of foods high in unsaturated fat with a caution to avoid excess calories. More recently, FDA has exempted from the "low fat" criterion olive oil, vegetable oil spreads, dressings for salads, shortenings, and olive oil-containing foods that bear a MUFAs from olive oil and CHD qualified health claim (http://www.cfsan.fda.gov/~dms/qhcolive.html), as well as canola oil, vegetable oil spreads, dressings for salads, shortenings and canola oil-containing foods that bear a UFAs from canola oil and CHD qualified health claim (http://www.cfsan.fda.gov/~dms/qhccanol.html). In the Dietary Guidelines for Americans, 2005, the recommendation for total fat intake was modified to an intake between 20 to 35 percent of calories, with most fats coming from sources of PUFAs and MUFAs (HHS and USDA, 2005).

Corn oil exceeds the "low fat" criterion because it is essentially entirely fat. Furthermore, FDA intends to exercise enforcement discretion for corn oil products that contain 4 g or more corn oil per RACC (see Section IV, F), and thus would not meet the "low fat" criterion. The scientific studies that suggest a relationship between UFAs from corn oil in replacement of SFAs and reduced risk of CHD used corn oil in cooking and various food combinations. The UFAs from corn oil and CHD qualified health claim will inform consumers that they may lower their risk of CHD by consuming UFAs from corn oil and corn oil products in place of SFAs, while not increasing caloric intake. FDA believes that this type of dietary information will help consumers maintain healthy dietary practices by providing consumers with information that can facilitate reductions of saturated fat and cholesterol intake since corn oil contains no cholesterol and less saturated fat than other fat sources. Corn oil is a plant food and does not contain cholesterol. Furthermore, FDA concurs with current dietary guidelines that consuming diets low in saturated fat and cholesterol is more important in reducing CHD risk than consuming diets low in total fat. Therefore, FDA has decided not to consider, in the exercise of its enforcement discretion, that corn oil, vegetable oil blends, vegetable oil spreads, dressings for salads, shortenings, and corn oil-containing foods that bear a UFAs from corn oil and CHD qualified health claim meet the "low fat" criterion.

"Low saturated fat" criterion

"Low saturated fat," as defined by 21 CFR 101.62(c)(2), means that the food must contain less than 1 g of saturated fat per RACC and not more than 15% of calories from saturated fat. A RACC of corn oil contains approximately 1.8 g of saturated fat and 13% of calories from saturated fat.

Corn oil does not meet the definition of a "low saturated fat" food. Furthermore, FDA intends to exercise enforcement discretion for corn oil products that contain 4 g or more corn oil per RACC (see Section IV., F.). Four g of corn oil contain approximately 0.5 g of SFAs, and corn oil products that contain this amount of SFAs from corn oil alone are likely to exceed the "low saturated fat" criterion. The scientific studies that suggest a relationship between UFAs from corn oil in replacement of SFAs and reduced risk of CHD used corn oil in cooking and various food combinations. The UFAs from corn oil and CHD qualified health claim will inform consumers that they may lower their risk of CHD by consuming UFAs from corn oil in place of SFAs, while not increasing caloric intake. FDA believes that this type of dietary information will help consumers maintain healthy dietary practices by providing consumers with information that can facilitate reductions of saturated fat and cholesterol intake, since corn oil contains no cholesterol and less saturated fat than other fat sources. Therefore, FDA has decided not to consider, in the exercise of its enforcement discretion, that corn oil, vegetable oil blends, vegetable oil spreads, dressings for salads, shortening, and corn-oil containing foods that bear a UFAs from corn oil and CHD qualified health claim meet the "low saturated fat" criterion.

FDA does, however, believe that it would be appropriate to consider, as a factor in the exercise of its enforcement discretion, that corn oil when labeled with the UFAs from corn oil and CHD qualified health claim place the statement: "See nutrition information for saturated fat content" immediately adjacent to the claim with no intervening material and in the same contrast as the claim itself. Furthermore, FDA believes that it would be appropriate to consider, as a factor in the exercise of its enforcement discretion, that corn oil products that bear the UFAs from corn oil and CHD qualified health claim and do not meet the "low saturated fat" criteria also place the statement: "See nutrition information for saturated fat content" immediately adjacent to the claim with no intervening material and in the same contrast as the claim itself.

Although FDA does not intend to consider the "low saturated fat" criterion as a factor in its exercise of enforcement discretion, FDA does intend to consider as a factor in its enforcement discretion that foods that are eligible to bear the claim, as stated later in this letter, meet certain elements of the saturated fat disqualifying criteria in 21 CFR 101.14(a)(4). This will ensure that foods bearing the claim will not contain excessive amounts of SFAs.

"Low cholesterol" criterion

Like all plant-based foods, corn oil and vegetable oil blends do not contain cholesterol, and therefore, a low cholesterol nutrient content requirement would not limit the use of a qualified health claim for UFAs from corn oil and CHD risk to be used on the label or in labeling of corn oil and vegetable oil blends. Several vegetable oil spreads, dressings for salads, shortenings and corn oil-containing foods may contain cholesterol from sources other than corn oil. Dietary cholesterol is known to increase serum total and LDL-cholesterol levels, which is a risk factor for CHD. Therefore, FDA intends to consider, as a factor in its exercise of enforcement discretion, that corn oil, vegetable oil blends, vegetable oil spreads, dressings for salads, shortenings and corn oil-containing foods labeled with a UFAs from corn oil and CHD qualified health claim meet the "low cholesterol" criteria as defined in 21 CFR 101.62(d)(2).

B. Disqualifying Nutrient Levels

Under the general requirements for health claims (21 CFR 101.14(e)(3)), a food may not bear a health claim if that food exceeds any of the disqualifying nutrient levels for total fat, saturated fat, cholesterol, or sodium established in § 101.14(a)(4). Disqualifying total fat levels for individual foods are above 13.0 g per RACC, per label serving size, and, for foods with a RACC of 30 g or less or 2 tablespoons or less, per 50 g. Disqualifying saturated fat levels for individual foods are above 4.0 g per RACC, per label serving size, and, for foods with a RACC of 30 g or less or 2 tablespoons or less, per 50 g. Disqualifying cholesterol levels for individual foods are above 60 mg per RACC, per label serving size, and, for foods with a RACC of 30 g or less or 2 tablespoons or less, per 50 g. Disqualifying sodium levels for individual foods are above 480 mg per RACC, per label serving size, and, for foods with a RACC of 30 g or less or 2 tablespoons or less, per 50 g.

The general requirements for health claims also provide for FDA to authorize a health claim for a food despite the fact that a nutrient in the food exceeds the disqualifying level, if the agency finds that such a claim will assist consumers in maintaining healthy dietary practices (21 CFR 101.14(e)(3)). In such cases, the label must also bear a disclosure statement that complies with 21 CFR 101.13(h), highlighting the nutrient that exceeds the disqualifying level.

The application of these regulatory provisions to UFAs from corn oil and CHD qualified health claims on corn oil, vegetable oil blends, vegetable oil spreads, dressings for salads, shortenings and corn oil-containing foods are discussed below. FDA does not intend to exercise its enforcement discretion for any type of meal product (21 CFR 101.13(l)) or main dish product (21 CFR 101.13(m)), as none of the scientific evidence that suggested a relationship between UFAs from corn oil in replacement of SFAs and reduced risk of CHD used these types of foods.

"Total fat" disqualifying levels

In the previous section (Section IV., A.), FDA explained that the agency has decided not to consider, in the exercise of its enforcement discretion, that corn oil, vegetable oil spreads, dressings for salads, shortenings, and corn oil-containing foods that bear a UFAs from corn oil and reduced risk of CHD qualified health claim meet the "low fat" criterion as defined by 21 CFR 101.62(b)(2). FDA notes that there is a large difference in the amount of total fat between the "low fat" criterion and the disqualifying total fat level. For example, the "low fat" criterion for individual foods is equal to or less than 3 g per RACC and per 50 g if the RACC is 30 g or less or 2 tablespoons or less. The disqualifying total fat level for individual foods is above 13 g per RACC, per label serving size and per 50 g if the RACC is 30 g or less or 2 tablespoon or less. Thus, there is a difference of 10 g for individual foods between the "low fat" criterion and the disqualifying total fat level.

Corn oil and vegetable oil blends exceed the disqualifying total fat level because they are essentially entirely fat. However, the UFAs from corn oil and CHD qualified health claim will inform consumers that they might lower their risk of CHD by consuming foods containing UFAs from corn oil in place of similar foods high in SFAs, while not increasing caloric intake. FDA believes that this type of dietary information will help consumers maintain healthy dietary practices by providing consumers with information that can facilitate reductions of saturated fat and cholesterol intake without increasing total calorie consumption. Furthermore, FDA concurs with the current Dietary Guidelines for Americans, 2005 that consuming diets low in saturated fat and cholesterol is more important in reducing CHD risk than consuming diets low in total fat. Therefore, FDA has decided not to consider, in the exercise of its enforcement discretion, that corn oil and vegetable oil blends meet the disqualifying total fat level to bear a UFAs from corn oil and CHD qualified health claim.

The scientific studies that suggest a relationship between UFAs from corn oil in replacement of SFAs and reduced risk of CHD used corn oil incorporated into various food combinations. Products labeled as margarine (21 CFR 166.110) must contain at least 80% vegetable oil by weight(18) and shortenings are essentially all fat. Foods that contain these levels of fat will necessarily exceed the disqualifying total fat level. If FDA imposed the disqualifying total fat level on these products it would prevent these products from bearing the claim. Corn oil-containing foods are generally not vehicles for delivering fat. However, given that FDA intends to exercise enforcement discretion for corn oil products that contain 4 g or more corn oil per RACC, and the food may be formulated with additional corn oil and still contribute to the claimed effect, FDA concludes that applying the disqualifying levels of total fat to corn oil-containing foods would unduly limit the foods that could contribute to beneficial effects from bearing the claim. Further, FDA has concluded that foods labeled with a UFAs from corn oil and CHD qualified health claim would assist consumers in maintaining healthy dietary practices, since the claim provides consumers with information to select products that have less SFAs and more UFAs while not increasing their total caloric intake. Therefore, FDA has decided not to consider, in the exercise of its enforcement discretion, that vegetable oil spreads, dressings for salads, shortenings and corn-oil containing foods that bear a UFAs from corn oil and CHD qualified health claim meet the total fat disqualifying level. However, FDA believes that it is appropriate to consider as a factor in the exercise of its enforcement discretion that when the total fat level in the food exceeds the disqualifying level as defined by 21 CFR 101.14(a)(4), the disclosure statement (i.e., See nutrition information for total fat content) must comply with 21 CFR 101.13(h).

"Saturated fat" disqualifying level

In the previous section (Section IV., A.), FDA explained that the agency has decided not to consider, in the exercise of its enforcement discretion, that corn oil, vegetable oil bends, vegetable oil spreads, dressings for salads, shortenings, and corn oil-containing foods that bear a UFAs from corn oil and reduced risk of CHD qualified health claim meet the "low saturated fat" criterion as defined by 21 CFR 101.62(b)(2). FDA notes that there is a difference in the amount of saturated fat between the "low saturated fat" criterion and the disqualifying saturated fat level. For example, the "low saturated fat" criterion for individual foods is equal to or less than 1 g per RACC and less than 15% of the calories from saturated fat. The disqualifying saturated fat level for individual foods is above 4 g per RACC, per label serving size and per 50 g and if the food has a RACC of 30 g or less or 2 tablespoon or less, the disqualifying saturated fat level is above 4g per 50 g.

Corn oil has 1.8 g of saturated fat per RACC, and because it has a small RACC (i.e., 30 g or less) corn oil will exceed the disqualifying saturated fat level based on the 50 gram-criterion (corn oil contains about 6.5 g of saturated fat per 50 g). Margarine (21 CFR 166.110) is at least 80% vegetable oil by weight. Vegetable oil blends and shortening are essentially all fat. All three products have a RACC of 30 g or less. If margarine and shortening is formulated with corn oil as the only vegetable oil source, such products would exceed the 50 gram-criterion for the disqualifying saturated fat level. Vegetable oil blends, if formulated to contain at least 4 g corn oil per serving, would likely exceed the 50 gram-criterion for the disqualifying saturated fat level. As mentioned above, the general requirements for health claims provide for FDA to authorize a health claim for a food despite the fact that a nutrient in the food exceeds the disqualifying level, if the agency finds that such a claim will assist consumers in maintaining healthy dietary practices (21 CFR 101.14(e)(3)). FDA believes that a qualified health claim about UFAs from corn oil and a reduced risk of CHD would assist consumers in maintaining healthy dietary practices, since the information in the claim informs consumers that replacing SFAs in the diet with UFAs from corn oil may reduce the risk of CHD. If FDA did impose the 50 gram-criterion for the disqualifying saturated fat level on vegetable oil blends, vegetable oil spreads and shortenings it would prevent these major corn oil products from bearing the claim. Therefore, FDA has decided not to consider, in the exercise of its enforcement discretion, that corn oil, vegetable oils blends, vegetable oil spreads, and shortenings that bear a UFAs from corn oil and CHD qualified health claim meet the 50 gram-criterion for the disqualifying saturated fat level. FDA does intend to consider, as a factor in the exercise of its enforcement discretion that corn oil, vegetable oil blends, vegetable oil spreads or shortenings labeled with the UFAs from corn oil and CHD qualified health claim meet the 4 g per RACC criterion for the disqualifying saturated fat level.

On the other hand, dressings for salads may be formulated with varying amounts of vegetable oil. French dressings (21 CFR 169.115) must contain at least 35% vegetable oil by weight; a product formulated entirely with corn oil and no other source of fat will contain about 2.3 g saturated fat per 50 g. Unless there were other sources of saturated fat in the dressing for salad, a dressing formulated with up to 50% corn oil should be able to meet the 50 gram-criterion for the disqualifying saturated fat level. FDA believes that not considering the 50 gram-criterion for the disqualifying saturated fat level for dressings for salads would not assist consumers in maintaining healthy dietary practices. Thus, FDA does intend to consider, as a factor in the exercise of its enforcement discretion that dressings for salads, when labeled with the UFAs from corn oil and CHD qualified health claim, meet the 50 gram-criterion for the disqualifying saturated fat level.

Corn oil-containing foods are generally not vehicles for delivering fat, unlike corn oil, vegetable oil blends, vegetable oil spreads, and shortenings, and contain many other ingredients that may contribute to or detract from a healthy diet. If formulated to contain 4 g corn oil per serving, a corn oil-containing food would contain about 0.5 g of saturated fat, which is below the disqualifying saturated fat level of 4 g per RACC (most corn oil-containing foods have a RACC greater than 30 g). Unless there were other sources of saturated fat in the corn oil-containing food, the food should be able to meet the 50 gram-criterion for the disqualifying saturated fat level. FDA believes that excusing corn oil-containing foods from the 50 gram-criterion for the disqualifying saturated fat level would not assist consumers in maintaining healthy dietary practices. Thus, FDA does intend to consider, as a factor in the exercise of its enforcement discretion for corn oil-containing foods labeled with a UFAs from corn oil and CHD qualified health claim, that such products meet the disqualifying saturated fat level as specified in 21 CFR 101.14(a)(4).

"Cholesterol" disqualifying level

FDA intends to consider, as a factor in the exercise of its enforcement discretion for corn oil and corn oil products labeled with a UFAs from corn oil and reduced risk of CHD qualified health claim, that such products meet the disqualifying cholesterol level as specified in 21 CFR 101.14(a)(4).

"Sodium" disqualifying level

FDA intends to consider, as a factor in the exercise of its enforcement discretion for corn oil and corn oil products labeled with a UFAs from corn oil and reduced risk of CHD qualified health claim, that such products meet the disqualifying sodium level as specified in 21 CFR 101.14(a)(4).

C. 10 Percent Minimum Nutrient Content Requirement

Under the general requirements for health claims, a conventional food may not bear a health claim unless it contains, prior to any nutrient addition, at least 10% of the Daily Value for vitamin A, vitamin C, iron, calcium, protein, or dietary fiber per RACC (21 CFR 101.14(e)(6)). The purpose of this provision is to prevent the use of health claims on foods with minimal nutrition value.

FDA has previously exempted certain foods from the 10% minimum nutrient content when it has been determined that such exemptions could assist consumers in maintaining healthy dietary practices. For example, the agency exempted spreads and dressings for salads from this requirement in the plant sterol/stanol esters and CHD health claim interim final rule (65 FR 54868 at 54711). FDA also considered a qualified health claim for walnuts and a reduced risk of CHD, even though walnuts did not meet the minimum 10% nutrient requirement (http://www.cfsan.fda.gov/~dms/qhcnuts3.html). In addition, FDA exempted olive oil and olive oil-containing dressings for salads and shortenings from the 10% minimum nutrient requirement for the MUFAs from Olive Oil and CHD Qualified Health Claim (http://www.cfsan.fda.gov/~dms/qhcolive.html) and canola oil and canola oil-containing dressings for salads and shortenings from the 10% minimum nutrient requirement for the UFAs from Canola Oil and CHD Qualified Health Claim (http://www.cfsan.fda.gov/~dms/qhccanol.html).

Corn oil, vegetable oil blends, certain vegetable oil spreads, dressings for salads, and shortenings do not meet the 10% minimum nutrient content requirement of 21 CFR 101.14(e)(6). However, corn oil, vegetable oil blends, certain vegetable oil spreads, dressings for salads and shortenings provide UFAs that can be used in place of SFAs in the diet. FDA believes that information to help consumers reduce saturated fat and cholesterol consumption would assist consumers in maintaining healthy dietary practices. If FDA did impose the 10% minimum nutrient content requirement for these food categories, it would prevent these major corn oil products from bearing the claim. Therefore, FDA has decided not to consider, in the exercise of its enforcement discretion, that corn oil, vegetable oil blends, dressings for salads, and shortenings that bear a UFAs from corn oil and CHD qualified health claim meet the 10% minimum nutrient content requirement.

Margarine (21 CFR 166.110), margarine substitutes, and margarine products labeled under 21 CFR 130.10 must contain more than 10% of the RDA for vitamin A and most commercially available margarine-like products also contain more than 10% of the RDA for vitamin D. Therefore, FDA intends to consider, in the exercise of its enforcement discretion, that vegetable oil spreads labeled with a UFAs from corn oil and CHD qualified health claim meet the 10% minimum nutrient content requirement.

FDA also considers it appropriate that corn oil-containing foods meet the 10% minimum nutrient content requirement. Corn oil-containing foods are generally not vehicles for delivering fat, unlike corn oil, vegetable oil blends, vegetable oil spreads, and shortenings, and contain many other ingredients that may contribute to or detract from a healthy diet. Thus, FDA believes that such foods should meet the 10% minimum nutrient content requirement. FDA believes that several corn oil-containing foods can be formulated to contain enough corn oil to be eligible for the claim and meet the 10% minimum nutrient content requirement. Therefore, FDA does intend to consider, as a factor in the exercise of its enforcement discretion, that corn oil-containing foods labeled with a UFAs from corn oil and CHD claim meet the 10% minimum nutrient content requirement.

D. Trans Fat Levels in Foods Eligible for the Claim

The petitioner requested that corn oil-containing products be required to contain no more than one gram of trans fatty acids per RACC. Currently, there is a lack of scientific evidence to establish a Daily Value for trans fatty acids but it is well known that trans fatty acids increase serum total and LDL-cholesterol levels (IOM, 2002). FDA has issued an advance notice of proposed rulemaking (ANPRM) to solicit comments on establishing trans fat nutrient content claims; to establish qualifying criteria for trans fat in current nutrient content claims for SFAs and cholesterol, lean and extra lean claims and health claims that contain a message about cholesterol-raising lipids; and, in addition, to establish disclosure and disqualifying criteria to help consumers make healthy food choices. The agency also solicited comment on whether it should consider statements about trans fat, either alone or in combination with saturated fat and cholesterol, as a footnote in the Nutrition Facts label or as a disclosure statement in conjunction with claims (68 FR 41507; July 11, 2003). FDA intends to consider the petitioner's request, that corn oil products contain no more than 1 gram trans fatty acids per RACC, in the context of the agency's activities related to the ANPRM. FDA believes that it would be premature to consider, as a factor in the exercise of its enforcement discretion, a specific nutrient disqualifying level for a UFAs from corn oil and CHD risk reduction qualified health claim, until it has evaluated the merits of a level based on the data and information it is currently evaluating in the context of the ANPRM. Therefore, FDA declines the petitioner's request to consider a trans fat qualifying level as a factor in the exercise of its enforcement discretion for this qualified health claim.

E. Context of the total daily diet

A provision of the general requirements for health claims requires that a health claim enable the public to comprehend the information provided and to understand the relative significance of such information in the context of the total daily diet (see § 403 (r)(3)(B)(iii) of the Act (21 U.S.C. § 343(r)(3)(B)(iii)) and 21 CFR 101.14(d)(2)(v)). For health claims pertaining to CHD that are authorized by regulation, FDA requires information relative to a total diet low in saturated fat and cholesterol because this is an essential part of dietary guidance for reducing the risk of CHD. However, the information in the UFAs from corn oil and CHD qualified health claim will provide consumers a method to reduce saturated fat and cholesterol intake, i.e., by consuming UFAs from corn oil and corn oil products in place of SFAs. Further, the scientific studies did not suggest that the intervention diet must be low in cholesterol (< 300 mg per day) in order to reduce the risk of CHD. Thus, FDA will not consider, as a factor in the exercise of its enforcement discretion, the use of a phrase or sentence relating to diets low in saturated fat and cholesterol.

F. Minimum Effective Amount of Corn Oil in Foods Eligible for the Claim

The general requirements for health claims require that, if the claim is about the effects of consuming the substance at other than decreased dietary levels, the level of the substance must be sufficiently high and in the appropriate form to justify the claim. Where no definition of high has been established, the claim must specify the daily dietary intake necessary to achieve the claimed effect (see 21 CFR 101.14(d)(2)(vii)).

The agency determined the minimum effective amount of UFAs from corn oil necessary to substitute in place of SFAs by first calculating the difference in the amount of UFAs, in grams,(19) between the high-UFA and high-SFA diets in the studies that demonstrated a reduction in serum total and LDL-cholesterol levels. This limited evidence suggests that the lowest amount of UFAs needed to replace SFAs that may result in significant reduction in serum total and LDL-cholesterol is 13.3 g of UFAs. Corn oil contains approximately 82% UFAs (USDA Nutrient Database for Standard Reference, Release 19). Consuming 16 g of corn oil per day provides 13.3 g of UFAs and 2.1 g of SFAs. Sixteen grams of corn oil is roughly one tablespoon or one RACC.

To determine the minimum amount of corn oil necessary to be in a food, the agency considered the number of eating occasions at which consumers might consume corn oil or corn oil products and the number of potential foods that could be labeled with a qualified health claim about UFAs from corn oil and CHD. Foods in these categories can be a part of every eating occasion, and the typical American eating pattern is three meals and one snack per day. Therefore, the determination of the qualifying level of UFAs from corn oil for a food to bear the claim will be based on four eating occasions per day. The minimum effective dose (16 g corn oil per day) based on four eating occasions per day of corn oil or the five categories of corn oil products is 4 g of corn oil per RACC per day. For consumers to know the amount of corn oil in a product, FDA intends to consider, as a factor in the exercise of its enforcement discretion, that foods that bear a UFAs from corn oil and CHD qualified health claim state the amount of corn oil per serving in the claim.

V. Conclusions

Based on FDA's consideration of the scientific evidence submitted with your petition, and other pertinent scientific evidence, FDA concludes that there is sufficient evidence for a qualified health claim, provided that the claim is appropriately worded so as to not mislead consumers. Thus, FDA intends to consider exercising enforcement discretion for the following qualified health claim:

"Very limited and preliminary scientific evidence suggests that eating about 1 tablespoon (16 grams) of corn oil daily may reduce the risk of heart disease due to the unsaturated fat content in corn oil. FDA concludes that there is little scientific evidence supporting this claim. To achieve this possible benefit, corn oil is to replace a similar amount of saturated fat and not increase the total number of calories you eat in a day. One serving of this product contains [x] grams of corn oil."

The appropriate disclosure statement "See nutrition information for total fat content." must be included on the label and comply with 21 CFR 101.13(h).

FDA intends to consider exercising enforcement for the above qualified health claim when all other factors for enforcement discretion identified in Section IV of this letter are met.

Please note that scientific information is subject to change, as are consumer consumption patterns. FDA intends to evaluate new information that becomes available to determine whether it necessitates a change in this decision. For example, scientific evidence may become available that will support significant scientific agreement or that will no longer support the use of a qualified health claim, or that raises safety concerns about that substance that is the subject of the claim.

Sincerely,

Michael M. Landa
Deputy Director for Regulatory Affairs
Center for Food Safety and Applied Nutrition


Appendix 1

No Saturated Fat Group

  • Childs et al., 1981
  • Grundt et al, 2004
  • Howell et al., 1998
  • Insull et al., 1994
  • Kohlmeier et al., 1988
  • Rose et al., 1965
  • Sirtori et al., 1986
  • Wagner et al., 2001
  • Chance et al., 1969
  • Engelberg, 1957
  • Grande et al., 1958
  • Tobian and Tuna, 1958
  • Watson, 1963
  • Carlson and Sterner, 1960
  • Ostlund et al., 2002
  • Tall et al., 1982
  • Haust and Beveridge, 1963

Duration of study less than 3 weeks

  • Howell et al., 1998
  • Laine et al., 1982
  • Wagner et al., 2001
  • Wardlaw et al., 1990
  • Fisher et al., 1983
  • Haust and Beveridge, 1963
  • Horlick L, 1959
  • Imaki et al., 1989
  • Kaplan et al., 1965
  • Kingsbury et al., 1961
  • Mitchell et al., 1989
  • Snook et al., 1985
  • Zanni et al., 1987
  • Ostlund et al., 2002
  • Schlierf et al., 1979
  • Tall et al., 1982
  • Zampelas et al., 1994

Republication

  • Lichtenstein et al., 1993
  • Jones et al., 1994
  • Lichtenstein et al., 1994a
  • Lichtenstein et al., 1994b
  • Cuchel et al., 1996
  • Schwab et al., 1998
  • Schwab et al., 2000

No Statistics

  • Engelberg, 1957
  • Rhoads et al., 1959
  • Keys et al., 1957
  • Horlick L, 1959
  • Kaplan et al., 1965
  • Kingsbury et al., 1961

Not enough information in article to evaluate diet

  • Lloyd et al., 1962
  • Keys et al., 1957

Used non validated surrogate endpoints

  • Albutt and Chance, 1969
  • Ostlund et al., 2002
  • Mitchell et al., 1989

References

Albutt, E.C and Chance, G.W. "Fasting plasma cholesterol esters in diabetic children consuming corn oil." American Journal of Clinical Nutrition, 22: 1552-54, 1969.

Carlson, L.A. and Sterner, G. "Essential hypercholesterolaemia in two siblings effect of corn oil on serum lipids." ACTA Paedieatrica, 49: 168-174, 1960.

Federal Judicial Center, Reference Manual on Scientific Evidence, Second Edition, 2000, pp. 93, 343.

Hill A.B. "The environment and disease: association or causation?" Proc R Soc Med, 58:295-300, 1965.

IOM (Institute of Medicine of the National Academies), Dietary Supplements: A Framework for Evaluating Safety, Chapter 7, Categories of Scientific Evidence - In Vitro Data. National Academy Press, Washington, D.C., 2005.

IOM (Institute of Medicine, National Academy of Sciences), Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids, Chapter 8, Dietary Fats: Total Fat and Fatty Acids.  National Academy Press, Washington, D.C., 2002.

Kris-Etherton, PM and Dietschy J. "Design criteria for studies examining individual fatty acid effects on cardiovascular disease risk factors: human and animal studies." American Journal of Clinical Nutrition, 65: 1590S-6S, 1997.

Lichtenstein, A.H., Ausman, L.M., Carrasco, W., Jenner, J.L., Gualtieri, L.J., Goldin, B.R., Ordovas, M. and Schaefer, E.J., "Effects of canola, corn, and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a National Cholesterol Education Program Step 2 Diet." Arteriosclerosis and Thrombosis, 13:1533-1542, 1993.

Lichtenstein, A.H., Ausman, L.M., Carrasco, W., Jenner, J.L., B.R., Ordovas, M. and Schaefer, E.J., "Hypercholesterolemic effect of dietary cholesterol in diets enriched in polyunsaturated and saturated fat." Arteriosclerosis and Thrombosis, 14:168-175, 1994.

Ng, T.K.W., Hassan, K., Lim, J.B., Lye, M.S., Ishak, R. "Nonhypercholesterolemic effects of a palm-oil diet in Malaysian volunteers." American Journal of Clinical Nutrition, 53: 1015S-20S, 1991.

Sirtori, C.R., Gatti, E., Tremoli, E., Galli, C., Gianfranceschi, G., Franceschini, G., Colli, S., Maderna, P., Marangoni, R., Perego, P., and Stragliotto, E. "Olive oil, corn oil, and n-3 fatty acids differently affect lipids and lipoproteins, platelets, and superoxide formation in type II hypercholesterolemia." American Journal of Clinical Nutrition, 56: 113-22, 1992.

Spilker, B. Guide to Clinical Studies. Raven Press, New York, New York, 1991, pp. 59-64.

U.S. Department of Agriculture, Agricultural Research Service. 2006. USDA Nutrient Database for Standard Reference, Release 19. Nutrient Data Laboratory Home Page, http://www.ars.usda.gov/nutrientdata.

U.S. Department of Health and Human Services (HHS) and U.S. Department of Agriculture (USDA), Dietary Guidelines for Americans, 2000.

U.S. Department of Health and Human Services (HHS) and U.S. Department of Agriculture (USDA), Dietary Guidelines for Americans, 2005.

Wilson, E.B. (1990). An Introduction to Scientific Research, (Toronto, Canada: General Publishing Company), pp. 46-48.


Notes

(1) "Interim Procedures for Qualified Health Claims in the Labeling of Conventional Human Food and Human Dietary Supplements" (July 10, 2003). [http://www.cfsan.fda.gov/~dms/nuttf-e.html]

(2) See Whitaker v. Thompson, 353 F.3d 947, 950-51 (D.C. Cir.) (upholding FDA's interpretation of what constitutes a health claim), cert. denied, 125 S. Ct. 310 (2004).

(3) See guidance entitled "Interim Evidence-based Ranking System for Scientific Data," July 10, 2003. [http://www.cfsan.fda.gov/~dms/hclmgui4.html]

(4) For brevity, "disease" will be used as shorthand for "disease or health-related condition" in the rest of the section.

(5) In an intervention study, subjects similar to each other are randomly assigned to either receive the intervention or not to receive the intervention, whereas in an observational study, the subjects (or their medical records) are observed for a certain outcome (i.e., disease). Intervention studies provide the strongest evidence for an effect. See guidance entitled "Significant Scientific Agreement in the Review of Health Claims for Conventional Foods and Dietary Supplements," December 22, 1999. [http://www.cfsan.fda.gov/~dms/ssaguide.html]

(6) A meta-analysis is the process of systematically combining and evaluating the results of clinical trials that have been completed or terminated (Spilker, 1991).

(7) Review articles summarize the findings of individual studies.

(8) Other examples include book chapters, abstracts, letters to the editor, and committee reports.

(9) See supra, note 3.

(10) Replication of scientific findings is important for evaluating the strength of scientific evidence (An Introduction to Scientific Research, E. Bright Wilson Jr., pages 46-48, Dover Publications, 1990).

(11) Consistency of findings among similar and different study designs is important for evaluating causation and the strength of scientific evidence (Hill A.B. The environment and disease: association or causation? Proc R Soc Med, 58:295-300, 1965.); See also Evidence Report/Technology Assessment No. 47, Systems to Rate the Strength of Scientific Evidence, Agency for Healthcare Research and Quality, defining "consistency" as "the extent to which similar findings are reported using similar and different study designs." [http://www.ahrq.gov/clinic/epcsums/strengthsum.htm#Contents]

(12) See supra, note 3.

(13) There is no scientific evidence that phytosterols in corn oil that replace a similar amount of saturated fatty acids (SFAs) provide the claimed health benefit (i.e., lowering of serum total and LDL-cholesterol levels). Thus, for this petition, the agency does not address the question of whether phytosterols in corn oil are a component of food and thus meet the definition of substance in the health claim regulations.

(14) National Heart, Blood and Lung Institute (NHLBI), Heart and Blood Vessel Diseases (http://www.nhlbi.nih.gov/health/dci/Diseases/Atherosclerosis/Atherosclerosis_WhatIs.html) and National Cholesterol Education Program, Page 3 (U.S. Department of Health and Human Services, 2001, http://www.nhlbi.nih.gov/guidelines/cholesterol/atp_iii.htm).

(15) See supra, note 10.

(16) See supra, note 11.

(17) The scientific evidence supporting the proposed claims shows a benefit in serum total and LDL-cholesterol levels, which are surrogate endpoints for the development of CHD. A common usage term for CHD is "heart disease," and so the terms "coronary heart disease" and "heart disease" are considered synonymous for use with authorized SSA health claims (see 21 CFR §§ 101.75(c)(2)(B), 101.81(c)(2)(B), 101.82(c)(2)(B), 101.83(c)(2)(C)) that pertain to a reduction in CHD risk.

(18) FDA recognizes that margarine-like products do not have to meet the fat criteria as defined in the standards of identity for margarine (21 CFR 166.110).

(19) The amount of UFAs in grams was calculated by multiplying the percent of energy by 2000 kcal and converting to grams.