||Last Updated: Nov 12th, 2006 - 20:38:00
Editor's note: Those who do not trust genetically modified crops should know that canola is one of the crops in the US that have been genetically modified. Unsaturated fatty acids, particularly polyunsaturated fatty acids can be decomposed forming toxic substances when subjected to high temperature during food processing.
Qualified Health Claims: Letter of Enforcement Discretion -
Unsaturated Fatty Acids from Canola Oil and Reduced Risk of Coronary Heart Disease
(Docket No. 2006Q-0091)
Guy H. Johnson, Ph.D.
Johnson Nutrition Solutions LLC
8711 Swan Street
Kalamazoo, MI 49009
RE: Qualified Health Claim Petition – Unsaturated Fatty Acids from Canola Oil and Reduced Risk of Coronary Heart Disease (Docket No. 2006Q-0091)
Dear Dr. Johnson:
This letter responds to the health claim petition dated January 7, 2006, submitted to the Food and Drug Administration (FDA or the agency) by the U.S. Canola Association pursuant to Section 403(r)(4) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 343(r)(4)). You are listed in the petition as the person to whom correspondence should be addressed. The petition requested that the agency authorize a qualified health claim characterizing the relationship between the consumption of unsaturated fatty acids (UFAs) from canola oil and a reduction in risk of coronary heart disease (CHD). This petition proposed as a model qualified health claim:
"Canola oil (19 grams – about 1 ½ tablespoons per day) may reduce the risk of coronary heart disease due to its unsaturated fat content, according to supportive but not conclusive research. Canola oil should replace a similar amount of saturated fat in the diet without increasing calories."
FDA filed the petition on March 2, 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 claim unconditionally. FDA considered the comment in its evaluation of this petition.
This letter sets forth the basis of FDA's determination that the current evidence for the proposed health claim 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 UFAs from canola oil and a reduced risk of 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.(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 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 UFAs from canola oil as the substance that is the subject of the proposed claim. UFAs are fat components that occur naturally in many foods. Therefore, the agency concludes that UFAs from canola oil, identified in the petition, are a component of food and thus meets the definition of substance in the health claim regulation (21 CFR 101.14(a)(2)).
Canola oil, also known as low erucic acid rapeseed (LEAR) oil, is the fully refined, bleached, and deodorized edible oil obtained from certain varieties of Brassica Napus or B. Campestris of the family Cruciferae. The plant varieties are those producing oil-bearing seeds with a low erucic acid content (21 CFR 184.1555(c)(1)).
FDA has not been petitioned to authorize a health claim or exercise its enforcement discretion for a qualified health claim for any vegetable oil high in UFAs, except for canola oil (LEAR oil). However, vegetable oil manufacturers and others may petition the agency to allow for the use of claims for vegetable oils high in UFAs relative to saturated fatty acids (SFAs). Health claim petitions must include all of the information required in 21 CFR 101.70, including scientific evidence that supports the relationship between a substance and a disease or health-related condition.
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 has identified CHD as the disease that is the subject of the proposed qualified health claim. The agency concludes that CHD is a disease and therefore the petitioner has satisfied the requirement in 21 CFR 101.14(a)(5).
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 the levels necessary to justify the claim must be demonstrated by the proponent of the claim, to FDA's satisfaction, to be safe and lawful under the 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 UFAs are ubiquitous, natural components of the food supply that are safe and lawful. The petition also asserts, under 21 CFR 101.14(b)(3)(i), that UFAs provide nutritive value to the diet by serving as a source of energy and, furthermore, certain individual UFAs contribute technical effects. Examples of UFAs with technical effects are oleic acid, which has been authorized as a direct food additive for use as a lubricant, binder, and a defoaming agent (21 CFR 172.860), and linoleic acid, which has been authorized for use in foods as a flavoring agent, adjuvant, and nutrient supplement (21 CFR 184.1065). FDA agrees that UFAs are ubiquitous, natural components of the food supply that provide nutritive value to the diet and that certain individual UFAs contribute technical effects.
In order to receive a possible benefit from consumption of UFAs from canola oil and a reduced risk of CHD, the scientific evidence suggests that the daily minimum amount of UFAs from canola oil that should be consumed in place of foods high in SFAs, while not increasing caloric intake, is approximately 17.7 g of UFAs, which corresponds to about 19 g of canola oil (see Section IV, paragraph F). An intake of 19 g of canola oil provides approximately 171 calories but because the qualified health claim specifies that canola 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) was not provided 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, 2005), 19 g of canola oil would provide 11.2 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, 2005), the PUFAs in canola oil consist solely of n-6 PUFAs. Based on a lack of information on adverse effects, a UL has not been set for n-6 PUFAs. Lacking safety data upon which to base a UL, the IOM has established an AMDR of five to ten percent of energy for n-6 PUFAs. 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 19 g of canola oil (5.6 g/day). Because the 99th percentile of intake was used to set the upper boundary of the AMDR for n-6 PUFAs, consuming 19 g of canola 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 canola 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 canola 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, 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.(13) These disease and surrogate endpoints were used to evaluate the potential effects of UFAs from canola oil on CHD risk. The petition cited 113 publications as evidence to substantiate the relationship for this claim. These publications consisted of: 18 review articles; one animal study; seven publications from National Institutes of Health (NIH), American Heart Association and various trade associations; one letter to the editor; 37 studies that did not evaluate the substance and disease relationship; seven meta-analyses and 42 articles that evaluated the substance and disease relationship.
A. Assessment of Background Materials
"Background materials" here refers to review articles, meta-analyses, letters to the editor, 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 study 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 canola oil. Therefore, FDA cannot draw any scientific conclusions from the animal study regarding UFAs from canola oil and CHD risk reduction.
C. Assessment of the Intervention Studies
FDA identified 42 intervention studies for its evaluation of the relationship between consumption of UFAs from canola oil and risk of CHD. Scientific conclusions could not be drawn from 34 of the 42 studies regarding the substance/disease relationship for one or more of the following reasons.
* Five studies did not measure a validated surrogate endpoint of CHD (i.e., blood total-cholesterol, blood 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 UFAs from canola oil and risk of CHD could not be drawn.
* Eighteen studies did not include a control group consuming SFAs for comparison to the relative effects of UFAs from canola oil (see Appendix 1). Therefore, it could not be determined if the replacement of SFAs with UFAs from canola oil reduced the risk of CHD. Hence, scientific conclusions could not be drawn from these studies.
* The duration of the study intervention was too short (less than three weeks) in nine studies (see Appendix 1) to adequately determine if changes in serum cholesterol levels were reflective of the intervention treatment (Bonanome et al., 1988). Hence, scientific conclusions could not be drawn from these studies.
* Five studies used UFAs that were not solely from canola oil and thus FDA could not determine if the effects were from UFAs from canola oil or from other types of oil (See Appendix 1). Therefore, no scientific conclusions could be drawn from these studies.
* Three 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.
Eight of the 42 intervention studies evaluated the relationship between UFAs from canola oil and CHD risk by replacing SFAs with UFAs from canola oil (Baudet et al., 1988; Lichtenstein et al., 1993; Sundram et al., 1995; Wardlaw et al., 1991; Sarkkinen et al., 1998; Uusitupa et al., 1994; Matheson et al., 1996; Noakes et al., 1998). Four of these studies provided all of the meals and snacks to the subjects and thoroughly controlled for all aspects of the dietary intervention (Baudet et al., 1988; Lichtenstein et al., 1993; Sundram et al., 1995; Wardlaw et al., 1991). In contrast, four studies relied on the participants to prepare and consume the diets at home, based on study instructions (Sarkkinen et al., 1998; Uusitupa et al., 1994; Matheson et al., 1996; Noakes et al., 1998). Both types of studies are considered to be an intervention design. However, the four studies that strictly controlled the subject's dietary intakes provide stronger evidence for the substance/ disease relationship since compliance was strictly monitored. Sundram et al. (1995) received a high methodological quality rating and the remaining seven studies received moderate methodological quality ratings. The eight studies are summarized below.
Baudet et al. (1988) was a randomized cross-over study in 20 nuns from France. The study compared a diet high in SFAs from butter and cream to a diet containing UFAs from low erucic acid rapeseed oil. The diets were six weeks in duration and all meals were provided to the subjects. The LEAR diet significantly (p<0<0<0<0<0<0< 300 mg per day) in order to reduce the risk of CHD. Thus, FDA will not consider, 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 Canola 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 canola oil necessary to substitute in place of SFAs by first calculating the difference in the amount of UFAs, in grams,(18) between the high-UFA and high-SFA diets in the three strictly controlled intervention 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 17.7 g of UFAs (Wardlaw et al., 1991). Canola oil contains approximately 92.9% UFAs (USDA Nutrient Database for Standard Reference, Release 18). Consuming 19 g of canola oil per day provides 17.7 g of UFAs. Nineteen grams of canola oil is equivalent to approximately 1.5 tablespoons. The RACC for canola oil is one tablespoon, which contains approximately 12.4 g of UFAs and 1 g of SFAs.
To determine the minimum amount of canola oil necessary to be in a food, the agency considered the number of eating occasions at which consumers might consume canola oil or canola oil products and the number of potential foods that could be labeled with a qualified health claim about UFAs from canola oil and CHD. Foods in these categories can be 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 canola oil for a food to bear the claim will be based on four eating occasions per day. The minimum effective dose (19 g canola oil per day) based on four eating occasions per day of canola oil or the four categories of canola oil-containing products is 4.75 g of canola oil per RACC per day. For consumers to know the amount of canola oil in a product, FDA intends to consider, in the exercise of its enforcement discretion, that foods that bear a UFAs from canola oil and CHD qualified health claim state the amount of canola oil per serving in the claim.
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:
"Limited and not conclusive scientific evidence suggests that eating about 1 ½ tablespoons (19 grams) of canola oil daily may reduce the risk of coronary heart disease due to the unsaturated fat content in canola oil. To achieve this possible benefit, canola 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 canola 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.
Barbara O. Schneeman, Ph.D.
Office of Nutritional Products, Labeling, and Dietary Supplements
Center for Food Safety and Applied Nutrition
Baudet MF., Jacotot B. "Dietary fats and lecithin-cholesterol acyltranserase activity in healthy humans." Annuals of Nutrition Metabolism, 32: 352-359, 1988.
Bonanome A., Grundy S.M., "Effect of dietary stearic acid on plasma cholesterol and lipoprotein levels" New England Journal of Medicine, 318:1244-48, 1988.
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.
Lichtenstein, A.H., Ausman, L.M., Carrasco, W., Jenner, J.L., Gualtieri, L.J., Goldin, B.R., Orgovas, 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.
Matheson, B., Walker, KZ., Taylor, D., Peterkin, R., Lugg, D., O'Dea, K. "Effect on serum lipids of monosaturated oil and margarine in the diet of an Antarctic expedition." American Journal of Clinical Nutrition, 63: 933-938, 1996.
Noakes, M., Clifton, PM. "Oil blends containing partially hydrogenated or interesterfied fats: differential effects on plasma lipids." American Journal of Clinical Nutrition, 68: 242-247, 1998.
Spilker, B. Guide to Clinical Studies. Raven Press, New York, New York, 1991, pp. 59-64.
Sarkkinen, ES., Uusitupa, MIJ., Gylling, H., Miettinen, TA. "Fat-modified diets influence serum concentrations of cholesterol precursors and pant sterols in hypercholesterolemic subjects." Metabolism, 47: 744-750, 1998.
Sundruam K., Hayes KC., Siru OH. "Both dietary 18:2 and 16:0 may be required to improve the serum LDL/HDL cholesterol ratio in normocholesterolemic men." Journal of Nutritional Biochemistry, 6: 1790187, 1995.
Uusitupa, M., Schwab, U., Mukimattila, S., Karhapaa, P., Sarkkinen, E., Maliranta, H., Agren, J., Penttila, I. "Effects of two high-fat diets with different fatty acid compositions on glucose and lipid metabolism in healthy young women." American Journal of Clinical Nutrition, 59: 1310-1316, 1994.
Wardlaw, GM., Snook, JT., Lin, M., Puangco, MA., Kwon, JS. "Serum lipid and apolipoprotein concentrations in healthy men on diets enriched in either canola oil or safflower oil." American Journal of Clinical Nutrition, 54: 104-110, 1991.
Wilson, E.B. (1990). An Introduction to Scientific Research, (Toronto, Canada: General Publishing Company), pp. 46-48.
U.S. Department of Agriculture, Agricultural Research Service. 2005. USDA Nutrient Database for Standard Reference, Release 18. 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.
Please see Docket No. 2006Q-0091, QHC1, for the following studies:
Duration of intervention period to short (less than 3 weeks)
Chan et al., 1991
Hodson et al., 2001
McDonald et al., 1989
Kratz et al., 2002
Kratz et al., 2002
Kratz et al., 2003
Truswell et al., 1992
Mutanen et al., 1992
Valesta et al., 1992
No comparison saturated fat group
Becker et al., 1999
Chan et al., 1991
Gylling et al., 1999
Jenkins et al., 1997
Li et al., 1998
Nydahl et al., 1995
Freese et al., 1994
Guiesserian et al., 2002
Gustafsson et al., 1994
Metcalf et al., 2003
Miettinen et al., 1994
Nielsen et al., 2002
Nydahl et al., 1994
Pedersen et al., 2000
Seppanen-Laakso et al., 1992
Seppanen-Laakso et al., 1993
Turpeinen et al., 1995
Valsta et al., 1995
Source of unsaturated fatty acids was not solely from canola oil
Luscombe et al, 1999
Metcalf et al., 2003
Muller et al., 2003
Smith et al., 2003
Howard et al., 1995
Lichtenstein et al., 1994
Jones et al., 1994
Valasta et al., 1996
No validated endpoint for measuring coronary heart disease
Freese et al., 1994
Melcalf et al., 2003
Kratz et al., 2002
Kratz et al., 2003
Turpeinen et al., 1995
Subjects diagnosed with coronary heart disease
Herrmann et al., 1995
(1) See guidance entitled "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) 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).
(14) See supra, note 10.
(15) See supra, note 11.
(16) FDA intends to exercise its enforcement discretion for canola oil and certain products containing canola oil, as such products were included in the studies that suggested benefit.
(17) 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).
(18) The amount of UFAs in grams was calculated by multiplying the percent of energy by 2000 kcal and converting to grams.
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