NC1167: N-3 Polyunsaturated Fatty Acids and Human Health and Disease (NC167)
Statement of Issues and Justification
The need as indicated by stakeholders: The Problem: Americans are unlikely to achieve the proposed dietary recommendations of increased long chain n-3 polyunsaturated fatty acids (PUFA) by increasing fish consumption, AHA Dietary Guidelines Revision 2000 (1). For example, there is no evidence that the public would modify their dietary patterns to include a suggested four servings of fatty fish weekly and the supply of fatty fish is insufficient to meet these proposed recommendations. Therefore, agricultural-based sources of n-3 PUFA must be investigated as an alternative means of achieving equivalent health benefits (health promotion/disease prevention). However, the family of n-3 PUFA comprises a heterogeneous group of fatty acids with potentially diverse health-related functions that remains to be investigated. The overall goal of this application is to determine the effectiveness of agricultural-based n-3 PUFA as compared to marine-based n-3 PUFA to promote health and prevent disease and identify agricultural and marine sources of n-3 PUFA to meet new dietary guidelines.This project addresses the "highest priority research" objectives as defined by the Agricultural Research, Extension and Education reform Act of 1998. This project also addresses Goal 3, Objective 3.1 (to optimize the health of consumers by improving the quality of diets, the quality of food, and the number of food choices) and Objective 3.2 (to promote health, safety, and access to quality health care) of the CSREES Strategic Plan. This project addresses three Food and Nutrition research priorities identified by the North Central Regional Association (NCRA) in Appendix A-1 of the NCRA manual, and as such, its focus on Food and Nutrition is among the highest priorities. The three priority research objectives to be addressed by NC-1167 include:
Priority Research Objective 1: Expand our understanding of the relationship between diet, health, and disease prevention with particular focus on dietary lipids.
Priority Research Objective 2: Elucidate health benefits associated with functional properties of food constituents.
Dietary guidelines for fat intakes were originally based on the formulae that predicted the impact of polyunsaturated fatty acids (PUFA), saturated fatty acids (SFA) and monounsaturated fatty acid (MUFA) on serum cholesterol levels as the cardinal biomarker of cardiovascular disease (CVD) risk (1). There has been an evolution in the dietary guidelines over the 1988-2000 period, which recognizes that while PUFA are associated with a reduction in serum cholesterol and CVD risk, not all PUFA are created equal with regards to their beneficial effects. For example, excessive consumption of n-6 PUFA is not without detrimental effects (1-3). The 2000 Revision of the American Heart Association (AHA) dietary guidelines (1) has abandoned the nutrient-based PUFA recommendation in favor of food-based recommendations of unsaturated fat consumption from fish, vegetables, legumes and nuts. These new guidelines emphasize that n-3 PUFA confer benefits over and above those attributable to improved serum lipid profiles. Despite this, consumers are unaware as to how much n-3 PUFA should be consumed, either in terms of absolute amounts, the forms of dietary n-3 PUFA, or the importance of the dietary n-3/n-6 ratio. Furthermore, consumers are unaware that different forms of dietary PUFA have differing health benefits based on their ability to impact the functional tissue long chain n-3 PUFAs, eicosapentaenoic (EPA) and docosahexaenoic acids (DHA).
Priority Research Objective 3: Design effective nutrition education programs and delivery methods that modify human behavior such that individuals, including those most at risk, choose healthier diets.
This project will enable construction of a profile that will delineate the practices used by nutrition professionals to improve consumers' n-3 intake. By profiling the n-3 counseling practices of registered dietitians, a snapshot of practitioner perceived effectiveness of altered dietary n-3 intake can be formed for conditions including but not limited to cardiovascular disease, stroke, arthritis symptoms, autoimmune disorders, neurological functions, cancer, pregnancy and birth outcomes. Then, utilizing the profile components, effective, theory-driven nutrition education programs and intervention strategies, including delivery methods, will be developed for nutrition professionals with possible adaptation for other health professions. Ultimately, this targeted nutrition education will result in improved n-3 intakes in consumers.
Importance of the work: Recommended n-3 intakes will be published for the first time by the Food and Nutrition Board, National Academy of Sciences, in 2002 and are likely to be well above current intakes. Nutrition professionals will need valid resources to implement the recommendations. Development of sound, food-based nutrition resources will 1) demonstrate the role of agricultural products in increasing n-3 intake to maintain health, 2) promote food, rather than supplement-based sources of n-3 fatty acids, and 3) ensure dissemination of accurate science-based information about n-3 fatty acids and health for health professionals and their clients. Members of NC-1167 will focus their efforts on identifying both the dietary n-3 forms and amounts that confer health promotion/disease prevention benefits.
NC-1167 maintains the focus of its predecessor projects in delineating the impact of dietary PUFA on the health of the US population with an emphasis on identifying the health benefits of the various dietary forms of n-3 PUFA, and the amounts of n-3 PUFA, as a means of establishing guidelines that will aid in setting human recommendations. NC-1167 scientists were among the first to recognize that diets formulated with n-6 PUFA-rich corn oil or safflower oil resulted in markedly elevated eicosanoid formation, particularly 2-series prostaglandins (PG) and 4-series leukotrienes (LT) while 3-series PGs and 5-series LTs were depressed (LA, CO, OH, IA, TN Stations). NC-1167 scientists have shown that aberrant eicosanoid production with high n-6 PUFA inhibits bone formation (IN, CO), and that n-3 PUFA moderates bone resorption and promotes bone formation. The NC-1167 group was among the first to report that high n-6 PUFA diets promote tumor growth (IA, WI, MN, TN) and that n-3 PUFA inhibited tumor proliferation (TN, MN). Other consequences of high n-6 PUFA diets elucidated by the NC-1167 group include increased low density lipoprotein (LDL) oxidation (NC), increased cytokine production and alterations in immune function (MO) and decreased receptor binding affinity and tissue sensitivity to insulin affecting energy metabolism (MI). NC-1167 studies have shown that increased n-3 PUFA can decrease triglyceride rich lipoproteins and CVD risk (CA, NE and TN). Recent studies (CO) have found elevations of n-6 PUFA in blood lipids of women delivering prematurely and increased n-3 PUFA decreased biomarkers of premature delivery (CO, IN). Infertility is associated with high n-6 PUFA diets, and n-3 PUFA consumption increases egg release into the oviduct (WY).
Alterations in the eating pattern of Americans have resulted in a markedly increased use of processed plant fats and oils in comparison to animal fats. PUFAs comprised approximately 7% of energy intake of US diets during the period 1987-1991 (4-6). Linoleic acid ( LA, n-6 PUFA) is the predominant PUFA in the American food supply and the average daily consumption between 1987 and 1991 was approximately 13 g/day, providing 84-89% of the total PUFA energy consumed (4,5). Thus, approximately 6% of daily energy is provided by n-6 LA acid alone. In contrast, the intake of n-3 PUFA during the 1987-1991 time period was approximately 1.6 g/day, providing approximately 0.7% of daily calories. (4-6). The major contributor to n-3 PUFA intake is -linolenic acid (LnA, 1.4 g/day, 0.6% of daily calories) with 0.1-0.2 g/day (0.05-0.1% daily calories) provided as EPA plus DHA, the functional long-chain n-3 PUFAs (4-6). Despite its high LA content, soybean oil is the major dietary source of LnA (6), but 50% is processed by hydrogenation for use in margarines, shortenings, and frying fats with increased trans fatty acid content and drastically reduced n-3 PUFA (7). The role of soybean oil as the major dietary source of n-3 PUFA in the US food supply is threatened by efforts to develop low n-3 PUFA cultivars in order to circumvent hydrogenation and assuage consumer concerns about dietary trans fatty acids (5,6,8). The conversion of dietary LnA acid to EPA and DHA, the functional n-3 PUFA in tissues, is dependent on both the amount of LnA and the dietary n-3/n-6 ratio (9). As emphasized previously, the optimal level of dietary n-6 PUFA, for wellness factors other than serum cholesterol, has yet to be determined. Work by NC-1167 scientists has shown that there are threshold levels of n-6 PUFA with increased risks for coronary thrombosis, cancer proliferation, immunosuppression, bone loss, infertility, premature delivery and perinatal health, and modest supplements of n-3 PUFA can reverse many of the detrimental effects of elevated n-6 PUFA consumption.
A crucial, and unanswered, question is whether dietary LnA acid can support tissue EPA and DHA levels at which health outcomes are improved. Evidence indicates that the current US dietary n-6/n-3 ratio of 11-12.5:1 does not allow for sufficient conversion of LnA to optimal tissue levels of EPA and DHA (6,9). The dietary n-6/n-3 ratio has remained largely unchanged over the past 40 years (10-12) and is considerably higher than the suggested optimal ratio of 2.3:1 (6). This has led to recommendations that US fish consumption be increased to approximately 4 servings of fatty fish per week in order that preformed dietary EPA and DHA intakes the functional tissue forms of n-3 PUFAs - meet the proposed daily goal of 0.65 g EPA plus DHA (13). Americans are unlikely to achieve the proposed dietary recommendations of long-chain n-3 PUFA by increasing fish consumption. There is no evidence that the public would modify their dietary patterns to include a suggested four servings of fatty fish weekly (6) and there is concern that the supply of fatty fish is insufficient to meet these proposed recommendations. The Food and Drug Administration has recently cautioned consumers to limit fish consumption because of concern with environmental heavy metal and pesticide contamination. Thus, the investigation of agricultural-based sources of dietary n-3 PUFA as alternatives to marine based n-3 PUFA for achieving health promotion and disease prevention benefits in the US population is crucial. While no single station has the expertise to investigate all the n-3 PUFA linked wellness outcomes, the expertise of the NC-1167 Committee ensures that our search for an appropriate dietary n-3 PUFA intake, both form, amount, and useful consumer information will focus on major health outcomes such as CVD, cancer, bone diseases, prematurity and perinatal health, emphasized in the Health People 2010 Report (14).
Consequences if not done: Without this research, the scientific rationale supporting the levels and types of dietary n-3 PUFA needed to reduce risk of chronic diseases, such as cancer inflammatory and cardiovascular diseases, will remain a matter of interpretation. This is important because of the prevalence of these diseases in the American population and their serious impact on the healthcare economy. It is imperative that we not lump all the n-3 fatty acids together with the assumption that they have similar biological properties.
Equally, it is a mistake to assume that it is sufficient to recommend more fish in the diet with little hope that these recommendations are achievable. The most effective methods to implement dietary behavior change are being rigorously studied, particularly in relation to reducing total fat intake. However, these educational theories have not been applied to the area of n-3 fatty acid intake and without this data success is questionable. In addition, education to increase intake of n-3 fatty acids is further complicated because it contradicts previous nutrition communications recommending dietary fat reduction.
Therefore, without these studies, n-3 PUFA as a tool for the health promotion and disease prevention will remain an interesting curiosity to the biomedical community. There is a need to determine how much and what type will result in a predictable outcomes and how to educate and motivate the public to achieve these desired outcomes.
Technical feasibility of the research: The scientists that make up the technical committee on NC-1167 are the leading authorities in their respective disciplines as it relates to the biological impact of dietary n-3 fatty acids. A review of annual reports and their publication record provides the basis for this statement. The methods outlined in this proposal are standard procedures developed and perfected by each of the investigators. As a result, each member provides a unique perspective to the problem, when seamlessly blended, will result in definitive answers. This applies to the natural as well as the social science portions of the proposal. For example, regarding the nutrition education component, this project is feasible because information will be sought from nutrition professionals who are highly organized into state and local districts. They meet on a regular basis and seek continuing education opportunities to maintain credentials. Specialized practice among nutrition professionals is common, thereby enabling us to identify practices specific to the diseases of interest. Development of an educational intervention is possible because members of the NC-1167 regional project possess n-3 fatty acid expertise and nutrition education experience, assuring scientific validity for both content and delivery components.
Advantages for doing the work as a multistate effort: The NC-1167 Research Project addresses the role of dietary n-3 PUFA in the promotion of health. No single station has the expertise or resources to investigate all the components needed to establish health driven guidelines for n-3 intakes. We will leverage our collective results into an integrative recommendation outlining the types and levels of n-3 fatty acids and their potential outcomes. We will use this information in conjunction with the nutrition education component as a means to increase n-3 PUFA consumption by Americans and to insure that the amount and types of n-3 PUFA are biologically meaningful. To accomplish this, data have to be generated using different levels and types of n-3 PUFA under a variety of experimental conditions with multiple clinical and biochemical endpoints involving conditions such as cardiovascular disease (TN, NC, CO), cancer (TN, MN), inflammation (MI, MO), diabetes (WY, MI, ND), reproductive issues (CO, WY) and bone metabolism (IN, CO). Similarly, a multistate effort (as directed by CO, KS, NE, NJ) makes it more technically feasible to have a large enough sample size of nutrition professionals for the nutrition education component. Intake of foods containing n-3 PUFA may vary by geographic locations, cultural background and demographic characteristics. A multistate effort provides the opportunity to address issues related to demographics, geography and ethnic diversity. Another advantage is the availability of a broad scope of technical and educational expertise for use in designing the intervention. A multistate effort will result in a larger sample size for the intervention. This will mean greater feedback on the nutrition education intervention practices and the ability to make statistically relevant group comparisons. This vigorous feedback will increase the likelihood that nutrition education programs designed to increase n-3 PUFA intake will be efficacious.
Likely impacts from successful completion of the work: Biomarkers will be identified thereby enabling successful educational interventions to be documented. Effective educational programs that increase nutrition practitioner n-3 PUFA counseling will increase consumption of food-based sources of n-3 fatty acids to improve the quality of life and help reduce diseases, such as heart disease and cancer. The resulting economic impacts include decreasing healthcare costs and those related to an increased need for production of agriculture-based n-3 fatty acid sources, such as flaxseed, stearadonic (SDA)-containing vegetable oils and n-3 enriched animal products. The potential for negative health and economic consequences of excessive and unsafe n-3 supplementation practices will be reduced.
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