NC1167: N-3 Polyunsaturated Fatty Acids and Human Health and Disease (NC167)

(Multistate Research Project)

Status: Inactive/Terminating

Project Menu

SAES-422 Reports

Annual/Termination Reports:

[03/01/2004] [12/14/2004] [11/12/2005]

Date of Annual Report: 03/01/2004

Report Information

Annual Meeting Dates: 11/06/2003 - 11/07/2003
Period the Report Covers: 11/01/2002 - 11/01/2003

Participants

Kenneth G.D. Allen (Colorado State University); Jennifer E.L. Anderson (Colorado State University); Mary A. Harris (Colorado State University); Jay Whelan (University of Tennessee); Nancy K. Lewis (University of Nebraska); Audrey Adler for Debra Palmer Keenan (Rutgers University); Kevin Fritschie (University of Missouri); Barbara Lohse (Kansas State University)l Kate Claycombe (Michigan State University); Ian Gray (Administrative Adviser, Michigan State University).

Brief Summary of Minutes

Minutes Attachment:

Attachment

Accomplishments

Accomplishments and Impacts The overall objectives of this Multistate Regional Project are: Objective #1: Evaluate the effect of different n-3 fatty acids, both form (source) and amount, on tissue functions and correlate these effects with changes in putative biomarkers relevant to health promotion and disease prevention. Objective #2: Experimental diets used in animal studies will examine dietary levels of n-3 PUFA that are achievable in human diets, based on human equivalent amounts (allometric scaling) in rodent models. Objective #3: Develop effective means for translating research knowledge about n-3 PUFA into consumer food choices. The outcomes and impacts of this Multistate Regional Project are: " Improved health of the US population. " Decreased incidence of age-related and/or degenerative diseases. " Education of clients by nutrition professional about health benefits of n-3 PUFA, both forms and amounts. " Oil processors will be introduced to the concerns health professionals have about meeting n-3 PUFA guidelines. " Stimulating the development of alternative sources of agriculturally-based LCn-3 PUFA. " Stimulating the development and marketing of new and creative agriculturally-based food products containing LCn-3 PUFA. " Enhanced awareness by the medical community of the benefits n-3 PUFA consumption. Milestones are: " Collection of data to be used as preliminary data for competitive grant submissions. " Submission of competitive grant applications to USADA and NIH. " Objective #3 is addressed in three consecutively dependent stages: (1) Development of Nutrition Education Intervention; (2) Implementation of the Intervention; and (3) Evaluation of Outcomes. Accomplishments and Impacts Experiments in animals have addressed the importance of preformed long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) in indices of premature delivery and cardiovascular disease. Experiments have shown that substitution of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and stearidonic acid (SDA), for linolenic acid (LnA) improves markers of premature delivery, ovulation and cardiovascular disease. For indices of premature delivery both DHA and SDA provided at 0.7 % of calories, the current US intake of total n-3 PUFA, were effective in reducing placental prostaglandin production. DHA provided at 0.7 % of calories also reduced placental collagenase and matrix metalloproteinase production. Both prostaglandin production and the amounts of collagenase and matrix metalloproteinases are important determinants of parturition, premature delivery and infant birth weight. These results show that substituting a LC n-3 PUFA was more effective than increasing LnA intake. Thus, a switch to foods providing these LC n-3 PUFA, without increasing the intake of n-3 PUFA is effective in improving markers of premature delivery and gestational duration both of which are major health problems for infants. Heart disease remains the major cause of mortality in the US and inflammation plays a major role in its development. Interleukin-6 (IL-6), a proinflammatory cytokine is secreted by a variety of cells and plays a role in the production of C-reactive protein which increases cardiovascular disease risk by increasing uptake of low density lipoprotein cholesterol. Anti-inflammatory n-3 fatty acids such as EPA (20:5, n-3) and SDA (18:4, n-3) inhibited lipopolysaccharide (LPS)-induced increases in IL-6 secretion in murine 3T3-L1 preadipocytes. In a cell culture experiment, data showed that preadipocytes secreted significantly higher levels of IL-6, and treatment of preadipocytes with both EPA and SDA decreases LPS-induced IL-6 secretion significantly. As a result, this demonstrates that one of the ways in which n-3 fatty acids can reduce cardiovascular disease risk may be via down regulating IL-6 in the preadipocytes. These results suggest that LC n-3 PUFA are effective in preventing some of the inflammatory processes of cardiovascular disease. These results address Objectives 1 and 2 and the first milestone of our original multistate proposal. In particular, the form of n-3 PUFA (EPA, DHA, SDA) has been identified as more important than providing more linolenic acid. This has important implications for human health in that consumers believe that all forms of n-3 PUFA have health benefits. The data from this project indicate that preformed LC n-3 PUFA are much more important in providing health benefits. Even increasing LnA intakes 3-fold to 2.0 % of calories does not afford the same benefits as simply substituting preformed LC n-3 PUFA for the current 0.7 % of calories provided by LnA. Despite the benefits of increased LC n-3 PUFA intakes, there is concern that infectious disease resistance is impaired by n-3 PUFA. Disease resistance using the murine listeriosis model has been examined. Listeriosis is an infectious disease of humans and animals that is caused by the intracellular, gram-positive bacteria, Listeria monocytogenes. This pathogen has been used by many investigators as a model organism to define the various factors and cells that are involved in the host response to intracellular pathogens. Cells of the innate immune system (i.e. macrophages, natural killer cells, neutrophils, dendritic cells) play a critical role in controlling bacterial growth during the initial stages of infection. It is this stage of host defense that seems most seriously impaired by LC n-3 PUFA, such as those provided by fish oil. The consequences are best illustrated by the reduced bacterial clearance we have observed in the liver and spleen 3 to 4 days post-infection. Typically at this time, we have found 10 to 100-fold more bacteria in the liver and spleen of mice fed diets rich in LCn-3 PUFA compared with mice fed diets rich in n-6 PUFA or low in total PUFA (i.e., soybean oil and lard, respectively). It has been shown that changes in bacterial clearance correlate with lower survival rates for mice consuming a high LCn-3 PUFA diet. We have some evidence that both LCn-3 PUFA found in fish oils eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) are equally effective at modulating host infectious disease resistance to this pathogen. However, we have not examined other n-3 PUFA, nor have we addressed the dose-response relationship between n-3 PUFA and host resistance. To date we have observed a significant adverse effect of LCn-3 PUFA at a level of intake equivalent to ~2 energy%. This is about 10-fold higher than the current average intake of LCn-3 PUFA for people in the U.S., however, it is not far from the levels that are currently being recommended by some health professionals (i.e., 0.65% of calories). These studies address objectives 1 and 2 and the first milestone of our original proposal. In order to disseminate the results from animal experiments members of the NC 1167 committee have begun to address the dietary behavior patterns that influence omega-3 fatty acid intakes, and to design effective omega-3 nutrition education interventions. This year we have developed and pilot tested an n-3 fatty acid food frequency. We have designed and evaluated an omega-3 fatty acid nutrition education intervention for heart patients and have shown that participants increased their n-3 fatty acid intakes after receiving the education. We have also assessed the impact of geographic region on omega-3 fatty acid intakes by surveying the intakes of elderly men in two geographic regions (a coastal and an internal region) of Saudi Arabia. Residents of the coastal region have significantly higher intakes than those in the internal regions of the country. IMPACT: Increasing n-3 fatty acid intakes will have a favorable impact on reducing risk of several chronic diseases such as cardiovascular disease, arthritis, and cancer and in the long term will reduce health care costs and increase quality of life for the elderly. Accurate assessment of n-3 fatty acid intakes requires effective nutrition education interventions for increasing n-3 fatty acid intakes. Understanding of factors that influence n-3 fatty acid intakes, such as geographic location, provide components and information needed by nutrition educators to increase n-3 fatty acid intakes in their clientele. During this past year, NC-1167 partners from Kansas, Colorado, New Jersey and Nebraska have worked as a team to develop a questionnaire for assessing omega-3 knowledge and practices of dietitians. For the formative phase of development, 10 dietitians from each state were called and ask to respond to open-ended questions. Responses to each open-ended question were grouped and from this a detailed questionnaire was developed. The detailed questionnaire was then adapted for completion using the web and this web survey was piloted with two dietitians from each state and further refinements have been made. Our plan at this time is to conduct the survey early in 2004 and to obtain responses using both telephone and web-based surveys. Information gathered from these surveys will provide a profile of baseline knowledge and practices of a random sample of dietitians in these four states. IMPACT: Consumers look to practicing dietitians as a source of accurate and unbiased information on nutrition. By assessing baseline knowledge and practices of dietitians we can understand their n-3 nutrition education needs and can design educational resources to meet these needs. These studies addressing dietary behavior patterns that influence omega-3 fatty acid intakes, and the design of effective omega-3 nutrition education interventions address Objective 3 and the third milestone of our original proposal.

Publications

Turek, J.J., Watkins, B.A., Schoenlein, I.A., Allen, K.G.D., Hayek, M.G. and Aldrich, C.G. Oxidized lipids depress canine growth, immune function, and bone formation. J. Nutr. Biochem. 14: 24-31, 2003. Yu, L., Perret, J., Parker,T. and Allen, K.G.D. Enzymatic modification to improve the water-absorbing and gelling properties of psyllium. Food Chem. 82: 243-248, 2003. Watkins, B.A., Li, Y., Romsos, D.R., Hoffman, W.E., Allen, K.G.D. and Seifert, M.F. CLA and Bone Modeling in Rats. In: Advances in Conjugated Linoleic Acid Research, Volume 2, pp 218-250 (Sebedio, J-L., Christie, W.W. and Adlof, R. Eds.) American Oil Chemists Society (AOCS) Press, Champaign IL, 2003. Allen, K.G.D., Perez, M.A., Hansen, R.A. and Harris, M.A. N-3 fatty acids alter eicosanoid and matrix metalloproteinase mediators of parturition in rats. Presented at Experimental Biology 2003 Meeting, San Diego, CA, April 11-15, 2003. FASEB J. 17, A1118 (Abstract # 695.1), 2003. Hansen, R.A. Short term effects of dietary fish oil on matrix metalloproteinases in dogs with anterior cruciate ligament disease. PhD Dissertation, Colorado State University, Fort Collins, CO, Summer 2003. Seal, S.J. Circulating PGE2 and PGF2? metabolite and long chain polyunsaturated fatty acid levels in full term pregnancy with docosahexaenoic acid supplementation. Masters Thesis, Colorado State University, Fort Collins, CO, Spring 2003. Hansen, R.A., Allen, K.G.D., Pluhar, E.G., Ogilvie, G.K., Fettman, M.J. and Harris, M.A. N-3 fatty acids decrease inflammatory mediators in arthritic dogs. Presented at Experimental Biology 2003 Meeting, San Diego, CA, April 11-15, 2003. FASEB J. 17, A330 (Abstract # 200.3), 2003. Allen, K.G.D. A role for dietary n-3 fatty acids in gestational length. Presented at The Institute of Food Technologists (IFT) Annual Meeting and Food Expo, July 12-16, 2003, Chicago IL, as part of Session 82: Symposium on Dietary n-6/n-3 Fatty Acid Balance. Abstract 82-3, page 207 of 2003 IFT Annual Meeting Technical Program Abstracts. Lee, J-Y., Lewis, N.M., Scheideler, S.E., Carr, T.P. 2003. Consumption of omega-3 fatty acid enriched eggs and serum lipids in humans. Journal of Nutraceuticals, Functional and Medical Foods. 4(1):3-13. Lewis, N., Plugge, S., Eskridge, K., Wander, R.C. 2003. Serum ALA increases with inclusion of one omega-3 enriched egg in the diet. The FASEB J. 17:A336. Al-Numair, Khalid and Lewis, Nancy M. 2003. Variation in source and consumption of omega-3 fatty acids in two different population groups in Saudi Arabia. 5th International Food Data Conference and 27th National Nutrient Databank Conference, Washington, D.C., Proceedings, p. 85. Heidal, Kimberly. 2003. Evaluating the effects of a nutrition education program on the consumption of omega-3 fatty acids for heart patients. Ph.D. Dissertation, University of Nebraska, Lincoln, NE. Lohse B, Shafer K. Problem-based learning is effective for extension education about omega-3 fats. Society for Nutrition Education Annual Conference Proceedings 36(1):33;2003. Lohse B, Nitzke S, Ney D. Introducing a problem-based unit into a lifespan nutrition class using a randomized design produces equivocal outcomes. J Amer Diet Assoc. 103(8):1020-1025;2003. Lohse Knous B, Nutritional Issues for Pharmacists: Dietary Supplements [Continuing Professional Education] 2003;29(4):1-23. Lawrence, KS:Pharmat, Inc. Weigh to Diet. Lesson (MF2595) and Leader?s Guide (MF2596). August 2003. http://www.oznet.ksu.edu/library/fntr2/MF2596.pdf http://www.oznet.ksu.edu/library/fntr2/MF2595.pdf

Impact Statements

Improved health of the US population.
Decreased incidence of age-related and/or degenerative diseases.
Education of clients by nutrition professional about health benefits of n-3 PUFA, both forms and amounts.
Oil processors will be introduced to the concerns health professionals have about meeting n-3 PUFA guidelines.
Stimulating the development of alternative sources of agriculturally-based LCn-3 PUFA.
Stimulating the development and marketing of new and creative agriculturally-based food products containing LCn-3 PUFA.
Enhanced awareness by the medical community of the benefits n-3 PUFA consumption.

Date of Annual Report: 12/14/2004

Report Information

Annual Meeting Dates: 11/04/2004 - 11/05/2004
Period the Report Covers: 10/01/2004 - 10/01/2005

Participants

Kenneth G.D. Allen (Colorado State University); Jennifer Anderson (Colorado State University); Jay Whelan (University of Tennessee); Nancy K. Lewis (University of Nebraska); Audrey Adler (Rutgers University); Debra Palmer Keenan (Rutgers University); Kevin Fritsche (University of Missouri); Barbara Lohse (Kansas State University); Richard Baybutt (Kansas State University); Kate Claycombe (Michigan State University); Robert Chapkin (Texas A & M); K. Shane Broughton (University of Wyoming); Doreen Woodward (Administrative Adviser; Michigan State University), Susan Welch (CSREES Representative, Washington, DC).
Members Absent: Rosemary Wander (University of North Carolina, Greensboro); Daniel Gallaher (University of Minnesota)

Brief Summary of Minutes

The meeting was called to order by the chair, K. Shane Broughton, at 1:15 pm, November 4, 2004 at the Kellogg Hotel & Conference Center, East Lansing, MI.
Kevin Fritsche served as secretary for this meeting.

Introductions & Opening Remarks:
The meeting opened with a welcome from John Baker, Acting Director of Michigan Ag. Expt. Station. He gave a brief overview of the areas of focus for the MAES: Food & Health, Environmental Stewardship, Food, Family & Fiber, Microbial Food Safety, Food Security.

We were introduced to our new USDA rep., Susan Welch. She told about her background as Natl. Program Leader for Nutrition Education Leadership. She informed us that the USDA has two open positions and the staff has been working hard over the past few months with finalizing the Dietary Guidelines Advising Report. Also, she told us that the NRI competitive grants program may get a $20M boost from Congress next fiscal year. How much of that will go into either of the nutrition-related programs (i.e., 31.0 and 31.5) is unclear. This is the first year of the new policy at the NRI regarding funding larger grants (~$500,000) and for longer (4 yrrs). As a result, in the 31.0 program only 10 of 104 applications were funded with a budget that has remained at ~$4M for many years. The new program (31.5) area on nutrition and obesity (31.5) the budget is ~$8.5M. These projects are supposed to integrate basic science with education, outreach, and outcomes. Ten out of 89 applications were funded in this program area. Susan encouraged us to consider applying for a conference grant to support the activities of this Multi-state project.

Doreen Woodward (Ad. Advisor, MSU) introduced herself and shared several helpful handouts regarding the NIMS reporting system and how to fill out the SAES-422 Annual Reports. She also reminded us that our mid-project report would be reviewed this Spring.

Research Seminar:
A research seminar entitled, Hepatic metabolism and its impact on fatty acid-regulated transcription factors was presented by Donald Jump (Prof. Physiol., Biochem. & Mol. Biol., MSU). The presentation was followed by many questions and a lively discussion.

Announcements:
1. The FDA allowed Health Claims for food rich in EPA and DHA were reviewed and discussed.
2. IFT Symposium: Members were asked if there was interest in organizing another symposium on n-3 PUFA nutrition for the annual IFT meeting. Several members had previously (July 2003) participated in such an activity at the invitation of Bruce Watkins, an IFT and NC1167 member. No one expressed an interest in organizing another IFT symposium, in part, because no one present was an IFT member.
3. EB05 Symposium: N-3 PUFA, Transitioning Research to Education will be on April 5, 2005 in San Diego. The deadline for submitting symposia proposals for EB06 is January. It was decided that we should wait until after our upcoming n-3 PUFA symposium before we submit another proposal. However, there was a consensus that we should sponsor a mini-symposium topic that could bring together all the abstracts in the n-3 PUFA area. Kevin Fritsche agreed to pursue this with Mary Banks at the ASNS office and report back to the committee within a few weeks.
4. Society for Nutrition Education (SNE): Members of the NC1167 committee will be organizing a symposium at SNEs upcoming meeting in Orlando, FL (July 24-27). Jay Whelan was nominated and agreed to be the opening speaker.
5. Evidence Report (#89) from HHS on N-3 PUFA impact on a number of human health conditions including: type II diabetes, metabolic syndrome, IBD, arthritis, SLE, and osteoporosis. Copies of the Summary were distributed and discussed. All committee members were encouraged to go to the Web site indicated in the Summary (i.e., www.ahrq.gov) and read the full document.

Nutrition Education Subcommittee Report: (Drs. Anderson, Lewis, Adler, Palmer-Keenan, Lohse)
(Note: Dr. Lohse, assigned to NC1167 from the Kansas Agricultural Experiment Station, moved to Pennsylvania State University in March, 2004, and will continue to be active in this committee.)

From October 1, 2003 to September 30, 2004, the Nutrition Education unit of NC 1167 developed a survey for registered dietitians to assess n-3 fat knowledge, practices regarding n-3 fat advice with patients, and n-3 fat continuing education venue preferences. Surveys were administered using two procedures: self-report web-based and telephone interview with interviewers recording responses on a web survey modified from the self-report version. Kansas (Pennsylvania) participated in pilot testing the process, interviewee training, and database development. Kansas (Pennsylvania) took the lead in database development and management and developing and administering the web-based survey. For the web-based survey 350 RDs from four states were invited to participate, and 74 RDs completed the survey; for the telephone format, 116 from a subject pool of 346 RDs from the four states completed surveys. Findings from190 participating registered dietitians are being analyzed and manuscript preparation is underway. Steps to develop an n-3 fatty acid knowledge intervention have been discussed in conference calls and sponsorship as well as grant submission are under consideration. Findings revealed limited knowledge by registered dietitians, yet a strong interest in learning more and in providing information to consumers and other clients, especially using a web-based format or handouts and printed materials.

For 2005, Pennsylvania will take the lead on data analysis of survey outcomes while New Jersey will lead analysis comparing survey administration modes. Colorado and Nebraska will take the lead on intervention development.

Following this report the group as a whole discussed the strength of the evidence to support benefits for a long list of health conditions. We attempted to categorize each health condition * EPA&DHA linkage as either: strong (A), modest (B), and weak or inconclusive (C), none (D). The subcommittee agreed to email this listing for further consideration by the entire committee.

The first day meeting was adjourned at 5:35 p.m.

The second day meeting was called to order at 8:40 by the chair.

Announcements:
1. Chair for next year will be Kevin Fritsche; secretary will be Kate Claycombe.
(Kate understands that she will be the incoming chair for 06 as per our newly agreed upon line of succession.)
2. Next years meeting will held in Fort Collins, CO and be hosted by Ken Allen and Jennifer Anderson, reps. from Colorado State University.
3. NC1167 Listserv: Debra Palmer Keenan wanted to know if she should maintain the listserv for this group. She did so last year, yet no one seemed to use it. We all agreed that we should keep it and USE IT. All committee members are to send her an email from our email address that we want on the listserv.

Station Reports:
The following member states gave brief research reports: Tennessee, Missouri, Colorado (2), Michigan, Nebraska, and Texas. These reports elicited many questions and some lively discussion. More complete reports are attached to these minutes.

Lunch & Guest Speaker:
We worked through lunch and had an informative discussion with Gale Strasburg, acting chair of the Food Science & Human Nutr. Dept. at MSU, regarding the recent reorganization of Colleges at MSU and the ongoing search for a new chair.

The meeting was adjourned at 1:45 pm.

Minutes Attachment:

Attachment

Accomplishments

Collaborative efforts of the basic science groups and nutrition education component were discussed. The collaboration has continued to strengthened as the project progresses; the group is developing into a cohesive core of n3 fatty acid researchers. For the basic researchers most of the collaborative efforts to date have been conceptual (i.e., at the level of experimental design). Specifically, each investigator has incorporated two common elements into there currently funded research programs: to address both n-3 form and amount relative to potency in their research models. Investigations being done include a number of different experimental conditions with various biological outcomes, unique to each researcher. Plans were made to enhance the collaboration between the basic researchers. On behalf of several participants, Dr. Whelan (Tenn) is preparing an application to the USDA to underwrite that cost of generating common basal and experimental animal diets containing human-equivalent amounts of various n-3 fatty acids. Each researcher will conduct studies with these common research diets. Such an approach is novel and will greatly facilitate direct comparisons of the relative potency of various n-3 fatty acids using numerous biological read-outs related to human health issues. The nutrition education researchers participating in this regional project generated novel baseline data regarding n-3 fatty acid knowledge of dieticians in several member states. They are prepared to impliment an educational outreach program that they have designed to increase awareness of and knowledge in the nutritional benefits associated with increased n-3 fatty acid consumption by the general public and by specific target populations. Impacts to be measured in the future will include: (1) enhanced knowledge of n-3 fatty acids by dieticians; (2) Increased frequency that the dieticians talk to patients about n-3 fatty acids; (3) Evidence of increase intake of n-3 fatty acids in the populations served by these health professionals within the participating states The impact of this project will be to provide essential primary data in a number of different systems to answer two fundamental questions regarding the recent recommendations to increase dietary n-3 fatty acid intake for health maintenance and disease prevention: (1) Which form of n-3 fatty acid are most potent? (2) How much is needed to provide health benefits? In addition, the nutrition education component will inform nutrition professionals on these results for education of RDs and their clients.

Publications

Allen, K.G.D., Bristow, S.J. and Yu, L. Hypolipidemic effects of modified psyllium preparations. J. Agric. Food Chem. 52: 4998-5003, 2004. Irons, R., Anderson, M.J., Zhang, M. and Fritsche K.L. (2003) Dietary fish oil impairs primary host resistance against L. monocytogenes more than the immunological memory response. J. Nutr. 133: 1163-1169. Zhang, M. and Fritsche K.L. (2004) Fatty acid-mediated inhibition of interleukin-12 production by murine macrophages is independent of peroxisome proliferator-activated receptor-g. Brit. J. Nutr. 91: 733-739. Anderson M and Fritsche KL (2004) Dietary polyunsaturated fatty acids modulate in vivo, antigen-driven CD4+ T-cell proliferation in mice. J. Nutr. 134: 1978-1983. Anderson, M. (2004) Dietary omega-3 polyunsaturated fatty acids and Th1 immunity. Ph.D. Dissertation, University of Missouri, Columbia, MO. Irons, R. (2004) Fish oil severely impairs immunity to Listeria monocytogenes without affecting the adaptive immune response. Ph.D. Dissertation, University of Missouri, Columbia, MO. Harkins, JM, Moustaid-Moussa, N, Penner, KM, Pestka, JJ, Chung, YJ, North, CM, and Claycombe, KJ. Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice. J Nutr. 134:2673-2677, 2004. Harkins, JM, Whelan J, Jones L, Ken Allen, and Claycombe, KJ. Inhibitory effect of SDA and EPA on 3T3-L1 preadipocyte secretion of interleukin-6 (IL-6). In preparation, 2004. Sindelar, Carrie A., Lewis, Nancy M., Scheerger, Sarah B., Plugge, Sheri L., Eskridge, Kent M., and Wander, Rosemary C. 2004. Serum lipids of physically active adults consuming omega-3 fatty acid-enriched eggs or standard eggs. Nutrition Research 24:731-739. Heidal, Kimberly, Lewis, Nancy, and Evans, Sharon. 2004. Survey of omega-3 food selections in heart patients living in the Midwest. Nutrition Research 24:741-747. Heidal, Kimberly, Lewis, Nancy M. 2004. Omega-3 fatty acid nutrition education resources. Journal of Nutrition Education and Behavior 36 (4):209-210. Al-Numair, Khalid and Lewis, Nancy M. 2004. Omega-3 fatty acid intake and incidence of nonfatal myocardial infarction differ between coastal and internal regions of Saudi Arabia. Ecology of Food and Nutrition 43:93-106. Ciubotaru I, Lee YS, Wander. Dietary fish oil decrease C-reaction protein, interleukin-6, and triacylglycerol to HDL-cholesterol ratio in postmenopausal women on HRT. J Nutr Biochem. 2003 Sep;14(9):513-21. Toobert DJ, Glasgow RE, Strycker LA, Barrera M Jr, Radcliffe JL, Wander RC, Bagdade JD. Biologic and quality-of-life outcomes from the Mediterranean Lifestyle Program: a randomized clinical trial. Diabetes Care. 2003 Aug;26(8):2288-93. Hall JA, Tooley KA, Gradin JL, Jewell DE, Wander RC. Effects of dietary n-6 and n-3 fatty acids and vitamin E on the immune response of healthy geriatric dogs. Am J Vet Res. 2003 Jun;64(6):762-72. Manns PJ, Williams DP, Snow CM, Wander RC. Physical activity, body fat, and serum C-reactive protein in postmenopausal women with and without hormone replacement. Am J Hum Biol. 2003 Jan-Feb;15(1):91-100. Whelan, J. and McEntee, M.F. 2003. NSAIDs, Prostaglandins and APC-Driven Intestinal Tumorigenesis. In: Cyclooxygenase-2 Blockade in Cancer Prevention and Therapy (Ed., Harris, R.E.) Humana Press, Inc.. Totowa, NJ D.W.L. Ma, J. Seo, L.A. Davidson, E.S. Callaway, Y.Y. Fan, J.R. Lupton and R.S. Chapkin. n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. Faseb Journal, April 2004, 10.1096/fj.03-0604fje, 18:1040-1042, 2004. L.M. Sanders, C.E. Henderson, M.Y. Hong, R. Barhoumi, R.C. Burghardt, R.J. Carroll, N.D. Turner, R.S. Chapkin and J.R. Lupton. Pro-oxidant environment of the colon compared to the small intestine may contribute to greater cancer susceptibility. Cancer Letters 208:155-161, 2004. K.C. Switzer, Y-Y. Fan, N. Wang, D.M. McMurray and R.S. Chapkin. Dietary n-3 polyunsaturated fatty acids promote activation-induced cell death in the Th1-polarized murine CD4+ T-cells. Journal of Lipid Research, 45:1482-1492, 2004. L.A. Davidson, D.V. Nyuyen, R.M. Hokanson, E.S. Callaway, R.B. Isett, N.D. Turner, E.R. Dougherty, J.R. Lupton, R.J. Carroll and R.S. Chapkin. Chemopreventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat. Cancer Research 64:6797-6804, 2004.

Impact Statements

Our data demonstrate that within human equivalent doses using long-chain n-3 fatty acids (DHA, EPA, SDA) is superior to a-linolenic acid.
We discovered that most nutrition health professionals as a general rule do not know enough about n-3 fatty acids to feel comfortable giving advice to their clients.

Date of Annual Report: 11/12/2005

Report Information

Annual Meeting Dates: 10/06/2005 - 10/07/2005
Period the Report Covers: 01/01/2005 - 12/01/2005

Participants

Audrey Adler (Rutgers University); Kenneth G.D. Allen (Colorado State University); Jennifer Anderson (Colorado State University); Richard Baybutt (Kansas State University); K. Shane Broughton (University of Wyoming); Robert Chapkin (Texas A & M); Kate Claycombe (Michigan State University); Kevin Fritsche (University of Missouri); Daniel Gallaher (University of Minnesota); Mary A. Harris (Colorado State University); Kimberly Heidal (East Carolina University); Debra Palmer Keenan (Rutgers University); Ye-Sun Lee representing Rosemary Wander (University of North Carolina, Greensboro); Nancy K. Lewis (University of Nebraska); Barbara Lohse (Kansas State University); Jay Whelan (University of Tennessee); Doreen Woodward (Administrative Adviser, Michigan State University).

Brief Summary of Minutes

The meeting was called to order by the chair, Kevin Fritsche at 8:30 a.m., October 6, 2005 at the Fort Collins Hilton, Fort Collins, CO. Kate Claycombe served as a secretary for this meeting.

Introductions & Opening Remarks:
The meeting opened with an around the introduction of participating members and a welcome by April Mason, Dean of College of Applied Human Sciences at Colorado State University. Dean Mason, with her background in Nutrition, commented on importance of our group's potentially contribution or impact on American public's dietary n-3 PUFA intake modification.

Susan Welsh was not able to attend the meeting due to other on-going USDA task (a self study report). Susan; however, sent a report via e-mail to the group on October 5th and offered to have a telephone conference during the meeting. Accordingly, nutrition education group members including Audrey Adler, Jennifer Anderson, Debra Palmer Keenan, Barbara Lohse and Nancy K. Lewis had a consultation session via telephone with Susan Welsh about ADA meeting and NC-1167 proposal renewal issues.

Nancy K. Lewis updated and made suggestion to submit an American Dietetic Association (ADA) meeting conference grant proposal for September 16-19, 2006 meeting. Appropriateness and suitability of NC-1167 group to take part in the American Dietetic Association's Annual meeting were discussed. Feasibility of USDA conference grant proposal submission, possible industry support dollars, and identification of NC-1167 member who would take the leadership role in USDA conference grant proposal submission was also discussed. Kevin Fritsche asked to review about the timeline for year 2007-2012 proposal submission by NC-1167 to USDA. The group decided to have the draft proposal finished by December 2006. Members agreed to start writing the proposal during the 2006 Experimental Biology meeting and 2006 ADA meeting, and through out the year 2006. Review of our current proposal for any accomplishments to date and new directions were proposed. Jay Whelan and Ken Allen agreed to take a leadership role in writing NC-1167 renewal proposal for year 2007-2012. Based on suggestions from all members, Kevin Fritsche suggested that NC-1167 proposal renewal should be based on systematic review to determine whether the group adequately addressed the forms and the amount issues from the current cycle. Doreen Woodward suggested considering having the renewal proposal actually be interwoven among all projects rather than having parallel goals. Jay Whelan suggested reviewing how much collaborative effort has been made or will be made through out the current period and in the future proposal.

Doreen Woodward (administrative advisor, Michigan State) updated the group about potential changes in CREES funding due to budget cuts and the possibility of future paradigm shifts. Thus, she suggested critical review of impacts and outcomes from our group in preparation for continuing support for our program. Doreen Woodward initiated an intense group discussion regarding how to measure impacts and how best to communicate impacts and outcomes using logic models. Doreen Woodward updated the group about the cancellation of the Annual Agricultural Experimental Station Director's meeting that was scheduled to be held at San Antonio (It was cancelled due to the hurricane). Doreen Woodward encouraged NC-1167 group members to communicate and update Agricultural Experimental Station Directors about group impacts and justifications of Multistate Research Programs.

Mary A. Harris gave a 30 min research report on the CSU IFAFS DHA Gestational Duration study- The Intervention Phase. Jennifer Anderson gave a 30 min research report on the CSU IFAFS DHA Gestational Duration Study - The Nutrition Education Phase. Lively input, questions and suggestions were exchanged by all participants of the meeting.
Breakout sessions were held at the Nutrition Department of CSU for Group I (Audrey Adler, Jennifer Anderson, Debra Palmer Keenan, Barbara Lohse, and Nancy K. Lewis) about the outreach and education goals. Group II (Allen, Baybutt, Broughton, Chapkin, Claycombe, Harris, Fritsche, Gallaher, and Whelan) met at the Hilton conference room to attend presentation of "Human equivalent dose modeling for omega-3 fatty acids" by Jay Whelan; followed by a discussion of animal (& cell culture) systems used to explore "form & amount" questions. Kevin Fritsche, Ken Allen and Jay Whelan indicated that n-3 PUFA - induced changes were still present in the studies in which US17 diets (with human equivalent levels of background PUFAs) were used. All members participated during the follow up group discussion regarding needs to establish standardization of n-3 PUFA DRIs.
Business items: The following issues were discussed: formation of a writing committee for the renewal for next cycle, continuation of group focus (form and amount), EB meeting updates, deadline for ADA meeting conference. All members agreed to meet one day early at EB 2006 meetings to set up the framework for our NC-1167 proposal renewal (for year 2007-2012). Jennifer Anderson and Jay Whelan were asked to serve as speakers at the up coming 2006 ADA meeting in Hawaii. Jennifer Anderson and Jay Whelan also agreed to write ADA conference proposal to be submitted to ADA (arranged with consultation with ADA meeting organizer by Nancy K. Lewis). Kevin Fritsche and Kate Claycombe agreed to write NC-1167 final report for year 2002-2007 period. Kevin Fritsche suggested to update the NC-1167 litserve and to add Daniel Gallaher.
Debra Palmer Keenan presented station report on behalf of the Nutrition education and outreach group (Audrey Adler, Jennifer Anderson, Debra Palmer Keenan, Barbara Lohse, and Nancy K. Lewis). Results from the web-based survey of registered dietitians revealed limited knowledge of forms and amounts of n-3 PUFA. Preparation of manuscript with emphasis on registered dietitians' strong interest in learning more to provide accurate information to consumers and other clients was indicated. Following this report, the group as a whole discussed the need to submit for a USDA/NRI conference grant by the December 13th deadline for year 2006.
The first day's meeting was adjourned at 5:35 p.m.

Jennifer Anderson and Jay Whelan met at 8:00 a.m. on Friday October 7th to finish drafting the ADA conference proposal. The second day meeting was called to order at 8:30 a.m. by the chair.

Station Reports:
The following member states gave research reports: North Carolina (2), Michigan, Texas, Missouri, Colorado, Tennessee, Wyoming, Nebraska, and Kansas. These reports elicited many questions and some lively discussion. More complete reports are attached to these minutes.

Progress/Goals: Collaborative efforts of the basic science groups and nutrition education component were discussed. In the basic science part, use of US17 diet by multiple stations generated significant biological effects even with human equivalent doses of background n-3 PUFAs. Additional data will answer questions regarding the most important forms and amounts of dietary n-3 fatty acids for health maintenance and disease prevention which will be strengthened by documenting the effect in a number of different disease model or systems. Jay Whelan shared his review findings about how dietary n-3 PUFA pools change in vivo according to different dietary forms and amount of n-3 PUFA intake. Preparation of the manuscript from nutrition education component was indicated. Using identified progress (up to date) and future goals Debra Palmer Keenan initiated drafting ideas for USDA NRI proposal.

Barbara Lohse agreed to serve as a secretary for year 2005-2006 and then chair for year 2006-2007. The meeting was adjourned at noon.

Accomplishments

During 2005, work was begun on interpreting and documenting the results of the 190 surveys completed with Registered Dietitians (RDs) concerning their knowledge of omega-3 fatty acids, how they use this information with clients, and if and how they would like to receive additional education in the future on this topic. Additional analysis of results has been completed to further inform the strategies for the next stage of this project. Multistate partners from Nebraska, New Jersey, Pennsylvania State University, Rutgers, and Colorado State University are continuing data analysis of web-based and telephone surveys of dietitians in the four states. We have also begun initial steps in development of an omega-3 fatty acid educational website directed at nutrition practitioners. The coming year we plan to conduct qualitative assessments to identify dietitians responses to draft educational materials and proposed website layout. Basic Science components of this project: The Tennessee Station completed the developed and testing of a mathematical model for allometric scaling of polyunsaturated fatty acids (PUFA) between rodent models and humans. Their results provide a framework to improve the predictability of pre-clinical screening using experimental models as a surrogate for potential human responses. This would minimize false positives in animal experiments and unnecessary and expensive clinical trials that are, in part, based on these animal experiments. The Tennessee and Missouri Stations collaborated in an application of this novel allometric scaling model. Using rodent diets designed and formulated at Tennessee, the Missouri station conducted a feeding trial to examine the impact on host infectious disease resistance of supplementing EPA only to a basal rodent diet that mimicked current U.S. PUFA intake. The data suggest that providing mice a diet with extra EPA at levels equivalent to 1.4 en% will significantly diminish resistance against the food-borne bacterial pathogen, Listeria monocytogenes. The others Stations focused on investigating the biological activity of SDA (18:4n-3), a novel omega-3 fatty acid that we propose may serve as a land-based alternative source for the long-chain n-3 fatty acids found in marine and fish oil sources, EPA (20:5n-3) and DHA (22:6n-3). The Michigan Station reported that preadipocytes secrete significantly higher levels of LPS-induced IL-6 compared to differentiated adipocytes in murine cell lines and in primary cells that were isolated from mouse adipose tissues. Also, we showed that both EPA and SDA decrease LPS-induced IL-6 mRNA expression and IL-6 secretion significantly in adipose MCS cells and in 3T3-L1 preadipocytes. The Colorado station reported that SDA significantly increased only EPA in reprodutive tissue, the conversion of SDA to DHA appears to be limited by the requisite delta-6 desaturase that is proposed to be a part of the delta-4 desaturation step. Only at the highest level (2 en%) did SDA reduce uterine PGE2 production or fetal membrane PGF2alpha production in relation to LnA, and SDA does not affect uterine PGF2alpha or fetal membrane PGE2 production differently than does LnA. Given findings that lower levels of SDA were not any more effective in increasing tissue percent EPA or diminishing PG production than were higher levels of LnA, and since LnA and SDA did not differ in their effects on MMP-2 and MMP-9, further research is necessary to justify the use and doses of SDA supplements that are necessary to suppress PG production, prevent preterm PROM, and extend gestational length. The Wyoming Station conducted the first study examining the effect of dietary SDA and its effect on ovulation. When present in the diet of rats at only 0.6 wt% there was an enhancement in ova release. The North Carolina Station investigated the modulatory effects of unoxidized and oxidized PUFA on the production of several inflammatory responsive, pro-atherogenic mediators and their upstream activated transcription factors in LPS-stimulated macrophages. U937 cells were differentiated into macrophages by stimulation with PMA, incubated with 50 µM unoxidized and 15-LO oxidized arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) for 24h, and then stimulated with LPS (1¼g/ml) for 48-72h. The unoxidized PUFA produced no significant differences in LPS-induced IL-1² and IL-6 concentrations but decreased significantly the amount of mCRP compared to control, with unoxidized EPA and DHA being significantly more potent agents than unoxidized AA. All three oxidized PUFA significantly decreased the amount of LPS-induced IL-1², IL-6, and mCRP, with oxidized EPA being more potent than oxidized DHA and AA. Also, the LPS-induced activation of NF-ºB, C/EBP-², and STAT-3 was changed by to a greater extent by the oxidized PUFA than the unoxidized PUFA. The Texas Station investigated dietary perturbation of caveolae lipid microdomains and their subsequent altering of protein functionality. Caveolae isolated from mice fed n-6 (control) or n-3 PUFA enriched diets were characteristically enriched in cholesterol and sphingomyelin. n-3 PUFA reduced cholesterol and caveolin-1 content in the caveolae fraction by 46% and 53%, respectively. Concomitantly, localization of caveolae resident signaling proteins, H-Ras and eNOS, was decreased by 45% and 52%, respectively, and H-Ras activation was reduced. In contrast, localization of non caveolae proteins, K-Ras and clathrin was unchanged. These findings suggest that caveolae can be targeted in vivo by lipid modifying dietary agents and highlight the potential for caveolae to be exploited for therapeutic applications.

Publications

Al-Numair, Khalid and Lewis, Nancy M. 2005. Omega-3 fatty acid consumption and food sources differ among elderly men living in coastal and internal regions of Saudi Arabia. Pakistan Journal of Nutrition 4(2):106-111. J. Series No. 14308. Ritter-Gooder, P. and Lewis, Nancy M. 2005. Validity and reliability of a quantitative food frequency questionnaire measuring N-3 fatty acid intakes in cardiac patients in the rural Midwest. Journal of the American Dietetic Association 105:A16. Ritter-Gooder, P. Validity and reliability of a quantitative food frequency questionnaire measuring omega-3 fatty acid intakes in cardiac patients in the Midwest. M.S. Thesis, University of Nebraska. 2005. Troxell, H., Anderson, J., Auld, G., Marx, N., Harris, M.A., Reece M.S. and Allen, K.G.D. Omega-3 for Baby and Me: Material Development for a WIC intervention to Increase DHA Intake During Pregnancy. Maternal and Child Health Journal 9: 189-197, 2005. Lohse B, Shafer KJ, Theory-driven n-3 polyunsaturated fatty acid education delivered by written correspondence and problem-based approaches. Nutrition Research. (In Press). Jones, L. and Whelan, J., Human Equivalent Dose Modeling for Omega-3 Fatty Acid Supplementation in C57BL/6J Mice. 2005. FASEB J. 590.3A. Irons, R and Fritsche K.L. (2005) Omega-3 polyunsaturated fatty acids impair in vivo interferon-gamma responsiveness via diminishing receptor signaling. J Infect Dis. 191(3): 481-6. Irons, R., Pinge-Filho, P., Fritsche, K. (2005) Dietary (n-3) polyunsaturated fatty acids do not affect the in vivo development and function of Listeria-specific CD4+ and CD8+ effector and memory/effector T cells in mice. J. Nutr. 135: 1151-1156. Fritsche, K., Irons, R., Pompos, L., Janes, J., Zheng Z. and Brown, C. (2005) Omega-3 polyunsaturated fatty acid impairment of early host resistance against Listeria monocytogenes infection is independent of neutrophil infiltration and function. Cell Immunol (in press) Perez, M.A., Hansen, R.A., Harris, M.A. and Allen, K.G.D. Dietary docosahexaenoic acid alters pregnant rat reproductive tissue prostaglandin and matrix metalloproteinase production. J. Nutr. Biochem. In Press 2005. Rose, Janelle R. Dietary stearidonic acid and pregnant rat uterine and fetal membrane mediators of premature delivery. Masters degree Thesis, Colorado State University. Fall Semester 2004. Perez, Mark A. Dietary docosahexaenoic acid alters pregnant rat reproductive tissue prostaglandin and matrix metalloproteinase production. Masters degree Thesis, Colorado State University. Fall Semester 2005. Krugman, J, Rowe T, Tonso E, Tonso T, Driscoll M, Clement B, Anderson L, Hirschi K, Rule DC, Culver B, and Broughton KS. 2005 Effect of stearidonic acid on eicosanoid metabolism and ovulation. FASEB J. 19:A1007 (590.2) Harkins JM, Moustaid-Moussa N, Chung YJ, Penner KM, Pestka JJ, North CM, Claycombe KJ. Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice. J Nutr. 134(10):2673-2677, 2004 Ciubotaru, I., Potempa, L.A., and Wander, R.C. 2005. Production of modified C-reactive protein in U937-derived macrophages. Accepted Society Experimental Biology and Medicine. Lee, Y.S. and Wander, R.C. 2005. Reduced effect on apoptosis of 4-hydroxyhexenal and oxidized LDL enriched with n-3 fatty acids from postmenopausal women. J Nutr. Biochem. Apr 16(4): 213-221. Hall, J.A., Henry, L.R., Jha, S., Skinner, M.M., Jewell, D.E., and Wander, R.C. 2005. Dietary (n-3) fatty acids alter plasma fatty acids and leukotriene B synthesis by stimulated neutrophils from healthy geriatric Beagles. Prostaglandins, Leukotrienes, Essential Fatty Acids. Nov 73(5):335-41. Irina Ciubotaru, Ph.D. 2005. The Anti-Inflammatory Effects of Eicosapentaenoic and Docosahexaenoic Acids found in Fish in vivo and in vitro. Thesis. D.W.L. Ma, J. Seo, L.A. Davidson, E.S. Callaway, Y.Y. Fan, J.R. Lupton and R.S. Chapkin. n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. Faseb Journal, April 2004, 10.1096/fj.03-0604fje, 18:1040-1042, 2004. D.W.L. Ma, J. Seo, K.C. Switzer, Y.Y. Fan, D.N. McMurray, J.R. Lupton and R.S. Chapkin. n-3 PUFA and membrane microdomains: a new frontier in bioactive lipid research. J Nutr Biochem 15: 700-706, 2004.

Impact Statements

NC1167 has changed the way the USDA reports fatty acid composition data and developed an effective educational program for the dissemination of health-related information to help the public meet current recommendations for increased n-3 fatty acid intake.
We have impacted how USDA dietary nutrient composition database laboratory report n-3 fatty acid content of foodstuffs, such that researchers now report all individual long-chain polyunsaturated fatty acids down to milligram quantities, not grams.
We have impacted nutrition education programs within our region. A recent survey conducted following a Clarifying the omega-3 fatty acid controversy seminar, part of the Lillian Fountain Smith Conference for Nutrition Educators, found that greater than 99% of respondents improved their n-3 fat knowledge and planned to include n-3 fat advice in their practices. Follow-up studies are planned to access the impact of our project on the actual n-3 PUFA consumption by people served by the health professionals exposed to our education programs.
NC1167 is one of the first groups to investigate the potential health benefits of novel plant-derived omega-3 fats relative to n-3 PUFA found in fish products. Such basic research is important because concerns many health professionals have expressed regarding the cost, availability, and safety of consuming n-3 PUFA from fish and fish products. It is too early to know whether this basic research will impact the information nutrition educators provide to the public or the extent to which consumers benefit from current recommendations for higher n-3 intake. However, we believe it will, in time.