Progress 10/01/02 to 09/30/07
Outputs
OUTPUTS: Human diets contain little n-3 polyunsaturated fatty acids (PUFA) and excessive amounts of n-6 PUFA. The objectives of this project were to identify the forms and amounts of dietary n-3 PUFA that decrease cardiovascular disease and premature delivery, increase gestational length (duration) and to effectively translate this information into consumer food choices Activities: Animal and human (blinded intervention trial) experiments were conducted and analyzed. Three large animal experiments were conducted with three forms and two amounts of dietary n-3 PUFA using pregnant rodents. Amounts of dietary n-3 PUFA were designed to reflect current and achievable amounts using the human equivalent dose method (allometric scaling). Human intervention trial examined modest (300 and 600 mg per day) supplements of the long-chain n-3 PUFA, docosahexaenoic acid (DHA) in pregnant women. Questionnaires assessing n-3 PUFA knowledge and practice in dieticians were developed and shared with
dieticians in Colorado, Nebraska, New Jersey and Kansas. Events: Findings were disseminated at Experimental Biology Meetings, Annual Meetings of the Multistate project members, invited presentations and seminars at Colorado, Michigan and New Jersey. Products: New knowledge about the efficacy and the mechanism by which dietary n-3 PUFA forms and amounts can alter gestation duration was obtained. The human equivalent dose (allometric scaling) method of translating experimental animal data into human relevant data was validated. The applicability and utility of long-chain n-3 PUFA supplementation in lengthening gestation was demonstrated in a large human trial.
PARTICIPANTS: Allen, Kenneth G.D. Principal Investigator. Design, implementation, interpretation of experiments. Publication of results. Harris, Mary A. Collaborator. Design, implementation, interpretation of experiments. Publication of results. Anderson, J.E.L. Principal Investigator. Design, implementation, interpretation of dissemination phase of this project. Rose, J.L. Graduate Research Assistant. Stearidonic acid (SDA) experiments Perez, M.A. Graduate Research Assistant. Docosahexaenoic acid (DHA) experiments. Troxell, H. Graduate Research Assistant. Menue design for DHA intervention study in pregnant women. Kim, P.Y. Graduate Research Assistant. Human myometrial cell culture experiments. Members of NC 1167 Multistate Project. Collaboration on experimental approach, design and writing of Multistate Project. Whelan, J. University of Tennessee. Collaborated on writing the Multistate Project. Sanborn, B. Colorado State University. Collaboration on the myometrial cell culture
studies.
TARGET AUDIENCES: Target Audiences: Nutrition scientists, Nutrition professionals, Dieticians, Extension professionals, Physicians, Food oil producers. Efforts: Classroom instruction, laboratory instruction, presentations at national meetings, publications in scientific journals, extension and outreach activities.
PROJECT MODIFICATIONS: None
Impacts
The results of this study show that modest, achievable dietary supplements of certain long-chain n-3 PUFA can increase gestation duration. Increased gestation duration, even by a modest few days, will decrease the significant mortality and morbidity due to shortened gestation. Provision of 600 mg per day supplementary docosahexaenoic acid (DHA), equivalent to about 0.3 percent of calories, increased gestation in pregnant women by four days. In addition, in animal experiments using human equivalent doses, we have shown that the form of n-3 PUFA is the most important factor in altering the indices of gestation duration. Inclusion of the preformed, long-chain n-3 PUFA DHA in the diet is the most effective n-3 PUFA. Linolenic acid (ALA, the parent n-3 PUFA) is not effective, even when provided at three times the amount found in current US diets. Simply replacing the current US dietary intake of ALA (about 0.7 percent of calories) with an equivalent amount of DHA
significantly decreases uterus and placenta prostaglandin (PG) and matrix metalloproteinase (MMP) production. Increasing dietary DHA three-fold had no significant additional advantage. Stearidonic acid (SDA) has been proposed as a plant-oil based long-chain n-3 alternative to fish based long-chain n-3 PUFA through genetically modified plant food oil crops. In animal experiments we have shown that SDA, fed at the current US diet intake of ALA (0.7 percent of calories)or at an enhanced 2.0 percent of calories, increases reproductive tissue eicosapentaenoic acid (EPA)but did not increase DHA. Also, SDA did not alter PG and MMP markers of shortened gestation. Our data suggest: dietary DHA is crucial, and needs only a modest dietary provision (0.3 to 0.7 percent of calories, about 0.6 to 1.5 g per day), ALA provision even at three times current US intake is ineffective, and while dietary SDA provision does increase EPA it does not afford a source that alters DHA or the indices of shortened
gestation. Surveys of Dieticians in Colorado, Nebraska, Kansas and New Jersey indicate the need for information and education regarding the most effective forms and amounts on n-3 PUFA and the appropriate dietary sources of these fatty acids in order to impact reproductive and neonatal health in the US.
Publications
- No publications reported this period
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Progress 01/01/06 to 12/31/06
Outputs
The multistate project goal is: to identify and evaluate agricultural and marine sources of n-3 polyunsaturated fatty acids (n-3 PUFA) to meet the new dietary guidelines for optimal health and reduction in the risk of disease throughout the life cycle. Colorado Agricultural Experiment Station objectives to meet this goal are: 1) to evaluate the effects of different n-3 fatty acids, both form (source) and amount, on biomarkers of gestational duration and premature delivery and 2) to develop effective means for translating research knowledge about n-3 PUFA into consumer food choices. Accomplishments: Using immortalized late-pregnancy human myometrial cells in culture we have shown that incubating these cells with 10 to 100 micromolar docosahexaenoic acid (DHA)decreases oxytocin (OT) induced Ca entry, decreases plasma membrane OT receptor density and number and decreases inositol trisphosphate (IP-3)signaling concentrations. However, very similar results are obtained
with equimolar arachidonic acid(AA), a n-6 polyunsaturated fatty acid. In an intact dog model with knee arthritis, where dogs lived at home with their owners, we have shown that 2.0 energy percent dietary DHA plus eicosapentaenoic acid (EPA) significantly suppressed mediators of joint (synovia)arthritis damage such as matrix metalloproteinase (MMP) 2 and 9, tissue inhibitors of MMP, and urokinase type plasminogen activator. Researchers from Colorado, Kansas, New Jersey and Nebraska working as a team have developed 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 both telephone and web survey methodologies. Kansas and New Jersey developed and conducted the surveys and
the data analysis. Results indicated that > 80% of the dietitians survey in the four states indicated a need for more education and knowledge about omega-3 fatty acids.
Impacts
Our data has clearly shown that modest amounts of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as docosahexaenoic acid (DHA) significantly increases gestation duration by 4 days. Also, DHA suppresses reproductive tissue (uterus, placenta) prostaglandins and matrix metalloproteinases that are involved in parturition. DHA also may decrease oxytocin mediated processes leading to early delivery. Thus we have demonstrated the efficacy, and some of the mechanisms, by which LC n-3 PUFA increase gestation and perinatal health. Shortened gestation and preterm delivery is associated with 70% of neonatal deaths. Lengthening gestation and decreasing preterm birth by modest dietary LC n-3 PUFA intakes will improve neonatal outcomes and reduce health care costs. We also have demonstrated that dietary LC-n-3 PUFA can decrease the progression of joint arthritis. Arthritis is increasing due to an increase in life expectancy and increased diet LC n-3 PUFA will reduce
the impact of this disease.
Publications
- Perez, M.A., Hansen, R.A., Harris, M.A. and Allen, K.G.D. 2006. Dietary docosahexaenoic acid alters pregnant rat reproductive tissue prostaglandin and matrix metalloproteinase production. J. Nutr. Biochem. 17: 446-453.
- Kelavkar, U.P., Hutzley, J., Dhir, R, Kim, P.Y, Allen, K.G.D. and McHugh, K. 2006. Prostate tumor growth and recurrence can be modulated by the omega (ω)-6 : ω-3 ratio in diet: Athymic mouse exnograft model simulating radical prostatectomy. Neoplasia, 8: 112-124.
- Hansen, R.A., Harris, M.A., Pluhar, G.E., Motta, T., Brevard, S., Ogilvie, G.K., Fettman, M.J. and Allen, K.G.D. 2007. Fish oil decreases matrix metalloproteinases in knee synovia of dogs with inflammatory joint disease. J. Nutr. Biochem. In Press.
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Progress 01/01/05 to 12/31/05
Outputs
The multistate project goal is: to identify and evaluate agricultural and marine sources of n-3 polyunsaturated fatty acids (n-3 PUFA) to meet the new dietary guidelines for optimal health and reduction in the risk of disease throughout the life cycle. Colorado Agricultural Experiment Station objectives to meet this goal are: 1) to evaluate the effects of different n-3 fatty acids, both form (source) and amount, on biomarkers of gestational duration and premature delivery and 2) to develop effective means for translating research knowledge about n-3 PUFA into consumer food choices. Accomplishments: using a stearidonic acid (SDA, a land based source of LC n-3 PUFA) we have shown that SDA provided at the current US intake of linolenic acid (0.7 percent of calories in the diet) increases pregnant rat uterine eicosapentaenoic acid (EPA). SDA significantly reduced uterine prostaglandin E2 production. However, in contrast to equal amounts of docosahexaenoic acid (DHA), SDA
did not decrease uterine metalloproteinase expression and activity. Using human late pregnancy myometrial (uterus) immortalized cells in culture we have shown that incubating cells with 10 to 30 micromolar docosahexaenoic acid (DHA) significantly reduces oxytocin mediated Ca entry and suppresses inositol phosphate signaling pathways. Similar experiments with n-6 arachidonic acid suggest that this effect is perhaps a generalized response to long-chain PUFA. Surveys of dieticians in several states suggests knowledge about the most appropriate and effective form of n-3 fatty acids in US diets does not reflect the science showing that LC n-3 PUFA such as DHA and EPA are far more effective than vegetable oil n-3 linolenic acid.
Impacts
Data from our laboratory and others has clearly shown that modest amounts of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), such as docosahexaenoic acid, significantly increases gestational duration in humans. Shortened gestation leading to low birth weight is a major cause of infant mortality and morbidity. Understanding the most effective dietary n-3 fatty acids that impact these outcomes is important for the health of the US population. These studies address both the form and the amount of dietary n-3 fatty acids necessary for health maintenance and disease prevention, and the mechanisms by which LC n-3 PUFA influences the biochemical processes of parturition. In addition, education of dieticians and hence their clients is an important feature of this project. Education about, and dissemination of information on, the most health effective dietary form and amount of n-3 PUFA will impact consumer health. Increasing gestational duration and hence limiting
low infant birth weight problems by effective (form and/or amount) dietary n-3 fatty acids, and education of dieticians and consumers, will improve infant health.
Publications
- Troxell, H., Anderson, J., Auld, G., Marx, N., Harris, M.A., Reece M.S. and Allen, K.G.D. 2005. 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.
- Perez, Mark A. 2005. Dietary docosahexaenoic acid alters pregnant rat reproductive tissue prostaglandin and matrix metalloproteinase production. Masters Thesis. Colorado State University, Dept. of FOod Science and Human Nutr., Fort Collins, CO. Fall Semester 2005.
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Progress 01/01/04 to 12/31/04
Outputs
The multi state (Regional) project goals are: to determine the quantitative importance of n-3 PUFA and the ratio of n-3 to n-6 PUFA on nutritional and functional markers associated with optimal health and disease prevention. Colorado Agricultutal Experiment Station goals of this project are:1)to test the hypothesis that dietary n-3 and n-6 fatty acids play important and modifiable roles in preterm delivery. Accomplishments: Using a cultured human myometrial cell line, we have shown that incorporation of docosahexaenoic acid (DHA) into cell membranes significantly reduces oxytocin mediated calcium entry by 30% to 80% in comparisson to oleic acid controls. This effect of DHA was apparent at cell culture media concentrations as low as 10 micromolar. Tus, the fatty acid environment of the myometrial membranes alters the cells response to oxytocin. Oxytocin mediated calcium entry is important in uterine contractions that play a role in parturition and delivery. Using
pregnant rats as the model we have shown that DHA (a long chain n-3 PUFA) when fed from conception through deliver of rat pups at a modest 0.7% of calories (the current US intake of linolenic acid) reduces uterus and placenta prostaglandin (PG) E2 and F2 alpha production and the expression of matrix metalloproteinases (MMP). Both PG and MMP govern parturition. Linolenic acid was not effective even when provided at 2.0% calories. These data suggest that preformed long chain n-3 fatty acids (such as DHA) decrease indicators of shortened gestational duration.
Impacts
Improving the tissue status of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as DHA will decrease premature delivery, increase gestational duration and improve infant health outcomes. In addition LC n-3 PUFA play important roles in reducing heart disease and increasing bone formation. In order to address these issues we need to know the most effective dietary means to increase LC n-3 PUFA status and tissue levels, and to examine their effects on these health outcomes. Understanding the most effective dietary n-3 fatty acids that impact these outcomes is important for the health of the US population. These studies address both the form and the amount of dietary n-3 fatty acids necessary for health maintence and disease prevention. Premature delivery and shortened gestation are major causes of infant mortality and morbidity and health problems often persist into adulthood. Reducing these problems by effective (form and/or amount) dietary n-3 fatty acids
will improve infant health.
Publications
- 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, In Press (accepted July 2004).
- Allen, K.G.D., Bristow, S.J. and Yu, L. 2004. Hypolipidemic effects of modified psyllium preparations. J. Agric. Food Chem. 52: 4998-5003.
- Harkins, J.M., Hazan, A.M., Allen, K., Penner, K.M., Pestka, J.J. and Claycombe, K.J. 2004. Modulation of IL-6 expression and secretion in adipose tissue in virto and in vivo by n-3 fatty acids. Presented at Experimental Biology 2004 Meeting, Washington DC, April 17-24, 2004. FASEB J. 18, A866 (Abstract # 587.4).
- Rose, Janelle Lynn. 2004. Dietary stearidonic acid and pregnant rat uterine and fetal membrane mediators of premature delivery. Masters Degree Thesis, Department of Food Science and Human Nutrition, Colorado State University.
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Progress 01/01/03 to 12/31/03
Outputs
Overall objective of the multi state (Regional) project: To determine the quantitative importance of n-3 PUFA and the ratio of n-3 to n-6 PUFA on various nutritional and functional markers associated with optimal health and disease prevention. Specifically: 1) reduce the risk of cardiovascular disease and cancer and 2) promote bone development and perinatal health. Colorado Agricultural Experiment Station (AES) specific objectives: 1) To test the hypothesis that dietary n-3 and n-6 fatty acids play important and potentially modifiable roles in preterm delivery and 2) in collaboration with Indiana AES, to determine the mechanism(s) by which fat and the amount of n-3 and n-6 PUFA affect bone formation and resorption. Accomplishments:Preterm delivery. In animal experiments we have examined the influence of dietary n-3 PUFA sources on prostaglandins (PG) involved in uterine contractions and cervical remodeling, and on matrix metalloproteinase (MMP) expression which
governs the tissue remodeling processes at parturition. We have shown that changing the dietary n-6/n-3 fatty acid ratio from 34:1 to 7:1 by increasing linolenic acid (LnA) at a constant linoleic (LnA) intake, had no effect on uterine and placental PGE2 and PGF2 alpha production in pregnant rats at day 20 of gestation. However, when DHA was substituted for LnA even at a modest 0.7 energy % (the current US diet intake of n-3 PUFA) both PGE2 and PGF2 alpha production were depressed in uterus and placenta of 20 day pregnant rats. In addition, placental collagenase activity which measures matrix MMP 1, 8 and 13 was significantly depressed by 0.7 energy % DHA, and MMP-2 and MMP-9 expression was also depressed by DHA but not by LnA. We have also investigated the effects of stearidonic acid (SDA) in this same model. SDA is a fatty acid that has double bonds at positions 6, 9,12 and 15. Thus, it bypasses the rate controlling step in the conversion of linolenic acid to DHA. SDA containing food
oils are being developed as a means of improving n-3 status; in some respects SDA containg oils are land-based alternatives to fish oils which often contain mercury and polychlorinated biphenyls. SDA provided to 20 day pregnant rats at the current US intake of n-3 fatty acids significantly depressed uterine and amnion PG production rates. SDA provision is more effective than increasing linolenic acid, and the deliterious effects of the dietary n-6/n-3 ratio are obviated. We are currently examining the expression of MMPs and their activators and inhibitors in this SDA model.
Impacts
Improving the tissue status of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as DHA will decrease premature delivery, increase gestational duration and improve infant health outcomes. In addition LC n-3 PUFA play important roles in reducing heart disease and increasing bone formation. In order to address these issues we need to know the most effective dietary means to increase LC n-3 PUFA status and tissue levels, and to examine their effects on these health outcomes. Understanding the most effective dietary n-3 fatty acids that impact these outcomes is important for the health of the US population. These studies address both the form and the amount of dietary n-3 fatty acids necessary for health maintence and disease prevention. Premature delivery and shortened gestation are major causes of infant mortality and morbidity and health problems often persist into adulthood. Reducing these problems by effective (form and/or amount) dietary n-3 fatty acids
will improve infant health.
Publications
- Turek, J.J., Watkins, B.A., Schoenlein, I.A., Allen, K.G.D., Hayek, M.G. and Aldrich, C.G. 2003. 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. 2003. 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. 2003. 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. 2003. 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., Allen, K.G.D., Pluhar, E.G., Ogilvie, G.K., Fettman, M.J. and Harris, M.A. 2003. 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. 2003. 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.
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