ISSFAL Statement on



ISSFAL Official Statement Number 5α–Linolenic Acid Supplementation and Conversion to n-3 Long Chain Polyunsaturated Fatty Acids in HumansJ. Thomas Brenna1, Norman Salem, Jr.2, Andrew J. Sinclair3, and Stephen C. Cunnane4, for the International Society for the Study of Fatty Acids and Lipids, ISSFAL.1Division of Nutritional Sciences, Cornell University, Savage Hall, Ithaca, NY, 14853 USA2Martek Biosciences, Inc., 6480 Dobbin Rd, Columbia, MD, 21045 USA3Deakin University, School of Exercise & Nutrition Sciences, 221 Burwood Highway, Burwood, Victoria 3125, Australia. 4Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada.A statement on PUFA nutrition developed and edited based on input from ISSFAL members and accepted by vote of the ISSFAL Board of Directors.Summary. Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets which are rich in linoleic acid (LA) show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors. IntroductionThe ability of mammals, and humans in particular, to metabolize alpha-linolenic acid (ALA, 18:3n-3) to its longer chain and more unsaturated forms including eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPAn-3, 22:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) is an important nutritional question since there is evidence that enhanced EPA and DHA status is important for optimal health. The principal n-3 fatty acids, ALA, EPA and DHA, are believed to each have a constellation of physiological functions and therefore it is important to understand the extent of their metabolism from ALA in various mammals in order to achieve an understanding of the n-3 PUFA that must be consumed to support desirable tissue levels. This statement addresses the degree to which the supplementation of the diet with ALA, EPA or DHA supports the tissue and blood levels of the major omega-3 PUFA in animals and in humans. “Supplementation” in this context refers specifically to the addition of a fatty acid to a diet that is otherwise not changed, which can be achieved by fortification of normal foods or by consumption of caplets. In vivo metabolic studies of various mammals, including tracer studies in humans using stable isotopically labeled fatty acids are considered. Since there is antagonism between n-3 and n-6 essential fatty acids (EFA) for tissue composition, their interplay is also briefly considered.Alpha-Linolenic Acid Supplementation – Tissue Compositional Studies in AnimalsSeveral reviews concerning the issue of ALA metabolism to EPA, DPAn-3 and DHA have appeared recently ADDIN EN.CITE <EndNote><Cite><Author>Brenna</Author><Year>2002</Year><RecNum>622</RecNum><record><rec-number>622</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Savage Hall, Cornell University, Ithaca, New York 14853, USA. jtb4@cornell.edu</auth-address><titles><title>Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man</title><secondary-title>Curr Opin Clin Nutr Metab Care</secondary-title></titles><pages>127-32</pages><volume>5</volume><number>2</number><keywords><keyword>Energy Metabolism</keyword><keyword>Fatty Acids, Omega-3/*biosynthesis</keyword><keyword>Fatty Acids, Omega-6</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>Humans</keyword><keyword>Oxidation-Reduction</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Mar</date></pub-dates></dates><accession-num>11844977</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite><Cite><Author>Burdge</Author><Year>2005</Year><RecNum>698</RecNum><record><rec-number>698</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G. C.</author><author>Calder, P. C.</author></authors></contributors><auth-address>Institute of Human Nutrition, University of Southampton, Southampton, UK. G.C.Burdge@soton.ac.uk</auth-address><titles><title>Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults</title><secondary-title>Reprod Nutr Dev</secondary-title></titles><periodical><full-title>Reprod Nutr Dev</full-title></periodical><pages>581-97</pages><volume>45</volume><number>5</number><keywords><keyword>Biological Availability</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Estrogens/metabolism</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage/*metabolism/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nutritional Requirements</keyword><keyword>Oxidation-Reduction</keyword><keyword>Sex Factors</keyword><keyword>alpha-Linolenic Acid/administration &amp;</keyword><keyword>dosage/*metabolism/pharmacokinetics/physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Sep-Oct</date></pub-dates></dates><accession-num>16188209</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite><Cite><Author>Burdge</Author><Year>2004</Year><RecNum>630</RecNum><record><rec-number>630</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G.</author></authors></contributors><auth-address>Institute of Human Nutrition, Biomedical Science Building, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. g.c.burdge@soton.ac.uk</auth-address><titles><title>Alpha-linolenic acid metabolism in men and women: nutritional and biological implications</title><secondary-title>Curr Opin Clin Nutr Metab Care</secondary-title><alt-title>Current opinion in clinical nutrition and metabolic care</alt-title></titles><pages>137-44</pages><volume>7</volume><number>2</number><keywords><keyword>Carbon Isotopes</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Energy Metabolism</keyword><keyword>Fatty Acids, Unsaturated/metabolism/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nutritional Requirements</keyword><keyword>Oxidation-Reduction</keyword><keyword>Sex Characteristics</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism/physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1363-1950 (Print)</isbn><accession-num>15075703</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Plourde</Author><Year>2007</Year><RecNum>631</RecNum><record><rec-number>631</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plourde, M.</author><author>Cunnane, S. C.</author></authors></contributors><auth-address>Research Center on Aging, Departments of Medicine, and Physiology and Biophysics, Universite de Sherbrooke, 1036 Belvedere St, South, Sherbrooke, QC J1H 4C4, Canada.</auth-address><titles><title>Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements</title><secondary-title>Appl Physiol Nutr Metab</secondary-title><alt-title>Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme</alt-title></titles><pages>619-34</pages><volume>32</volume><number>4</number><keywords><keyword>*Diet</keyword><keyword>*Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/metabolism</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/metabolism</keyword><keyword>Fatty Acids, Essential/*biosynthesis</keyword><keyword>Humans</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1715-5312 (Print)</isbn><accession-num>17622276</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Sinclair</Author><Year>2002</Year><RecNum>629</RecNum><record><rec-number>629</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sinclair, A. J.</author><author>Attar-Bashi, N. M.</author><author>Li, D.</author></authors></contributors><auth-address>Department of Food Science, RMIT University, Melbourne, Victoria, 3001, Australia. andrew.sinclair@rmit.edu.au</auth-address><titles><title>What is the role of alpha-linolenic acid for mammals?</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>1113-23</pages><volume>37</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Humans</keyword><keyword>Mammals</keyword><keyword>Neoplasms/physiopathology</keyword><keyword>Nutrition Policy</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism/*physiology</keyword></keywords><dates><year>2002</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>12617463</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[13-17]. Rodent studies show that diets containing ALA as the only n-3 PUFA leads to tissue composition reflecting the full diversity of n-3 polyunsaturates. However, observations from several laboratories have indicated that the tissue concentrations of the long chain n-3 polyunsaturates, particularly DHA, are lower in an ALA-based diet than one in which the preformed LCPUFA are present. For example, one study showed that rat brain and retinal DHA were greater in pups fed a diet with preformed EPA and DHA compared to diets containing only ALA. Even when the ALA intake was increased by a factor of 10 greater than the EPA/DHA levels, the retinal DHA content remained below the value found for retina in the preformed DHA diet and led to a diminution of the arachidonic acid (AA) content ADDIN EN.CITE <EndNote><Cite><Author>Woods</Author><Year>1996</Year><RecNum>632</RecNum><record><rec-number>632</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Woods, J.</author><author>Ward, G.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Department of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814, USA.</auth-address><titles><title>Is docosahexaenoic acid necessary in infant formula? Evaluation of high linolenate diets in the neonatal rat</title><secondary-title>Pediatr Res</secondary-title><alt-title>Pediatric research</alt-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>687-94</pages><volume>40</volume><number>5</number><keywords><keyword>Animal Feed</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Female</keyword><keyword>Growth</keyword><keyword>Lipid Metabolism</keyword><keyword>Pregnancy</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage</keyword></keywords><dates><year>1996</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0031-3998 (Print)</isbn><accession-num>8910933</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[20]. Similarly, in guinea pigs, both the brain and retina DHA levels were greater when a diet containing 1% ALA and 1.8% DHA was fed relative to one with only 7.1% ALA ADDIN EN.CITE <EndNote><Cite><Author>Abedin</Author><Year>1999</Year><RecNum>575</RecNum><record><rec-number>575</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Abedin, L.</author><author>Lien, E. L.</author><author>Vingrys, A. J.</author><author>Sinclair, A. J.</author></authors></contributors><auth-address>Department of Food Science, Royal Melbourne Institute of Technology University, Victoria, Australia.</auth-address><titles><title>The effects of dietary alpha-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>475-82</pages><volume>34</volume><number>5</number><keywords><keyword>Animal</keyword><keyword>Arachidonic Acid/metabolism</keyword><keyword>Brain/*drug effects/metabolism</keyword><keyword>Comparative Study</keyword><keyword>Docosahexaenoic Acids/*administration &amp; dosage/pharmacology</keyword><keyword>Female</keyword><keyword>Guinea Pigs</keyword><keyword>Heart/*drug effects</keyword><keyword>Liver/*drug effects/metabolism</keyword><keyword>Myocardium/metabolism</keyword><keyword>Phospholipids/metabolism</keyword><keyword>Retina/*drug effects/metabolism</keyword><keyword>Support, Non-U.S. Gov&apos;t</keyword><keyword>Thromboxane B2/analogs &amp; derivatives/blood</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage/pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>May</date></pub-dates></dates><accession-num>10380119</accession-num><urls><related-urls><url>;[22]. In the heart, the DHA level was over 7-fold greater in the DHA diet relative to the ALA only diet. The liver was an even more extreme case, with DHA 17-fold greater when preformed DHA was in the diet. Glial cell phospholipids of neonatal rats contained more DHA when the dams were fed a diet containing DHA than when they were fed only ALA ADDIN EN.CITE <EndNote><Cite><Author>Bowen</Author><Year>2005</Year><RecNum>633</RecNum><record><rec-number>633</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bowen, R. A.</author><author>Clandinin, M. T.</author></authors></contributors><auth-address>Nutrition and Metabolism Research Group, Department of Agricultural, Food and Nutritional Science, Uniersity of Alberta, Edmonton, Canada.</auth-address><titles><title>Maternal dietary 22 : 6n-3 is more effective than 18 : 3n-3 in increasing the 22 : 6n-3 content in phospholipids of glial cells from neonatal rat brain</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>601-11</pages><volume>93</volume><number>5</number><keywords><keyword>Animals</keyword><keyword>Animals, Suckling</keyword><keyword>Brain/*metabolism</keyword><keyword>Docosahexaenoic Acids/*administration &amp; dosage</keyword><keyword>Female</keyword><keyword>*Maternal Nutrition Physiology</keyword><keyword>Milk</keyword><keyword>Neuroglia/chemistry/*metabolism</keyword><keyword>Phosphatidylcholines/analysis/metabolism</keyword><keyword>Phosphatidylethanolamines/analysis/metabolism</keyword><keyword>Phosphatidylinositols/analysis/metabolism</keyword><keyword>Phosphatidylserines/analysis/metabolism</keyword><keyword>Phospholipids/analysis/*metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage</keyword></keywords><dates><year>2005</year><pub-dates><date>May</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>15975158</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[24]. When DHA is added to a 1?wt% ALA diet fed to the artificially reared rat pup, there is a significant increase in the DHA content of the brain and the liver DHA content more than doubles ADDIN EN.CITE <EndNote><Cite><Author>Lefkowitz</Author><Year>2005</Year><RecNum>634</RecNum><record><rec-number>634</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lefkowitz, W.</author><author>Lim, S. Y.</author><author>Lin, Y.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.</auth-address><titles><title>Where does the developing brain obtain its docosahexaenoic acid? Relative contributions of dietary alpha-linolenic acid, docosahexaenoic acid, and body stores in the developing rat</title><secondary-title>Pediatr Res</secondary-title><alt-title>Pediatric research</alt-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>157-65</pages><volume>57</volume><number>1</number><keywords><keyword>*Animal Feed</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Brain/*embryology</keyword><keyword>Brain Chemistry</keyword><keyword>Chromatography, Gas</keyword><keyword>Dietary Fats</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Infant Formula/metabolism</keyword><keyword>Liver/metabolism</keyword><keyword>Phospholipids/metabolism</keyword><keyword>Rats</keyword><keyword>Time Factors</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0031-3998 (Print)</isbn><accession-num>15531740</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[26]. When rodents or guinea pigs are fed a diet with high levels of ALA, increased tissue content of EPA and DPAn-3 is commonly observed. In guinea pigs fed a high ALA diet, the DPAn-3 content of the brain, retina, heart and liver were at a higher level than in the DHA diet, as may be expected from much higher ALA content in the diet relative to the DHA ADDIN EN.CITE <EndNote><Cite><Author>Abedin</Author><Year>1999</Year><RecNum>575</RecNum><record><rec-number>575</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Abedin, L.</author><author>Lien, E. L.</author><author>Vingrys, A. J.</author><author>Sinclair, A. J.</author></authors></contributors><auth-address>Department of Food Science, Royal Melbourne Institute of Technology University, Victoria, Australia.</auth-address><titles><title>The effects of dietary alpha-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>475-82</pages><volume>34</volume><number>5</number><keywords><keyword>Animal</keyword><keyword>Arachidonic Acid/metabolism</keyword><keyword>Brain/*drug effects/metabolism</keyword><keyword>Comparative Study</keyword><keyword>Docosahexaenoic Acids/*administration &amp; dosage/pharmacology</keyword><keyword>Female</keyword><keyword>Guinea Pigs</keyword><keyword>Heart/*drug effects</keyword><keyword>Liver/*drug effects/metabolism</keyword><keyword>Myocardium/metabolism</keyword><keyword>Phospholipids/metabolism</keyword><keyword>Retina/*drug effects/metabolism</keyword><keyword>Support, Non-U.S. Gov&apos;t</keyword><keyword>Thromboxane B2/analogs &amp; derivatives/blood</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage/pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>May</date></pub-dates></dates><accession-num>10380119</accession-num><urls><related-urls><url>;[22]. Similarly, when guinea pigs were fed a high level of ALA, many tissues had very substantial increases in ALA, EPA and DPAn-3 but comparatively little increase in DHA ADDIN EN.CITE <EndNote><Cite><Author>Fu</Author><Year>2000</Year><RecNum>635</RecNum><record><rec-number>635</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fu, Z.</author><author>Sinclair, A. J.</author></authors></contributors><auth-address>Department of Food Science, RMIT University, Melbourne, Victoria, Australia.</auth-address><titles><title>Increased alpha-linolenic acid intake increases tissue alpha-linolenic acid content and apparent oxidation with little effect on tissue docosahexaenoic acid in the guinea pig</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>395-400</pages><volume>35</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Dietary Fats, Unsaturated/*administration &amp; dosage</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Fatty Acids, Omega-3/analysis</keyword><keyword>Guinea Pigs</keyword><keyword>Lung/metabolism</keyword><keyword>Male</keyword><keyword>Myocardium/metabolism</keyword><keyword>Organ Specificity</keyword><keyword>Oxidation-Reduction</keyword><keyword>Skin/metabolism</keyword><keyword>Spleen/metabolism</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage/*metabolism</keyword></keywords><dates><year>2000</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>10858024</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[29]. In a study of several tissues of the suckling rat, increasing the ALA content of the maternal diet led to increased ALA, EPA and DPAn-3 in the whole body, skin and epididymal fat pads; however, there was no effect on the DHA content of these tissues nor of the brain or muscles ADDIN EN.CITE <EndNote><Cite><Author>Bowen</Author><Year>2000</Year><RecNum>636</RecNum><record><rec-number>636</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bowen, R. A.</author><author>Clandinin, M. T.</author></authors></contributors><auth-address>Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada.</auth-address><titles><title>High dietary 18:3n-3 increases the 18:3n-3 but not the 22:6n-3 content in the whole body, brain, skin, epididymal fat pads, and muscles of suckling rat pups</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>389-94</pages><volume>35</volume><number>4</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Animals</keyword><keyword>Animals, Suckling/*metabolism</keyword><keyword>Body Weight</keyword><keyword>Brain/metabolism</keyword><keyword>Dietary Fats/*administration &amp; dosage</keyword><keyword>Epididymis</keyword><keyword>Fatty Acids/analysis/*metabolism</keyword><keyword>Female</keyword><keyword>*Lactation</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Muscles/metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Skin/metabolism</keyword><keyword>Stomach/metabolism</keyword></keywords><dates><year>2000</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>10858023</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[32]. The predominant fate of ALA is catabolism ADDIN EN.CITE <EndNote><Cite><Author>Cunnane</Author><Year>1997</Year><RecNum>637</RecNum><record><rec-number>637</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cunnane, S. C.</author><author>Anderson, M. J.</author></authors></contributors><auth-address>Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Canada.</auth-address><titles><title>The majority of dietary linoleate in growing rats is beta-oxidized or stored in visceral fat</title><secondary-title>J Nutr</secondary-title><alt-title>The Journal of nutrition</alt-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>146-52</pages><volume>127</volume><number>1</number><keywords><keyword>Adipose Tissue/*metabolism</keyword><keyword>Animals</keyword><keyword>Body Weight/drug effects</keyword><keyword>Diet</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>Linoleic Acids/*metabolism/*pharmacokinetics</keyword><keyword>Male</keyword><keyword>Oxidation-Reduction</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Tissue Distribution</keyword></keywords><dates><year>1997</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0022-3166 (Print)</isbn><accession-num>9040558</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Plourde</Author><Year>2007</Year><RecNum>631</RecNum><record><rec-number>631</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plourde, M.</author><author>Cunnane, S. C.</author></authors></contributors><auth-address>Research Center on Aging, Departments of Medicine, and Physiology and Biophysics, Universite de Sherbrooke, 1036 Belvedere St, South, Sherbrooke, QC J1H 4C4, Canada.</auth-address><titles><title>Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements</title><secondary-title>Appl Physiol Nutr Metab</secondary-title><alt-title>Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme</alt-title></titles><pages>619-34</pages><volume>32</volume><number>4</number><keywords><keyword>*Diet</keyword><keyword>*Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/metabolism</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/metabolism</keyword><keyword>Fatty Acids, Essential/*biosynthesis</keyword><keyword>Humans</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1715-5312 (Print)</isbn><accession-num>17622276</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[16, 34] and carbon recycling to acetate ADDIN EN.CITE <EndNote><Cite><Author>Cunnane</Author><Year>2003</Year><RecNum>638</RecNum><record><rec-number>638</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cunnane, S. C.</author><author>Ryan, M. A.</author><author>Nadeau, C. R.</author><author>Bazinet, R. P.</author><author>Musa-Veloso, K.</author><author>McCloy, U.</author></authors></contributors><auth-address>Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada M5S 3E2. s.cunnane@utoronto.ca</auth-address><titles><title>Why is carbon from some polyunsaturates extensively recycled into lipid synthesis?</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>477-84</pages><volume>38</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Carbon/*metabolism</keyword><keyword>Carbon Isotopes</keyword><keyword>Dietary Fats/metabolism</keyword><keyword>Fatty Acids, Unsaturated/*metabolism</keyword><keyword>Humans</keyword><keyword>Ketones/metabolism</keyword><keyword>Lipids/*biosynthesis</keyword><keyword>Oxidation-Reduction</keyword><keyword>Tissue Distribution</keyword></keywords><dates><year>2003</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>12848297</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[36]. In rodents, only about 16% of an ALA dose is found in rat tissues, mainly adipose, and 6% was elongated/desaturated ADDIN EN.CITE <EndNote><Cite><Author>Lin</Author><Year>2007</Year><RecNum>711</RecNum><record><rec-number>711</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lin, Y. H.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Section of Nutritional Neuroscience, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9410, USA.</auth-address><titles><title>Whole body distribution of deuterated linoleic and alpha-linolenic acids and their metabolites in the rat</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>2709-24</pages><volume>48</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Deuterium/metabolism</keyword><keyword>Deuterium Exchange Measurement</keyword><keyword>Dietary Fats, Unsaturated/administration &amp; dosage/metabolism</keyword><keyword>Female</keyword><keyword>Gas Chromatography-Mass Spectrometry</keyword><keyword>Linoleic Acid/administration &amp; dosage/*pharmacokinetics</keyword><keyword>Male</keyword><keyword>Rats</keyword><keyword>Rats, Long-Evans</keyword><keyword>Time Factors</keyword><keyword>Tissue Distribution</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*pharmacokinetics</keyword></keywords><dates><year>2007</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>17876057</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[38]. As carnivores with regular DHA intakes, cats express extremely low levels of in vivo desaturases such that it has only been observed in PUFA deficiency ADDIN EN.CITE <EndNote><Cite><Author>Pawlosky</Author><Year>1994</Year><RecNum>557</RecNum><record><rec-number>557</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R.</author><author>Barnes, A.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Laboratory of Membrane Biochemistry and Biophysics, DICBR, National Institute on Alcoholism and Alcohol Abuse, Rockville, MD 20852.</auth-address><titles><title>Essential fatty acid metabolism in the feline: relationship between liver and brain production of long-chain polyunsaturated fatty acids</title><secondary-title>J Lipid Res</secondary-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><pages>2032-40</pages><volume>35</volume><number>11</number><keywords><keyword>Animal</keyword><keyword>Arachidonic Acid/biosynthesis</keyword><keyword>Brain/*metabolism</keyword><keyword>Cats</keyword><keyword>Comparative Study</keyword><keyword>Corn Oil/administration &amp; dosage</keyword><keyword>Deuterium</keyword><keyword>Dietary Fats, Unsaturated/administration &amp; dosage</keyword><keyword>Fatty Acid Desaturases/metabolism</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fatty Acids, Essential/*metabolism</keyword><keyword>Fatty Acids, Unsaturated/*biosynthesis</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/metabolism</keyword><keyword>Liver/*metabolism</keyword><keyword>Male</keyword><keyword>Mass Fragmentography</keyword><keyword>Plant Oils/administration &amp; dosage</keyword><keyword>alpha-Linolenic Acid/metabolism</keyword></keywords><dates><year>1994</year><pub-dates><date>Nov</date></pub-dates></dates><accession-num>7868981</accession-num><urls><related-urls><url>;[40]; even a diet with the very high ALA content of 17 wt% led to plasma PC with EPA, DPAn-3 and DHA below detectable limits ADDIN EN.CITE <EndNote><Cite><Author>Rivers</Author><Year>1975</Year><RecNum>640</RecNum><record><rec-number>640</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rivers, J. P.</author><author>Sinclair, A. J.</author><author>Craqford, M. A.</author></authors></contributors><titles><title>Inability of the cat to desaturate essential fatty acids</title><secondary-title>Nature</secondary-title><alt-title>Nature</alt-title></titles><pages>171-3</pages><volume>258</volume><number>5531</number><keywords><keyword>Animals</keyword><keyword>Cats/*metabolism</keyword><keyword>Dietary Fats/metabolism</keyword><keyword>Fatty Acid Desaturases/*deficiency</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fatty Acids, Essential/*metabolism</keyword><keyword>Fatty Acids, Unsaturated/*metabolism</keyword><keyword>Female</keyword><keyword>Male</keyword></keywords><dates><year>1975</year><pub-dates><date>Nov 13</date></pub-dates></dates><isbn>0028-0836 (Print)</isbn><accession-num>1186900</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[42]. Adding 2.3% EPA and 0.4% DHA to this diet with low ALA (0.9%) led to cat plasma PC with 8 % EPA, 0.8% DPAn-3 and 4.1% DHA. In dogs, omnivorous animals, increasing the EPA and DHA content of the diet led to an increase in plasma DHA even though the reference diet with high ALA contained more than 10-fold more n-3 fatty acid ADDIN EN.CITE <EndNote><Cite><Author>Heinemann</Author><Year>2005</Year><RecNum>641</RecNum><record><rec-number>641</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Heinemann, K. M.</author><author>Waldron, M. K.</author><author>Bigley, K. E.</author><author>Lees, G. E.</author><author>Bauer, J. E.</author></authors></contributors><auth-address>Department of Small Animal Clinical Sciences, Texas A&amp;M University, College Station, 77843, USA.</auth-address><titles><title>Long-chain (n-3) polyunsaturated fatty acids are more efficient than alpha-linolenic acid in improving electroretinogram responses of puppies exposed during gestation, lactation, and weaning</title><secondary-title>J Nutr</secondary-title><alt-title>The Journal of nutrition</alt-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>1960-6</pages><volume>135</volume><number>8</number><keywords><keyword>Animals</keyword><keyword>Dogs</keyword><keyword>Electroretinography</keyword><keyword>Fatty Acids, Omega-3</keyword><keyword>Fatty Acids, Unsaturated/*pharmacology</keyword><keyword>Female</keyword><keyword>Lactation/drug effects/*physiology</keyword><keyword>Linoleic Acid/*pharmacology</keyword><keyword>Models, Animal</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy, Animal/drug effects/*physiology</keyword><keyword>Retina/drug effects/*physiology</keyword><keyword>Triglycerides/*pharmacology</keyword><keyword>Weaning</keyword></keywords><dates><year>2005</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0022-3166 (Print)</isbn><accession-num>16046723</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[44]. Similarly, ALA diets do not well support the DHA content of canine milk as does providing much lower levels of preformed EPA/DHA ADDIN EN.CITE <EndNote><Cite><Author>Bauer</Author><Year>2004</Year><RecNum>642</RecNum><record><rec-number>642</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bauer, J. E.</author><author>Heinemann, K. M.</author><author>Bigley, K. E.</author><author>Lees, G. E.</author><author>Waldron, M. K.</author></authors></contributors><auth-address>Comparative Nutrition Laboratory, Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&amp;M University, College Station, TX 77843-4474, USA. jbauer@cvm.tamu.edu</auth-address><titles><title>Maternal diet alpha-linolenic acid during gestation and lactation does not increase docosahexaenoic acid in canine milk</title><secondary-title>J Nutr</secondary-title><alt-title>The Journal of nutrition</alt-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>2035S-2038S</pages><volume>134</volume><number>8 Suppl</number><keywords><keyword>Animals</keyword><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Dogs</keyword><keyword>Fatty Acids, Unsaturated/*metabolism</keyword><keyword>Female</keyword><keyword>Lactation/metabolism</keyword><keyword>Milk/*chemistry</keyword><keyword>Pregnancy</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism</keyword></keywords><dates><year>2004</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0022-3166 (Print)</isbn><accession-num>15284396</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[46]. Piglets fed a diet with 1.7% of fatty acids as ALA supplemented with DHA (0.7%) had lung phospholipid DHA markedly increased compared to the control group consuming 1.7% ALA as the only dietary omega-3 ADDIN EN.CITE <EndNote><Cite><Author>Huang</Author><Year>1996</Year><RecNum>643</RecNum><record><rec-number>643</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Huang, M. C.</author><author>Craig-Schmidt, M. C.</author></authors></contributors><auth-address>Department of Nutrition and Food Science, Auburn University, AL 36849, USA.</auth-address><titles><title>Arachidonate and docosahexaenoate added to infant formula influence fatty acid composition and subsequent eicosanoid production in neonatal pigs</title><secondary-title>J Nutr</secondary-title><alt-title>The Journal of nutrition</alt-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>2199-208</pages><volume>126</volume><number>9</number><keywords><keyword>Animals</keyword><keyword>Animals, Newborn/*metabolism</keyword><keyword>Arachidonic Acids/administration &amp; dosage/analysis/*pharmacology</keyword><keyword>Body Weight/physiology</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/analysis/*pharmacology</keyword><keyword>Eicosanoids/analysis/*biosynthesis</keyword><keyword>Epoprostenol/metabolism</keyword><keyword>Fatty Acids/*analysis</keyword><keyword>Humans</keyword><keyword>Infant Food/analysis/*standards</keyword><keyword>Infant, Newborn</keyword><keyword>Lung/chemistry/metabolism</keyword><keyword>Male</keyword><keyword>Phosphatidylcholines/analysis/metabolism</keyword><keyword>Phosphatidylethanolamines/analysis/metabolism</keyword><keyword>Phosphorus/chemistry</keyword><keyword>Swine/*metabolism</keyword><keyword>Thromboxanes/metabolism</keyword></keywords><dates><year>1996</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0022-3166 (Print)</isbn><accession-num>8814208</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[47]. Similarly, when DHA was added to piglet formula containing ALA, there was a significant increase in DHA in liver TG, PE, PC, PS and PI ADDIN EN.CITE <EndNote><Cite><Author>de la Presa-Owens</Author><Year>1998</Year><RecNum>441</RecNum><record><rec-number>441</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>de la Presa-Owens, S.</author><author>Innis, S. M.</author><author>Rioux, F. M.</author></authors></contributors><auth-address>Department of Paediatrics, University of British Columbia Vancouver, Vancouver, BC, Canada V5Z 4H4.</auth-address><titles><title>Addition of triglycerides with arachidonic acid or docosahexaenoic acid to infant formula has tissue- and lipid class-specific effects on fatty acids and hepatic desaturase activities in formula-fed piglets</title><secondary-title>J Nutr</secondary-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>1376-84</pages><volume>128</volume><number>8</number><keywords><keyword>Animal</keyword><keyword>Arachidonic Acid/*administration &amp; dosage</keyword><keyword>Brain/metabolism</keyword><keyword>Chylomicrons/blood</keyword><keyword>Dietary Fats/administration &amp; dosage</keyword><keyword>Docosahexaenoic Acids/*administration &amp; dosage</keyword><keyword>Fatty Acid Desaturases/*metabolism</keyword><keyword>Fatty Acids/*metabolism</keyword><keyword>*Infant Food</keyword><keyword>Kidney/metabolism</keyword><keyword>Lipoproteins, HDL/blood</keyword><keyword>Lipoproteins, LDL/blood</keyword><keyword>Liver/enzymology/metabolism</keyword><keyword>Male</keyword><keyword>Myocardium/metabolism</keyword><keyword>Phospholipids/metabolism</keyword><keyword>Support, Non-U.S. Gov&apos;t</keyword><keyword>Swine</keyword><keyword>Triglycerides/*administration &amp; dosage/metabolism</keyword></keywords><dates><year>1998</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>9687559</accession-num><urls><related-urls><url>;[48]. Increasing levels of menhaden oil in piglet formula led to increases in EPA, DPAn-3 and DHA in plasma in comparison to a base formula containing ALA ADDIN EN.CITE <EndNote><Cite><Author>Arbuckle</Author><Year>1991</Year><RecNum>514</RecNum><record><rec-number>514</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Arbuckle, L. D.</author><author>Rioux, F. M.</author><author>Mackinnon, M. J.</author><author>Hrboticky, N.</author><author>Innis, S. M.</author></authors></contributors><auth-address>Department of Human Nutrition, University of British Columbia, Vancouver, Canada.</auth-address><titles><title>Response of (n-3) and (n-6) fatty acids in piglet brain, liver and plasma to increasing, but low, fish oil supplementation of formula</title><secondary-title>J Nutr</secondary-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>1536-47</pages><volume>121</volume><number>10</number><keywords><keyword>Animal</keyword><keyword>Animals, Newborn</keyword><keyword>Diet</keyword><keyword>Fatty Acids/blood/*chemistry</keyword><keyword>Fish Oils/pharmacokinetics/*pharmacology</keyword><keyword>Food, Formulated</keyword><keyword>Milk/analysis</keyword><keyword>Organ Weight/drug effects</keyword><keyword>Phospholipids/blood/chemistry</keyword><keyword>Support, Non-U.S. Gov&apos;t</keyword><keyword>Swine</keyword><keyword>Tissue Distribution</keyword></keywords><dates><year>1991</year><pub-dates><date>Oct</date></pub-dates></dates><accession-num>1765817</accession-num><urls><related-urls><url>;[49]. Brain, liver and adipose DHA increased in a dose-response manner when a DHA-containing oil at up to 1.66% of fatty acids is fed to piglets over 28 days ADDIN EN.CITE <EndNote><Cite><Author>Huang</Author><Year>2007</Year><RecNum>700</RecNum><record><rec-number>700</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Huang, M. C.</author><author>Brenna, J. T.</author><author>Chao, A. C.</author><author>Tschanz, C.</author><author>Diersen-Schade, D. A.</author><author>Hung, H. C.</author></authors></contributors><auth-address>Department of Public Health, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80705, Taiwan. mechhu@kmu.edu.tw</auth-address><titles><title>Differential tissue dose responses of (n-3) and (n-6) PUFA in neonatal piglets fed docosahexaenoate and arachidonoate</title><secondary-title>J Nutr</secondary-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>2049-55</pages><volume>137</volume><number>9</number><keywords><keyword>Adipose Tissue/drug effects/metabolism</keyword><keyword>Animal Feed</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Arachidonic Acid/blood/*pharmacokinetics</keyword><keyword>Brain/drug effects/metabolism</keyword><keyword>Docosahexaenoic Acids/blood/*pharmacokinetics</keyword><keyword>Fatty Acids, Omega-3/*metabolism</keyword><keyword>Fatty Acids, Omega-6/*metabolism</keyword><keyword>Liver/drug effects/metabolism</keyword><keyword>Retina/drug effects/metabolism</keyword><keyword>Swine</keyword></keywords><dates><year>2007</year><pub-dates><date>Sep</date></pub-dates></dates><accession-num>17709441</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[50]. Non-human primate studies are perhaps the most enlightening of all animal studies because PUFA metabolism is similar among omnivorous primates ADDIN EN.CITE <EndNote><Cite><Author>Su</Author><Year>1999</Year><RecNum>377</RecNum><record><rec-number>377</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Su, H. M.</author><author>Bernardo, L.</author><author>Mirmiran, M.</author><author>Ma, X. H.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.</auth-address><titles><title>Dietary 18:3n-3 and 22:6n-3 as sources of 22:6n-3 accretion in neonatal baboon brain and associated organs</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>S347-50.</pages><volume>34</volume><number>Suppl</number><keywords><keyword>Animal</keyword><keyword>Animals, Newborn</keyword><keyword>Brain/*metabolism</keyword><keyword>Carbon Isotopes</keyword><keyword>Diet</keyword><keyword>Dietary Fats, Unsaturated/*pharmacokinetics</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Fatty Acids, Omega-3/*pharmacokinetics</keyword><keyword>Human</keyword><keyword>Insects</keyword><keyword>Liver/metabolism</keyword><keyword>Meat</keyword><keyword>Papio</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Tissue Distribution</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>1999</year></dates><accession-num>10419199</accession-num><urls><related-urls><url>;[51], and the primate brain is a much larger proportion of body weight than in subprimates. Several studies have been conducted in perinatal baboons investigating the relative efficacy of ALA and preformed DHA to supply DHA to developing tissue. In six week old neonates, 0.23% of a dose of ALA was found in the brain as DHA, whereas 1.7% of a DHA dose was found in the brain as DHA, giving a ratio of efficacy of 7:1 ADDIN EN.CITE <EndNote><Cite><Author>Su</Author><Year>1999</Year><RecNum>376</RecNum><record><rec-number>376</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Su, H. M.</author><author>Bernardo, L.</author><author>Mirmiran, M.</author><author>Ma, X. H.</author><author>Corso, T. N.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.</auth-address><titles><title>Bioequivalence of dietary alpha-linolenic and docosahexaenoic acids as sources of docosahexaenoate accretion in brain and associated organs of neonatal baboons</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>87-93.</pages><volume>45</volume><number>1</number><keywords><keyword>Administration, Oral</keyword><keyword>Animal</keyword><keyword>Animals, Newborn</keyword><keyword>Docosahexaenoic Acids/blood/*pharmacokinetics</keyword><keyword>Erythrocytes/metabolism</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Infant Food</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Occipital Lobe/*metabolism</keyword><keyword>Organ Specificity</keyword><keyword>Papio</keyword><keyword>Pigment Epithelium of Eye/metabolism</keyword><keyword>Retina/metabolism</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Therapeutic Equivalency</keyword><keyword>alpha-Linolenic Acid/blood/*pharmacokinetics</keyword></keywords><dates><year>1999</year></dates><accession-num>9890614</accession-num><urls><related-urls><url>;[52]. This ratio was 20:1 for ALA and preformed DHA provided to pregnant animals ADDIN EN.CITE <EndNote><Cite><Author>Greiner</Author><Year>1997</Year><RecNum>24</RecNum><record><rec-number>24</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Greiner, R. C.</author><author>Winter, J.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><titles><title>Brain docosahexaenoate accretion in fetal baboons: bioequivalence of dietary alpha-linolenic and docosahexaenoic acids</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>826-34.</pages><volume>42</volume><number>6</number><keywords><keyword>Animal</keyword><keyword>Brain/embryology/*metabolism</keyword><keyword>Dietary Fats/*pharmacokinetics</keyword><keyword>Docosahexaenoic Acids/*pharmacokinetics</keyword><keyword>Fatty Acids/analysis</keyword><keyword>Female</keyword><keyword>Fetal Development/physiology</keyword><keyword>Liver/embryology/metabolism</keyword><keyword>Papio</keyword><keyword>Pregnancy</keyword><keyword>Retina/embryology/metabolism</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>*Therapeutic Equivalency</keyword><keyword>alpha-Linolenic Acid/*pharmacokinetics</keyword></keywords><dates><year>1997</year></dates><label>98057251</label><urls></urls></record></Cite></EndNote>[53]. When DHA was added to a formula containing ALA fed to baboon neonates, there was a significant DHA increase in the brain, retina, liver, erythrocytes and plasma relative to those fed the same formula without DHA, and the increase in retinal DHA was directly related to retinal function ADDIN EN.CITE <EndNote><Cite><Author>Diau</Author><Year>2003</Year><RecNum>598</RecNum><record><rec-number>598</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Diau, G. Y.</author><author>Loew, E. R.</author><author>Wijendran, V.</author><author>Sarkadi-Nagy, E.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.</auth-address><titles><title>Docosahexaenoic and arachidonic acid influence on preterm baboon retinal composition and function</title><secondary-title>Invest Ophthalmol Vis Sci</secondary-title></titles><pages>4559-66</pages><volume>44</volume><number>10</number><keywords><keyword>Animal Feed</keyword><keyword>Animals</keyword><keyword>Animals, Newborn/metabolism</keyword><keyword>Arachidonic Acids/*administration &amp; dosage</keyword><keyword>Comparative Study</keyword><keyword>Docosahexaenoic Acids/*administration &amp; dosage</keyword><keyword>Electroretinography</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Female</keyword><keyword>Male</keyword><keyword>Papio</keyword><keyword>Pregnancy</keyword><keyword>Research Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Retina/*physiology</keyword></keywords><dates><year>2003</year><pub-dates><date>Oct</date></pub-dates></dates><accession-num>14507905</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[54]. Very recent studies demonstrate a dose-response between dietary DHA and cerebral cortex DHA, accompanied by global changes in gene expression at moderate and high DHA levels ADDIN EN.CITE <EndNote><Cite><Author>Hsieh</Author><Year>2007</Year><RecNum>701</RecNum><record><rec-number>701</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hsieh, A. T.</author><author>Anthony, J. C.</author><author>Diersen-Schade, D. A.</author><author>Rumsey, S. C.</author><author>Lawrence, P.</author><author>Li, C.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.</auth-address><titles><title>The influence of moderate and high dietary long chain polyunsaturated fatty acids (LCPUFA) on baboon neonate tissue fatty acids</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>537-45</pages><volume>61</volume><number>5 Pt 1</number><keywords><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Arachidonic Acid/administration &amp; dosage/chemistry/*metabolism</keyword><keyword>Brain Chemistry</keyword><keyword>Dietary Fats/*metabolism</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/chemistry/*metabolism</keyword><keyword>Fatty Acids/chemistry/*metabolism</keyword><keyword>Fatty Acids, Unsaturated/chemistry/*metabolism</keyword><keyword>Humans</keyword><keyword>Infant Formula/chemistry</keyword><keyword>Infant, Newborn</keyword><keyword>Papio</keyword><keyword>Random Allocation</keyword><keyword>Tissue Distribution</keyword><keyword>Tissue Extracts/chemistry</keyword></keywords><dates><year>2007</year><pub-dates><date>May</date></pub-dates></dates><accession-num>17413857</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite><Cite><Author>Kothapalli</Author><Year>2007</Year><RecNum>702</RecNum><record><rec-number>702</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kothapalli, K. S.</author><author>Anthony, J. C.</author><author>Pan, B. S.</author><author>Hsieh, A. T.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Savage Hall, Ithaca, New York, United States of America.</auth-address><titles><title>Differential cerebral cortex transcriptomes of baboon neonates consuming moderate and high docosahexaenoic acid formulas</title><secondary-title>PLoS ONE</secondary-title></titles><periodical><full-title>PLoS ONE</full-title></periodical><pages>e370</pages><volume>2</volume><number>4</number><dates><year>2007</year></dates><accession-num>17426818</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[55, 56]. These studies indicate that dietary ALA contributes to DHA deposition in fetal and neonatal brain, but the relative efficacy of dietary preformed DHA is far higher.Alpha-Linolenic Acid Supplementation – Tissue Compositional Studies in AdultsReviews by Plourde and Cunnane ADDIN EN.CITE <EndNote><Cite><Author>Plourde</Author><Year>2007</Year><RecNum>631</RecNum><record><rec-number>631</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plourde, M.</author><author>Cunnane, S. C.</author></authors></contributors><auth-address>Research Center on Aging, Departments of Medicine, and Physiology and Biophysics, Universite de Sherbrooke, 1036 Belvedere St, South, Sherbrooke, QC J1H 4C4, Canada.</auth-address><titles><title>Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements</title><secondary-title>Appl Physiol Nutr Metab</secondary-title><alt-title>Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme</alt-title></titles><pages>619-34</pages><volume>32</volume><number>4</number><keywords><keyword>*Diet</keyword><keyword>*Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/metabolism</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/metabolism</keyword><keyword>Fatty Acids, Essential/*biosynthesis</keyword><keyword>Humans</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1715-5312 (Print)</isbn><accession-num>17622276</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[16] and by Burdge and Calder ADDIN EN.CITE <EndNote><Cite><Author>Burdge</Author><Year>2005</Year><RecNum>698</RecNum><record><rec-number>698</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G. C.</author><author>Calder, P. C.</author></authors></contributors><auth-address>Institute of Human Nutrition, University of Southampton, Southampton, UK. G.C.Burdge@soton.ac.uk</auth-address><titles><title>Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults</title><secondary-title>Reprod Nutr Dev</secondary-title></titles><periodical><full-title>Reprod Nutr Dev</full-title></periodical><pages>581-97</pages><volume>45</volume><number>5</number><keywords><keyword>Biological Availability</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Estrogens/metabolism</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage/*metabolism/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nutritional Requirements</keyword><keyword>Oxidation-Reduction</keyword><keyword>Sex Factors</keyword><keyword>alpha-Linolenic Acid/administration &amp;</keyword><keyword>dosage/*metabolism/pharmacokinetics/physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Sep-Oct</date></pub-dates></dates><accession-num>16188209</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[14] of human studies of the effects of ALA supplementation on plasma fatty acid composition have been published recently and the results are summarized in Table 1.Many of these studies of human plasma fatty acid composition involved a high dosage of ALA feeding (up to 40 g/d) and for a prolonged period of time (up to 42 weeks). There was in most cases a significant increase in the plasma EPA content upon ALA supplementation. Generally, where it was reported, the DPA n-3 was also increased after ALA supplementation. However, with few exceptions, these studies did not find a significant increase in plasma DHA. Burdge and Calder concluded that ALA supplementation of human subjects generally led to an increase in EPA and in several studies, in DPAn-3, but in little or no effects on DHA content in plasma fractions and in circulating blood cells ADDIN EN.CITE <EndNote><Cite><Author>Burdge</Author><Year>2005</Year><RecNum>698</RecNum><record><rec-number>698</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G. C.</author><author>Calder, P. C.</author></authors></contributors><auth-address>Institute of Human Nutrition, University of Southampton, Southampton, UK. G.C.Burdge@soton.ac.uk</auth-address><titles><title>Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults</title><secondary-title>Reprod Nutr Dev</secondary-title></titles><periodical><full-title>Reprod Nutr Dev</full-title></periodical><pages>581-97</pages><volume>45</volume><number>5</number><keywords><keyword>Biological Availability</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Estrogens/metabolism</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage/*metabolism/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nutritional Requirements</keyword><keyword>Oxidation-Reduction</keyword><keyword>Sex Factors</keyword><keyword>alpha-Linolenic Acid/administration &amp;</keyword><keyword>dosage/*metabolism/pharmacokinetics/physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Sep-Oct</date></pub-dates></dates><accession-num>16188209</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[14]. A cross-study analysis of ALA supplementation in humans found increased plasma ALA and EPA but no increase in DHA ADDIN EN.CITE <EndNote><Cite><Author>Arterburn</Author><Year>2006</Year><RecNum>659</RecNum><record><rec-number>659</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Arterburn, L. M.</author><author>Hall, E. B.</author><author>Oken, H.</author></authors></contributors><auth-address>Martek Biosciences Corporation, Columbia, MD, USA. larterburn@</auth-address><titles><title>Distribution, interconversion, and dose response of n-3 fatty acids in humans</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1467S-1476S</pages><volume>83</volume><number>6 Suppl</number><keywords><keyword>Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/blood/*pharmacokinetics</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/blood/*pharmacokinetics</keyword><keyword>Erythrocytes/chemistry/metabolism</keyword><keyword>Fatty Acids, Omega-3/administration &amp; dosage/blood/pharmacokinetics</keyword><keyword>Humans</keyword><keyword>Milk, Human/chemistry</keyword><keyword>Organ Specificity</keyword><keyword>Tissue Distribution</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/blood/*pharmacokinetics</keyword></keywords><dates><year>2006</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>16841856</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[57]. Of importance, the size of the plasma DHA pool is far greater that of EPA; therefore it may take longer time until a small contribution of ALA conversion to the plasma DHA pool is detected. A flax oil supplementation study found no increase in either breastmilk DHA or in plasma DHA ADDIN EN.CITE <EndNote><Cite><Author>Francois</Author><Year>2003</Year><RecNum>660</RecNum><record><rec-number>660</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Francois, C. A.</author><author>Connor, S. L.</author><author>Bolewicz, L. C.</author><author>Connor, W. E.</author></authors></contributors><auth-address>Division of Endocrinology, Metabolism and Clinical Nutrition, the Department of Medicine, Oregon Health and Science University, Portland 97239-3098, USA.</auth-address><titles><title>Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>226-33</pages><volume>77</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/analysis/*metabolism</keyword><keyword>Fatty Acids/blood/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>*Lactation</keyword><keyword>Linseed Oil/*administration &amp; dosage/metabolism</keyword><keyword>Milk, Human/*chemistry</keyword></keywords><dates><year>2003</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12499346</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[21]. Overall, these data are very consistent with the idea that ALA is effective in increasing the EPA and DPAn-3 content in the human blood stream but has little effect on DHA content.Notably, the studies that reported a significant increase in plasma DHA levels altered the oils in the diet, changing both ALA and LA. Long term effects of ALA supplementation were investigated by substituting of perilla oil, high in ALA, for soy oil in foods for 20 Japanese elderly subjects. At three months, changes in serum fatty acids were consistent with results in Table 1 since all but DHA increased; at 10 months DHA increased 21%, and then returned to baseline three months after being switched back to soy ADDIN EN.CITE <EndNote><Cite><Author>Ezaki</Author><Year>1999</Year><RecNum>628</RecNum><record><rec-number>628</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ezaki, O.</author><author>Takahashi, M.</author><author>Shigematsu, T.</author><author>Shimamura, K.</author><author>Kimura, J.</author><author>Ezaki, H.</author><author>Gotoh, T.</author></authors></contributors><auth-address>Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo, Japan. ezaki@nih.go.jp</auth-address><titles><title>Long-term effects of dietary alpha-linolenic acid from perilla oil on serum fatty acids composition and on the risk factors of coronary heart disease in Japanese elderly subjects</title><secondary-title>J Nutr Sci Vitaminol (Tokyo)</secondary-title></titles><pages>759-72</pages><volume>45</volume><number>6</number><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Cookery</keyword><keyword>Coronary Disease/*etiology</keyword><keyword>Dietary Fats/*pharmacology</keyword><keyword>Enzyme-Linked Immunosorbent Assay</keyword><keyword>Fatty Acids/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Lipids/blood</keyword><keyword>Lipoproteins/blood</keyword><keyword>Lipoproteins, LDL/blood</keyword><keyword>Male</keyword><keyword>Plant Oils/*pharmacology</keyword><keyword>Risk Factors</keyword><keyword>alpha-Linolenic Acid/*pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>Dec</date></pub-dates></dates><accession-num>10737229</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[25]. These data suggest that modest long term changes in dietary ALA intake may be of value for increasing DHA status. However, perilla oil contains about one third the LA as soy oil, so this result is confounded by a reduction in LA as well as ALA supplementation. These data are consistent with results showing that the DHA status can be improved by switching from oils rich in omega-6 PUFA to a blend incorporating an oil containing a substantial quantity of ALA and less LA. A study in India showed considerable increases in DHA in plasma but not in platelets, as well as in EPA, by partially substituting canola oil for sunflower (75% LA) or groundnut (peanut) oil to obtain cooking oils with 25-40% linoleic acid (LA) and 4% ALA ADDIN EN.CITE <EndNote><Cite><Author>Ghafoorunissa</Author><Year>2002</Year><RecNum>694</RecNum><record><rec-number>694</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ghafoorunissa,</author><author>Vani, A.</author><author>Laxmi, R.</author><author>Sesikeran, B.</author></authors></contributors><auth-address>National Institute of Nutrition (ICMR), Hyderabad-500 007, AP, India. ghafoorunissanin@</auth-address><titles><title>Effects of dietary alpha-linolenic acid from blended oils on biochemical indices of coronary heart disease in Indians</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>1077-86</pages><volume>37</volume><number>11</number><keywords><keyword>Adult</keyword><keyword>Apolipoproteins/blood</keyword><keyword>Biological Markers/blood</keyword><keyword>Blood Platelets/cytology/drug effects/metabolism</keyword><keyword>Coronary Disease/*blood/*drug therapy</keyword><keyword>Cross-Over Studies</keyword><keyword>Female</keyword><keyword>Fibrinogen/metabolism</keyword><keyword>Fish Oils/chemistry/*pharmacology</keyword><keyword>Humans</keyword><keyword>India</keyword><keyword>Lipids/*blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Phospholipids/blood/chemistry</keyword><keyword>Plant Oils/chemistry/*pharmacology</keyword><keyword>Platelet Aggregation/drug effects</keyword><keyword>alpha-Linolenic Acid/*pharmacology</keyword></keywords><dates><year>2002</year><pub-dates><date>Nov</date></pub-dates></dates><accession-num>12558058</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[58]. Typical safflower and peanut oils have very low ALA (<0.1%), while canola is an excellent source of ALA (~11%) and is usually not higher in LA than peanut oil. Diets with very low ALA with high LA may be driving low omega-3 LCPUFA status in these subjects. Further research to confirm these findings is needed.4572068580Table 1. Changes in blood EPA and DHA in humans after ALA supplementation or feeding.ReferenceSubjectsDuration (weeks)ALA(g·d-1)ALA formBloodfractionChange inEPADHA1Szapary, 07 ADDIN EN.CITE <EndNote><Cite><Author>Szapary</Author><Year>2007</Year><RecNum>647</RecNum><record><rec-number>647</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Szapary, P. O. </author><author>Bloedon, L. T. </author><author>Balikai, S.</author><author>Chittams, J. </author><author>Cunnane, S. C. </author><author>Berlin, J. A.</author></authors></contributors><titles><title>Effects of flaxseed on markers of cardiovascular risk: Results from a randomized clinical trial</title><secondary-title>J Am Coll Nutr</secondary-title></titles><volume>in press.</volume><dates><year>2007</year></dates><urls></urls></record></Cite></EndNote>[1]30 M/F1040FSTL+ 12%ns2Goyens, 06 ADDIN EN.CITE <EndNote><Cite><Author>Goyens</Author><Year>2006</Year><RecNum>654</RecNum><record><rec-number>654</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Goyens, P. L.</author><author>Spilker, M. E.</author><author>Zock, P. L.</author><author>Katan, M. B.</author><author>Mensink, R. P.</author></authors></contributors><auth-address>Department of Human Biology, Maastricht University, Maastricht, Netherlands. p.goyens@hb.unimaas.nl</auth-address><titles><title>Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>44-53</pages><volume>84</volume><number>1</number><keywords><keyword>Breath Tests</keyword><keyword>Carbon Isotopes</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Double-Blind Method</keyword><keyword>Fatty Acids, Unsaturated/analysis/blood/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Linoleic Acid/administration &amp; dosage/blood/*metabolism</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Oxidation-Reduction</keyword><keyword>Phospholipids/analysis/blood/*metabolism</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/blood/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>16825680</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[4]10 M/F61.1% EnMPL+ 9.7%ns3Harper, 06 ADDIN EN.CITE <EndNote><Cite><Author>Harper</Author><Year>2006</Year><RecNum>646</RecNum><record><rec-number>646</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Harper, C. R.</author><author>Edwards, M. J.</author><author>DeFilipis, A. P.</author><author>Jacobson, T. A.</author></authors></contributors><auth-address>Department of Medicine, Office of Health Promotion and Disease Prevention, Emory University, Atlanta, GA, USA. charper@emory.edu</auth-address><titles><title>Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans</title><secondary-title>J Nutr</secondary-title><alt-title>The Journal of nutrition</alt-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>83-7</pages><volume>136</volume><number>1</number><keywords><keyword>Cholesterol/blood</keyword><keyword>Fatty Acids, Omega-3/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Linseed Oil/*pharmacology</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>alpha-Linolenic Acid/metabolism/*pharmacology</keyword></keywords><dates><year>2006</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0022-3166 (Print)</isbn><accession-num>16365063</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[5]31 M/F263FSOCTL+ 53%+ 4%4De Groot, 04 ADDIN EN.CITE <EndNote><Cite><Author>de Groot</Author><Year>2004</Year><RecNum>653</RecNum><record><rec-number>653</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>de Groot, R. H.</author><author>Hornstra, G.</author><author>van Houwelingen, A. C.</author><author>Roumen, F.</author></authors></contributors><auth-address>Department of Human Biology and the Nutrition, Maastricht University, Maastricht, Netherlands. rhm.degroot@np.unimaas.nl</auth-address><titles><title>Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>251-60</pages><volume>79</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Birth Weight/drug effects</keyword><keyword>Dietary Fats/administration &amp; dosage/*pharmacology</keyword><keyword>Docosahexaenoic Acids/*blood</keyword><keyword>Double-Blind Method</keyword><keyword>Female</keyword><keyword>Fetal Blood/*metabolism</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Nutritional Status</keyword><keyword>Postpartum Period/*blood</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Outcome</keyword><keyword>Questionnaires</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism/*pharmacology</keyword></keywords><dates><year>2004</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>14749231</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[7]29 F262.8MPLnsns5James, 03 ADDIN EN.CITE <EndNote><Cite><Author>James</Author><Year>2003</Year><RecNum>650</RecNum><record><rec-number>650</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>James, M. J.</author><author>Ursin, V. M.</author><author>Cleland, L. 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M.</author><author>Ahola, I.</author><author>Ahlstrom, A.</author></authors></contributors><auth-address>Department of Nutrition, University of Helsinki, Finland.</auth-address><titles><title>Rapeseed oil and sunflower oil diets enhance platelet in vitro aggregation and thromboxane production in healthy men when compared with milk fat or habitual diets</title><secondary-title>Thromb Haemost</secondary-title><alt-title>Thrombosis and haemostasis</alt-title></titles><pages>352-6</pages><volume>67</volume><number>3</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Animals</keyword><keyword>Blood Platelets/metabolism</keyword><keyword>Brassica</keyword><keyword>Dietary Fats, Unsaturated/*pharmacology</keyword><keyword>Fatty Acids/blood</keyword><keyword>Food Habits</keyword><keyword>Helianthus</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Milk/*analysis</keyword><keyword>Plant Oils/pharmacology</keyword><keyword>Platelet Aggregation/*physiology</keyword><keyword>Reference Values</keyword><keyword>Thromboxanes/*biosynthesis</keyword></keywords><dates><year>1992</year><pub-dates><date>Mar 2</date></pub-dates></dates><isbn>0340-6245 (Print)</isbn><accession-num>1641826</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[39]26 M3.55.4CplateletsNRns19Kwon et al.,91 ADDIN EN.CITE <EndNote><Cite><Author>Kwon</Author><Year>1991</Year><RecNum>706</RecNum><record><rec-number>706</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kwon, J. S.</author><author>Snook, J. T.</author><author>Wardlaw, G. M.</author><author>Hwang, D. H.</author></authors></contributors><auth-address>Department of Human Nutrition, Ohio State University, Columbus.</auth-address><titles><title>Effects of diets high in saturated fatty acids, canola oil, or safflower oil on platelet function, thromboxane B2 formation, and fatty acid composition of platelet phospholipids</title><secondary-title>Am J Clin Nutr</secondary-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>351-8</pages><volume>54</volume><number>2</number><keywords><keyword>Adenosine Triphosphate/blood</keyword><keyword>Adult</keyword><keyword>Arachidonic Acid</keyword><keyword>Arachidonic Acids/blood</keyword><keyword>Blood Platelets/*physiology</keyword><keyword>Collagen/pharmacology</keyword><keyword>Dietary Fats/administration &amp; dosage/*pharmacology</keyword><keyword>Dietary Fats, Unsaturated/administration &amp; dosage/*pharmacology</keyword><keyword>Fatty Acids/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Fatty Acids, Monounsaturated/administration &amp; dosage/pharmacology</keyword><keyword>Humans</keyword><keyword>Linolenic Acids/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Oleic Acid</keyword><keyword>Oleic Acids/blood</keyword><keyword>Phospholipids/*blood</keyword><keyword>Platelet Aggregation/drug effects</keyword><keyword>Platelet Aggregation Inhibitors/pharmacology</keyword><keyword>Safflower Oil/administration &amp; dosage/pharmacology</keyword><keyword>Thromboxane B2/*biosynthesis</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1991</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>1677525</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[41]30 M81% EnCplateletsnsns20Clark, 92 ADDIN EN.CITE <EndNote><Cite><Author>Clark</Author><Year>1992</Year><RecNum>676</RecNum><record><rec-number>676</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Clark, K. J.</author><author>Makrides, M.</author><author>Neumann, M. A.</author><author>Gibson, R. A.</author></authors></contributors><auth-address>Department of Paediatrics and Child Health, Flinders Medical Centre, Adelaide, South Australia.</auth-address><titles><title>Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas</title><secondary-title>J Pediatr</secondary-title><alt-title>The Journal of pediatrics</alt-title></titles><pages>S151-8</pages><volume>120</volume><number>4 Pt 2</number><keywords><keyword>Arachidonic Acid/blood</keyword><keyword>Breast Feeding</keyword><keyword>Docosahexaenoic Acids/blood</keyword><keyword>Fatty Acids/analysis/*blood</keyword><keyword>Humans</keyword><keyword>*Infant Food/analysis</keyword><keyword>Infant, Newborn/*blood</keyword><keyword>Linoleic Acid</keyword><keyword>*Linoleic Acids/analysis</keyword><keyword>*Linolenic Acids/analysis</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1992</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-3476 (Print)</isbn><accession-num>1348533</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[43]21 M/F (infants)10+2.6% EnFSOTL RBC+105%+38%21Jensen, 96 ADDIN EN.CITE <EndNote><Cite><Author>Jensen</Author><Year>1996</Year><RecNum>695</RecNum><record><rec-number>695</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jensen, C. L.</author><author>Chen, H.</author><author>Fraley, J. K.</author><author>Anderson, R. E.</author><author>Heird, W. C.</author></authors></contributors><auth-address>Department of Pediatrics, USDA, ARS Children&apos;s Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA.</auth-address><titles><title>Biochemical effects of dietary linoleic/alpha-linolenic acid ratio in term infants</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>107-13</pages><volume>31</volume><number>1</number><keywords><keyword>Dietary Fats/*pharmacology</keyword><keyword>Erythrocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*blood</keyword><keyword>alpha-Linolenic Acid/*blood</keyword></keywords><dates><year>1996</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>8649227</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[45]80 M/F(infants)17+0.55, +1.3, + 2.9% EnCPLRBCns,+136%,+264%ns,+155%,+309%ns,ns,+152%ns,ns,+147%Legend: FS, flaxseed; FSO, liquid flax oil; FSOC, flax oil capsule; M, margarine; C, canola; TL, total lipids; PL, phospholipids; CE, cholesterol esters, PBMC, peripheral blood mononuclear cells, RBC, red blood cells; ns = no significant change (p>0.05), % En, percent of dietary energy. Changes in the last two columns are relative to the values in the control groups.Table modified from Plourde and Cunnane ADDIN EN.CITE <EndNote><Cite><Author>Plourde</Author><Year>2007</Year><RecNum>631</RecNum><record><rec-number>631</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plourde, M.</author><author>Cunnane, S. C.</author></authors></contributors><auth-address>Research Center on Aging, Departments of Medicine, and Physiology and Biophysics, Universite de Sherbrooke, 1036 Belvedere St, South, Sherbrooke, QC J1H 4C4, Canada.</auth-address><titles><title>Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements</title><secondary-title>Appl Physiol Nutr Metab</secondary-title><alt-title>Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme</alt-title></titles><pages>619-34</pages><volume>32</volume><number>4</number><keywords><keyword>*Diet</keyword><keyword>*Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/metabolism</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/metabolism</keyword><keyword>Fatty Acids, Essential/*biosynthesis</keyword><keyword>Humans</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1715-5312 (Print)</isbn><accession-num>17622276</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[16].00Table 1. Changes in blood EPA and DHA in humans after ALA supplementation or feeding.ReferenceSubjectsDuration (weeks)ALA(g·d-1)ALA formBloodfractionChange inEPADHA1Szapary, 07 ADDIN EN.CITE <EndNote><Cite><Author>Szapary</Author><Year>2007</Year><RecNum>647</RecNum><record><rec-number>647</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Szapary, P. O. </author><author>Bloedon, L. T. </author><author>Balikai, S.</author><author>Chittams, J. </author><author>Cunnane, S. C. </author><author>Berlin, J. A.</author></authors></contributors><titles><title>Effects of flaxseed on markers of cardiovascular risk: Results from a randomized clinical trial</title><secondary-title>J Am Coll Nutr</secondary-title></titles><volume>in press.</volume><dates><year>2007</year></dates><urls></urls></record></Cite></EndNote>[1]30 M/F1040FSTL+ 12%ns2Goyens, 06 ADDIN EN.CITE <EndNote><Cite><Author>Goyens</Author><Year>2006</Year><RecNum>654</RecNum><record><rec-number>654</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Goyens, P. L.</author><author>Spilker, M. E.</author><author>Zock, P. L.</author><author>Katan, M. B.</author><author>Mensink, R. P.</author></authors></contributors><auth-address>Department of Human Biology, Maastricht University, Maastricht, Netherlands. p.goyens@hb.unimaas.nl</auth-address><titles><title>Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>44-53</pages><volume>84</volume><number>1</number><keywords><keyword>Breath Tests</keyword><keyword>Carbon Isotopes</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Double-Blind Method</keyword><keyword>Fatty Acids, Unsaturated/analysis/blood/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Linoleic Acid/administration &amp; dosage/blood/*metabolism</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Oxidation-Reduction</keyword><keyword>Phospholipids/analysis/blood/*metabolism</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/blood/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>16825680</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[4]10 M/F61.1% EnMPL+ 9.7%ns3Harper, 06 ADDIN EN.CITE <EndNote><Cite><Author>Harper</Author><Year>2006</Year><RecNum>646</RecNum><record><rec-number>646</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Harper, C. R.</author><author>Edwards, M. J.</author><author>DeFilipis, A. P.</author><author>Jacobson, T. A.</author></authors></contributors><auth-address>Department of Medicine, Office of Health Promotion and Disease Prevention, Emory University, Atlanta, GA, USA. charper@emory.edu</auth-address><titles><title>Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans</title><secondary-title>J Nutr</secondary-title><alt-title>The Journal of nutrition</alt-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>83-7</pages><volume>136</volume><number>1</number><keywords><keyword>Cholesterol/blood</keyword><keyword>Fatty Acids, Omega-3/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Linseed Oil/*pharmacology</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>alpha-Linolenic Acid/metabolism/*pharmacology</keyword></keywords><dates><year>2006</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0022-3166 (Print)</isbn><accession-num>16365063</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[5]31 M/F263FSOCTL+ 53%+ 4%4De Groot, 04 ADDIN EN.CITE <EndNote><Cite><Author>de Groot</Author><Year>2004</Year><RecNum>653</RecNum><record><rec-number>653</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>de Groot, R. H.</author><author>Hornstra, G.</author><author>van Houwelingen, A. C.</author><author>Roumen, F.</author></authors></contributors><auth-address>Department of Human Biology and the Nutrition, Maastricht University, Maastricht, Netherlands. rhm.degroot@np.unimaas.nl</auth-address><titles><title>Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>251-60</pages><volume>79</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Birth Weight/drug effects</keyword><keyword>Dietary Fats/administration &amp; dosage/*pharmacology</keyword><keyword>Docosahexaenoic Acids/*blood</keyword><keyword>Double-Blind Method</keyword><keyword>Female</keyword><keyword>Fetal Blood/*metabolism</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Nutritional Status</keyword><keyword>Postpartum Period/*blood</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Outcome</keyword><keyword>Questionnaires</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism/*pharmacology</keyword></keywords><dates><year>2004</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>14749231</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[7]29 F262.8MPLnsns5James, 03 ADDIN EN.CITE <EndNote><Cite><Author>James</Author><Year>2003</Year><RecNum>650</RecNum><record><rec-number>650</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>James, M. J.</author><author>Ursin, V. M.</author><author>Cleland, L. G.</author></authors></contributors><auth-address>Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia. michael.james@adelaide.edu.au</auth-address><titles><title>Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1140-5</pages><volume>77</volume><number>5</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Cytokines/antagonists &amp; inhibitors/biosynthesis</keyword><keyword>Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/blood/*pharmacokinetics</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/blood/*pharmacokinetics</keyword><keyword>Fatty Acids, Omega-3/metabolism/*pharmacokinetics/pharmacology</keyword><keyword>Fatty Acids, Unsaturated/blood</keyword><keyword>Female</keyword><keyword>Fish Oils/administration &amp; dosage</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Patient Compliance</keyword><keyword>Tissue Distribution</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>May</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12716664</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[9]15 M/F31.5FSOCPL+ 23%ns6Finnegan, 03 ADDIN EN.CITE <EndNote><Cite><Author>Finnegan</Author><Year>2003</Year><RecNum>651</RecNum><record><rec-number>651</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Finnegan, Y. E.</author><author>Minihane, A. M.</author><author>Leigh-Firbank, E. C.</author><author>Kew, S.</author><author>Meijer, G. W.</author><author>Muggli, R.</author><author>Calder, P. C.</author><author>Williams, C. M.</author></authors></contributors><auth-address>Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, University of Reading, Reading, United Kingdom.</auth-address><titles><title>Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>783-95</pages><volume>77</volume><number>4</number><keywords><keyword>Antioxidants/analysis</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Dietary Fats, Unsaturated/administration &amp; dosage</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage</keyword><keyword>Fasting</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fatty Acids, Omega-3/*administration &amp; dosage</keyword><keyword>Fish Oils/*administration &amp; dosage</keyword><keyword>Food</keyword><keyword>Hyperlipidemias/*blood</keyword><keyword>Insulin/blood</keyword><keyword>*Lipid Peroxidation</keyword><keyword>Lipids/*blood</keyword><keyword>Phospholipids/blood</keyword><keyword>Placebos</keyword><keyword>Plant Oils/*administration &amp; dosage</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage</keyword></keywords><dates><year>2003</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12663273</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[12]29 M/F264.5MPL+ 90%ns7Wallace, 03 ADDIN EN.CITE <EndNote><Cite><Author>Wallace</Author><Year>2003</Year><RecNum>652</RecNum><record><rec-number>652</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wallace, F. 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C.</author></authors></contributors><auth-address>Institute of Human Nutrition, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.</auth-address><titles><title>Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>679-89</pages><volume>89</volume><number>5</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Analysis of Variance</keyword><keyword>Cell Division</keyword><keyword>Cytokines/biosynthesis</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage</keyword><keyword>Double-Blind Method</keyword><keyword>Drug Administration Schedule</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fish Oils/*administration &amp; dosage</keyword><keyword>Humans</keyword><keyword>Interleukin-6/*immunology</keyword><keyword>Leukocytes, Mononuclear/*drug effects/immunology</keyword><keyword>Male</keyword><keyword>Phospholipids/chemistry</keyword><keyword>T-Lymphocyte Subsets/immunology</keyword><keyword>Thiobarbituric Acid Reactive Substances/analysis</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage</keyword><keyword>alpha-Tocopherol/blood</keyword></keywords><dates><year>2003</year><pub-dates><date>May</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>12720588</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[19]8 M123.5FSOCPL+ 60%+ 2%8Francois, 03 ADDIN EN.CITE <EndNote><Cite><Author>Francois</Author><Year>2003</Year><RecNum>660</RecNum><record><rec-number>660</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Francois, C. A.</author><author>Connor, S. L.</author><author>Bolewicz, L. C.</author><author>Connor, W. E.</author></authors></contributors><auth-address>Division of Endocrinology, Metabolism and Clinical Nutrition, the Department of Medicine, Oregon Health and Science University, Portland 97239-3098, USA.</auth-address><titles><title>Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>226-33</pages><volume>77</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/analysis/*metabolism</keyword><keyword>Fatty Acids/blood/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>*Lactation</keyword><keyword>Linseed Oil/*administration &amp; dosage/metabolism</keyword><keyword>Milk, Human/*chemistry</keyword></keywords><dates><year>2003</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12499346</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[21]7 F410FSOCTL228%ns9Li, 99 ADDIN EN.CITE <EndNote><Cite><Author>Li</Author><Year>1999</Year><RecNum>627</RecNum><record><rec-number>627</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, D.</author><author>Sinclair, A.</author><author>Wilson, A.</author><author>Nakkote, S.</author><author>Kelly, F.</author><author>Abedin, L.</author><author>Mann, N.</author><author>Turner, A.</author></authors></contributors><auth-address>Department of Food Science, RMIT University, Melbourne, Victoria, Australia.</auth-address><titles><title>Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men</title><secondary-title>Am J Clin Nutr</secondary-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>872-82</pages><volume>69</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Arteriosclerosis/*etiology</keyword><keyword>Blood Chemical Analysis</keyword><keyword>Blood Platelets/drug effects/metabolism</keyword><keyword>*Diet, Vegetarian</keyword><keyword>Dietary Fats/*pharmacology</keyword><keyword>Fatty Acids/analysis</keyword><keyword>Fatty Acids, Unsaturated/analysis</keyword><keyword>Hematologic Tests</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Phospholipids/blood/chemistry</keyword><keyword>Risk Factors</keyword><keyword>Thrombosis/*etiology</keyword><keyword>Triglycerides/blood/chemistry</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>May</date></pub-dates></dates><accession-num>10232625</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[23]17 M63.7MPL+ 13%ns17 M615.4MPL+ 250%ns10Ezaki, 99 ADDIN EN.CITE <EndNote><Cite><Author>Ezaki</Author><Year>1999</Year><RecNum>628</RecNum><record><rec-number>628</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ezaki, O.</author><author>Takahashi, M.</author><author>Shigematsu, T.</author><author>Shimamura, K.</author><author>Kimura, J.</author><author>Ezaki, H.</author><author>Gotoh, T.</author></authors></contributors><auth-address>Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo, Japan. ezaki@nih.go.jp</auth-address><titles><title>Long-term effects of dietary alpha-linolenic acid from perilla oil on serum fatty acids composition and on the risk factors of coronary heart disease in Japanese elderly subjects</title><secondary-title>J Nutr Sci Vitaminol (Tokyo)</secondary-title></titles><pages>759-72</pages><volume>45</volume><number>6</number><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Cookery</keyword><keyword>Coronary Disease/*etiology</keyword><keyword>Dietary Fats/*pharmacology</keyword><keyword>Enzyme-Linked Immunosorbent Assay</keyword><keyword>Fatty Acids/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Lipids/blood</keyword><keyword>Lipoproteins/blood</keyword><keyword>Lipoproteins, LDL/blood</keyword><keyword>Male</keyword><keyword>Plant Oils/*pharmacology</keyword><keyword>Risk Factors</keyword><keyword>alpha-Linolenic Acid/*pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>Dec</date></pub-dates></dates><accession-num>10737229</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[25]20 M/F42+3perillaTL+45%+21%11Allman, 95 ADDIN EN.CITE <EndNote><Cite><Author>Allman</Author><Year>1995</Year><RecNum>656</RecNum><record><rec-number>656</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Allman, M. A.</author><author>Pena, M. M.</author><author>Pang, D.</author></authors></contributors><auth-address>Department of Biochemistry, University of Sydney, Australia.</auth-address><titles><title>Supplementation with flaxseed oil versus sunflowerseed oil in healthy young men consuming a low fat diet: effects on platelet composition and function</title><secondary-title>Eur J Clin Nutr</secondary-title><alt-title>European journal of clinical nutrition</alt-title></titles><pages>169-78</pages><volume>49</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Arachidonic Acid/metabolism</keyword><keyword>Blood Platelets/*drug effects/*metabolism/physiology</keyword><keyword>*Diet, Fat-Restricted</keyword><keyword>Dietary Fats, Unsaturated/*administration &amp; dosage</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>*Energy Intake</keyword><keyword>Fatty Acids, Omega-3/*metabolism</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>*Food, Fortified</keyword><keyword>Humans</keyword><keyword>Linseed Oil/*administration &amp; dosage</keyword><keyword>Male</keyword><keyword>Plant Oils/*administration &amp; dosage</keyword><keyword>Platelet Aggregation/drug effects</keyword><keyword>Platelet Aggregation Inhibitors/*administration &amp; dosage</keyword><keyword>Prospective Studies</keyword><keyword>alpha-Linolenic Acid/metabolism</keyword></keywords><dates><year>1995</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0954-3007 (Print)</isbn><accession-num>7774533</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[27]11 M3.222FSplatelets1.2ns12Nordstrom, 95 ADDIN EN.CITE <EndNote><Cite><Author>Nordstrom</Author><Year>1995</Year><RecNum>645</RecNum><record><rec-number>645</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nordstrom, D. C.</author><author>Honkanen, V. E.</author><author>Nasu, Y.</author><author>Antila, E.</author><author>Friman, C.</author><author>Konttinen, Y. T.</author></authors></contributors><auth-address>Fourth Department of Medicine, Helsinki University Central Hospital, Finland.</auth-address><titles><title>Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed</title><secondary-title>Rheumatol Int</secondary-title><alt-title>Rheumatology international</alt-title></titles><pages>231-4</pages><volume>14</volume><number>6</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Arthritis, Rheumatoid/blood/*diet therapy</keyword><keyword>Double-Blind Method</keyword><keyword>Fatty Acids/analysis/blood</keyword><keyword>Female</keyword><keyword>Finland</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Trace Elements/analysis/blood</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage/*blood/therapeutic use</keyword></keywords><dates><year>1995</year></dates><isbn>0172-8172 (Print)</isbn><accession-num>7597378</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[28]22 M/F129.6FSOTL+ 0.02%+ 0.5%13Cunnane, 95 ADDIN EN.CITE <EndNote><Cite><Author>Cunnane</Author><Year>1995</Year><RecNum>649</RecNum><record><rec-number>649</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cunnane, S. C.</author><author>Hamadeh, M. J.</author><author>Liede, A. C.</author><author>Thompson, L. U.</author><author>Wolever, T. M.</author><author>Jenkins, D. J.</author></authors></contributors><auth-address>Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Canada.</auth-address><titles><title>Nutritional attributes of traditional flaxseed in healthy young adults</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>62-8</pages><volume>61</volume><number>1</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Adult</keyword><keyword>Anthropometry</keyword><keyword>Antioxidants/metabolism</keyword><keyword>Blood Glucose/drug effects</keyword><keyword>Cholesterol/blood</keyword><keyword>Cross-Over Studies</keyword><keyword>Defecation/drug effects</keyword><keyword>Dietary Fiber/administration &amp; dosage</keyword><keyword>Fatty Acids, Omega-3/blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Lipid Peroxidation/drug effects</keyword><keyword>Male</keyword><keyword>Nutritional Status</keyword><keyword>*Seeds</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism/pharmacology</keyword></keywords><dates><year>1995</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>7825540</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[30]10 M/F49FSPL+ 33%ns14Mantzioris, 95 ADDIN EN.CITE <EndNote><Cite><Author>Mantzioris</Author><Year>1995</Year><RecNum>648</RecNum><record><rec-number>648</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mantzioris, E.</author><author>James, M. J.</author><author>Gibson, R. A.</author><author>Cleland, L. G.</author></authors></contributors><auth-address>Rheumatology Unit, Royal Adelaide Hospital, Australia.</auth-address><titles><title>Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>320-4</pages><volume>61</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Anthropometry</keyword><keyword>Diet Records</keyword><keyword>Dietary Fats/*metabolism</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Energy Intake</keyword><keyword>Fatty Acids/blood</keyword><keyword>Humans</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/administration &amp; dosage/*metabolism/pharmacology</keyword><keyword>Male</keyword><keyword>Phospholipids/blood</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism/pharmacology</keyword></keywords><dates><year>1995</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>7840069</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[31]15 M413.7MPL+ 138%+ 14%15Freese, 94 ADDIN EN.CITE <EndNote><Cite><Author>Freese</Author><Year>1994</Year><RecNum>657</RecNum><record><rec-number>657</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freese, R.</author><author>Mutanen, M.</author><author>Valsta, L. M.</author><author>Salminen, I.</author></authors></contributors><auth-address>Department of Applied Chemistry and Microbiology, University of Helsinki, Finland.</auth-address><titles><title>Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/alpha-linolenic acid ratio on platelet aggregation</title><secondary-title>Thromb Haemost</secondary-title><alt-title>Thrombosis and haemostasis</alt-title></titles><pages>73-7</pages><volume>71</volume><number>1</number><keywords><keyword>Adenosine Diphosphate/pharmacology</keyword><keyword>Adult</keyword><keyword>Antithrombin III/analysis</keyword><keyword>Collagen/pharmacology</keyword><keyword>Dietary Fats/*pharmacology</keyword><keyword>Fatty Acids, Monounsaturated/administration &amp; dosage/*pharmacology</keyword><keyword>Humans</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/analysis/*pharmacology</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Plant Oils/administration &amp; dosage/chemistry</keyword><keyword>Platelet Aggregation/*drug effects</keyword><keyword>Thrombin/pharmacology</keyword><keyword>alpha-Linolenic Acid/analysis/*pharmacology</keyword></keywords><dates><year>1994</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0340-6245 (Print)</isbn><accession-num>7909389</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[33]20 M65.6CCE-27%ns16Kelley, 93 ADDIN EN.CITE <EndNote><Cite><Author>Kelley</Author><Year>1993</Year><RecNum>644</RecNum><record><rec-number>644</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kelley, D. S.</author><author>Nelson, G. J.</author><author>Love, J. E.</author><author>Branch, L. B.</author><author>Taylor, P. C.</author><author>Schmidt, P. C.</author><author>Mackey, B. E.</author><author>Iacono, J. M.</author></authors></contributors><auth-address>USDA, ARS, WHNRC, Presidio of San Francisco, California 94129.</auth-address><titles><title>Dietary alpha-linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>533-7</pages><volume>28</volume><number>6</number><keywords><keyword>8,11,14-Eicosatrienoic Acid/analysis</keyword><keyword>Adult</keyword><keyword>Bleeding Time</keyword><keyword>Blood Coagulation/*drug effects</keyword><keyword>Dietary Fats/*pharmacology</keyword><keyword>Eicosapentaenoic Acid/analysis</keyword><keyword>Fatty Acids/analysis</keyword><keyword>Fatty Acids, Unsaturated/analysis</keyword><keyword>Humans</keyword><keyword>Leukocytes, Mononuclear/chemistry/*drug effects</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/analysis</keyword><keyword>Linolenic Acids/*pharmacology</keyword><keyword>Lipids/blood</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Prothrombin Time</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1993</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>8102770</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[35]10 M821FSOPBMC+100%ns17Chan, 93 ADDIN EN.CITE <EndNote><Cite><Author>Chan</Author><Year>1993</Year><RecNum>658</RecNum><record><rec-number>658</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chan, J. K.</author><author>McDonald, B. E.</author><author>Gerrard, J. M.</author><author>Bruce, V. M.</author><author>Weaver, B. J.</author><author>Holub, B. J.</author></authors></contributors><auth-address>Department of Foods and Nutrition, University of Manitoba, Winnipeg, Canada.</auth-address><titles><title>Effect of dietary alpha-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>811-7</pages><volume>28</volume><number>9</number><keywords><keyword>Adult</keyword><keyword>Bleeding Time</keyword><keyword>Blood Platelets/*drug effects</keyword><keyword>Dietary Fats/pharmacology</keyword><keyword>Fatty Acids, Unsaturated/*blood</keyword><keyword>Humans</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*pharmacology</keyword><keyword>Male</keyword><keyword>Phospholipids/blood</keyword><keyword>Prostaglandins/*biosynthesis</keyword></keywords><dates><year>1993</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>8231657</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[37]8 M614CPL+100%ns18Mutanen, 92 ADDIN EN.CITE <EndNote><Cite><Author>Mutanen</Author><Year>1992</Year><RecNum>655</RecNum><record><rec-number>655</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mutanen, M.</author><author>Freese, R.</author><author>Valsta, L. M.</author><author>Ahola, I.</author><author>Ahlstrom, A.</author></authors></contributors><auth-address>Department of Nutrition, University of Helsinki, Finland.</auth-address><titles><title>Rapeseed oil and sunflower oil diets enhance platelet in vitro aggregation and thromboxane production in healthy men when compared with milk fat or habitual diets</title><secondary-title>Thromb Haemost</secondary-title><alt-title>Thrombosis and haemostasis</alt-title></titles><pages>352-6</pages><volume>67</volume><number>3</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Animals</keyword><keyword>Blood Platelets/metabolism</keyword><keyword>Brassica</keyword><keyword>Dietary Fats, Unsaturated/*pharmacology</keyword><keyword>Fatty Acids/blood</keyword><keyword>Food Habits</keyword><keyword>Helianthus</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Milk/*analysis</keyword><keyword>Plant Oils/pharmacology</keyword><keyword>Platelet Aggregation/*physiology</keyword><keyword>Reference Values</keyword><keyword>Thromboxanes/*biosynthesis</keyword></keywords><dates><year>1992</year><pub-dates><date>Mar 2</date></pub-dates></dates><isbn>0340-6245 (Print)</isbn><accession-num>1641826</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[39]26 M3.55.4CplateletsNRns19Kwon et al.,91 ADDIN EN.CITE <EndNote><Cite><Author>Kwon</Author><Year>1991</Year><RecNum>706</RecNum><record><rec-number>706</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kwon, J. S.</author><author>Snook, J. T.</author><author>Wardlaw, G. M.</author><author>Hwang, D. H.</author></authors></contributors><auth-address>Department of Human Nutrition, Ohio State University, Columbus.</auth-address><titles><title>Effects of diets high in saturated fatty acids, canola oil, or safflower oil on platelet function, thromboxane B2 formation, and fatty acid composition of platelet phospholipids</title><secondary-title>Am J Clin Nutr</secondary-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>351-8</pages><volume>54</volume><number>2</number><keywords><keyword>Adenosine Triphosphate/blood</keyword><keyword>Adult</keyword><keyword>Arachidonic Acid</keyword><keyword>Arachidonic Acids/blood</keyword><keyword>Blood Platelets/*physiology</keyword><keyword>Collagen/pharmacology</keyword><keyword>Dietary Fats/administration &amp; dosage/*pharmacology</keyword><keyword>Dietary Fats, Unsaturated/administration &amp; dosage/*pharmacology</keyword><keyword>Fatty Acids/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Fatty Acids, Monounsaturated/administration &amp; dosage/pharmacology</keyword><keyword>Humans</keyword><keyword>Linolenic Acids/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Oleic Acid</keyword><keyword>Oleic Acids/blood</keyword><keyword>Phospholipids/*blood</keyword><keyword>Platelet Aggregation/drug effects</keyword><keyword>Platelet Aggregation Inhibitors/pharmacology</keyword><keyword>Safflower Oil/administration &amp; dosage/pharmacology</keyword><keyword>Thromboxane B2/*biosynthesis</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1991</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>1677525</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[41]30 M81% EnCplateletsnsns20Clark, 92 ADDIN EN.CITE <EndNote><Cite><Author>Clark</Author><Year>1992</Year><RecNum>676</RecNum><record><rec-number>676</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Clark, K. J.</author><author>Makrides, M.</author><author>Neumann, M. A.</author><author>Gibson, R. A.</author></authors></contributors><auth-address>Department of Paediatrics and Child Health, Flinders Medical Centre, Adelaide, South Australia.</auth-address><titles><title>Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas</title><secondary-title>J Pediatr</secondary-title><alt-title>The Journal of pediatrics</alt-title></titles><pages>S151-8</pages><volume>120</volume><number>4 Pt 2</number><keywords><keyword>Arachidonic Acid/blood</keyword><keyword>Breast Feeding</keyword><keyword>Docosahexaenoic Acids/blood</keyword><keyword>Fatty Acids/analysis/*blood</keyword><keyword>Humans</keyword><keyword>*Infant Food/analysis</keyword><keyword>Infant, Newborn/*blood</keyword><keyword>Linoleic Acid</keyword><keyword>*Linoleic Acids/analysis</keyword><keyword>*Linolenic Acids/analysis</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1992</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-3476 (Print)</isbn><accession-num>1348533</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[43]21 M/F (infants)10+2.6% EnFSOTL RBC+105%+38%21Jensen, 96 ADDIN EN.CITE <EndNote><Cite><Author>Jensen</Author><Year>1996</Year><RecNum>695</RecNum><record><rec-number>695</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jensen, C. L.</author><author>Chen, H.</author><author>Fraley, J. K.</author><author>Anderson, R. E.</author><author>Heird, W. C.</author></authors></contributors><auth-address>Department of Pediatrics, USDA, ARS Children&apos;s Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA.</auth-address><titles><title>Biochemical effects of dietary linoleic/alpha-linolenic acid ratio in term infants</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>107-13</pages><volume>31</volume><number>1</number><keywords><keyword>Dietary Fats/*pharmacology</keyword><keyword>Erythrocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*blood</keyword><keyword>alpha-Linolenic Acid/*blood</keyword></keywords><dates><year>1996</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>8649227</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[45]80 M/F(infants)17+0.55, +1.3, + 2.9% EnCPLRBCns,+136%,+264%ns,+155%,+309%ns,ns,+152%ns,ns,+147%Legend: FS, flaxseed; FSO, liquid flax oil; FSOC, flax oil capsule; M, margarine; C, canola; TL, total lipids; PL, phospholipids; CE, cholesterol esters, PBMC, peripheral blood mononuclear cells, RBC, red blood cells; ns = no significant change (p>0.05), % En, percent of dietary energy. Changes in the last two columns are relative to the values in the control groups.Table modified from Plourde and Cunnane ADDIN EN.CITE <EndNote><Cite><Author>Plourde</Author><Year>2007</Year><RecNum>631</RecNum><record><rec-number>631</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plourde, M.</author><author>Cunnane, S. C.</author></authors></contributors><auth-address>Research Center on Aging, Departments of Medicine, and Physiology and Biophysics, Universite de Sherbrooke, 1036 Belvedere St, South, Sherbrooke, QC J1H 4C4, Canada.</auth-address><titles><title>Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements</title><secondary-title>Appl Physiol Nutr Metab</secondary-title><alt-title>Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme</alt-title></titles><pages>619-34</pages><volume>32</volume><number>4</number><keywords><keyword>*Diet</keyword><keyword>*Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/metabolism</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/metabolism</keyword><keyword>Fatty Acids, Essential/*biosynthesis</keyword><keyword>Humans</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1715-5312 (Print)</isbn><accession-num>17622276</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[16].Supplementation trials have been conducted with purified EPA ethyl ester, and all consistently show increases in both EPA and DPAn-3 but no change in DHA in the blood. Table 2 outlines seven studies of EPA supplementation in adults which all show increases in EPA but no increases in DHA. Purified EPA ethyl ester (3.6 g) was given for 4 weeks to healthy volunteers, both platelet and erythrocyte phospholipid EPA was significantly increased but there was no change in DHA ADDIN EN.CITE <EndNote><Cite><Author>Terano</Author><Year>1983</Year><RecNum>661</RecNum><record><rec-number>661</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Terano, T.</author><author>Hirai, A.</author><author>Hamazaki, T.</author><author>Kobayashi, S.</author><author>Fujita, T.</author><author>Tamura, Y.</author><author>Kumagai, A.</author></authors></contributors><titles><title>Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects</title><secondary-title>Atherosclerosis</secondary-title><alt-title>Atherosclerosis</alt-title></titles><pages>321-31</pages><volume>46</volume><number>3</number><keywords><keyword>Administration, Oral</keyword><keyword>Adult</keyword><keyword>Blood Platelets/analysis/*drug effects</keyword><keyword>Blood Viscosity/*drug effects</keyword><keyword>Eicosapentaenoic Acid</keyword><keyword>Erythrocytes/analysis/*drug effects</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage/*pharmacology</keyword><keyword>Humans</keyword><keyword>Lipids/analysis</keyword><keyword>Male</keyword><keyword>Platelet Aggregation</keyword></keywords><dates><year>1983</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0021-9150 (Print)</isbn><accession-num>6303363</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Hirai</Author><Year>1989</Year><RecNum>662</RecNum><record><rec-number>662</rec-number><ref-type name="Book Section">5</ref-type><contributors><authors><author>Hirai, A.</author><author>Terano, T,</author><author>Saito, H.</author><author>Tamura, Y.</author></authors><secondary-authors><author>Spiller, G.A.</author><author>Scala, J.</author></secondary-authors></contributors><titles><title>Omega-3 fatty acids: Epidemiological and clinical aspects</title><secondary-title>New Protective Roles for Selected Nutrients</secondary-title></titles><pages>229-252</pages><dates><year>1989</year></dates><pub-location>New York</pub-location><publisher>Alan R Liss</publisher><urls></urls></record></Cite></EndNote>[2, 3]. Highly purified EPA (3.8 g/d) was fed to healthy men for 7 weeks and serum phospholipid EPA and DPAn-3 were significantly increased but DHA decreased ADDIN EN.CITE <EndNote><Cite><Author>Grimsgaard</Author><Year>1997</Year><RecNum>663</RecNum><record><rec-number>663</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Grimsgaard, S.</author><author>Bonaa, K. H.</author><author>Hansen, J. B.</author><author>Nordoy, A.</author></authors></contributors><auth-address>Institute of Community Medicine, University of Tromso, Norway.</auth-address><titles><title>Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>649-59</pages><volume>66</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Body Weight</keyword><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/adverse effects/*pharmacology</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*pharmacology</keyword><keyword>Exercise</keyword><keyword>Fatty Acids/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Patient Compliance</keyword><keyword>Phospholipids/blood</keyword><keyword>Triglycerides/*blood</keyword></keywords><dates><year>1997</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>9280188</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[6]. In middle aged men, after 4 g/d of EPA was fed for 6 weeks, there was a marked increase in plasma phospholipid EPA and DPAn-3 but no increase in DHA ADDIN EN.CITE <EndNote><Cite><Author>Mori</Author><Year>2000</Year><RecNum>664</RecNum><record><rec-number>664</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mori, T. A.</author><author>Burke, V.</author><author>Puddey, I. B.</author><author>Watts, G. F.</author><author>O&apos;Neal, D. N.</author><author>Best, J. D.</author><author>Beilin, L. J.</author></authors></contributors><auth-address>Department of Medicine, The University of Western Australia and The West Australian Heart Research Institute, Perth. tmori@cyllene.uwa.edu.au</auth-address><titles><title>Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1085-94</pages><volume>71</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Centrifugation, Density Gradient</keyword><keyword>Cholesterol/blood</keyword><keyword>Cholesterol, HDL/blood/chemistry</keyword><keyword>Cholesterol, LDL/blood/chemistry</keyword><keyword>Docosahexaenoic Acids/blood/*metabolism</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/blood/*metabolism</keyword><keyword>Humans</keyword><keyword>Hypercholesterolemia/blood/*metabolism</keyword><keyword>Insulin/blood</keyword><keyword>Lipids/*blood</keyword><keyword>Lipoproteins/*blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Particle Size</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2000</year><pub-dates><date>May</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>10799369</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[8]. In another study of healthy subjects, 4 g/d of EPA was fed for 4 weeks and platelet EPA was increased many-fold, DPAn-3 was significantly increased but DHA was unaltered ADDIN EN.CITE <EndNote><Cite><Author>Park</Author><Year>2002</Year><RecNum>665</RecNum><record><rec-number>665</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Park, Y.</author><author>Harris, W.</author></authors></contributors><auth-address>Department of Medicine, University of Missouri-Kansas City, Missouri 64108, USA.</auth-address><titles><title>EPA, but not DHA, decreases mean platelet volume in normal subjects</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>941-6</pages><volume>37</volume><number>10</number><keywords><keyword>Administration, Oral</keyword><keyword>Adult</keyword><keyword>Blood Platelets/cytology/*drug effects</keyword><keyword>Blood Volume/*drug effects</keyword><keyword>Collagen/pharmacology</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Plant Oils/pharmacology</keyword><keyword>Platelet Activation/drug effects</keyword><keyword>Single-Blind Method</keyword><keyword>Temperature</keyword><keyword>Time Factors</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>12530552</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[10]. In type 2 diabetic patients, consuming 4g/d of EPA for 6 weeks led to a 5-fold increase in plasma phospholipid EPA and a significant increase in DPAn-3, but no change in DHA ADDIN EN.CITE <EndNote><Cite><Author>Woodman</Author><Year>2002</Year><RecNum>666</RecNum><record><rec-number>666</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Woodman, R. J.</author><author>Mori, T. A.</author><author>Burke, V.</author><author>Puddey, I. B.</author><author>Watts, G. F.</author><author>Beilin, L. J.</author></authors></contributors><auth-address>Department of Medicine, The University of Western Australia, Perth, Australia. rwoodman@cyllene.uwa.edu.au</auth-address><titles><title>Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1007-15</pages><volume>76</volume><number>5</number><keywords><keyword>Aged</keyword><keyword>Blood Glucose/*analysis</keyword><keyword>Blood Pressure/*drug effects</keyword><keyword>Blood Pressure Monitoring, Ambulatory</keyword><keyword>Diabetes Mellitus, Type 2/blood/*complications/*physiopathology</keyword><keyword>Docosahexaenoic Acids/adverse effects/*pharmacology</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*pharmacology</keyword><keyword>Fatty Acids/blood</keyword><keyword>Female</keyword><keyword>Heart Rate</keyword><keyword>Humans</keyword><keyword>Hypertension/*complications</keyword><keyword>Insulin/physiology</keyword><keyword>Lipids/*blood</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Phospholipids/blood</keyword><keyword>Plant Oils/pharmacology</keyword></keywords><dates><year>2002</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12399272</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[11]. In one psychiatric trial of schizophrenics, 1, 2 or 4 g EPA/d for 12 weeks produced significant increases in erythrocyte membrane EPA but not DHA ADDIN EN.CITE <EndNote><Cite><Author>Peet</Author><Year>2002</Year><RecNum>667</RecNum><record><rec-number>667</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peet, M.</author><author>Horrobin, D. F.</author></authors></contributors><auth-address>Swallownest Court, Aughton Road, S26 4TH, Sheffield, UK.</auth-address><titles><title>A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms</title><secondary-title>J Psychiatr Res</secondary-title><alt-title>Journal of psychiatric research</alt-title></titles><pages>7-18</pages><volume>36</volume><number>1</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Antipsychotic Agents/therapeutic use</keyword><keyword>Clozapine/therapeutic use</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*analogs &amp; derivatives/*therapeutic</keyword><keyword>use</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Platelet Aggregation Inhibitors/adverse effects/*therapeutic use</keyword><keyword>Psychiatric Status Rating Scales</keyword><keyword>Schizophrenia/*drug therapy</keyword><keyword>Schizophrenic Psychology</keyword></keywords><dates><year>2002</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0022-3956 (Print)</isbn><accession-num>11755456</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[59]. One other omega-3 PUFA, stearidonic acid (SDA, 18:4n-3), has also been studied as a precursor for long chain omega-3 in humans. SDA is an intermediate metabolite between ALA and EPA in the omega-3 biosynthetic pathway. Supplementation of SDA led to an elevated increase in EPA compared to ALA supplementation, but no increase in DHA ADDIN EN.CITE <EndNote><Cite><Author>James</Author><Year>2003</Year><RecNum>650</RecNum><record><rec-number>650</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>James, M. J.</author><author>Ursin, V. M.</author><author>Cleland, L. G.</author></authors></contributors><auth-address>Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia. michael.james@adelaide.edu.au</auth-address><titles><title>Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1140-5</pages><volume>77</volume><number>5</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Cytokines/antagonists &amp; inhibitors/biosynthesis</keyword><keyword>Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/blood/*pharmacokinetics</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/blood/*pharmacokinetics</keyword><keyword>Fatty Acids, Omega-3/metabolism/*pharmacokinetics/pharmacology</keyword><keyword>Fatty Acids, Unsaturated/blood</keyword><keyword>Female</keyword><keyword>Fish Oils/administration &amp; dosage</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Patient Compliance</keyword><keyword>Tissue Distribution</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>May</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12716664</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Harris</Author><Year>2008</Year><RecNum>709</RecNum><record><rec-number>709</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Harris, W. S.</author><author>Lemke, S. L.</author><author>Hansen, S. N.</author><author>Goldstein, D. A.</author><author>Dirienzo, M. A.</author><author>Su, H.</author><author>Nemeth, M. A.</author><author>Taylor, M. L.</author><author>Ahmed, G.</author><author>George, C.</author></authors></contributors><auth-address>Sanford Research/USD, 1100 East 21st Street, Suite 700, Sioux Falls, SD, 57105, USA, harrisw@.</auth-address><titles><title>Stearidonic Acid-Enriched Soybean Oil Increased the Omega-3 Index, an Emerging Cardiovascular Risk Marker</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><dates><year>2008</year><pub-dates><date>Aug 6</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>18683001</accession-num><urls><related-urls><url> </url></related-urls></urls><language>Eng</language></record></Cite></EndNote>[9, 60], consistent with studies of ALA and EPA.centertopTable 2. Changes in blood DHA in humans after EPA supplementation or feeding.ReferenceSubjectsDuration (weeks)EPA(g·d-1)EPA formBloodfractionChange inEPADHA1Terano, 83 ADDIN EN.CITE <EndNote><Cite><Author>Terano</Author><Year>1983</Year><RecNum>661</RecNum><record><rec-number>661</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Terano, T.</author><author>Hirai, A.</author><author>Hamazaki, T.</author><author>Kobayashi, S.</author><author>Fujita, T.</author><author>Tamura, Y.</author><author>Kumagai, A.</author></authors></contributors><titles><title>Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects</title><secondary-title>Atherosclerosis</secondary-title><alt-title>Atherosclerosis</alt-title></titles><pages>321-31</pages><volume>46</volume><number>3</number><keywords><keyword>Administration, Oral</keyword><keyword>Adult</keyword><keyword>Blood Platelets/analysis/*drug effects</keyword><keyword>Blood Viscosity/*drug effects</keyword><keyword>Eicosapentaenoic Acid</keyword><keyword>Erythrocytes/analysis/*drug effects</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage/*pharmacology</keyword><keyword>Humans</keyword><keyword>Lipids/analysis</keyword><keyword>Male</keyword><keyword>Platelet Aggregation</keyword></keywords><dates><year>1983</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0021-9150 (Print)</isbn><accession-num>6303363</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[2]8 M43.6EEPL+ 128%ns2Hirai, 89 ADDIN EN.CITE <EndNote><Cite><Author>Hirai</Author><Year>1989</Year><RecNum>662</RecNum><record><rec-number>662</rec-number><ref-type name="Book Section">5</ref-type><contributors><authors><author>Hirai, A.</author><author>Terano, T,</author><author>Saito, H.</author><author>Tamura, Y.</author></authors><secondary-authors><author>Spiller, G.A.</author><author>Scala, J.</author></secondary-authors></contributors><titles><title>Omega-3 fatty acids: Epidemiological and clinical aspects</title><secondary-title>New Protective Roles for Selected Nutrients</secondary-title></titles><pages>229-252</pages><dates><year>1989</year></dates><pub-location>New York</pub-location><publisher>Alan R Liss</publisher><urls></urls></record></Cite></EndNote>[3]8 M43.6EEPL+ 131%ns3Grimsgaard, 97 ADDIN EN.CITE <EndNote><Cite><Author>Grimsgaard</Author><Year>1997</Year><RecNum>663</RecNum><record><rec-number>663</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Grimsgaard, S.</author><author>Bonaa, K. H.</author><author>Hansen, J. B.</author><author>Nordoy, A.</author></authors></contributors><auth-address>Institute of Community Medicine, University of Tromso, Norway.</auth-address><titles><title>Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>649-59</pages><volume>66</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Body Weight</keyword><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/adverse effects/*pharmacology</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*pharmacology</keyword><keyword>Exercise</keyword><keyword>Fatty Acids/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Patient Compliance</keyword><keyword>Phospholipids/blood</keyword><keyword>Triglycerides/*blood</keyword></keywords><dates><year>1997</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>9280188</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[6]75 M73.8EEPL+297%-15%4Mori, 00 ADDIN EN.CITE <EndNote><Cite><Author>Mori</Author><Year>2000</Year><RecNum>664</RecNum><record><rec-number>664</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mori, T. A.</author><author>Burke, V.</author><author>Puddey, I. B.</author><author>Watts, G. F.</author><author>O&apos;Neal, D. N.</author><author>Best, J. D.</author><author>Beilin, L. J.</author></authors></contributors><auth-address>Department of Medicine, The University of Western Australia and The West Australian Heart Research Institute, Perth. tmori@cyllene.uwa.edu.au</auth-address><titles><title>Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1085-94</pages><volume>71</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Centrifugation, Density Gradient</keyword><keyword>Cholesterol/blood</keyword><keyword>Cholesterol, HDL/blood/chemistry</keyword><keyword>Cholesterol, LDL/blood/chemistry</keyword><keyword>Docosahexaenoic Acids/blood/*metabolism</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/blood/*metabolism</keyword><keyword>Humans</keyword><keyword>Hypercholesterolemia/blood/*metabolism</keyword><keyword>Insulin/blood</keyword><keyword>Lipids/*blood</keyword><keyword>Lipoproteins/*blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Particle Size</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2000</year><pub-dates><date>May</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>10799369</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[8]19 M/F64EEPL+ 8%ns5Park, 04 ADDIN EN.CITE <EndNote><Cite><Author>Park</Author><Year>2002</Year><RecNum>665</RecNum><record><rec-number>665</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Park, Y.</author><author>Harris, W.</author></authors></contributors><auth-address>Department of Medicine, University of Missouri-Kansas City, Missouri 64108, USA.</auth-address><titles><title>EPA, but not DHA, decreases mean platelet volume in normal subjects</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>941-6</pages><volume>37</volume><number>10</number><keywords><keyword>Administration, Oral</keyword><keyword>Adult</keyword><keyword>Blood Platelets/cytology/*drug effects</keyword><keyword>Blood Volume/*drug effects</keyword><keyword>Collagen/pharmacology</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Plant Oils/pharmacology</keyword><keyword>Platelet Activation/drug effects</keyword><keyword>Single-Blind Method</keyword><keyword>Temperature</keyword><keyword>Time Factors</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>12530552</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[10]10 M/F44EEPlatelets+1550%ns6Woodman, 02 ADDIN EN.CITE <EndNote><Cite><Author>Woodman</Author><Year>2002</Year><RecNum>666</RecNum><record><rec-number>666</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Woodman, R. J.</author><author>Mori, T. A.</author><author>Burke, V.</author><author>Puddey, I. B.</author><author>Watts, G. F.</author><author>Beilin, L. J.</author></authors></contributors><auth-address>Department of Medicine, The University of Western Australia, Perth, Australia. rwoodman@cyllene.uwa.edu.au</auth-address><titles><title>Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1007-15</pages><volume>76</volume><number>5</number><keywords><keyword>Aged</keyword><keyword>Blood Glucose/*analysis</keyword><keyword>Blood Pressure/*drug effects</keyword><keyword>Blood Pressure Monitoring, Ambulatory</keyword><keyword>Diabetes Mellitus, Type 2/blood/*complications/*physiopathology</keyword><keyword>Docosahexaenoic Acids/adverse effects/*pharmacology</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*pharmacology</keyword><keyword>Fatty Acids/blood</keyword><keyword>Female</keyword><keyword>Heart Rate</keyword><keyword>Humans</keyword><keyword>Hypertension/*complications</keyword><keyword>Insulin/physiology</keyword><keyword>Lipids/*blood</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Phospholipids/blood</keyword><keyword>Plant Oils/pharmacology</keyword></keywords><dates><year>2002</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12399272</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[11]17 M/F64EEPL+ 540%ns7Peet, 01 ADDIN EN.CITE <EndNote><Cite><Author>Peet</Author><Year>2001</Year><RecNum>668</RecNum><record><rec-number>668</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peet, M.</author><author>Brind, J.</author><author>Ramchand, C. N.</author><author>Shah, S.</author><author>Vankar, G. K.</author></authors></contributors><auth-address>Academic Department of Psychiatry, Northern General Hospital, The Longley Centre, Norwood Grange Drive, S5 7JT, Sheffield, UK. m.peet@sheffield.ac.uk</auth-address><titles><title>Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia</title><secondary-title>Schizophr Res</secondary-title><alt-title>Schizophrenia research</alt-title></titles><pages>243-51</pages><volume>49</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Antipsychotic Agents/administration &amp; dosage/*therapeutic use</keyword><keyword>Arachidonic Acids/administration &amp; dosage/*therapeutic use</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/therapeutic use</keyword><keyword>Double-Blind Method</keyword><keyword>Humans</keyword><keyword>Pilot Projects</keyword><keyword>Schizophrenia/*drug therapy</keyword><keyword>Schizophrenic Psychology</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr 30</date></pub-dates></dates><isbn>0920-9964 (Print)</isbn><accession-num>11356585</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[18]32, 32, or 27 M/F121,2, or 4EERBC + 17%, 24%, or 39%nsLegend: EE, ethyl ester; PL, phospholipids; RBC, red blood cells; ns = no significant change (p>0.05). Changes in the last two columns are relative to the values in the control groups.00Table 2. Changes in blood DHA in humans after EPA supplementation or feeding.ReferenceSubjectsDuration (weeks)EPA(g·d-1)EPA formBloodfractionChange inEPADHA1Terano, 83 ADDIN EN.CITE <EndNote><Cite><Author>Terano</Author><Year>1983</Year><RecNum>661</RecNum><record><rec-number>661</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Terano, T.</author><author>Hirai, A.</author><author>Hamazaki, T.</author><author>Kobayashi, S.</author><author>Fujita, T.</author><author>Tamura, Y.</author><author>Kumagai, A.</author></authors></contributors><titles><title>Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects</title><secondary-title>Atherosclerosis</secondary-title><alt-title>Atherosclerosis</alt-title></titles><pages>321-31</pages><volume>46</volume><number>3</number><keywords><keyword>Administration, Oral</keyword><keyword>Adult</keyword><keyword>Blood Platelets/analysis/*drug effects</keyword><keyword>Blood Viscosity/*drug effects</keyword><keyword>Eicosapentaenoic Acid</keyword><keyword>Erythrocytes/analysis/*drug effects</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage/*pharmacology</keyword><keyword>Humans</keyword><keyword>Lipids/analysis</keyword><keyword>Male</keyword><keyword>Platelet Aggregation</keyword></keywords><dates><year>1983</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0021-9150 (Print)</isbn><accession-num>6303363</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[2]8 M43.6EEPL+ 128%ns2Hirai, 89 ADDIN EN.CITE <EndNote><Cite><Author>Hirai</Author><Year>1989</Year><RecNum>662</RecNum><record><rec-number>662</rec-number><ref-type name="Book Section">5</ref-type><contributors><authors><author>Hirai, A.</author><author>Terano, T,</author><author>Saito, H.</author><author>Tamura, Y.</author></authors><secondary-authors><author>Spiller, G.A.</author><author>Scala, J.</author></secondary-authors></contributors><titles><title>Omega-3 fatty acids: Epidemiological and clinical aspects</title><secondary-title>New Protective Roles for Selected Nutrients</secondary-title></titles><pages>229-252</pages><dates><year>1989</year></dates><pub-location>New York</pub-location><publisher>Alan R Liss</publisher><urls></urls></record></Cite></EndNote>[3]8 M43.6EEPL+ 131%ns3Grimsgaard, 97 ADDIN EN.CITE <EndNote><Cite><Author>Grimsgaard</Author><Year>1997</Year><RecNum>663</RecNum><record><rec-number>663</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Grimsgaard, S.</author><author>Bonaa, K. H.</author><author>Hansen, J. B.</author><author>Nordoy, A.</author></authors></contributors><auth-address>Institute of Community Medicine, University of Tromso, Norway.</auth-address><titles><title>Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>649-59</pages><volume>66</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Body Weight</keyword><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/adverse effects/*pharmacology</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*pharmacology</keyword><keyword>Exercise</keyword><keyword>Fatty Acids/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Patient Compliance</keyword><keyword>Phospholipids/blood</keyword><keyword>Triglycerides/*blood</keyword></keywords><dates><year>1997</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>9280188</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[6]75 M73.8EEPL+297%-15%4Mori, 00 ADDIN EN.CITE <EndNote><Cite><Author>Mori</Author><Year>2000</Year><RecNum>664</RecNum><record><rec-number>664</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mori, T. A.</author><author>Burke, V.</author><author>Puddey, I. B.</author><author>Watts, G. F.</author><author>O&apos;Neal, D. N.</author><author>Best, J. D.</author><author>Beilin, L. J.</author></authors></contributors><auth-address>Department of Medicine, The University of Western Australia and The West Australian Heart Research Institute, Perth. tmori@cyllene.uwa.edu.au</auth-address><titles><title>Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1085-94</pages><volume>71</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Centrifugation, Density Gradient</keyword><keyword>Cholesterol/blood</keyword><keyword>Cholesterol, HDL/blood/chemistry</keyword><keyword>Cholesterol, LDL/blood/chemistry</keyword><keyword>Docosahexaenoic Acids/blood/*metabolism</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/blood/*metabolism</keyword><keyword>Humans</keyword><keyword>Hypercholesterolemia/blood/*metabolism</keyword><keyword>Insulin/blood</keyword><keyword>Lipids/*blood</keyword><keyword>Lipoproteins/*blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Particle Size</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2000</year><pub-dates><date>May</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>10799369</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[8]19 M/F64EEPL+ 8%ns5Park, 04 ADDIN EN.CITE <EndNote><Cite><Author>Park</Author><Year>2002</Year><RecNum>665</RecNum><record><rec-number>665</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Park, Y.</author><author>Harris, W.</author></authors></contributors><auth-address>Department of Medicine, University of Missouri-Kansas City, Missouri 64108, USA.</auth-address><titles><title>EPA, but not DHA, decreases mean platelet volume in normal subjects</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>941-6</pages><volume>37</volume><number>10</number><keywords><keyword>Administration, Oral</keyword><keyword>Adult</keyword><keyword>Blood Platelets/cytology/*drug effects</keyword><keyword>Blood Volume/*drug effects</keyword><keyword>Collagen/pharmacology</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Plant Oils/pharmacology</keyword><keyword>Platelet Activation/drug effects</keyword><keyword>Single-Blind Method</keyword><keyword>Temperature</keyword><keyword>Time Factors</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>12530552</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[10]10 M/F44EEPlatelets+1550%ns6Woodman, 02 ADDIN EN.CITE <EndNote><Cite><Author>Woodman</Author><Year>2002</Year><RecNum>666</RecNum><record><rec-number>666</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Woodman, R. J.</author><author>Mori, T. A.</author><author>Burke, V.</author><author>Puddey, I. B.</author><author>Watts, G. F.</author><author>Beilin, L. J.</author></authors></contributors><auth-address>Department of Medicine, The University of Western Australia, Perth, Australia. rwoodman@cyllene.uwa.edu.au</auth-address><titles><title>Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1007-15</pages><volume>76</volume><number>5</number><keywords><keyword>Aged</keyword><keyword>Blood Glucose/*analysis</keyword><keyword>Blood Pressure/*drug effects</keyword><keyword>Blood Pressure Monitoring, Ambulatory</keyword><keyword>Diabetes Mellitus, Type 2/blood/*complications/*physiopathology</keyword><keyword>Docosahexaenoic Acids/adverse effects/*pharmacology</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*pharmacology</keyword><keyword>Fatty Acids/blood</keyword><keyword>Female</keyword><keyword>Heart Rate</keyword><keyword>Humans</keyword><keyword>Hypertension/*complications</keyword><keyword>Insulin/physiology</keyword><keyword>Lipids/*blood</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Phospholipids/blood</keyword><keyword>Plant Oils/pharmacology</keyword></keywords><dates><year>2002</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12399272</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[11]17 M/F64EEPL+ 540%ns7Peet, 01 ADDIN EN.CITE <EndNote><Cite><Author>Peet</Author><Year>2001</Year><RecNum>668</RecNum><record><rec-number>668</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peet, M.</author><author>Brind, J.</author><author>Ramchand, C. N.</author><author>Shah, S.</author><author>Vankar, G. K.</author></authors></contributors><auth-address>Academic Department of Psychiatry, Northern General Hospital, The Longley Centre, Norwood Grange Drive, S5 7JT, Sheffield, UK. m.peet@sheffield.ac.uk</auth-address><titles><title>Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia</title><secondary-title>Schizophr Res</secondary-title><alt-title>Schizophrenia research</alt-title></titles><pages>243-51</pages><volume>49</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Antipsychotic Agents/administration &amp; dosage/*therapeutic use</keyword><keyword>Arachidonic Acids/administration &amp; dosage/*therapeutic use</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/therapeutic use</keyword><keyword>Double-Blind Method</keyword><keyword>Humans</keyword><keyword>Pilot Projects</keyword><keyword>Schizophrenia/*drug therapy</keyword><keyword>Schizophrenic Psychology</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr 30</date></pub-dates></dates><isbn>0920-9964 (Print)</isbn><accession-num>11356585</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[18]32, 32, or 27 M/F121,2, or 4EERBC + 17%, 24%, or 39%nsLegend: EE, ethyl ester; PL, phospholipids; RBC, red blood cells; ns = no significant change (p>0.05). Changes in the last two columns are relative to the values in the control groups.The conversion of ALA to omega-3 LCPUFA in infants may be more efficient than in adults. Two studies of infants included in Table 1 showed increases in DHA when ALA was added to infant formulas that had no LCPUFA, and holding LA constant. Jensen et al. ADDIN EN.CITE <EndNote><Cite><Author>Jensen</Author><Year>1996</Year><RecNum>695</RecNum><record><rec-number>695</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jensen, C. L.</author><author>Chen, H.</author><author>Fraley, J. K.</author><author>Anderson, R. E.</author><author>Heird, W. C.</author></authors></contributors><auth-address>Department of Pediatrics, USDA, ARS Children&apos;s Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA.</auth-address><titles><title>Biochemical effects of dietary linoleic/alpha-linolenic acid ratio in term infants</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>107-13</pages><volume>31</volume><number>1</number><keywords><keyword>Dietary Fats/*pharmacology</keyword><keyword>Erythrocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*blood</keyword><keyword>alpha-Linolenic Acid/*blood</keyword></keywords><dates><year>1996</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>8649227</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[45] found an increase in both PL and RBC DHA at the highest levels of ALA used, while Clark et al., ADDIN EN.CITE <EndNote><Cite><Author>Clark</Author><Year>1992</Year><RecNum>676</RecNum><record><rec-number>676</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Clark, K. J.</author><author>Makrides, M.</author><author>Neumann, M. A.</author><author>Gibson, R. A.</author></authors></contributors><auth-address>Department of Paediatrics and Child Health, Flinders Medical Centre, Adelaide, South Australia.</auth-address><titles><title>Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas</title><secondary-title>J Pediatr</secondary-title><alt-title>The Journal of pediatrics</alt-title></titles><pages>S151-8</pages><volume>120</volume><number>4 Pt 2</number><keywords><keyword>Arachidonic Acid/blood</keyword><keyword>Breast Feeding</keyword><keyword>Docosahexaenoic Acids/blood</keyword><keyword>Fatty Acids/analysis/*blood</keyword><keyword>Humans</keyword><keyword>*Infant Food/analysis</keyword><keyword>Infant, Newborn/*blood</keyword><keyword>Linoleic Acid</keyword><keyword>*Linoleic Acids/analysis</keyword><keyword>*Linolenic Acids/analysis</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1992</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-3476 (Print)</isbn><accession-num>1348533</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[43] found an increase in plasma total lipid DHA using a similar increment of ALA. Clark et al. also included a group that consumed similar ALA but one-fourth the LA level, replaced by oleic acid, that showed increases of EPA and DHA of 229% and 29%, respectively, in erythrocyte total lipids. Tracer data is in general accord with these findings, as outlined below. However, dietary preformed DHA raises blood and tissue DHA beyond that achievable with usual changes in dietary ALA or LA intakes in infants ADDIN EN.CITE <EndNote><Cite><Author>Cunnane</Author><Year>2000</Year><RecNum>14</RecNum><record><rec-number>14</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cunnane, S. C.</author><author>Francescutti, V.</author><author>Brenna, J. T.</author><author>Crawford, M. A.</author></authors></contributors><auth-address>Department of Nutritional Sciences, University of Toronto, Canada. s.cunnane@utoronto.ca</auth-address><titles><title>Breast-fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula-fed infants not consuming dietary docosahexaenoate</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>105-11</pages><volume>35</volume><number>1</number><keywords><keyword>Brain/*metabolism</keyword><keyword>*Breast Feeding</keyword><keyword>Comparative Study</keyword><keyword>Docosahexaenoic Acids/*administration &amp; dosage/analysis/*metabolism</keyword><keyword>Human</keyword><keyword>Infant</keyword><keyword>*Infant Food</keyword><keyword>Milk, Human/chemistry</keyword><keyword>Support, Non-U.S. Gov&apos;t</keyword><keyword>Weight Gain</keyword></keywords><dates><year>2000</year></dates><accession-num>10695931</accession-num><urls><related-urls><url>;[61].In contrast to the results with EPA supplementation, many studies have demonstrated that humans given preformed DHA supplements rapidly incorporate the fatty acid into the blood stream ADDIN EN.CITE <EndNote><Cite><Author>Arterburn</Author><Year>2006</Year><RecNum>659</RecNum><record><rec-number>659</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Arterburn, L. M.</author><author>Hall, E. B.</author><author>Oken, H.</author></authors></contributors><auth-address>Martek Biosciences Corporation, Columbia, MD, USA. larterburn@</auth-address><titles><title>Distribution, interconversion, and dose response of n-3 fatty acids in humans</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1467S-1476S</pages><volume>83</volume><number>6 Suppl</number><keywords><keyword>Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/blood/*pharmacokinetics</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/blood/*pharmacokinetics</keyword><keyword>Erythrocytes/chemistry/metabolism</keyword><keyword>Fatty Acids, Omega-3/administration &amp; dosage/blood/pharmacokinetics</keyword><keyword>Humans</keyword><keyword>Milk, Human/chemistry</keyword><keyword>Organ Specificity</keyword><keyword>Tissue Distribution</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/blood/*pharmacokinetics</keyword></keywords><dates><year>2006</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>16841856</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Grimsgaard</Author><Year>1997</Year><RecNum>663</RecNum><record><rec-number>663</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Grimsgaard, S.</author><author>Bonaa, K. H.</author><author>Hansen, J. B.</author><author>Nordoy, A.</author></authors></contributors><auth-address>Institute of Community Medicine, University of Tromso, Norway.</auth-address><titles><title>Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>649-59</pages><volume>66</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Body Weight</keyword><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/adverse effects/*pharmacology</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*pharmacology</keyword><keyword>Exercise</keyword><keyword>Fatty Acids/*blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Patient Compliance</keyword><keyword>Phospholipids/blood</keyword><keyword>Triglycerides/*blood</keyword></keywords><dates><year>1997</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>9280188</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Mori</Author><Year>2000</Year><RecNum>664</RecNum><record><rec-number>664</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mori, T. A.</author><author>Burke, V.</author><author>Puddey, I. B.</author><author>Watts, G. F.</author><author>O&apos;Neal, D. N.</author><author>Best, J. D.</author><author>Beilin, L. J.</author></authors></contributors><auth-address>Department of Medicine, The University of Western Australia and The West Australian Heart Research Institute, Perth. tmori@cyllene.uwa.edu.au</auth-address><titles><title>Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1085-94</pages><volume>71</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Centrifugation, Density Gradient</keyword><keyword>Cholesterol/blood</keyword><keyword>Cholesterol, HDL/blood/chemistry</keyword><keyword>Cholesterol, LDL/blood/chemistry</keyword><keyword>Docosahexaenoic Acids/blood/*metabolism</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/blood/*metabolism</keyword><keyword>Humans</keyword><keyword>Hypercholesterolemia/blood/*metabolism</keyword><keyword>Insulin/blood</keyword><keyword>Lipids/*blood</keyword><keyword>Lipoproteins/*blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Particle Size</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2000</year><pub-dates><date>May</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>10799369</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Park</Author><Year>2002</Year><RecNum>665</RecNum><record><rec-number>665</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Park, Y.</author><author>Harris, W.</author></authors></contributors><auth-address>Department of Medicine, University of Missouri-Kansas City, Missouri 64108, USA.</auth-address><titles><title>EPA, but not DHA, decreases mean platelet volume in normal subjects</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>941-6</pages><volume>37</volume><number>10</number><keywords><keyword>Administration, Oral</keyword><keyword>Adult</keyword><keyword>Blood Platelets/cytology/*drug effects</keyword><keyword>Blood Volume/*drug effects</keyword><keyword>Collagen/pharmacology</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/blood/*pharmacology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Plant Oils/pharmacology</keyword><keyword>Platelet Activation/drug effects</keyword><keyword>Single-Blind Method</keyword><keyword>Temperature</keyword><keyword>Time Factors</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>12530552</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Woodman</Author><Year>2002</Year><RecNum>666</RecNum><record><rec-number>666</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Woodman, R. J.</author><author>Mori, T. A.</author><author>Burke, V.</author><author>Puddey, I. B.</author><author>Watts, G. F.</author><author>Beilin, L. J.</author></authors></contributors><auth-address>Department of Medicine, The University of Western Australia, Perth, Australia. rwoodman@cyllene.uwa.edu.au</auth-address><titles><title>Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1007-15</pages><volume>76</volume><number>5</number><keywords><keyword>Aged</keyword><keyword>Blood Glucose/*analysis</keyword><keyword>Blood Pressure/*drug effects</keyword><keyword>Blood Pressure Monitoring, Ambulatory</keyword><keyword>Diabetes Mellitus, Type 2/blood/*complications/*physiopathology</keyword><keyword>Docosahexaenoic Acids/adverse effects/*pharmacology</keyword><keyword>Double-Blind Method</keyword><keyword>Eicosapentaenoic Acid/adverse effects/*pharmacology</keyword><keyword>Fatty Acids/blood</keyword><keyword>Female</keyword><keyword>Heart Rate</keyword><keyword>Humans</keyword><keyword>Hypertension/*complications</keyword><keyword>Insulin/physiology</keyword><keyword>Lipids/*blood</keyword><keyword>Lipoproteins/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Phospholipids/blood</keyword><keyword>Plant Oils/pharmacology</keyword></keywords><dates><year>2002</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12399272</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Innis</Author><Year>1996</Year><RecNum>669</RecNum><record><rec-number>669</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Innis, S. M.</author><author>Hansen, J. W.</author></authors></contributors><auth-address>Department of Paediatrics, University of British Columbia, Vancouver, Canada.</auth-address><titles><title>Plasma fatty acid responses, metabolic effects, and safety of microalgal and fungal oils rich in arachidonic and docosahexaenoic acids in healthy adults</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>159-67</pages><volume>64</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Algae/*chemistry</keyword><keyword>Arachidonic Acid/*administration &amp; dosage/blood</keyword><keyword>Cholesterol/blood</keyword><keyword>Dietary Fats, Unsaturated/*administration &amp; dosage</keyword><keyword>Docosahexaenoic Acids/*administration &amp; dosage/blood</keyword><keyword>Double-Blind Method</keyword><keyword>Fatty Acids/*blood</keyword><keyword>Fungi/*chemistry</keyword><keyword>Humans</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/blood</keyword><keyword>Male</keyword><keyword>Phospholipids/blood</keyword><keyword>Placebos</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>1996</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>8694015</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[6, 8, 10, 11, 57, 62]. There is a dose-dependent rise in plasma phospholipid DHA when various doses of DHA were given for 14 days ADDIN EN.CITE <EndNote><Cite><Author>Innis</Author><Year>1996</Year><RecNum>669</RecNum><record><rec-number>669</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Innis, S. M.</author><author>Hansen, J. W.</author></authors></contributors><auth-address>Department of Paediatrics, University of British Columbia, Vancouver, Canada.</auth-address><titles><title>Plasma fatty acid responses, metabolic effects, and safety of microalgal and fungal oils rich in arachidonic and docosahexaenoic acids in healthy adults</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>159-67</pages><volume>64</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Algae/*chemistry</keyword><keyword>Arachidonic Acid/*administration &amp; dosage/blood</keyword><keyword>Cholesterol/blood</keyword><keyword>Dietary Fats, Unsaturated/*administration &amp; dosage</keyword><keyword>Docosahexaenoic Acids/*administration &amp; dosage/blood</keyword><keyword>Double-Blind Method</keyword><keyword>Fatty Acids/*blood</keyword><keyword>Fungi/*chemistry</keyword><keyword>Humans</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/blood</keyword><keyword>Male</keyword><keyword>Phospholipids/blood</keyword><keyword>Placebos</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>1996</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>8694015</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[62]. In a cross-study meta-regression analysis of the dose-response relationship of plasma phospholipid DHA, a plateau is reached at a daily value of about 3 g DHA/d in studies of 1-6 months in duration. Steady state levels of DHA were reached within about 1 month in plasma and 4-6 months in erythrocytes after DHA supplementation was begun ADDIN EN.CITE <EndNote><Cite><Author>Arterburn</Author><Year>2006</Year><RecNum>659</RecNum><record><rec-number>659</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Arterburn, L. M.</author><author>Hall, E. B.</author><author>Oken, H.</author></authors></contributors><auth-address>Martek Biosciences Corporation, Columbia, MD, USA. larterburn@</auth-address><titles><title>Distribution, interconversion, and dose response of n-3 fatty acids in humans</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1467S-1476S</pages><volume>83</volume><number>6 Suppl</number><keywords><keyword>Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/blood/*pharmacokinetics</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/blood/*pharmacokinetics</keyword><keyword>Erythrocytes/chemistry/metabolism</keyword><keyword>Fatty Acids, Omega-3/administration &amp; dosage/blood/pharmacokinetics</keyword><keyword>Humans</keyword><keyword>Milk, Human/chemistry</keyword><keyword>Organ Specificity</keyword><keyword>Tissue Distribution</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/blood/*pharmacokinetics</keyword></keywords><dates><year>2006</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>16841856</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[57]. Human autopsy studies show that infants consuming formulas without preformed DHA have lower brain DHA than infants receiving DHA via breastmilk, and this relationship was not detected for arachidonic acid ADDIN EN.CITE <EndNote><Cite><Author>Farquharson</Author><Year>1992</Year><RecNum>86</RecNum><record><rec-number>86</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Farquharson, J.</author><author>Cockburn, F.</author><author>Patrick, W. A.</author><author>Jamieson, E. C.</author><author>Logan, R. W.</author></authors></contributors><auth-address>Department of Biochemistry, University Department of Child Health, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK.</auth-address><titles><title>Infant cerebral cortex phospholipid fatty-acid composition and diet</title><secondary-title>Lancet</secondary-title></titles><pages>810-3.</pages><volume>340</volume><number>8823</number><keywords><keyword>Age Factors</keyword><keyword>Animal</keyword><keyword>Arachidonic Acids/analysis</keyword><keyword>Cerebral Cortex/*chemistry</keyword><keyword>Dietary Fats/*administration &amp; dosage/analysis</keyword><keyword>Docosahexaenoic Acids/analysis</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage/*analysis</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Infant</keyword><keyword>Infant Food</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>*Milk</keyword><keyword>Milk, Human</keyword><keyword>Palmitic Acids/analysis</keyword><keyword>Phospholipids/*analysis</keyword></keywords><dates><year>1992</year></dates><accession-num>1357244</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Makrides, M.</author><author>Neumann, M. A.</author><author>Byard, R. W.</author><author>Simmer, K.</author><author>Gibson, R. A.</author></authors></contributors><auth-address>Department of Paediatrics and Child Health, Flinders Medical Centre, Bedford Park, Adelaide, South Australia.</auth-address><titles><title>Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants</title><secondary-title>Am J Clin Nutr</secondary-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>189-94</pages><volume>60</volume><number>2</number><keywords><keyword>Arachidonic Acid/analysis</keyword><keyword>*Bottle Feeding</keyword><keyword>*Breast Feeding</keyword><keyword>Cerebral Cortex/*chemistry</keyword><keyword>Docosahexaenoic Acids/analysis/blood</keyword><keyword>Erythrocytes/*chemistry</keyword><keyword>Fatty Acids, Unsaturated/*analysis/blood</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Infant</keyword><keyword>Infant Food/analysis</keyword><keyword>Infant, Newborn</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/analysis</keyword><keyword>Male</keyword><keyword>Regression Analysis</keyword><keyword>Retina/*chemistry</keyword><keyword>alpha-Linolenic Acid/analysis</keyword></keywords><dates><year>1994</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>7913291</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Jamieson, E. C.</author><author>Farquharson, J.</author><author>Logan, R. W.</author><author>Howatson, A. G.</author><author>Patrick, W. J.</author><author>Weaver, L. T.</author><author>Cockburn, F.</author></authors></contributors><auth-address>Department of Biochemistry, University Department of Child Health, Yorkhill NHS Trust, Glasgow, Scotland.</auth-address><titles><title>Infant cerebellar gray and white matter fatty acids in relation to age and diet</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>1065-71.</pages><volume>34</volume><number>10</number><keywords><keyword>Aging/*metabolism</keyword><keyword>Cerebellum/cytology/*metabolism</keyword><keyword>*Diet</keyword><keyword>Fatty Acids/*metabolism</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Infant</keyword><keyword>Male</keyword></keywords><dates><year>1999</year></dates><accession-num>10580334</accession-num><urls><related-urls><url>;[63-65].Competition of n-3 and n-6 Fatty AcidsThis statement is concerned primarily with omega-3 supplementation, rather than dietary adjustments of other components. Nevertheless, it is clear that the metabolism of n-3 fatty acids depends on other nutrients, in particular, n-6 fatty acids, due to the competition of n-3 and n-6 fatty acids for the same enzymes and transport systems. They also compete for incorporation into more complex lipids that comprise mammalian tissues, and high levels of n-6 PUFA replace, and reduce, n-3 PUFA. The main n-6 fatty acids are LA and arachidonic acid (AA), the former being a major dietary constituent in western countries and those parts of the developing world with substantial intakes of seed oils ADDIN EN.CITE <EndNote><Cite><Author>Lands</Author><Year>1990</Year><RecNum>601</RecNum><record><rec-number>601</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lands, W. E.</author><author>Morris, A.</author><author>Libelt, B.</author></authors></contributors><auth-address>Department of Biological Chemistry, University of Illinois, Chicago 60612.</auth-address><titles><title>Quantitative effects of dietary polyunsaturated fats on the composition of fatty acids in rat tissues</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>505-16</pages><volume>25</volume><number>9</number><keywords><keyword>Adipose Tissue/chemistry</keyword><keyword>Animals</keyword><keyword>Chromatography, Gas</keyword><keyword>Dietary Fats, Unsaturated/*pharmacology</keyword><keyword>Erythrocytes/chemistry</keyword><keyword>Fatty Acids/*analysis</keyword><keyword>Fatty Acids, Nonesterified/analysis</keyword><keyword>Female</keyword><keyword>Lipids/blood/isolation &amp; purification</keyword><keyword>Liver/chemistry</keyword><keyword>Male</keyword><keyword>Organ Specificity</keyword><keyword>Rats</keyword><keyword>Rats, Inbred Strains</keyword><keyword>Research Support, Non-U.S. Gov&apos;t</keyword><keyword>Research Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Sex Factors</keyword><keyword>Triglycerides/analysis</keyword><keyword>Weight Gain/drug effects</keyword></keywords><dates><year>1990</year><pub-dates><date>Sep</date></pub-dates></dates><accession-num>2250586</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[66]. The intake of LA has increased dramatically mainly due to the intake of soybean oil in the US ADDIN EN.CITE <EndNote><Cite><Author>Hibbeln</Author><Year>2004</Year><RecNum>671</RecNum><record><rec-number>671</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hibbeln, J. R.</author><author>Nieminen, L. R.</author><author>Lands, W. E.</author></authors></contributors><auth-address>Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. jhibbeln@mail.</auth-address><titles><title>Increasing homicide rates and linoleic acid consumption among five Western countries, 1961-2000</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>1207-13</pages><volume>39</volume><number>12</number><keywords><keyword>*Homicide</keyword><keyword>Humans</keyword><keyword>Linoleic Acid/*administration &amp; dosage/pharmacology</keyword><keyword>Western World</keyword></keywords><dates><year>2004</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>15736917</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[67], as well as sunflower, safflower, and others. The intake of n-3 fatty acids has been relatively constant over the past decades, especially in the USA, though it has risen in countries where canola oil has been introduced in the last two decades. There is concern that increased intake of LA has led to an increase in AA in tissue lipids and a decrease in n-3 content. Evidence of n-3 and n-6 fatty acid antagonism has come from tissue compositional studies as well as radioisotope studies performed in vitro. Early studies of rat liver microsomes showed that the delta-6 desaturase activity measured in vitro with various substrates was subject to competitive inhibition by other substrates. In particular, desaturation of ALA to 18:4n-3 was inhibited by LA and, conversely, LA conversion to 18:3n-6 was inhibited by ALA ADDIN EN.CITE <EndNote><Cite><Author>Brenner</Author><Year>1966</Year><RecNum>672</RecNum><record><rec-number>672</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Brenner, R. R.</author><author>Peluffo, R. O.</author></authors></contributors><titles><title>Effect of saturated and unsaturated fatty acids on the desaturation in vitro of palmitic, stearic, oleic, linoleic, and linolenic acids</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><pages>5213-9</pages><volume>241</volume><number>22</number><keywords><keyword>Animals</keyword><keyword>Chromatography, Gas</keyword><keyword>Fatty Acids/*pharmacology</keyword><keyword>Fatty Acids, Essential/*metabolism</keyword><keyword>Glycerophosphates/pharmacology</keyword><keyword>Kinetics</keyword><keyword>Linoleic Acids/*metabolism</keyword><keyword>Liver/cytology/*metabolism</keyword><keyword>Lysophosphatidylcholines/pharmacology</keyword><keyword>Microsomes/*metabolism</keyword><keyword>Oleic Acids/*metabolism</keyword><keyword>Palmitic Acids/*metabolism</keyword><keyword>Rats</keyword><keyword>Stearic Acids/*metabolism</keyword></keywords><dates><year>1966</year><pub-dates><date>Nov 25</date></pub-dates></dates><isbn>0021-9258 (Print)</isbn><accession-num>5927998</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[68]. Altered ratios of n-3 and n-6 fatty acids can markedly alter tissue fatty acid compositions in rodents ADDIN EN.CITE <EndNote><Cite><Author>Bourre</Author><Year>1993</Year><RecNum>673</RecNum><record><rec-number>673</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bourre, J. M.</author><author>Dumont, O.</author><author>Pascal, G.</author><author>Durand, G.</author></authors></contributors><auth-address>Institut National de la Sante et de la Recherche Medicale, INSERM unite 26, Hopital Fernand Widal, Paris, France.</auth-address><titles><title>Dietary alpha-linolenic acid at 1.3 g/kg maintains maximal docosahexaenoic acid concentration in brain, heart and liver of adult rats</title><secondary-title>J Nutr</secondary-title><alt-title>The Journal of nutrition</alt-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>1313-9</pages><volume>123</volume><number>7</number><keywords><keyword>Administration, Oral</keyword><keyword>Animals</keyword><keyword>Brain/*drug effects/metabolism</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Female</keyword><keyword>Heart/*drug effects</keyword><keyword>Linolenic Acids/administration &amp; dosage/*pharmacology</keyword><keyword>Liver/*drug effects/metabolism</keyword><keyword>Myocardium/metabolism</keyword><keyword>Nutritional Requirements</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1993</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0022-3166 (Print)</isbn><accession-num>8100576</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Mohrhauer</Author><Year>1963</Year><RecNum>674</RecNum><record><rec-number>674</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mohrhauer, H.</author><author>Holman, R. T.</author></authors></contributors><titles><title>Effect of Linolenic Acid Upon the Metabolism of Linoleic Acid</title><secondary-title>J Nutr</secondary-title><alt-title>The Journal of nutrition</alt-title></titles><periodical><full-title>J Nutr</full-title></periodical><pages>67-74</pages><volume>81</volume><keywords><keyword>*Fatty Acids, Essential</keyword><keyword>*Linoleic Acid</keyword><keyword>*Metabolism</keyword><keyword>*Pharmacology</keyword><keyword>*Rats</keyword><keyword>*Research</keyword></keywords><dates><year>1963</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0022-3166 (Print)</isbn><accession-num>14061405</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[69, 70], pigs ADDIN EN.CITE <EndNote><Cite><Author>Arbuckle</Author><Year>1992</Year><RecNum>513</RecNum><record><rec-number>513</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Arbuckle, L. D.</author><author>Rioux, F. M.</author><author>MacKinnon, M. J.</author><author>Innis, S. M.</author></authors></contributors><auth-address>Department of Human Nutrition, University of British Columbia, Vancouver, Canada.</auth-address><titles><title>Formula alpha-linolenic (18:3(n - 3)) and linoleic (18:2(n - 6)) acid influence neonatal piglet liver and brain saturated fatty acids, as well as docosahexaenoic acid (22:6(n - 3))</title><secondary-title>Biochim Biophys Acta</secondary-title></titles><pages>262-7</pages><volume>1125</volume><number>3</number><keywords><keyword>Animal</keyword><keyword>Animals, Newborn</keyword><keyword>*Brain Chemistry</keyword><keyword>Docosahexaenoic Acids/analysis</keyword><keyword>Fatty Acids/*metabolism</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>*Food, Formulated</keyword><keyword>Linolenic Acids/metabolism</keyword><keyword>Liver/*chemistry</keyword><keyword>Male</keyword><keyword>Phospholipids/chemistry</keyword><keyword>Support, Non-U.S. Gov&apos;t</keyword><keyword>Swine</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1992</year><pub-dates><date>May 8</date></pub-dates></dates><accession-num>1350737</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Blank, C.</author><author>Neumann, M. A.</author><author>Makrides, M.</author><author>Gibson, R. A.</author></authors></contributors><auth-address>Department of Paediatrics and Child Health, Flinders Medical Centre, Bedford Park, South Australia 5042, Australia.</auth-address><titles><title>Optimizing DHA levels in piglets by lowering the linoleic acid to alpha-linolenic acid ratio</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>1537-43</pages><volume>43</volume><number>9</number><keywords><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Body Weight</keyword><keyword>Brain Chemistry/drug effects</keyword><keyword>Chromatography, Gas</keyword><keyword>Dietary Fats/administration &amp; dosage/*pharmacology</keyword><keyword>Docosahexaenoic Acids/blood/*metabolism</keyword><keyword>Erythrocytes/chemistry/drug effects</keyword><keyword>Female</keyword><keyword>Linoleic Acid/administration &amp; dosage/*pharmacology</keyword><keyword>Liver/chemistry/drug effects</keyword><keyword>Nutrition Physiology</keyword><keyword>Swine/blood/growth &amp; development/*metabolism</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*pharmacology</keyword></keywords><dates><year>2002</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>12235186</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[71, 72] and humans ADDIN EN.CITE <EndNote><Cite><Author>Clark</Author><Year>1992</Year><RecNum>676</RecNum><record><rec-number>676</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Clark, K. J.</author><author>Makrides, M.</author><author>Neumann, M. A.</author><author>Gibson, R. A.</author></authors></contributors><auth-address>Department of Paediatrics and Child Health, Flinders Medical Centre, Adelaide, South Australia.</auth-address><titles><title>Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas</title><secondary-title>J Pediatr</secondary-title><alt-title>The Journal of pediatrics</alt-title></titles><pages>S151-8</pages><volume>120</volume><number>4 Pt 2</number><keywords><keyword>Arachidonic Acid/blood</keyword><keyword>Breast Feeding</keyword><keyword>Docosahexaenoic Acids/blood</keyword><keyword>Fatty Acids/analysis/*blood</keyword><keyword>Humans</keyword><keyword>*Infant Food/analysis</keyword><keyword>Infant, Newborn/*blood</keyword><keyword>Linoleic Acid</keyword><keyword>*Linoleic Acids/analysis</keyword><keyword>*Linolenic Acids/analysis</keyword><keyword>alpha-Linolenic Acid</keyword></keywords><dates><year>1992</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-3476 (Print)</isbn><accession-num>1348533</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[43], including alteration of the nervous system ADDIN EN.CITE <EndNote><Cite><Author>Sanders</Author><Year>1984</Year><RecNum>677</RecNum><record><rec-number>677</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sanders, T. A.</author><author>Mistry, M.</author><author>Naismith, D. J.</author></authors></contributors><titles><title>The influence of a maternal diet rich in linoleic acid on brain and retinal docosahexaenoic acid in the rat</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>57-66</pages><volume>51</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Brain/embryology</keyword><keyword>Brain Chemistry/*drug effects</keyword><keyword>Dietary Fats/*pharmacology</keyword><keyword>Docosahexaenoic Acids</keyword><keyword>Fatty Acids/analysis</keyword><keyword>Fatty Acids, Unsaturated/*analysis</keyword><keyword>Female</keyword><keyword>Fetus</keyword><keyword>Glycerophosphates/analysis</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*pharmacology</keyword><keyword>Male</keyword><keyword>Pregnancy</keyword><keyword>Rats</keyword><keyword>Rats, Inbred Strains</keyword><keyword>Retina/*analysis/drug effects/embryology</keyword></keywords><dates><year>1984</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>6228249</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Su</Author><Year>1996</Year><RecNum>378</RecNum><record><rec-number>378</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Su, H. M.</author><author>Keswick, L. A.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.</auth-address><titles><title>Increasing dietary linoleic acid in young rats increases and then decreases docosahexaenoic acid in retina but not in brain</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>1289-98.</pages><volume>31</volume><number>12</number><keywords><keyword>Animal</keyword><keyword>Brain/*metabolism</keyword><keyword>Dietary Fats, Unsaturated/*administration &amp; dosage</keyword><keyword>Docosahexaenoic Acids/blood/*metabolism</keyword><keyword>Fatty Acids/blood/metabolism</keyword><keyword>Female</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*administration &amp; dosage</keyword><keyword>Liver/metabolism</keyword><keyword>Milk/metabolism</keyword><keyword>Pregnancy</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Retina/*metabolism</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword></keywords><dates><year>1996</year></dates><accession-num>8972463</accession-num><urls><related-urls><url>;[73, 74]. In view of the important interaction of n-3 and n-6 essential fatty acids for tissue fatty acid content, Lands has integrated dietary data on rodent tissue composition and provided empirical equations that predict some features of tissue essential fatty acid composition ADDIN EN.CITE <EndNote><Cite><Author>Lands</Author><Year>1992</Year><RecNum>678</RecNum><record><rec-number>678</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lands, W. E.</author><author>Libelt, B.</author><author>Morris, A.</author><author>Kramer, N. C.</author><author>Prewitt, T. E.</author><author>Bowen, P.</author><author>Schmeisser, D.</author><author>Davidson, M. H.</author><author>Burns, J. H.</author></authors></contributors><auth-address>Department of Biological Chemistry, University of Illinois, Chicago.</auth-address><titles><title>Maintenance of lower proportions of (n - 6) eicosanoid precursors in phospholipids of human plasma in response to added dietary (n - 3) fatty acids</title><secondary-title>Biochim Biophys Acta</secondary-title><alt-title>Biochimica et biophysica acta</alt-title></titles><pages>147-62</pages><volume>1180</volume><number>2</number><keywords><keyword>Aged</keyword><keyword>Dietary Fats, Unsaturated/*administration &amp; dosage</keyword><keyword>Fatty Acids, Omega-3/*administration &amp; dosage</keyword><keyword>Fatty Acids, Omega-6</keyword><keyword>Fatty Acids, Unsaturated/*analysis</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Hyperlipidemias/diet therapy</keyword><keyword>Male</keyword><keyword>Mathematics</keyword><keyword>Phospholipids/*blood</keyword><keyword>Questionnaires</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>1992</year><pub-dates><date>Dec 10</date></pub-dates></dates><isbn>0006-3002 (Print)</isbn><accession-num>1463766</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[75], and enable relative changes in plasma PUFA to be estimated based on comparison of any particular set of diets. A recently updated calculator is available in which the values for LA, ALA, long chain n-6 (meaning 20 and 22-C length polyunsaturates) and long chain n-3 fatty acid intakes can be entered, and plasma phospholipid n6 and n-3 long chain polyunsaturate content can be predicted: calculator can be used to estimate how increasing ALA against a constant and Western dietary level of n-6 fatty acid dietary intake (approx 6 en%), will lead to increases in plasma phospholipid long chain n-3 fatty acids. (HUFA are defined as highly unsaturated fatty acids with 20- or 22 carbons and three or more double bonds). For example, if typical American values (in en%) for LA (6.82) and n-6 HUFA (0.08) are used as the background diet, then adding n-3 PUFA in increments of 0.3 en% for ALA are equivalent to adding n-3 HUFA increments of 0.02 en% in terms of the effects on n3 HUFA content in plasma phospholipids, suggesting an equivalency factor of about 15 to 1 for ALA and n-3 HUFA. It must be cautioned that the term n-3 HUFA here indicates the sum of all of the n-3 HUFA: EPA, DPAn-3 and DHA; however, only the EPA and DPAn-3 are increasing in this example and while in most studies there is no significant increase of DHA. In other words, the equations summarizing many dietary experiments indicate than dietary EPA is about 15-fold more effective than dietary ALA in increasing the EPA/DPAn-3 content of human plasma phospholipids. An estimate has been made concerning how recommended intake of n-3 HUFA can be decreased when LA intake is decreased in order to decrease competition for tissue lipid content ADDIN EN.CITE <EndNote><Cite><Author>Hibbeln</Author><Year>2006</Year><RecNum>679</RecNum><record><rec-number>679</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hibbeln, J. R.</author><author>Nieminen, L. R.</author><author>Blasbalg, T. L.</author><author>Riggs, J. A.</author><author>Lands, W. E.</author></authors></contributors><auth-address>Laboratory of Membrane Biochemistry and Biophysics and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-2088, USA. jhibbeln@mail.</auth-address><titles><title>Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1483S-1493S</pages><volume>83</volume><number>6 Suppl</number><keywords><keyword>Cost of Illness</keyword><keyword>*Diet</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Fatty Acids, Omega-3/*administration &amp; dosage</keyword><keyword>Fatty Acids, Omega-6/*administration &amp; dosage</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Morbidity</keyword><keyword>Mortality</keyword><keyword>*Nutrition Policy</keyword><keyword>Nutritional Requirements</keyword><keyword>Nutritional Status</keyword><keyword>World Health</keyword></keywords><dates><year>2006</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>16841858</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[76]. In depth consideration of the impact of reductions in n-6 PUFA are the subject of separate treatments ADDIN EN.CITE <EndNote><Cite><Author>Lands</Author><Year>2008</Year><RecNum>708</RecNum><record><rec-number>708</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lands, B.</author></authors></contributors><auth-address>6100 Westchester Park Drive, #1219, College Park, MD 20740 USA. wemlands@</auth-address><titles><title>A critique of paradoxes in current advice on dietary lipids</title><secondary-title>Prog Lipid Res</secondary-title><alt-title>Progress in lipid research</alt-title></titles><periodical><full-title>Prog Lipid Res</full-title><abbr-1>Progress in lipid research</abbr-1></periodical><alt-periodical><full-title>Prog Lipid Res</full-title><abbr-1>Progress in lipid research</abbr-1></alt-periodical><pages>77-106</pages><volume>47</volume><number>2</number><dates><year>2008</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0163-7827 (Print)</isbn><accession-num>18177743</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[77]Isotope studies of in vivo ALA and EPA metabolismEarly studies of in vivo ALA metabolism in rodents indicated that conversion of ALA through EPA and to DHA does occur ADDIN EN.CITE <EndNote><Cite><Author>Sinclair</Author><Year>1975</Year><RecNum>680</RecNum><record><rec-number>680</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sinclair, A. J.</author></authors></contributors><titles><title>Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat</title><secondary-title>Lipids</secondary-title><alt-title>Lipids</alt-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><alt-periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></alt-periodical><pages>175-84</pages><volume>10</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Arachidonic Acids/metabolism</keyword><keyword>Brain/*metabolism</keyword><keyword>Carbon Radioisotopes</keyword><keyword>Dietary Fats</keyword><keyword>Fatty Acids, Unsaturated/*metabolism</keyword><keyword>Female</keyword><keyword>Lactation</keyword><keyword>Linoleic Acids/metabolism</keyword><keyword>Linolenic Acids/metabolism</keyword><keyword>Liver/*metabolism</keyword><keyword>Phospholipids/biosynthesis</keyword><keyword>Pregnancy</keyword><keyword>Rats</keyword><keyword>Time Factors</keyword><keyword>Triglycerides/biosynthesis</keyword></keywords><dates><year>1975</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0024-4201 (Print)</isbn><accession-num>1128172</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[78]. Subsequently, stable isotope labeled fatty acids were employed to demonstrate elongation and desaturation of ALA to EPA and DHA in human subjects ADDIN EN.CITE <EndNote><Cite><Author>Emken</Author><Year>1990</Year><RecNum>681</RecNum><record><rec-number>681</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Emken, E. A.</author><author>Adlof, R. O.</author><author>Rakoff, H.</author><author>Rohwedder, W. K.</author><author>Gulley, R. M.</author></authors></contributors><auth-address>Vegetable Oil Research, USDA, Peoria, IL 61604.</auth-address><titles><title>Metabolism in vivo of deuterium-labelled linolenic and linoleic acids in humans</title><secondary-title>Biochem Soc Trans</secondary-title><alt-title>Biochemical Society transactions</alt-title></titles><pages>766-9</pages><volume>18</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Deuterium/diagnostic use</keyword><keyword>Dietary Fats</keyword><keyword>Fatty Acids, Essential/*blood</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>Humans</keyword><keyword>Kinetics</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*metabolism</keyword><keyword>Linolenic Acids/*metabolism</keyword><keyword>Male</keyword><keyword>Radioisotope Dilution Technique</keyword><keyword>Time Factors</keyword></keywords><dates><year>1990</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0300-5127 (Print)</isbn><accession-num>2083671</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[79]. This was followed by several studies in human infants where metabolism of ALA to EPA and DHA was evident ADDIN EN.CITE <EndNote><Cite><Author>Carnielli</Author><Year>1996</Year><RecNum>10</RecNum><record><rec-number>10</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Carnielli, V. P.</author><author>Wattimena, D. J.</author><author>Luijendijk, I. H.</author><author>Boerlage, A.</author><author>Degenhart, H. J.</author><author>Sauer, P. J.</author></authors></contributors><auth-address>Department of Pediatrics, Erasmus University Rotterdam, The Netherlands.</auth-address><titles><title>The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>169-74.</pages><volume>40</volume><number>1</number><keywords><keyword>Arachidonic Acid/*biosynthesis</keyword><keyword>Carbon Isotopes</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Human</keyword><keyword>Infant, Newborn</keyword><keyword>Infant, Premature/*metabolism</keyword><keyword>Infant, Very Low Birth Weight/*metabolism</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*metabolism</keyword><keyword>Mass Fragmentography/methods</keyword><keyword>Phospholipids/blood</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>1996</year></dates><accession-num>8798265</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Salem, N., Jr.</author><author>Wegher, B.</author><author>Mena, P.</author><author>Uauy, R.</author></authors></contributors><auth-address>Laboratory of Membrane Biochemistry and Biophysics, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.</auth-address><titles><title>Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>49-54</pages><volume>93</volume><number>1</number><keywords><keyword>Arachidonic Acid/*biosynthesis</keyword><keyword>Deuterium</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Fatty Acids, Essential/metabolism</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Mass Fragmentography</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Time Factors</keyword></keywords><dates><year>1996</year><pub-dates><date>Jan 9</date></pub-dates></dates><accession-num>8552667</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Sauerwald, T. U.</author><author>Hachey, D. L.</author><author>Jensen, C. L.</author><author>Chen, H.</author><author>Anderson, R. E.</author><author>Heird, W. C.</author></authors></contributors><auth-address>USDA/ARS Children&apos;s Nutrition Research Center, Department of Pediatrics, Houston, Texas 77030, USA.</auth-address><titles><title>Intermediates in endogenous synthesis of C22:6 omega 3 and C20:4 omega 6 by term and preterm infants</title><secondary-title>Pediatr Res</secondary-title><alt-title>Pediatric research</alt-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>183-7</pages><volume>41</volume><number>2</number><keywords><keyword>Arachidonic Acid/*biosynthesis</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Gestational Age</keyword><keyword>Humans</keyword><keyword>Infant, Newborn/*metabolism</keyword><keyword>Infant, Premature/*metabolism</keyword><keyword>Phospholipids/blood</keyword></keywords><dates><year>1997</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0031-3998 (Print)</isbn><accession-num>9029636</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[80-82], as well as a later paper showing a downward trend in conversion efficiency with gestational age at birth in preterm infants ADDIN EN.CITE <EndNote><Cite><Author>Uauy</Author><Year>2000</Year><RecNum>43</RecNum><record><rec-number>43</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Uauy, R.</author><author>Mena, P.</author><author>Wegher, B.</author><author>Nieto, S.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago.</auth-address><titles><title>Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>127-35.</pages><volume>47</volume><number>1</number><keywords><keyword>Fatty Acids, Unsaturated/administration &amp; dosage/*biosynthesis/blood</keyword><keyword>*Fetal Development</keyword><keyword>*Gestational Age</keyword><keyword>Human</keyword><keyword>Infant, Newborn</keyword><keyword>Infant, Premature</keyword><keyword>Support, Non-U.S. Gov&apos;t</keyword></keywords><dates><year>2000</year></dates><accession-num>10625093</accession-num><call-num>Pediatric Research: RJ1.P372</call-num><urls><related-urls><url>;[83]. A very recent study using a whole body natural isotope tracer approach reports that an average of 42% of DHA is biosynthesized from ALA in 1 month old infants consuming formulas with 0.64%w/w DHA. This drops to 11% by 3 months of age, and 7% at 7 months ADDIN EN.CITE <EndNote><Cite><Author>Carnielli</Author><Year>2007</Year><RecNum>697</RecNum><record><rec-number>697</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Carnielli, V. P.</author><author>Simonato, M.</author><author>Verlato, G.</author><author>Luijendijk, I.</author><author>De Curtis, M.</author><author>Sauer, P. J.</author><author>Cogo, P. E.</author></authors></contributors><auth-address>Division of Neonatology, Institute of Maternal-Infantile Sciences, Polytechnic University of Marche, Ancona, Italy. lab2@pediatria.unipd.it</auth-address><titles><title>Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids</title><secondary-title>Am J Clin Nutr</secondary-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1323-30</pages><volume>86</volume><number>5</number><keywords><keyword>Arachidonic Acid/biosynthesis</keyword><keyword>Dietary Fats, Unsaturated/*administration &amp; dosage</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Fatty Acids, Unsaturated/*biosynthesis</keyword><keyword>Fetal Blood/chemistry</keyword><keyword>Humans</keyword><keyword>*Infant Formula</keyword><keyword>Infant, Newborn</keyword><keyword>Infant, Premature</keyword><keyword>Phospholipids/blood</keyword></keywords><dates><year>2007</year><pub-dates><date>Nov</date></pub-dates></dates><accession-num>17991642</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[84]. Adult metabolism of stable isotope labeled fatty acids in vivo has been reviewed several times ADDIN EN.CITE <EndNote><Cite><Author>Brenna</Author><Year>2002</Year><RecNum>622</RecNum><record><rec-number>622</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Savage Hall, Cornell University, Ithaca, New York 14853, USA. jtb4@cornell.edu</auth-address><titles><title>Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man</title><secondary-title>Curr Opin Clin Nutr Metab Care</secondary-title></titles><pages>127-32</pages><volume>5</volume><number>2</number><keywords><keyword>Energy Metabolism</keyword><keyword>Fatty Acids, Omega-3/*biosynthesis</keyword><keyword>Fatty Acids, Omega-6</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>Humans</keyword><keyword>Oxidation-Reduction</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Mar</date></pub-dates></dates><accession-num>11844977</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite><Cite><Author>Burdge</Author><Year>2004</Year><RecNum>630</RecNum><record><rec-number>630</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G.</author></authors></contributors><auth-address>Institute of Human Nutrition, Biomedical Science Building, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. g.c.burdge@soton.ac.uk</auth-address><titles><title>Alpha-linolenic acid metabolism in men and women: nutritional and biological implications</title><secondary-title>Curr Opin Clin Nutr Metab Care</secondary-title><alt-title>Current opinion in clinical nutrition and metabolic care</alt-title></titles><pages>137-44</pages><volume>7</volume><number>2</number><keywords><keyword>Carbon Isotopes</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Energy Metabolism</keyword><keyword>Fatty Acids, Unsaturated/metabolism/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nutritional Requirements</keyword><keyword>Oxidation-Reduction</keyword><keyword>Sex Characteristics</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism/physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1363-1950 (Print)</isbn><accession-num>15075703</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Plourde</Author><Year>2007</Year><RecNum>631</RecNum><record><rec-number>631</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plourde, M.</author><author>Cunnane, S. C.</author></authors></contributors><auth-address>Research Center on Aging, Departments of Medicine, and Physiology and Biophysics, Universite de Sherbrooke, 1036 Belvedere St, South, Sherbrooke, QC J1H 4C4, Canada.</auth-address><titles><title>Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements</title><secondary-title>Appl Physiol Nutr Metab</secondary-title><alt-title>Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme</alt-title></titles><pages>619-34</pages><volume>32</volume><number>4</number><keywords><keyword>*Diet</keyword><keyword>*Dietary Supplements</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/metabolism</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/metabolism</keyword><keyword>Fatty Acids, Essential/*biosynthesis</keyword><keyword>Humans</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1715-5312 (Print)</isbn><accession-num>17622276</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[13, 15, 16]. Generally, the results have clearly shown metabolism of ALA to EPA with decreasing amounts of DPAn-3 and DHA ADDIN EN.CITE <EndNote><Cite><Author>Burdge</Author><Year>2003</Year><RecNum>683</RecNum><record><rec-number>683</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G. C.</author><author>Finnegan, Y. E.</author><author>Minihane, A. M.</author><author>Williams, C. M.</author><author>Wootton, S. A.</author></authors></contributors><auth-address>Institute of Human Nutrition, University of Southampton, UK. g.c.burdge@soton.ac.uk</auth-address><titles><title>Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>311-21</pages><volume>90</volume><number>2</number><keywords><keyword>Carbon Dioxide/metabolism</keyword><keyword>Dietary Fats, Unsaturated/administration &amp; dosage/metabolism</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/metabolism</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/metabolism</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage</keyword><keyword>Humans</keyword><keyword>Lipids/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Oxidation-Reduction</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage/*metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>12908891</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Burdge</Author><Year>2002</Year><RecNum>684</RecNum><record><rec-number>684</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G. C.</author><author>Wootton, S. A.</author></authors></contributors><auth-address>Institute of Human Nutrition, University of Southampton, Southampton, UK. g.c.burdge@soton.ac.uk</auth-address><titles><title>Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>411-20</pages><volume>88</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>Analysis of Variance</keyword><keyword>Carbon Isotopes/diagnostic use</keyword><keyword>Eicosapentaenoic Acid/*metabolism</keyword><keyword>Fatty Acids, Omega-3/blood</keyword><keyword>Fatty Acids, Unsaturated/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Lipids/blood</keyword><keyword>Liver/*metabolism</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>12323090</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Pawlosky</Author><Year>2001</Year><RecNum>600</RecNum><record><rec-number>600</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R. J.</author><author>Hibbeln, J. R.</author><author>Novotny, J. A.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Food Composition Laboratory, Beltsville, MD 20705, USA. pawlosky@bhnrc.</auth-address><titles><title>Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans</title><secondary-title>J Lipid Res</secondary-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><pages>1257-65</pages><volume>42</volume><number>8</number><keywords><keyword>Absorption</keyword><keyword>Adult</keyword><keyword>Chylomicrons/blood</keyword><keyword>Computer Simulation</keyword><keyword>Diet</keyword><keyword>Dietary Fats/administration &amp; dosage</keyword><keyword>Energy Intake</keyword><keyword>Fatty Acids, Omega-3/administration &amp; dosage/blood</keyword><keyword>Female</keyword><keyword>Half-Life</keyword><keyword>Humans</keyword><keyword>Kinetics</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Models, Biological</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>11483627</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite><Cite><Author>Vermunt</Author><Year>2000</Year><RecNum>452</RecNum><record><rec-number>452</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vermunt, S. H.</author><author>Mensink, R. P.</author><author>Simonis, M. M.</author><author>Hornstra, G.</author></authors></contributors><auth-address>Department of Human Biology, Maastricht University, The Netherlands.</auth-address><titles><title>Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13C-alpha-linolenic acid</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>137-42</pages><volume>35</volume><number>2</number><keywords><keyword>5,8,11,14,17-Eicosapentaenoic Acid/blood/pharmacology</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Carbon Isotopes</keyword><keyword>Docosahexaenoic Acids/blood/pharmacology</keyword><keyword>Energy Intake</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fatty Acids, Omega-3/blood/*pharmacology</keyword><keyword>Fatty Acids, Unsaturated/blood</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Male</keyword><keyword>Middle Age</keyword><keyword>Oleic Acid/pharmacology</keyword><keyword>Oxidation-Reduction</keyword><keyword>Pilot Projects</keyword><keyword>alpha-Linolenic Acid/*metabolism/*pharmacology</keyword></keywords><dates><year>2000</year><pub-dates><date>Feb</date></pub-dates></dates><accession-num>10757543</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R. 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L.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Food Composition Laboratory, Beltsville Human Nutrition Research Center, US Department of Agriculture, Beltsville, MD, USA. bpawl@mail.</auth-address><titles><title>Effects of beef- and fish-based diets on the kinetics of n-3 fatty acid metabolism in human subjects</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>565-72</pages><volume>77</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Animals</keyword><keyword>Cattle</keyword><keyword>Deuterium/diagnostic use</keyword><keyword>Fatty Acid Desaturases/*metabolism</keyword><keyword>Fatty Acids, Omega-3/administration &amp; dosage/*pharmacokinetics</keyword><keyword>Fatty Acids, Omega-6</keyword><keyword>Fatty Acids, Unsaturated/administration &amp;</keyword><keyword>dosage/*biosynthesis/blood/pharmacokinetics</keyword><keyword>Female</keyword><keyword>Fishes</keyword><keyword>Food Analysis</keyword><keyword>*Food Habits</keyword><keyword>Gas Chromatography-Mass Spectrometry</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Meat</keyword><keyword>Models, Biological</keyword><keyword>Seafood</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>12600844</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>McCloy</Author><Year>2004</Year><RecNum>686</RecNum><record><rec-number>686</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McCloy, U.</author><author>Ryan, M. 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C.</author></authors></contributors><auth-address>Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 3E2. ursula.mccoy@utoronto.ca</auth-address><titles><title>A comparison of the metabolism of eighteen-carbon 13C-unsaturated fatty acids in healthy women</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>474-85</pages><volume>45</volume><number>3</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Administration, Oral</keyword><keyword>Adult</keyword><keyword>Breath Tests</keyword><keyword>Carbon Isotopes</keyword><keyword>Fatty Acids, Unsaturated/administration &amp;</keyword><keyword>dosage/blood/*chemistry/*metabolism</keyword><keyword>Female</keyword><keyword>Health</keyword><keyword>Humans</keyword><keyword>Oxidation-Reduction</keyword><keyword>Time Factors</keyword></keywords><dates><year>2004</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>14679164</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Goyens</Author><Year>2006</Year><RecNum>687</RecNum><record><rec-number>687</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Goyens, P. 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A.</author><author>Millward, D. J.</author></authors></contributors><auth-address>Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.</auth-address><titles><title>Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>269-80</pages><volume>46</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Arachidonic Acid/metabolism</keyword><keyword>Area Under Curve</keyword><keyword>Chromatography, Gas</keyword><keyword>*Diet</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Erythrocytes/*metabolism</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>Humans</keyword><keyword>Linoleic Acid/*chemistry</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Models, Biological</keyword><keyword>Phospholipids/*blood/metabolism</keyword><keyword>Risk</keyword><keyword>Time Factors</keyword><keyword>alpha-Linolenic Acid/*chemistry</keyword></keywords><dates><year>2005</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>15576848</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[4, 85-91] with one paper finding little or no DHA formed in young men ADDIN EN.CITE <EndNote><Cite><Author>Burdge</Author><Year>2002</Year><RecNum>689</RecNum><record><rec-number>689</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G. C.</author><author>Jones, A. E.</author><author>Wootton, S. A.</author></authors></contributors><auth-address>Institute of Human Nutrition, Level C, West Wing, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. gcb@soton.ac.uk</auth-address><titles><title>Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>355-63</pages><volume>88</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>Carbon Isotopes/metabolism</keyword><keyword>Eicosapentaenoic Acid/*metabolism</keyword><keyword>Fatty Acids/blood/metabolism</keyword><keyword>Fatty Acids, Unsaturated/*metabolism</keyword><keyword>Humans</keyword><keyword>Liver/*metabolism</keyword><keyword>Male</keyword><keyword>Triglycerides/metabolism</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>12323085</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[92]. Burdge has proposed than women have a greater activity of elongation/desaturation than do men ADDIN EN.CITE <EndNote><Cite><Author>Burdge</Author><Year>2004</Year><RecNum>630</RecNum><record><rec-number>630</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G.</author></authors></contributors><auth-address>Institute of Human Nutrition, Biomedical Science Building, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. g.c.burdge@soton.ac.uk</auth-address><titles><title>Alpha-linolenic acid metabolism in men and women: nutritional and biological implications</title><secondary-title>Curr Opin Clin Nutr Metab Care</secondary-title><alt-title>Current opinion in clinical nutrition and metabolic care</alt-title></titles><pages>137-44</pages><volume>7</volume><number>2</number><keywords><keyword>Carbon Isotopes</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Energy Metabolism</keyword><keyword>Fatty Acids, Unsaturated/metabolism/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Nutritional Requirements</keyword><keyword>Oxidation-Reduction</keyword><keyword>Sex Characteristics</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/*metabolism/physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1363-1950 (Print)</isbn><accession-num>15075703</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[15] and the finding has been confirmed in a second laboratory, though at a lower level of ALA conversion ADDIN EN.CITE <EndNote><Cite><Author>Pawlosky</Author><Year>2003</Year><RecNum>690</RecNum><record><rec-number>690</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R.</author><author>Hibbeln, J.</author><author>Lin, Y.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>The Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcoholism and Alcohol Abuse, NIH, Room 116, 12420 Parklawn Dr, Rockville, MD 20852, USA. bpawlosky@dicbr.niaaa.</auth-address><titles><title>n-3 fatty acid metabolism in women</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>993-4; discussion 994-5</pages><volume>90</volume><number>5</number><keywords><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Fatty Acids/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Sex Factors</keyword><keyword>alpha-Linolenic Acid/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>14667193</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[93]. These findings are consistent with higher plasma DHA concentrations in women compared to men ADDIN EN.CITE <EndNote><Cite><Author>Giltay</Author><Year>2004</Year><RecNum>703</RecNum><record><rec-number>703</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Giltay, E. J.</author><author>Gooren, L. J.</author><author>Toorians, A. W.</author><author>Katan, M. B.</author><author>Zock, P. L.</author></authors></contributors><auth-address>Psychiatric Center GGZ Delfland, Delft, Netherlands. giltay@dds.nl</auth-address><titles><title>Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects</title><secondary-title>Am J Clin Nutr</secondary-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>1167-74</pages><volume>80</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aromatase Inhibitors/*pharmacology</keyword><keyword>Cyproterone Acetate/*pharmacology</keyword><keyword>Docosahexaenoic Acids/*blood/metabolism</keyword><keyword>Estradiol/administration &amp; dosage/blood/physiology</keyword><keyword>Estrogens/administration &amp; dosage/*physiology</keyword><keyword>Ethinyl Estradiol/administration &amp; dosage/pharmacology</keyword><keyword>Female</keyword><keyword>Follicle Stimulating Hormone/blood/physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Sex Characteristics</keyword><keyword>Testosterone/administration &amp; dosage/blood/*physiology</keyword><keyword>Transsexualism</keyword></keywords><dates><year>2004</year><pub-dates><date>Nov</date></pub-dates></dates><accession-num>15531662</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite><Cite><Author>Bakewell</Author><Year>2006</Year><RecNum>704</RecNum><record><rec-number>704</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bakewell, L.</author><author>Burdge, G. C.</author><author>Calder, P. C.</author></authors></contributors><auth-address>Institute of Human Nutrition, Developmental Origins of Health and Disease Division, University of Southampton, Southampton SO16 7PX, UK.</auth-address><titles><title>Polyunsaturated fatty acid concentrations in young men and women consuming their habitual diets</title><secondary-title>Br J Nutr</secondary-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>93-9</pages><volume>96</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Cholesterol Esters/blood</keyword><keyword>Dietary Carbohydrates/administration &amp; dosage</keyword><keyword>Dietary Proteins/administration &amp; dosage</keyword><keyword>Docosahexaenoic Acids/blood</keyword><keyword>Fatty Acids/administration &amp; dosage</keyword><keyword>Fatty Acids, Nonesterified/blood</keyword><keyword>Fatty Acids, Unsaturated/*administration &amp; dosage/blood</keyword><keyword>Female</keyword><keyword>Food Habits/*physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Micronutrients/administration &amp; dosage</keyword><keyword>Phosphatidylcholines/blood</keyword><keyword>Sex Factors</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2006</year><pub-dates><date>Jul</date></pub-dates></dates><accession-num>16869996</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[94, 95]. The extent of conversion of ALA to DHA is influenced by the dietary long chain polyunsaturated fatty acid content ADDIN EN.CITE <EndNote><Cite><Author>Burdge</Author><Year>2003</Year><RecNum>683</RecNum><record><rec-number>683</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G. C.</author><author>Finnegan, Y. E.</author><author>Minihane, A. M.</author><author>Williams, C. M.</author><author>Wootton, S. A.</author></authors></contributors><auth-address>Institute of Human Nutrition, University of Southampton, UK. g.c.burdge@soton.ac.uk</auth-address><titles><title>Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>311-21</pages><volume>90</volume><number>2</number><keywords><keyword>Carbon Dioxide/metabolism</keyword><keyword>Dietary Fats, Unsaturated/administration &amp; dosage/metabolism</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/metabolism</keyword><keyword>Eicosapentaenoic Acid/administration &amp; dosage/metabolism</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fatty Acids, Unsaturated/administration &amp; dosage</keyword><keyword>Humans</keyword><keyword>Lipids/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Oxidation-Reduction</keyword><keyword>alpha-Linolenic Acid/*administration &amp; dosage/*metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>12908891</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Burdge</Author><Year>2002</Year><RecNum>684</RecNum><record><rec-number>684</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burdge, G. C.</author><author>Wootton, S. 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L.</author><author>Spilker, M. E.</author><author>Zock, P. L.</author><author>Katan, M. B.</author><author>Mensink, R. P.</author></authors></contributors><auth-address>Department of Human Biology, Maastricht University, Maastricht, Netherlands. p.goyens@hb.unimaas.nl</auth-address><titles><title>Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio</title><secondary-title>Am J Clin Nutr</secondary-title><alt-title>The American journal of clinical nutrition</alt-title></titles><periodical><full-title>Am J Clin Nutr</full-title></periodical><pages>44-53</pages><volume>84</volume><number>1</number><keywords><keyword>Breath Tests</keyword><keyword>Carbon Isotopes</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Double-Blind Method</keyword><keyword>Fatty Acids, Unsaturated/analysis/blood/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Linoleic Acid/administration &amp; dosage/blood/*metabolism</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Oxidation-Reduction</keyword><keyword>Phospholipids/analysis/blood/*metabolism</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage/blood/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0002-9165 (Print)</isbn><accession-num>16825680</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Hussein</Author><Year>2005</Year><RecNum>688</RecNum><record><rec-number>688</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hussein, N.</author><author>Ah-Sing, E.</author><author>Wilkinson, P.</author><author>Leach, C.</author><author>Griffin, B. A.</author><author>Millward, D. J.</author></authors></contributors><auth-address>Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.</auth-address><titles><title>Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>269-80</pages><volume>46</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Arachidonic Acid/metabolism</keyword><keyword>Area Under Curve</keyword><keyword>Chromatography, Gas</keyword><keyword>*Diet</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Erythrocytes/*metabolism</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>Humans</keyword><keyword>Linoleic Acid/*chemistry</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Models, Biological</keyword><keyword>Phospholipids/*blood/metabolism</keyword><keyword>Risk</keyword><keyword>Time Factors</keyword><keyword>alpha-Linolenic Acid/*chemistry</keyword></keywords><dates><year>2005</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>15576848</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Pawlosky</Author><Year>2003</Year><RecNum>690</RecNum><record><rec-number>690</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R.</author><author>Hibbeln, J.</author><author>Lin, Y.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>The Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcoholism and Alcohol Abuse, NIH, Room 116, 12420 Parklawn Dr, Rockville, MD 20852, USA. bpawlosky@dicbr.niaaa.</auth-address><titles><title>n-3 fatty acid metabolism in women</title><secondary-title>Br J Nutr</secondary-title><alt-title>The British journal of nutrition</alt-title></titles><periodical><full-title>Br J Nutr</full-title></periodical><pages>993-4; discussion 994-5</pages><volume>90</volume><number>5</number><keywords><keyword>Diet</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Fatty Acids/*metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Sex Factors</keyword><keyword>alpha-Linolenic Acid/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0007-1145 (Print)</isbn><accession-num>14667193</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Pawlosky</Author><Year>2001</Year><RecNum>600</RecNum><record><rec-number>600</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R. J.</author><author>Hibbeln, J. R.</author><author>Novotny, J. A.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Food Composition Laboratory, Beltsville, MD 20705, USA. pawlosky@bhnrc.</auth-address><titles><title>Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans</title><secondary-title>J Lipid Res</secondary-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><pages>1257-65</pages><volume>42</volume><number>8</number><keywords><keyword>Absorption</keyword><keyword>Adult</keyword><keyword>Chylomicrons/blood</keyword><keyword>Computer Simulation</keyword><keyword>Diet</keyword><keyword>Dietary Fats/administration &amp; dosage</keyword><keyword>Energy Intake</keyword><keyword>Fatty Acids, Omega-3/administration &amp; dosage/blood</keyword><keyword>Female</keyword><keyword>Half-Life</keyword><keyword>Humans</keyword><keyword>Kinetics</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Models, Biological</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>11483627</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite><Cite><Author>Vermunt</Author><Year>2000</Year><RecNum>452</RecNum><record><rec-number>452</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vermunt, S. H.</author><author>Mensink, R. P.</author><author>Simonis, M. M.</author><author>Hornstra, G.</author></authors></contributors><auth-address>Department of Human Biology, Maastricht University, The Netherlands.</auth-address><titles><title>Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13C-alpha-linolenic acid</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>137-42</pages><volume>35</volume><number>2</number><keywords><keyword>5,8,11,14,17-Eicosapentaenoic Acid/blood/pharmacology</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Carbon Isotopes</keyword><keyword>Docosahexaenoic Acids/blood/pharmacology</keyword><keyword>Energy Intake</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fatty Acids, Omega-3/blood/*pharmacology</keyword><keyword>Fatty Acids, Unsaturated/blood</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Male</keyword><keyword>Middle Age</keyword><keyword>Oleic Acid/pharmacology</keyword><keyword>Oxidation-Reduction</keyword><keyword>Pilot Projects</keyword><keyword>alpha-Linolenic Acid/*metabolism/*pharmacology</keyword></keywords><dates><year>2000</year><pub-dates><date>Feb</date></pub-dates></dates><accession-num>10757543</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Mayes, C.</author><author>Burdge, G. C.</author><author>Bingham, A.</author><author>Murphy, J. L.</author><author>Tubman, R.</author><author>Wootton, S. A.</author></authors></contributors><auth-address>Neonatal Intensive Care Unit, Royal Maternity Hospital, Belfast, UK.</auth-address><titles><title>Variation in [U-13C] alpha linolenic acid absorption, beta-oxidation and conversion to docosahexaenoic acid in the pre-term infant fed a DHA-enriched formula</title><secondary-title>Pediatr Res</secondary-title><alt-title>Pediatric research</alt-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>271-5</pages><volume>59</volume><number>2</number><keywords><keyword>Breath Tests</keyword><keyword>Carbon Dioxide/administration &amp; dosage</keyword><keyword>Carbon Isotopes</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/*metabolism</keyword><keyword>Humans</keyword><keyword>*Infant Food</keyword><keyword>Infant, Newborn</keyword><keyword>Oxidation-Reduction</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0031-3998 (Print)</isbn><accession-num>16439591</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[4, 85-88, 91, 93, 96]. ALA metabolism to EPA and DHA has been observed in humans of all ages from premature infants ADDIN EN.CITE <EndNote><Cite><Author>Carnielli</Author><Year>1996</Year><RecNum>10</RecNum><record><rec-number>10</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Carnielli, V. P.</author><author>Wattimena, D. J.</author><author>Luijendijk, I. H.</author><author>Boerlage, A.</author><author>Degenhart, H. J.</author><author>Sauer, P. J.</author></authors></contributors><auth-address>Department of Pediatrics, Erasmus University Rotterdam, The Netherlands.</auth-address><titles><title>The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>169-74.</pages><volume>40</volume><number>1</number><keywords><keyword>Arachidonic Acid/*biosynthesis</keyword><keyword>Carbon Isotopes</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Human</keyword><keyword>Infant, Newborn</keyword><keyword>Infant, Premature/*metabolism</keyword><keyword>Infant, Very Low Birth Weight/*metabolism</keyword><keyword>Linoleic Acid</keyword><keyword>Linoleic Acids/*metabolism</keyword><keyword>Mass Fragmentography/methods</keyword><keyword>Phospholipids/blood</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>1996</year></dates><accession-num>8798265</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Mayes, C.</author><author>Burdge, G. C.</author><author>Bingham, A.</author><author>Murphy, J. L.</author><author>Tubman, R.</author><author>Wootton, S. A.</author></authors></contributors><auth-address>Neonatal Intensive Care Unit, Royal Maternity Hospital, Belfast, UK.</auth-address><titles><title>Variation in [U-13C] alpha linolenic acid absorption, beta-oxidation and conversion to docosahexaenoic acid in the pre-term infant fed a DHA-enriched formula</title><secondary-title>Pediatr Res</secondary-title><alt-title>Pediatric research</alt-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>271-5</pages><volume>59</volume><number>2</number><keywords><keyword>Breath Tests</keyword><keyword>Carbon Dioxide/administration &amp; dosage</keyword><keyword>Carbon Isotopes</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/*metabolism</keyword><keyword>Humans</keyword><keyword>*Infant Food</keyword><keyword>Infant, Newborn</keyword><keyword>Oxidation-Reduction</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0031-3998 (Print)</isbn><accession-num>16439591</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Salem</Author><Year>1996</Year><RecNum>564</RecNum><record><rec-number>564</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Salem, N., Jr.</author><author>Wegher, B.</author><author>Mena, P.</author><author>Uauy, R.</author></authors></contributors><auth-address>Laboratory of Membrane Biochemistry and Biophysics, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.</auth-address><titles><title>Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>49-54</pages><volume>93</volume><number>1</number><keywords><keyword>Arachidonic Acid/*biosynthesis</keyword><keyword>Deuterium</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Fatty Acids, Essential/metabolism</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Mass Fragmentography</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Time Factors</keyword></keywords><dates><year>1996</year><pub-dates><date>Jan 9</date></pub-dates></dates><accession-num>8552667</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Sauerwald, T. U.</author><author>Hachey, D. L.</author><author>Jensen, C. L.</author><author>Chen, H.</author><author>Anderson, R. E.</author><author>Heird, W. C.</author></authors></contributors><auth-address>USDA/ARS Children&apos;s Nutrition Research Center, Department of Pediatrics, Houston, Texas 77030, USA.</auth-address><titles><title>Intermediates in endogenous synthesis of C22:6 omega 3 and C20:4 omega 6 by term and preterm infants</title><secondary-title>Pediatr Res</secondary-title><alt-title>Pediatric research</alt-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>183-7</pages><volume>41</volume><number>2</number><keywords><keyword>Arachidonic Acid/*biosynthesis</keyword><keyword>Docosahexaenoic Acids/*metabolism</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Gestational Age</keyword><keyword>Humans</keyword><keyword>Infant, Newborn/*metabolism</keyword><keyword>Infant, Premature/*metabolism</keyword><keyword>Phospholipids/blood</keyword></keywords><dates><year>1997</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0031-3998 (Print)</isbn><accession-num>9029636</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[80-82, 96] to adults in their sixth decade ADDIN EN.CITE <EndNote><Cite><Author>Hussein</Author><Year>2005</Year><RecNum>688</RecNum><record><rec-number>688</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hussein, N.</author><author>Ah-Sing, E.</author><author>Wilkinson, P.</author><author>Leach, C.</author><author>Griffin, B. A.</author><author>Millward, D. J.</author></authors></contributors><auth-address>Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom.</auth-address><titles><title>Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>269-80</pages><volume>46</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Arachidonic Acid/metabolism</keyword><keyword>Area Under Curve</keyword><keyword>Chromatography, Gas</keyword><keyword>*Diet</keyword><keyword>Docosahexaenoic Acids/metabolism</keyword><keyword>Eicosapentaenoic Acid/metabolism</keyword><keyword>Erythrocytes/*metabolism</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Fatty Acids, Unsaturated/metabolism</keyword><keyword>Humans</keyword><keyword>Linoleic Acid/*chemistry</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Models, Biological</keyword><keyword>Phospholipids/*blood/metabolism</keyword><keyword>Risk</keyword><keyword>Time Factors</keyword><keyword>alpha-Linolenic Acid/*chemistry</keyword></keywords><dates><year>2005</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>15576848</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Pawlosky</Author><Year>2001</Year><RecNum>600</RecNum><record><rec-number>600</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R. J.</author><author>Hibbeln, J. R.</author><author>Novotny, J. A.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Food Composition Laboratory, Beltsville, MD 20705, USA. pawlosky@bhnrc.</auth-address><titles><title>Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans</title><secondary-title>J Lipid Res</secondary-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><pages>1257-65</pages><volume>42</volume><number>8</number><keywords><keyword>Absorption</keyword><keyword>Adult</keyword><keyword>Chylomicrons/blood</keyword><keyword>Computer Simulation</keyword><keyword>Diet</keyword><keyword>Dietary Fats/administration &amp; dosage</keyword><keyword>Energy Intake</keyword><keyword>Fatty Acids, Omega-3/administration &amp; dosage/blood</keyword><keyword>Female</keyword><keyword>Half-Life</keyword><keyword>Humans</keyword><keyword>Kinetics</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Models, Biological</keyword><keyword>alpha-Linolenic Acid/*metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>11483627</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite><Cite><Author>Vermunt</Author><Year>2000</Year><RecNum>452</RecNum><record><rec-number>452</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vermunt, S. H.</author><author>Mensink, R. P.</author><author>Simonis, M. M.</author><author>Hornstra, G.</author></authors></contributors><auth-address>Department of Human Biology, Maastricht University, The Netherlands.</auth-address><titles><title>Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13C-alpha-linolenic acid</title><secondary-title>Lipids</secondary-title></titles><periodical><full-title>Lipids</full-title><abbr-1>Lipids</abbr-1></periodical><pages>137-42</pages><volume>35</volume><number>2</number><keywords><keyword>5,8,11,14,17-Eicosapentaenoic Acid/blood/pharmacology</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Carbon Isotopes</keyword><keyword>Docosahexaenoic Acids/blood/pharmacology</keyword><keyword>Energy Intake</keyword><keyword>Fatty Acids/blood</keyword><keyword>Fatty Acids, Omega-3/blood/*pharmacology</keyword><keyword>Fatty Acids, Unsaturated/blood</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Male</keyword><keyword>Middle Age</keyword><keyword>Oleic Acid/pharmacology</keyword><keyword>Oxidation-Reduction</keyword><keyword>Pilot Projects</keyword><keyword>alpha-Linolenic Acid/*metabolism/*pharmacology</keyword></keywords><dates><year>2000</year><pub-dates><date>Feb</date></pub-dates></dates><accession-num>10757543</accession-num><urls><related-urls><url> name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R. J.</author><author>Hibbeln, J. R.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Laboratory of Metabolic Control, National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. bpawl@mail.</auth-address><titles><title>Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>935-43</pages><volume>48</volume><number>4</number><keywords><keyword>Fatty Acids, Essential/blood/*metabolism/pharmacokinetics</keyword><keyword>Fatty Acids, Omega-3/blood/*metabolism/pharmacokinetics</keyword><keyword>Female</keyword><keyword>Gas Chromatography-Mass Spectrometry</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>*Models, Biological</keyword><keyword>Pharmacokinetics</keyword><keyword>Sex Factors</keyword><keyword>*Smoking</keyword></keywords><dates><year>2007</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>17234605</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[87, 88, 91, 97]. DHA biosynthesis may be impaired in disease states such as retinitis pigmentosa ADDIN EN.CITE <EndNote><Cite><Author>Hoffman</Author><Year>2001</Year><RecNum>693</RecNum><record><rec-number>693</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hoffman, D. R.</author><author>DeMar, J. C.</author><author>Heird, W. C.</author><author>Birch, D. G.</author><author>Anderson, R. E.</author></authors></contributors><auth-address>Retina Foundation of the Southwest, 9900 North Central Expressway, Dallas, TX 75231, USA. dhoffman@</auth-address><titles><title>Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>1395-401</pages><volume>42</volume><number>9</number><keywords><keyword>Adult</keyword><keyword>Breath Tests</keyword><keyword>Carbon Dioxide/analysis</keyword><keyword>Carbon Isotopes</keyword><keyword>Docosahexaenoic Acids/*blood</keyword><keyword>Fatty Acid Desaturases/metabolism</keyword><keyword>Fatty Acids, Omega-3/metabolism</keyword><keyword>Gas Chromatography-Mass Spectrometry</keyword><keyword>Humans</keyword><keyword>Kinetics</keyword><keyword>*Linkage (Genetics)</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Oxidation-Reduction</keyword><keyword>Retinitis Pigmentosa/*blood/genetics</keyword><keyword>*X Chromosome</keyword><keyword>alpha-Linolenic Acid/diagnostic use/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>11518758</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[98] and is altered by smoking ADDIN EN.CITE <EndNote><Cite><Author>Pawlosky</Author><Year>2007</Year><RecNum>692</RecNum><record><rec-number>692</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pawlosky, R. J.</author><author>Hibbeln, J. R.</author><author>Salem, N., Jr.</author></authors></contributors><auth-address>Laboratory of Metabolic Control, National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. bpawl@mail.</auth-address><titles><title>Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers</title><secondary-title>J Lipid Res</secondary-title><alt-title>Journal of lipid research</alt-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><alt-periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></alt-periodical><pages>935-43</pages><volume>48</volume><number>4</number><keywords><keyword>Fatty Acids, Essential/blood/*metabolism/pharmacokinetics</keyword><keyword>Fatty Acids, Omega-3/blood/*metabolism/pharmacokinetics</keyword><keyword>Female</keyword><keyword>Gas Chromatography-Mass Spectrometry</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>*Models, Biological</keyword><keyword>Pharmacokinetics</keyword><keyword>Sex Factors</keyword><keyword>*Smoking</keyword></keywords><dates><year>2007</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-2275 (Print)</isbn><accession-num>17234605</accession-num><urls><related-urls><url> </url></related-urls></urls><language>eng</language></record></Cite></EndNote>[97]. Non-human primates have been used to investigate ALA metabolism in internal organs and compartments not accessible in humans. Early studies of acute omega-3 deficiency in rhesus monkeys confirmed the importance of a source of omega-3 for neural development ADDIN EN.CITE <EndNote><Cite><Author>Neuringer</Author><Year>1986</Year><RecNum>705</RecNum><record><rec-number>705</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Neuringer, M.</author><author>Connor, W. E.</author><author>Lin, D. S.</author><author>Barstad, L.</author><author>Luck, S.</author></authors></contributors><titles><title>Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>4021-5</pages><volume>83</volume><number>11</number><keywords><keyword>Animals</keyword><keyword>Brain/*embryology/growth &amp; development/metabolism</keyword><keyword>Electroretinography</keyword><keyword>Fatty Acids, Essential/deficiency</keyword><keyword>Fatty Acids, Unsaturated/*deficiency</keyword><keyword>Female</keyword><keyword>Macaca mulatta</keyword><keyword>Membrane Lipids/metabolism</keyword><keyword>Phosphatidylethanolamines/metabolism</keyword><keyword>Pregnancy</keyword><keyword>Retina/*embryology/growth &amp; development/metabolism</keyword><keyword>Visual Acuity</keyword><keyword>Visual Cortex/embryology/growth &amp; development/metabolism</keyword><keyword>Visual Pathways/embryology/growth &amp; development</keyword></keywords><dates><year>1986</year><pub-dates><date>Jun</date></pub-dates></dates><accession-num>3459166</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[99], and recent work suggests that deprivation of omega-3 early in life cannot be fully reversed in retina with ALA feeding ADDIN EN.CITE <EndNote><Cite><Author>Anderson</Author><Year>2005</Year><RecNum>615</RecNum><record><rec-number>615</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Anderson, G. J.</author><author>Neuringer, M.</author><author>Lin, D. S.</author><author>Connor, W. E.</author></authors></contributors><auth-address>Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.</auth-address><titles><title>Can prenatal N-3 fatty acid deficiency be completely reversed after birth? Effects on retinal and brain biochemistry and visual function in rhesus monkeys</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>865-72</pages><volume>58</volume><number>5</number><keywords><keyword>Animals</keyword><keyword>Brain/*metabolism</keyword><keyword>Electroretinography</keyword><keyword>Erythrocytes/metabolism</keyword><keyword>*Fatty Acids, Omega-3/blood</keyword><keyword>Fatty Acids, Unsaturated/*deficiency</keyword><keyword>Macaca mulatta/*physiology</keyword><keyword>Research Support, N.I.H., Extramural</keyword><keyword>Research Support, Non-U.S. Gov&apos;t</keyword><keyword>Research Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Retina/*metabolism/physiopathology</keyword><keyword>*Visual Acuity</keyword><keyword>alpha-Linolenic Acid/administration &amp; dosage</keyword></keywords><dates><year>2005</year><pub-dates><date>Nov</date></pub-dates></dates><accession-num>16257925</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[100]. Studies of DHA in pregnancy show that preformed DHA accumulates at 20-33 times the level of DHA biosynthesized from ALA in liver, retina, and brain, and the amount of ALA found as DHA is <0.1% of dose ADDIN EN.CITE <EndNote><Cite><Author>Greiner</Author><Year>1997</Year><RecNum>24</RecNum><record><rec-number>24</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Greiner, R. C.</author><author>Winter, J.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><titles><title>Brain docosahexaenoate accretion in fetal baboons: bioequivalence of dietary alpha-linolenic and docosahexaenoic acids</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>826-34.</pages><volume>42</volume><number>6</number><keywords><keyword>Animal</keyword><keyword>Brain/embryology/*metabolism</keyword><keyword>Dietary Fats/*pharmacokinetics</keyword><keyword>Docosahexaenoic Acids/*pharmacokinetics</keyword><keyword>Fatty Acids/analysis</keyword><keyword>Female</keyword><keyword>Fetal Development/physiology</keyword><keyword>Liver/embryology/metabolism</keyword><keyword>Papio</keyword><keyword>Pregnancy</keyword><keyword>Retina/embryology/metabolism</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>*Therapeutic Equivalency</keyword><keyword>alpha-Linolenic Acid/*pharmacokinetics</keyword></keywords><dates><year>1997</year></dates><label>98057251</label><urls></urls></record></Cite></EndNote>[53]. Similar results are found in four week old neonates at two weeks post-dose ADDIN EN.CITE <EndNote><Cite><Author>Su</Author><Year>1999</Year><RecNum>376</RecNum><record><rec-number>376</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Su, H. M.</author><author>Bernardo, L.</author><author>Mirmiran, M.</author><author>Ma, X. H.</author><author>Corso, T. N.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.</auth-address><titles><title>Bioequivalence of dietary alpha-linolenic and docosahexaenoic acids as sources of docosahexaenoate accretion in brain and associated organs of neonatal baboons</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>87-93.</pages><volume>45</volume><number>1</number><keywords><keyword>Administration, Oral</keyword><keyword>Animal</keyword><keyword>Animals, Newborn</keyword><keyword>Docosahexaenoic Acids/blood/*pharmacokinetics</keyword><keyword>Erythrocytes/metabolism</keyword><keyword>Female</keyword><keyword>Human</keyword><keyword>Infant Food</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Occipital Lobe/*metabolism</keyword><keyword>Organ Specificity</keyword><keyword>Papio</keyword><keyword>Pigment Epithelium of Eye/metabolism</keyword><keyword>Retina/metabolism</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Therapeutic Equivalency</keyword><keyword>alpha-Linolenic Acid/blood/*pharmacokinetics</keyword></keywords><dates><year>1999</year></dates><accession-num>9890614</accession-num><urls><related-urls><url>;[52]. DHA synthesis has also been demonstrated in late term fetal baboons at levels several fold above those seen for neonate baboons ADDIN EN.CITE <EndNote><Cite><Author>Su</Author><Year>2001</Year><RecNum>421</RecNum><record><rec-number>421</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Su, H. M.</author><author>Huang, M. C.</author><author>Saad, N. M.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.</auth-address><titles><title>Fetal baboons convert 18:3n-3 to 22:6n-3 in vivo. A stable isotope tracer study</title><secondary-title>J Lipid Res</secondary-title></titles><periodical><full-title>J Lipid Res</full-title><abbr-1>Journal of lipid research</abbr-1></periodical><pages>581-6</pages><volume>42</volume><number>4</number><keywords><keyword>Animal</keyword><keyword>Brain/embryology/*metabolism</keyword><keyword>Carbon Radioisotopes/*metabolism</keyword><keyword>Docosahexaenoic Acids/blood/*metabolism</keyword><keyword>Female</keyword><keyword>Fetus/*metabolism</keyword><keyword>Food, Formulated</keyword><keyword>Human</keyword><keyword>Kinetics</keyword><keyword>Liver/embryology/*metabolism</keyword><keyword>Papio/embryology/*metabolism</keyword><keyword>Pigment Epithelium of Eye/embryology/metabolism</keyword><keyword>Pregnancy</keyword><keyword>Retina/embryology/metabolism</keyword><keyword>Support, U.S. Gov&apos;t, P.H.S.</keyword><keyword>Tissue Distribution</keyword><keyword>alpha-Linolenic Acid/blood/*metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr</date></pub-dates></dates><accession-num>11290830</accession-num><urls><related-urls><url>;[101]. DHA levels rise in a dose-dependent manner in liver, heart, and retina of 12 week old baboons consuming preformed DHA ADDIN EN.CITE <EndNote><Cite><Author>Hsieh</Author><Year>2007</Year><RecNum>701</RecNum><record><rec-number>701</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hsieh, A. T.</author><author>Anthony, J. C.</author><author>Diersen-Schade, D. A.</author><author>Rumsey, S. C.</author><author>Lawrence, P.</author><author>Li, C.</author><author>Nathanielsz, P. W.</author><author>Brenna, J. T.</author></authors></contributors><auth-address>Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.</auth-address><titles><title>The influence of moderate and high dietary long chain polyunsaturated fatty acids (LCPUFA) on baboon neonate tissue fatty acids</title><secondary-title>Pediatr Res</secondary-title></titles><periodical><full-title>Pediatr Res</full-title></periodical><pages>537-45</pages><volume>61</volume><number>5 Pt 1</number><keywords><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Arachidonic Acid/administration &amp; dosage/chemistry/*metabolism</keyword><keyword>Brain Chemistry</keyword><keyword>Dietary Fats/*metabolism</keyword><keyword>Docosahexaenoic Acids/administration &amp; dosage/chemistry/*metabolism</keyword><keyword>Fatty Acids/chemistry/*metabolism</keyword><keyword>Fatty Acids, Unsaturated/chemistry/*metabolism</keyword><keyword>Humans</keyword><keyword>Infant Formula/chemistry</keyword><keyword>Infant, Newborn</keyword><keyword>Papio</keyword><keyword>Random Allocation</keyword><keyword>Tissue Distribution</keyword><keyword>Tissue Extracts/chemistry</keyword></keywords><dates><year>2007</year><pub-dates><date>May</date></pub-dates></dates><accession-num>17413857</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>[55]. A key point is that although metabolism to DHA was observed in most studies of stable isotope-labeled ALA in humans in vivo, the quantity of labeled DHA produced was very small. Highly sensitive mass spectrometric techniques used for these studies are capable of trace level detection. This low level of conversion is consistent with the studies summarized in Table 1, indicating that ALA supplementation of the diet does not alter blood stream DHA content; dietary ALA supports a small flux of DHA through this biosynthetic pathway, but apparently provides a negligible net flow of mass from ALA to DHA when overall omega-3 are above levels required to prevent frank deficiency. Summary 1. ALA conversion to EPA, DPAn-3 and DHA in tracer studies has been observed in nearly all humans studied from birth through late middle age and in both males and females. 2. The majority of evidence from isotopic tracer studies shows that the conversion of ALA to DHA is on the order of 1% in infants, and considerably lower in adults. This is consistent with measurements of whole body ALA oxidation which is the predominant fate of ALA in both rodents and humans. These “conversion rates” must be viewed as markers of flux through this metabolic pathway but must not be assumed to represent a net change in mass.3. Very few studies in adults show that blood stream or breast milk DHA concentrations increase following several weeks of increased dietary ALA supply, whereas most studies do not. ALA appears to contribute little to circulating DHA when added to a diet that already contains some ALA and high LA levels. 4. Supplementation of the diet with high levels of ALA leads to small but significant increases in EPA and DPAn-3 although supplementation with preformed EPA is approximately 15-fold more efficacious in this regard.5. 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