Impact of high flaxseed diet on mitogen-induced proliferation, IL-2 production, cell subsets and fatty acid composition of spleen cells from pregnant and F1 generation Sprague-Dawley rats

Food and Chemical Toxicology

Volumn 41, Issue 6, 2003, Pages 905-915

  Babu, U S ^a   Wiesenfeld, P W ^a   Collins, T F X ^a   Sprando, R ^a   Flynn, T J ^a   Black, T ^a   Olejnik, N ^a   Raybourne, R B ^a  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

Flaxseed; IL 2; Lymphocyte subsets; Rats; Spleen cell proliferation; Linolenic acid

Indexed keywords

ARACHIDONIC ACID; CONCANAVALIN A; FATTY ACID; INTERLEUKIN 2; LINOLEIC ACID; MITOGENIC AGENT; PHYTOHEMAGGLUTININ;

ANIMAL CELL; ARTICLE; CELL PROLIFERATION; CELL SUBPOPULATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DIET; DIET SUPPLEMENTATION; FEMALE; LACTATION; LINSEED; LYMPHOCYTE; MALE; NONHUMAN; PREGNANCY; RAT; SPLEEN CELL; WEANING;

ANIMALIA;

EID: 0038402625     PISSN: 02786915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0278-6915(03)00043-7     Document Type: Article

References (99)

1. Adlercreutz H., Fotsis T., Bannwart C., Wahala K., Makela T., Brunow G., Hase T. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J. Steroid Biochem. 25(5B):1986;791-797.
2. Ahmann G.B., Sachs D.H., Hodes R.J. Requirement for an Ia-bearing accessory cell in Con A-induced T cell proliferation. Journal of Immunology. 121:1978;1981-1989.
3. Allman M.A., Pena M.M., Pang D. Supplementation with flaxseed oil versus sunflower seed oil in healthy young men consuming a low fat diet. effects on platelet composition and function European Journal of Clinical Nutrition. 19:1995;169-178.
4. Anel A., Naval J., Gonzalez B., Uriel J., Pineiro A. Fatty acid metabolism in human lymphocytes. II. Activation of fatty acid desaturase-elongase systems during blastic transformation. Biochemistry Biophysica Acta. 1044(3):1990;332-339.
5. Ardawi M.S., Newsholme E.A. Metabolism of ketone bodies, oleate and glucose in lymphocytes of the rat. Biochemical Journal. 221:1984;255-260.
6. Babu U.S., Bunning V.K., Wiesenfeld P., Raybourne R.B., O'Donnell M. Effect of dietary flaxseed on fatty acid composition, superoxide, nitric oxide generation and antilisterial activity of peritoneal macrophages from female Sprague-Dawley rats. Life Sciences. 60:1997;545-554.
7. Bala S., Failla M.L. Copper deficiency reversibly impairs DNA synthesis in activated T lymphocytes by limiting interleukin 2 activity. Proceedings of the National Academy of Sciences of the United States of America. 89:1992;6794-6797.
8. Bala S., Failla M.L. Copper repletion restores the number and function of CD4 cells in copper-deficient rats. Journal of Nutrition. 123(6):1993;991-996.
9. Bartha J.L., Comino-Delgado R., Martinez-Del Fresno P., Ortega M.J., Fernandez-Lorente J.R., Cabello J.M. Lymphocyte subpopulations after normal pregnancy and spontaneous abortion in primigravidas. Journal of Reproductive Medicine. 45:2000;567-571.
10. Bermas B.L., Hill J.A. Proliferative responses to recall antigens are associated with pregnancy outcome in women with a history of recurrent spontaneous abortion. Journal of Clinical Investigation. 100:1997;1330-1334.
11. Bierenbaum M.L., Reichstein R., Watkins T.R. Reducing atherogenic risk in hyperlipidemic humans with flax seed supplementation. a preliminary report Journal of American College of Nutrition. 12(5):1993;501-504.
12. Birkeland S.A., Kristoffersen K. Lymphocyte transformation with mitogens and antigens during normal human pregnancy. a longitudinal study Scandinavian Journal of Immunology. 11:1980;321-325.
13. Bjerve K.S., Fischer S., Wammer F., Egeland T. alpha-Linolenic acid and long-chain omega-3 fatty acid supplementation in three patients with omega-3 fatty acid deficiency. effect on lymphocyte function, plasma and red cell lipids, and prostanoid formation American Journal of Clinical Nutrition. 49:1989;290-300.
14. Blok W.L., Katan M.B., van der Meer J.W. Modulation of inflammation and cytokine production by dietary (n-3) fatty acids. Journal of Nutrition. 126:1996;1515-1533.
15. Brenner R.R. Effect of unsaturated acids on membrane structure and enzyme kinetics. Progress in Lipid Research. 23(2):1984;69-96.
16. Brouard C., Pascaud M. Modulation of rat and human lymphocyte function by n-6 and n-3 polyunsaturated fatty acids and acetylsalicylic acid. Annals of Nutrition and Metabolism. 37:1993;146-159.
17. Brunelli R., Frasca D., Baschieri S., Spano M., Fattorossi A., Mosiello L.F., D'Amelio R., Zichella L., Doria G. Changes in thymocyte subsets induced by estradiol administration or pregnancy. Annals of the New York Academy of Sciences. 650:1992;109-114.
18. Calder P.C., Bond J.A., Newsholme E.A. Fatty acid inhibition of concanavalin A-stimulated lymphocyte proliferation. Biochemical Society Transactions. 17:1989;1042-1043.
19. Calder P.C., Bond J.A., Bevan S.J., Hunt S.V., Newsholme E.A. Effect of fatty acids on the proliferation of concanavalin A-stimulated rat lymph node lymphocytes. International Journal of Biochemistry. 23:1991;579-588.
20. Calder P.C., Bevan S.J., Newsholme E.A. The inhibition of T-lymphocyte proliferation by fatty acids is via an eicosanoid-independent mechanism. Immunology. 75:1992;108-115.
21. Carter J.F. Potential of flaxseed and flaxseed oil in baked goods and other products in human nutrition. Cereal Foods World. 38(10):1993;753-759.
22. Clark W.F., Muir A.D., Westcott N.D., Parbtani A. A novel treatment for Lupus nephritis. lignan precursor derived from flax Lupus. 9:2000;429-436.
23. Clark W.F., Kortas C., Heidenheim A.P., Garland J., Spanner E., Parbtani A. Flaxseed in Lupus nephritis. a two-year nonplacebo-controlled crossover study Journal of the American College of Nutrition. 20:2001;143-148.
24. Cunnane S.C., Ganguli S., Menard C., Liede A.C., Hanadeh M.J., Chen Z.Y., Wolever T.M., Jenkins D.J. High alpha-linolenic acid flaxseed (Linum usitatissimum). some nutritional properties in humans British Journal of Nutrition. 69(2):1993;443-453.
25. Cunnane S.C., Hamadeh M.J., Liede A.C., Thompson L.U., Wolever T.M., Jenkins D.J. Nutritional attributes of traditional flaxseed in healthy young adults. American Journal of Clinical Nutrition. 61:1994;62-68.
26. D'Ambola J.B., Aeberhard E.E., Trang N., Gaffar S., Barrett C.T., Sherman M.P. Effect of dietary (n-3) and (n-6) fatty acids on in vivo pulmonary bacterial clearance by neonatal rabbits. Journal of Nutrition. 121:1991;1262-1269.
27. Dell C.A., Likhodii S.S., Musa K., Ryan M.A., Burnham W.M., Cunnane S.C. Lipid and fatty acid profiles in rats consuming different high-fat ketogenic diets. Lipids. 36:2001;373-378.
28. Fritsche K.L., Johnston P.V. Modulation of eicosanoid production and cell-mediated cytotoxicity by dietary alpha-linolenic acid in BALB/c mice. Lipids. 24:1989;305-311.
29. Fritsche K.L., Cassity N.A., Huang S.C. Effect of dietary fat source on antibody production and lymphocyte proliferation in chickens. Poultry Science. 70:1991;611-617.
30. Fritsche K.L., Cassity N.A. Dietary n-3 fatty acids reduce antibody-dependent cell cytotoxicity and alter eicosanoid release by chicken immune cells. Poultry Science. 71:1992;1646-1657.
31. Fritsche K.L., Shahbazian L.M., Feng C., Berg J.N. Dietary fish oil reduces survival and impairs bacterial clearance in C3H/Hen mice challenged with Listeria monocytogenes. Clinical Science. 92:1997;95-101.
32. Gallai V., Sarchielli P., Trequattrini A., Franceschini M., Floridi A., Firenze C., Alberti A., Di Benedetto D., Stragliotto E. Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. Journal of Neuroimmunology. 56(2):1995;143-153.
33. Gonzalez-Esquerra R., Lesson S. Effect of menhaden oil and flaxseed in broiler sensory quality and lipid composition of poultry. British Poultry Science. 41(4):2000;481-488.
34. Guo T.L., Zhang X.L., Bartolucci E., McCay J.A., White K.L., You L. Genistein and methoxychlor modulate the activity of natural killer cells and the expression of phenotypic markers by thymocytes and splenocytes in F(0) and F(1) generations of Sprague-Dawley rats. Toxicology. 172:2002;205-215.
35. Hwang D. Essential fatty acids and immune response. FASEB Journal. 3(9):1989;2052-2061.
36. Ingram A.J., Parbtani A., Clark W.F., Spanner E., Huff M.W., Philbrick D.J., Holub B.J. Effects of flaxseed and flax oil diets in a rat-5/6 renal ablation model. American Journal of Kidney Diseases. 25:1995;320-329.
37. James M.J., Gibson R.A., Cleland L.G. Dietary polyunsaturated fatty acids and inflammatory mediator production. American Journal of Clinical Nutrition. 71:2000;343. S-348S.
38. Jeffery N.M., Sanderson P., Sherrington E.J., Newsholme E.A., Calder P.C. The ratio of n-6 to n-3 polyunsaturated fatty acids in the rat diet alters serum lipid levels and lymphocyte functions. Lipids. 31:1996;737-745.
39. Jeffery N.M., Cortina M., Newsholme E.A., Calder P.C. Effects of variations in the proportions of saturated, monounsaturated and polyunsaturated fatty acids in the rat diet on spleen lymphocyte functions. British Journal of Nutrition. 77:1997;805-823.
40. Jeffery N.M., Newsholme E.A., Calder P.C. Level of polyunsaturated fatty acids and the n-6 to n-3 polyunsaturated fatty acid ratio in the rat diet alter serum lipid levels and lymphocyte functions. Prostaglandins Leukotrienes and Essential Fatty Acids. 57:1997;149-160.
41. Jenab M., Thompson L.U. The influence of flaxseed and lignans on colon carcinogenesis and glucoronidase activity. Carcinogenesis. 17(6):1996;1343-1348.
42. Johnstone F.D., Thong K.J., Bird A.G., Whitelaw J. Lymphocyte subpopulations in early human pregnancy. Obstetrics and Gynecology. 83:1994;941-946.
43. Jolly C.A., Jiang Y.H., Chapkin R.S., McMurray D.N. Dietary (n-3) polyunsaturated fatty acids suppress murine lymphoproliferation, interleukin-2 secretion, and the formation of diacylglycerol and ceramide. Journal of Nutrition. 127:1997;37-43.
44. Jolly C.A., McMurray D.N., Chapkin R.S. Effect of dietary n-3 fatty acids on interleukin-2 and interleukin-2 receptor alpha expression in activated murine lymphocytes. Prostaglandins, Leukotrienes and Essential Fatty Acids. 58(4):1998;289-293.
45. Kaku S., Yunoki S., Ohkura K., Sugano M., Nonaka M., Tachibana H., Yamada K. Interactions of dietary fats and proteins on fatty acid composition of immune cells and LTB4 production by peritoneal exudate cells of rats. Bioscience, Biotechnology, and Biochemistry. 65:2001;315-321.
46. Kelley D.S., Nelson G.J., Serrato C.M., Schmidt P.C., Branch L.B. Effects of type of dietary fat on indices of immune status of rabbits. Journal of Nutrition. 118:1988;1376-1384.
47. Kelley D.S., Branch L.B., Love J.E., Taylor P.C., Rivera Y.M., Iacono J.M. Dietary alpha-linolenic acid and immunocompetence in humans. American Journal of Clinical Nutrition. 53:1991;40-46.
48. Kelley D.S. Alpha-linolenic acid and immune response. Nutrition. 8:1992;215-217.
49. Kelley D.S., Daudu P.A. Fat intake and immune response. Progress in Food and Nutrition Science. 17(1):1993;41-63.
50. Kelley D.S., Nelson G.J., Love J.E., Branch L.B., Taylor P.C., Schmidt P.C., Mackey B.E., Iacono J.M. Dietary linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans. Lipids. 28:1993;533-537.
51. Kelley D.S. Modulation of human immune and inflammatory responses by dietary fatty acids. Nutrition. 17:2001;669-673.
52. Kumar G.S., Das U.N., Kumar K.V., Madhavi N., Das N.P., Tan B.K.H. Effect of n-6 and n-3 fatty acids on the proliferation of human lymphocytes and their secretion of TNF- and IL-2 in vitro. Nutrition Research. 2:1992;815-823.
53. L'Abbe M.R., Trick K.D., Beare-Rogers J.L. Dietary (n-3) fatty acids affect rat heart, liver and aorta protective enzyme activities and lipid peroxidation. Journal of Nutrition. 121:1991;1331-1340.
54. Li D., Sinclair A., Wilson A., Nakkote S., Kelly F., Abedin L., Mann N., Turner A. Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men. American Journal of Clinical Nutrition. 69(5):1999;872-882.
55. Makrydimas G., Plachouras N., Higueras M.T., Thilaganathan B., Nicolaides K. Maternal peripheral blood lymphocyte subpopulations in normal and pathological pregnancies. Fetal Diagnosis and Therapy. 9:1994;371-378.
56. Malinowski A., Szpakowski M., Tchorzewski H., Zeman K., Pawlowicz P., Wozniak P. T lymphocyte subpopulations and lymphocyte proliferative activity in normal and pre-eclamptic pregnancy. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 53:1994;27-31.
57. Mantzioris E., James M.J., Gibson R.A., Cleland L.G. Dietary substitution with a linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues. American Journal of Clinical Nutrition. 59:1994;1304-1309. (1994).
58. Mantzioris E., Cleland L.G., Gibson R.A., Neumann M.A., Demasi M., James M.J. Biochemical effects of a diet containing foods enriched with n-3 fatty acids. American Journal of Clinical Nutrition. 72:2000;42-48.
59. Marshall L.A., Johnston P.V. The influence of dietary essential fatty acids on rat immunocompetent cell prostaglandin synthesis and mitogen-induced blastogenesis. Journal of Nutrition. 115:1985;1572-1580.
60. May C.L., Calder P.C. Unsaturated fatty acids inhibit lymphocyte protein kinase C activity. Biochemical Society Transactions. 21(4):1993;377. S.
61. Mayatepek E., Paul K., Leichsenring M., Pfisterer M., Wagner D., Domann M., Sonntag H.G., Bremer H.J. Influence of dietary (n-3)-polyunsaturated fatty acids on leukotriene B4 and prostaglandin E2 synthesis and course of experimental tuberculosis in guinea pigs. Infection. 22:1994;106-112.
62. McMurray D.N., Jolly C.A., Chapkin R.S. Effects of dietary n-3 fatty acids on T cell activation and T cell receptor-mediated signaling in a murine model. Journal of Infectious Diseases. 182(Supp. 1):2000;S103-S107.
63. Miotti P.G., Liomba G., Dallabetta G.A., Hoover D.R., Chiphangwi J.D., Saah A.J. T lymphocyte subsets during and after pregnancy. analysis in human immunodeficiency virus type 1-infected and uninfected Malawian mothers Journal of Infectious Diseases. 165:1992;1116-1119.
64. Morris D.D., Henry M.M., Moore J.N., Fischer J.K. Effect of dietary alpha-linolenic acid on endotoxin-induced production of tumor necrosis factor by peritoneal macrophages in horses. American Journal of Veterinary Research. 52:1991;528-532.
65. Neckers L.M., Cossman J. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proceedings of The National Academy of Sciences U S A. 80(11):1983;3494-3498.
66. Nesbitt P.D., Thompson L.U. Lignans in homemade and commercial products containing flaxseed. Nutrition and Cancer. 29:1997;222-227.
67. Ogborn M.R., Nitschmann E., Weiler H., Leswick D., Bankovic-Calic N. Flaxseed ameliorates interstital nephritis in rat polycystic kidney disease. Kidney International. 55(2):1999;417-423.
68. Peterson L.D., Jeffery N.M., Thies F., Sanderson P., Newsholme E.A., Calder P.C. Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity. Lipids. 33:1998;171-180.
69. Rand M.L., Hennissen A.A., Hornstra G. Effects of dietary palm oil on arterial thrombosis, platelet responses and platelet membrane fluidity in rats. Lipids. 23:1988;1019-1023.
70. Ranich T., Bhathena S.J., Velasques M.T. Protective effects of dietary phytoestrogens in chronic renal disease. Journal of Renal Nutrition. 11(4):2001;183-193.
71. Ratnayake W.M.N., Behrens W.A., Fischer P.W.F., L'Abbe M.R., Mongeau R., Beare-Rogers J.L. Chemical and nutritional studies of flaxseed (variety Linott) in rats. Journal of Nutritional Biochemistry. 3:1992;232-240.
72. Reeves P.G., Nielsen F.H., Fahey G.C. Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. Journal of Nutrition. 123(11):1993;1939-1951.
73. Rich K.C., Siegel J.N., Jennings C., Rydman R.J., Landay A.L. CD4+ lymphocytes in perinatal human immunodeficiency virus (HIV) infection. evidence for pregnancy-induced immune depression in uninfected and HIV-infected women Journal of Infectious Diseases. 172:1995;1221-1227.
74. Rossetti R.G., Seiler C.M., DeLuca P., Laposata M., Zurier R.B. Oral administration of unsaturated fatty acids. effects on human peripheral blood T lymphocyte proliferation Journal of Leukocyte Biology. 62:1997;438-443.
75. Rotondo D., Earl C.R., Laing K.J., Kaimakamis D. Inhibition of cytokine-stimulated thymic lymphocyte proliferation by fatty acids. the role of eicosanoids Biochimica et Biophysica Acta. 1223:1994;185-194.
76. Rotter B.A., Oh Y.N. MTS/PMS colorimetric assay is unsuitable for measuring mitogenic responses in porcine blood lymphocytes. Journal of Immunological Methods. 199(2):1996;205-209.
77. Russell A.S., Johnston C., Chew C., Maksymowych W.P. Evidence for reduced Th1 function in normal pregnancy. a hypothesis for the remission of rheumatoid arthritis Journal of Rheumatology. 24:1997;1045-1050.
78. Sabahi F., Rola-Plesczcynski M., O'Connell S., Frenkel L.D. Qualitative and quantitative analysis of T lymphocytes during normal human pregnancy. American Journal of Reproductive Immunology. 33:1995;381-393.
79. Sano M., Mitsuyama M., Watanabe Y., Nomoto K. Impairment of T cell-mediated immunity to Listeria monocytogenes in pregnant mice. Microbiology and Immunology. 30:1986;165-176.
80. Schumacher J., DeGraves F.J., Spano J.S. Clinical and clinicopathologic effects of large doses of raw linseed oil as compared to mineral oil in healthy horses. Journal of Veterinary Internal Medicine. 11(5):1997;296-299.
81. Serraino M., Thompson L.U. The effect of flaxseed supplementation on the initiation and promotional stages of mammary tumorigenesis. Nutrition and Cancer. 17:1992;153-159.
82. Serraino M., Thompson L.U. Flaxseed supplementation and early markers of colon carcinogenesis. Cancer Letters. 63:1992;159-165.
83. Shimaoka Y., Hidaka Y., Tada H., Nakamura T., Mitsuda N., Morimoto Y., Murata Y., Amino N. Changes in cytokine production during and after normal pregnancy. American Journal of Reproductive Immunology. 44:2000;143-147.
84. Soyland E., Nenseter M.S., Braathen L., Drevon C.A. Very long chain n-3 and n-6 polyunsaturated fatty acids inhibit proliferation of human T-lymphocytes in vitro. European Journal of Clinical Investigation. 23(2):1993;112-121.
85. Speizer L.A., Watson M.J., Brunton L.L. Differential effects of omega-3 fish oils on protein kinase activities in vitro. American Journal of Physiology. 261(1 Pt 1):1991;E109-114.
86. Sprando R.L., Collins T.F., Black T.N., Olejnik N., Rorie J.I., Scott M., Wiesenfeld P., Babu U.S., O'Donnell M. The effect of maternal exposure to flaxseed on spermatogenesis in F(1) generation rats. Food and Chemical Toxicology. 38:2000;325-334.
87. Sprando R.L., Collins T.F., Wiesenfeld P., Babu U.S., Rees C., Black T., Olejnik N., Rorie J. Testing the potential of flaxseed to affect spermatogenesis. morphometry Food and Chemical Toxicology. 38:2000;887-892.
88. Stubbs C.D., Smith A.D. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochemistry Biophysica Acta. 779(1):1984;89-137.
89. Szekeres-Bartho J., Autran B., Debre P., Andreu G., Denver L., Chaouat G. Immunoregulatory effects of a suppressor factor from healthy pregnant women's lymphocytes after progesterone induction. Cellular Immunology. 122:1989;281-294.
90. Thies F., Nebe-von-Caron G., Powell J.R., Yaqoob P., Newsholme E.A., Calder P.C. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y. American Journal of Clinical Nutrition. 73:2001;539-548.
91. Thies F., Nebe-von-Caron G., Powell J.R., Yaqoob P., Newsholme E.A., Calder P.C. Dietary supplementation with γ-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. Journal of Nutrition. 131:2001;1918-1927.
92. Thompson L.U., Rickard S.E., Orcheson L.J., Seidl M.M. Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis. 17:1996;1373-1376.
93. Turek J.J., Schoenlein I.A., Clark L.K., Van Alstine W.G. Dietary polyunsaturated fatty acid effects on immune cells of the porcine lung. Journal of Leukocyte Biology. 56:1994;599-604.
94. Veillette A., Bookman M.A., Horak E.M., Bolen J.B. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 55:1988;301-308.
95. Vine J.B., Geppert T.D., Lipsky P.E. T4 cell activation by immobilized phytohemagglutinin. differential capacity to induce IL-2 responsiveness and IL-2 production Journal of Immunology. 141:1988;2593-2600.
96. Wang D.N., Su B.T., Shi M.Y. The effects of suppressive activities mediated by cells on the protection of fetus against maternal immune rejection. Scientia Sinica. Series B, Chemical, Biological, Agricultural, Medical and Earth Sciences. 28:1985;863-871.
97. Wiesenfeld P.W., Babu U.S., O'Donnell M.W. Effect of long-chain fatty acids in the culture medium on fatty acid composition of WEHI-3 and J774A. 1 cells. Comparative Biochemistry and Physiology Part B. 128(1):2001;123-134.
98. Wiesenfeld, P.W., Babu, U.S., Collins, T.F.X., Sprando, R., O'Donnell, M.W., Flynn, T.J., Black, T., Olejnik, N. 2003. Flaxseed increased α-linolenic acid and eicosapentanoic acid and decreased arachidonic acid in serum and tissues of rat dams and offspring. Food and Chemical Toxicology (In press).
99. Wu D., Meydani S.N., Meydani M., Hayek M.G., Huth P., Nicolosi R.J. Immunologic effects of marine- and plant-derived n-3 polyunsaturated fatty acids in nonhuman primates. American Journal of Clinical Nutrition. 63:1996;273-280.