Lipids

, Volume 37, Issue 12, pp 1113–1123 | Cite as

What is the role of α-linolenic acid for mammals?

  • Andrew J. Sinclair
  • Nadia M. Attar-Bashi
  • Duo Li
Review

Abstract

This review examines the data pertaining to an important and often underrated EFA, α-linolenic acid (ALA). It examines its sources, metabolism, and biological effects in various population studies, in vitro, animal, and human intervention studies. The main role of ALA was assumed to be as a precursor to the longer-chain n-3 PUFA, EPA and DHA, and particularly for supplying DHA for neural tissue. This paper reveals that the major metabolic route of ALA metabolism is β-oxidation. Furthermore, ALA accumulates in specific sites in the body of mammals (carcass, adipose, and skin), and only a small proportion of the fed ALA is converted to DHA. There is some evidence that ALA may be involved with skin and fur function. There is continuing debate regarding whether ALA has actions of its own in relation to the cardiovascular system and neural function. Cardiovascular disease and cancer are two of the major burdens of disease in the 21st century, and emerging evidence suggests that diets containing ALA are associated with reductions in total deaths and sudden cardiac death. There may be aspects of the action and, more importantly, the metabolism of ALA that need to be elucidated, and these will help us understand the biological effects of this compound better. Additionally, we must not forget that ALA is part of the whole diet and should be seen in this context, not in isolation.

Abbreviations

ALA

α-linolenic acid

CE

cholesterol ester

DPA

docosapentaenoic acid

PG

prostaglandin

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Burr, G.O., and Burr, M.M. (1930) On the Nature and Role of Fatty Acids Essential in Nutrition, J. Biol. Chem. 86, 587–621.Google Scholar
  2. 2.
    Cunnane, S.C., Ryan, M.A., Craig, K.S., Brookes, S., Koletzko, B., Demmelmair, H., Singer, J., and Kyle, D.J. (1995) Synthesis of Linoleate and α-Linolenate by Chain Elongation in the Rat, Lipids 30, 781–783.PubMedGoogle Scholar
  3. 3.
    Murakami, Y., Tsuyama, M., Kobayashi, Y., Kodama, H., and Iba, K. (2000) Trienoic Fatty Acids and Plant Tolerance of High Temperature, Science 287, 476–479.PubMedCrossRefGoogle Scholar
  4. 4.
    Koch, T., Krumm, T., Jung, V., Engelbert, J., and Boland, W. (1999) Differential Induction of Plant Volatile Biosynthesis in the Lima Bean by Early and Late Intermediates of the Octadecanoid-Signalling Pathway, Plant Physiol 121, 153–162.PubMedCrossRefGoogle Scholar
  5. 5.
    Simopoulos, A.P. and Salem, N., Jr. (1989) n-3 Fatty Acids in Eggs from Free-Range Greek Chickens, N. Engl. J. Med. 321, 1412 (letter).PubMedCrossRefGoogle Scholar
  6. 6.
    Raper, N.R., Cronin, F.J., and Exler, J. (1992) n-3 Fatty Acid Content of the U.S. Food Supply, J. Am. Coll. Nutr. 11, 304–308.PubMedGoogle Scholar
  7. 7.
    Ayerza, R. (1995) Oil Content and Fatty Acid Composition of Chia (Salvia hispanica L.) from Five Northwestern Locations in Argentina, J. Am. Oil Chem. Soc. 72, 1079–1081.Google Scholar
  8. 8.
    Periera, C., Li, D., and Sinclair, A.J. (2001) The α-Linolenic Acid Content of Commonly Available Green Vegetables in Australia, Int. J. Vitam. Nutr. Res. 71, 223–228.CrossRefGoogle Scholar
  9. 9.
    Holman, R.T. (1968) Biological Activities of and Requirements for Polyunsaturated Fatty Acids, Prog. Chem. Fats Other Lipids 9, 611–680.Google Scholar
  10. 10.
    Yamamoto, S., and Smith, W.I. (2002) Molecular Biology of the Arachidonate Cascade (second edition), Prostaglandins Other Lipid Mediat. 68–69, 1 (Preface).CrossRefGoogle Scholar
  11. 11.
    Cunnane, S.C. (1999) The Long History of Essential Fatty Acids but Belated Knowledge About Linoleate Deficiency per se: A Paradox, J. Nutr. 129, 446.PubMedGoogle Scholar
  12. 12.
    Burr, G.O. (1942) Significance of the Essential Fatty Acids, Fed. Proc. 1, 224–233.Google Scholar
  13. 13.
    Mohrhauer, H., and Holman, R.T. (1963) The Effect of Dose Level of Essential Fatty Acids Upon Fatty Acid Composition of the Rat Liver, J. Lipid Res. 4, 151–159.PubMedGoogle Scholar
  14. 14.
    Pan, D.A., and Storlien, L.H. (1993) Dietary Lipid Profile Is a Determinant of Tissue Phospholipid Fatty Acid Composition and Rate of Weight Gain in Rats, J. Nutr. 123, 512–519.PubMedGoogle Scholar
  15. 15.
    Tinoco, J., Williams, M.A., Hincenbergs, I., and Lyman, R.L. (1971) Evidence for Non-essentiality of Linolenic Acid in the Diet of the Rat, J. Nutr. 101, 937–943.PubMedGoogle Scholar
  16. 16.
    Crawford, M.A., and Sinclair, A.J. (1972) The Limitations of Whole Tissue Analysis to Define Linolenic Acid Deficiency, J. Nutr. 102, 1315–1322.PubMedGoogle Scholar
  17. 17.
    O'Brien, J.S., and Sampson, E.L. (1965) Fatty Acid and Fatty Aldehyde Composition of the Major Brain Lipids in Normal Human Gray Matter, White Matter and Myelin, J. Lipid Res. 6, 545–551.PubMedGoogle Scholar
  18. 18.
    Crawford, M.A., and Sinclair, A.J. (1972) Nutritional Influences in the Evolution of the Mammalian Brain, in CIBA Foundation Symposium on Lipids, Malnutrition and the Developing Brain, pp. 267–287, Associated Scientific Publishers, Amsterdam.Google Scholar
  19. 19.
    Fleisler, S.J., and Anderson, R.E. (1983) Chemistry and Metabolism of Lipids in the Vertebrate Retina, Prog. Lipid Res. 22, 79–131.CrossRefGoogle Scholar
  20. 20.
    Wheeler, T.G., Benolken, R.M., and Anderson, R.E. (1975) Visual Membranes: Specificity of Fatty Acid Precursors for the Electrical Response to Illumination, Science 188, 1312–1314.PubMedCrossRefGoogle Scholar
  21. 21.
    Sinclair, A.J. (2000) Commentary on the Workshop Statement, Prostaglandins, Leukot. Essent. Fatty Acids 63, 135–137.CrossRefGoogle Scholar
  22. 22.
    Chyb, S., Raghu, P., and Hardie, R.C. (1999) Polyunsaturated Fatty Acids Activate the Drosophila Light-Sensitive Channels TRP and TRPL, Nature 397, 255–259.PubMedCrossRefGoogle Scholar
  23. 23.
    Salem, N., Jr., and Ward, G.R. (1993) Are Omega-3 Fatty Acids Essential Nutrients for Mammals? World Rev. Nutr. Dietet. 72, 128–147.Google Scholar
  24. 24.
    Greiner, R.S., Moriguchi, T., Hutton, A., Slotnick, B.M., and Salem, N., Jr. (1999) Rats with Low Levels of Brain Docosahexaenoic Acid Show Impaired Performance in Olfactory-Based and Spatial Learning Tasks, Lipids 34, S239-S243.PubMedGoogle Scholar
  25. 25.
    Bourre, J.M., Durand, G., Erre, J.P., and Aran, J.M. (1999) Changes in Auditory Brainstem Responses in α-Linolenic Acid Deficiency as a Function of Age in Rats, Audiology 38, 13–18.PubMedCrossRefGoogle Scholar
  26. 26.
    Umezawa, M., Kogishi, K., Tojo, H., Yoshimura, S., Seriu, N., Ohta, A., Takeda, T., and Hosokawa, M. (1999) High-Linoleate and High α-Linolenate Diets Affect Learning Ability and Natural Behavior in SAMR1 Mice, J. Nutr. 129, 431–437.PubMedGoogle Scholar
  27. 27.
    Ahmad, A., Moriguchi, T., and Salem, N., Jr. (2002) Decrease in Neuron Size in Docosahexaenoic Acid-Deficient Brain, Pediatr. Neurol. 26, 210–218.PubMedCrossRefGoogle Scholar
  28. 28.
    Ahmad, A., Murthy, M., Greiner, R.S., Moriguchi, T., and Salem, N., Jr. (2002) A Decrease in Cell Size Accompanies a Loss of Docosahexaenoate in the Rat Hippocampus, Nutr. Neurosci. 5, 103–113.PubMedCrossRefGoogle Scholar
  29. 29.
    Ikemoto, A., Nitta, A., Furukawa, S., Ohishi, M., Nakamura, A., Fujii, Y., and Okuyama, H. (2000) Dietary n-3 Fatty Acid Deficiency Decreases Nerve Growth Factor Content in Rat Hippocampus, Neurosci. Lett. 285, 99–102.PubMedCrossRefGoogle Scholar
  30. 30.
    Kurlak, L.O., and Stephenson, T.J. (1999) Plausible Explanations for Effects of Long Chain Polyunsaturated Fatty Acids (LCPUFA) on Neonates, Arch. Dis. Child Fetal Neonatal Ed. 80, 148–154.CrossRefGoogle Scholar
  31. 31.
    Lauritzen, L., Hansen, H.S., Jorgensen, M.H., and Michaelson, K.F. (2001) The Essentiality of Long Chain n-3 Fatty Acids in Relation to Development and Function of the Brain and Retina, Prog. Lipid Res. 40, 1–94.PubMedCrossRefGoogle Scholar
  32. 32.
    Salem, N., Jr., Litman, B., Kim, H.-Y., and Gawrisch, K. (2001) Mechanisms of Action of Docosahexaenoic Acid in the Nervous System, Lipids 36, 945–959.PubMedCrossRefGoogle Scholar
  33. 33.
    Litman, B.J., Niu, S.L., Polozova, A., and Mitchell, D.C. (2001) The Role of Docosahexaenoic Acid Containing Phospholipids in Modulating G Protein-Coupled Signaling Pathways: Visual Transduction, J. Mol. Neurosci. 16, 237–242.PubMedCrossRefGoogle Scholar
  34. 34.
    Feller, S.E., Gawrisch, K., and MacKerell, A.D. (2002) Polyunsaturated Fatty Acids in Lipid Bilayers: Instrinsic and Environmental Contributions to Their Unique Physical Properties, J. Am. Chem. Soc. 124, 318–326.PubMedCrossRefGoogle Scholar
  35. 35.
    Bowen, R.A.R., and Clandinin, M.T. (2002) Dietary Low Linolenic Acid Compared with Docosahexaenoic Acid Alter Synaptic Plasma Membrane Phospholipid Fatty Acid Composition and Sodium-Potassium ATPase Kinetics in Developing Rats, J. Neurochem. 83, 764–774.PubMedCrossRefGoogle Scholar
  36. 36.
    Zimmer, L., Delion-Vancassel, S., Durand, G., Guilloteau, D., Bodard, S., Besnard, J.C., and Chalon, S. (2000) Modification of Dopamine Neurotransmission in the Nucleus Accumbens of Rats Deficient in n-3 Polyunsaturated Fatty Acids, J. Lipid Res. 41, 32–40.PubMedGoogle Scholar
  37. 37.
    Vaidyanathan, V.V., Rao, K.V.R., and Sastry, P.S. (1994) Regulation of Diacylglycerol Kinase in Rat Brain Membranes by Docosahexaenoic Acid, Neurosci. Lett. 179, 171–174.PubMedCrossRefGoogle Scholar
  38. 38.
    Rojas, C.V., Greiner, R.S., Martinez, J.I., Salem, N., Jr., and Uauy, R. (2002) Long-Term n-3 Fatty Acid Deficiency Modifies Peroxisome Proliferator-Activated Receptor β mRNA Abundance in Rat Ocular Tissues, Lipids 37, 367–374.PubMedCrossRefGoogle Scholar
  39. 39.
    Kitajka, K., Puskas, L.G., Zvara, A., Hackler, L., Jr., Barcelo-Coblijn, G., Yeo, Y.K., and Farkas, T. (2002) The Role of n-3 Polyunsaturated Fatty Acids in Brain: Modulation of Rat Brain Gene Expression by Dietary n-3 Fatty Acids, Proc. Natl. Acad. Sci. USA 99, 2619–2624.PubMedCrossRefGoogle Scholar
  40. 40.
    De Urquiza, A.M., Liu, S., Sjoberg, M., Zetterstrom, R.H., Griffiths, W., Sjovall, J., and Perlmann, T. (2000) Docosahexaenoic Acid, a Ligand for the Retinoid X Receptor in Mouse Brain, Science 290, 2140–2144.PubMedCrossRefGoogle Scholar
  41. 41.
    Garcia, M.C., Ward, G., Ma, Y.-C., Salem, N., Jr., and Kim, H.-Y. (1998) Effect of Docosahexaenoic Acid on the Synthesis of Phosphatidylserine in Rat Brain Microsomes and C6 Glioma Cells, J. Neurochem. 70, 24–30.PubMedCrossRefGoogle Scholar
  42. 42.
    Akbar, M., and Kim, H.-Y. (2002) Protective Effects of Docosahexaenoic Acid in Staurosporine-Induced Apoptosis: Involvement of Phosphatidyl-3-kinase Pathway, J. Neurochem. 82, 655–665.PubMedCrossRefGoogle Scholar
  43. 43.
    Ikemoto, A., Kobayashi, T., Watanabe, S., and Okuyama, H. (1997) Membrane Fatty Acid Modifications of PC12 Cells by Arachidonate or Docosahexaenoate Affect Neurite Outgrowth but Not Norepinephrine Release, Neurochem. Res. 22, 671–678.PubMedCrossRefGoogle Scholar
  44. 44.
    Martin, R.E. (1998) Docosahexaenoic Acid Decreases Phospholipase A2 Activity in the Neurites/Nerve Growth Cones of PC12 Cells, J. Neurosci. Res. 54, 805–813.PubMedCrossRefGoogle Scholar
  45. 45.
    Lauritzen, I., Blondeau, N., Heurteaux, C., Widmann, C., Romey, G., and Lazdunski, M. (2000) Polyunsaturated Fatty Acids Are Potent Neuroprotectors, EMBO J. 19, 1784–1793.PubMedCrossRefGoogle Scholar
  46. 46.
    Mostofsky, D.I., Yehuda, S., Rabinovitz, S., and Carasso, R. (2000) The Control of Blepharospasm by Essential Fatty Acids Neuropsychobiology 41, 154–157.PubMedCrossRefGoogle Scholar
  47. 47.
    Hansen, H.S., and Jensen, B. (1985) Essential Function of Linoleic Acid Esterified in Acylglucosylceramide and Acylceramide in Maintaining the Epidermal Water Permeability Barrier. Evidence from Feeding Studies with Oleate, Linoleate, Arachidonate, Columbinate and α-linolenate, Biochim. Biophys. Acta 834, 357–363.PubMedGoogle Scholar
  48. 48.
    Ziboh, V.A., Miller, C.C., and Cho, Y. (2000) Metabolism of Polyunsaturated Fatty Acids by Skin Epidermal Enzymes: Generation of Antinflammatory and Antiproliferative Metabolites, Am. J. Clin. Nutr. 71, 361S-366S.PubMedGoogle Scholar
  49. 49.
    Koch, T., Krumm, T., Jung, V., Engelberth, J., and Boland, W. (1999) Differential Induction of Plant Volatile Biosynthesis in the Lima Bean by Early and Late Intermediates of the Octadecanoid-Signaling Pathway, Plant Physiol. 121, 153–162.PubMedCrossRefGoogle Scholar
  50. 50.
    Martin, M., Leon, J., Dammann, C., Albar, J.P., Griffiths, G., and Sanchez-Serrano, J.J. (1999) Anti-sense Depletion of Potato Leaf Omega 3 Fatty Acid Desaturase Lowers Linolenic Acid Content and Reduces Gene Activation in Response to Wounding, Eur. J. Biochem. 262, 283–290.PubMedCrossRefGoogle Scholar
  51. 51.
    Imbusch, R., and Mueller, M.J. (2000) Formation of Isoprostane F2-like Compounds from α-Linolenic Acid in Plants, Free Radic. Biol. Med. 28, 720–726.PubMedCrossRefGoogle Scholar
  52. 52.
    Yokoyama, M., Yamaguchi, S., Inomata, S., Komatsu, K., Yoshida, S., Iida, T., Yokokawa, Y., Yamaguchi, M., Kaihara, S., and Takimoto, A. (2000) Stress-Induced Factor in Flower Formation of Lemna Is an α-Ketol Derivative of Linolenic Acid, Plant Cell Physiolol. 41, 110–113.Google Scholar
  53. 53.
    Baudouin, E., Meskiene, I., and Hirt, H. (1999) Unsaturated Fatty Acids Inhibit MP2C, a Protein Phosphatase 2C Involved in the Wound-Induced MAP Kinase Pathway Regulation, Plant J. 20, 343–348.PubMedCrossRefGoogle Scholar
  54. 54.
    Cunnane, S.C., Menard, C.R., Likhodii, S.S., Brenna, J.T., and Crawford, M.A. (1999) Carbon Recycling into de novo Lipogenesis Is a Major Pathway in Neonatal Metabolism of Linoleate and α-Linolenate, Prostaglandins Leukot. Essent. Fatty Acids 60, 387–392.PubMedCrossRefGoogle Scholar
  55. 55.
    Rokkones, T. (1953) A Dietary Factor Essential for Hair Growth in Rats, Intern. Z. Vitaminforsch. 25, 86–98.Google Scholar
  56. 56.
    Fiennes, R.N.T.W., Sinclair, A.J., and Crawford, M.A. (1973) Essential Fatty Acid Studies in Primates. Linolenic Acid Requirements of Capuchins, J. Med. Prim. 2, 155–169.Google Scholar
  57. 57.
    Fu, Z., and Sinclair, A.J. (2000) Novel Pathway of Metabolism of α-Linolenic Acid in the Guinea Pig, Pediatr. Res. 47, 414–417.PubMedGoogle Scholar
  58. 58.
    Leyton, J., Drury, P.J., and Crawford, M.A. (1987) Differential Oxidation of Saturated and Unsaturated Fatty Acids in vivo in the Rat, Br. J. Nutr. 57, 383–393.PubMedCrossRefGoogle Scholar
  59. 59.
    Vermunt, S.H., Mensink, R.P., Simonis, M.M., and Hornstra, G. (2000) Effects of Dietary α-Linolenic Acid on the Conversion and Oxidation of 13C-α-Linolenic Acid, Lipids 35, 137–142.PubMedGoogle Scholar
  60. 60.
    Brenna, J.T. (2002) Efficiency of Conversion of α-Linolenic Acid to Long Chain n-3 Fatty Acids in Man, Curr. Opin. Clin. Nutr. Metab. Care 5, 127–132.PubMedCrossRefGoogle Scholar
  61. 61.
    DeLany, J.P., Windhauser, M.M., Champagne, C.M., and Bray, G.A. (2000) Differential Oxidation of Individual Dietary Fatty Acids in Humans, Am. J. Clin. Nutr. 79, 905–911.Google Scholar
  62. 62.
    Sinclair, A.J. (1975) Incorporation of Radioactive Polyunsaturated Fatty Acids into Liver and Brain of the Developing Rat, Lipids 10, 175–184.PubMedGoogle Scholar
  63. 63.
    Menard, C.R., Goodman, K.J., Corso, T.N., Brenna, J.T., and Cunnane, S.C. (1998) Recycling of Carbon into Lipids Synthesized de novo Is a Quantitatively Important Pathway of α-[U-13C]Linolenate Utilization in the Developing Rat Brain, J. Neurochem. 71, 2151–2180.PubMedCrossRefGoogle Scholar
  64. 64.
    Edmond, J., Higa, T.A., Korsack, R.A., Bergner, E.A., and Lee, W.-N.P. (1998) Fatty Acid Transport and Utilization for the Developing Brain, J. Neurochem. 70, 1227–1234.PubMedCrossRefGoogle Scholar
  65. 65.
    Voss, A.M., Reinhart, S., Sankarappa, S., and Sprecher, H. (1991) Metabolism of 22:5n-3 to 22:6n-3 in Rat Liver Is Independent of 4-Desaturase, J. Biol. Chem. 266, 19995–20000.PubMedGoogle Scholar
  66. 66.
    Moore, S.A., Hurt, E., Yoder, E., Sprecher, H., and Spector, A.A. (1995) Docosahexaenoic Acid Synthesis in Human Skin Fibroblasts Involves Peroxisomal Retroconversion of Tetracosahexaenoic Acid, J. Lipid Res. 36, 2433–2443.PubMedGoogle Scholar
  67. 67.
    Martinez, M., Vazquez, E., Garcia-Silva, M.T., Manzanares, J., Bertran, J.M., Castello, F., and Mougan, I. (2000) Therapeutic Effects of Docosahexaenoic Acid Ethyl Ester in Patients with Generalized Peroxisomal Disorders, Am. J. Clin. Nutr. 71, 376S-385S.PubMedGoogle Scholar
  68. 68.
    Bowen, R.A., and Clandinin, M.T. (2000) 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, Lipids 35, 389–394.PubMedCrossRefGoogle Scholar
  69. 69.
    Poumès-Ballihaut, C., Langelier, B., Houlier, F., Alessandri, J., Durand, G., Latge, C., and Guesnet, P. (2001) Comparative Bioavailability of Dietary α-Linolenic Acid and Docosahexaenoic Acid in the Growing Rat, Lipids 36, 793–800.PubMedCrossRefGoogle Scholar
  70. 70.
    Thiele, J.J., Weber, S.U., and Packer, L.L. (1999) Sebaceous Gland Secretion Is a Major Physiologic Route of Vitamin E Delivery to Skin, J. Invest. Dermatol. 113, 1006–1010.PubMedCrossRefGoogle Scholar
  71. 71.
    Lloyd, D.H. (1989) Essential Fatty Acids and Skin Disease, J. Small Anim. Prac. 30, 207–212.Google Scholar
  72. 72.
    Ando, H., Ryu, A., Hashimoto, A., Oka, M., and Ichihashi, M. (1998) Linoleic Acid and α-Linolenic Acid Lighten Ultraviolet-Induced Hyperpigmentation of the Skin, Arch. Dermatol. Res. 290, 375–381.PubMedCrossRefGoogle Scholar
  73. 73.
    Hartop, P.J., and Prottey, C. (1976) Changes in Transepidermal Water Loss and the Composition of Epidermal Lecithin After Applications of Pure Fatty Acid Triglycerides to the Skin of Essential Fatty Acid Deficient Rats, J. Dermatol. 95, 255–264.CrossRefGoogle Scholar
  74. 74.
    Reisbick, S., Neuringer, M., and Connor, W.E. (1992) Postnatal Deficiency of Omega-3 Fatty Acids in Monkeys: Fluid Intake and Urine Concentration, Physiol. Behav. 51, 473–479.PubMedCrossRefGoogle Scholar
  75. 75.
    Armitage, J.A., Burns, P., Sinclair, A.J., Weisinger, H.S., Vingrys, A.J., and Weisinger, R.S. (2000) Perinatal Omega 3 Fatty Acid Deprivation Alters Thirst and Sodium Appetite in Adult Rats, Appetite 37, 258.Google Scholar
  76. 76.
    Weisinger, H.S., Armitage, J.A., Sinclair, A.J., Vingrys, A.J., Burns, P., and Weisinger, R.S. (2001) Peri-natal Omega 3 Fatty Acid Deficiency Affects Blood Pressure, Fluid and Metabolite Homeostasis, Nature Med. 7, 258–259.PubMedCrossRefGoogle Scholar
  77. 77.
    Langley-Evans, S.C. (2000) Critical Differences Between Two Low Protein Diet Protocols in the Programming of Hypertension in the Rat, Int. J. Food Sci. Nutr., 51, 11–17.PubMedCrossRefGoogle Scholar
  78. 78.
    Gerster, H. (1998) Can Adults Adequately Convert α-Linolenic Acid to Eicosapentaenoic Acid and Docosahexaenoic Acid? Internat. J. Vit. Nutr. Res. 68, 159–173.Google Scholar
  79. 79.
    Abedin, L., Lien, E.L., Vingrys, A.J., and Sinclair, A.J. (1999) The Effects of Dietary α-Linolenic Acid Compared with Docosahexaenoic Acid on Brain, Retina, Liver, and Heart in the Guinea Pig, Lipids 34, 475–482.PubMedCrossRefGoogle Scholar
  80. 80.
    Greiner, R.C., Winter, J., Nathanielsz, P.W., and Brenna, J.T. (1997) Brain Docosahexaenoate Accretion in Fetal Baboons: Bioequivalence of Dietary α-Linolenic and Docosahexaenoic Acids, Pediatr. Res. 42, 826–834.PubMedGoogle Scholar
  81. 81.
    Su, H.M., Bernardo, L., Mirmiran, M., Ma, X.H., Nathanielsz, P.W., and Brenna, J.J. (1999) Dietary 18∶3n-3 and 22∶6n-3 as Sources of 22∶6n-3 Accretion in Neonatal Baboon Brain and Associated Organs, Lipids 34, S347-S350.PubMedGoogle Scholar
  82. 82.
    Woods, J., Ward, G., and Salem, N., Jr. (1996) Is Docosahexaenoic Acid Necessary in Infant Formulas? Evaluation of High Linolenate Diets in the Neonatal Rat, Pediatr. Res. 40, 687–694.PubMedGoogle Scholar
  83. 83.
    Su, H.M., Huang, M.C., Saad, N.M., Nathanielsz, P.W., and Brenna, J.T. (2001) Fetal Baboons Convert 18∶3n-3 to 22∶6n-3 in vivo: A Stable Isotope Tracer Study, J. Lipid Res. 42, 581–586.PubMedGoogle Scholar
  84. 84.
    Fu, Z., and Sinclair, A.J. (2000) Increased α-Linolenic Acid Intake Increases Tissue α-Linolenic Acid Content and Apparent Oxidation with Little Effect on Tissue Docosahexaenoic Acid in the Guinea Pig, Lipids 35, 395–400.PubMedCrossRefGoogle Scholar
  85. 85.
    Li, D., Sinclair, A., Wilson, A., Nakkote, S., Kelly, F., Abedin, L., Mann, N., and Turner, A. (1999) Effect of Dietary α-Linolenic acid on Thrombotic Risk Factors in Vegetarian Men, Am. J. Clin. Nutr. 69, 872–882.PubMedGoogle Scholar
  86. 86.
    Mantzioris, E., James, M.J., Gibson, R.A., and Cleland, L.G. (1994) Dietary Substitution with an α-Linolenic Acid-rich Vegetable Oil Increases Eicosapentaenoic Acid Concentrations in Tissues, Am. J. Clin. Nutr. 59, 1304–1309.PubMedGoogle Scholar
  87. 87.
    Emken, E.A., Adlof, R.O., and Gulley, G.M. (1994) Dietary Linoleic Acid Influences the Desaturation and Acylation of Deuterium-Labelled Linoleic and α-Linolenic Acid in Young Adult Males, Biochim. Biophys. Acta 1213, 277–288.PubMedGoogle Scholar
  88. 88.
    Pawlosky, R.J., Hibbeln, J.R., Novotny, J.A., and Salem, N., Jr. (2001) Physiological Compartmental Analysis of α-Linolenic Acid Metabolism in Adult Humans, J. Lipid Res. 42, 1257–1265.PubMedGoogle Scholar
  89. 89.
    Burdge, G.C., and Wootton, S.A. (2002) Conversion of α-Linolenic Acid to Eicosapentaenoic, Docosapentaenoic and Docosahexaenoic Acids in Young Women, Br. J. Nutr. 88, 411–420.PubMedGoogle Scholar
  90. 90.
    Burdge, G.C., Jones, A.E., and Wootton, S.A. (2002) Eicosapentaenoic and Docosapentaenoic Acids Are the Principal Products of α-Linolenic Acid Metabolism in Young Men, Br. J. Nutr. 88, 355–363.PubMedCrossRefGoogle Scholar
  91. 91.
    Adam, O., Wolfram, G., and Zollner, N. (1986) Effect of α-Linolenic Acid in the Human Diet on Linoleic Acid Metabolism and Prostaglandin Biosynthesis, J. Lipid Res. 27, 421–426.PubMedGoogle Scholar
  92. 92.
    Mest, H.J., Beitz, J., Heinroth, I., Block, H.U., and Forster, W. (1983) The Influence of Linseed Diet on Fatty Acid Pattern in Phospholipids and Thromboxane Formation in Platelets in Man, Klin. Wochenschr. 61, 187–191.PubMedCrossRefGoogle Scholar
  93. 93.
    Ezaki, O., Takahashi, M., Shigematsu, T., Shimamura, K., Kimura, J., Ezaki, H., and Gotoh, T. (1999) Long-Term Effects of Dietary α-Linolenic Acid from Perilla Oil on Serum Fatty Acid Composition and on the Risk Factors of Coronary Heart Disease in Japanese Elderly Subjects, J. Nutr. Sci. Vitaminol. 45, 759–762.PubMedGoogle Scholar
  94. 94.
    Cho, H.P., Nakamura, M.T., and Clarke, S.D. (1999) Cloning, Expression, and Nutritional Regulation of the Mammalian Δ6-Desaturase, J. Biol. Chem. 274, 471–477.PubMedCrossRefGoogle Scholar
  95. 95.
    O'Dea, K., Steel, M., Naughton, J.M., Sinclair, A.J., Hopkins, G., Angus, J., He, G.-W., Niall, M., and Martin, T.J. (1988) Butter-Enriched Diets Reduce Arterial Prostacyclin-Production in Rats, Lipids 23, 234–241.PubMedGoogle Scholar
  96. 96.
    Salem, N., Jr., Wegher, B., Mena, P., and Uauy, R. (1996) Arachidonic and Docosahexaenoic Acids Are Biosynthesized from Their 18-Carbon Precursors in Human Infants, Proc. Natl. Acad. Sci. USA 93, 49–54.PubMedCrossRefGoogle Scholar
  97. 97.
    Uauy, R., Mena, P., Wegher, B., Nieto, S., and Salem, N., Jr. (2000) Long Chain Polyunsaturated Fatty Acid Formation in Neonates: Effect of Gestational Age and Intrauterine Growth, Pediatr. Res. 47, 127–135.PubMedGoogle Scholar
  98. 98.
    Cunnane, S.C., Francescutti, V., Brenna, J.T., and Crawford, M.A. (2000) Breast-fed Infants Achieve a Higher Rate of Brain and Whole Body Docosahexaenoate Accumulation Than Formula-Fed Infants Not Consuming Dietary Docosahexaenoate, Lipids 35, 105–111.PubMedCrossRefGoogle Scholar
  99. 99.
    Balendiran, G.K., Schnutgen, F., Scapin, G., Borchers, T., Xhong, N., Lim, K., Godbout, R., Spener, F., and Sacchettini, J.C. (2000) Crystal Structure and Thermodynamic Analysis of Human Brain Fatty Acid-Binding Protein, J. Biol. Chem. 275, 27045–27054.PubMedGoogle Scholar
  100. 100.
    Pawlosky, R., Barnes, A., and Salem, N., Jr. (1994) Essential Fatty Acid Metabolism in the Feline: Relationship Between Liver and Brain Production of Long-Chain Polyunsaturated Fatty Acids, J. Lipid Res. 35, 2032–2040.PubMedGoogle Scholar
  101. 101.
    Cho, H.P., Nakamura, M., and Clarke, S.D. (1999) Cloning, Expression, and Fatty Acid Regulation of the Human Δ5-Desaturase, J. Biol. Chem. 274, 37335–37339.PubMedCrossRefGoogle Scholar
  102. 102.
    Weisinger, H.S., Vingrys, A.J., and Sinclair, A.J. (1996) The Effect of Docosahexaenoic Acid on the Electroretinogram of the Guinea Pig, Lipids 31, 65–70.PubMedCrossRefGoogle Scholar
  103. 103.
    Jeffrey, B.G., Mitchell, D.C., Gibson, R.A., and Neuringer, M. (2002) n-3 Fatty Acid Deficiency Alters Recovery of the Rod Photoresponse in Rhesus Monkeys, Invest. Ophthalmol. Vis. Sci. 43, 2806–2814.PubMedGoogle Scholar
  104. 104.
    Jeffrey, B.G., Mitchell, D.C., Hibbeln, J.R., Gibson, R.A., Chedester, A.L., and Salem, N., Jr. (2002) Visual Acuity and Retinal Function in Infant Monkeyas Fed Long-Chain PUFA, Lipids 37, 839–848.PubMedCrossRefGoogle Scholar
  105. 105.
    De Deckere, E.A.M., Korver, O., Verschuren, P.M., and Katan, M. (1998) Health Aspects of Fish and n-3 Polyunsaturated Fatty Acids from Plant and Marine Origin, Eur. J. Clin. Nutr. 52, 749–753.PubMedCrossRefGoogle Scholar
  106. 106.
    Mori, T.A., Bao, D.Q., Burke, V., Puddey, I.B., and Beilin, L.J. (1999) Docosahexaenoic Acid but Not Eicosapentaenoic Acid Lowers Ambulatory Blood Pressure and Heart Rate in Humans, Hypertension 34, 253–260.PubMedGoogle Scholar
  107. 107.
    Kang, J.X., and Leaf, A. (2000) Prevention of Fatal Cardiac Arrhythmias by Polyunsaturated Fatty Acids, Am. J. Clin. Nutr. 71, 202S-207S.PubMedGoogle Scholar
  108. 108.
    Price, P.T., Nelso, C.M., and Clarke, S.D. (2000) Omega 3 Polyunsaturated Fatty Acid Regulation of Gene Expression, Curr. Opin. Lipidol. 11, 3–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Singh, R.B., Niaz, M.A., Sharma, J.P., Kumar, R., Rastogi, V., and Moshiri, M. (1997) Randomized, Double-Blind, Placebo-Controlled Trial of Marine Omega-3 Oil and Mustard Oil in Patients with Suspected Acute Myocardial Infarction: The Indian Experiment of Infarct Survival-4, Cardiovasc. Drugs Therap. 11, 485–491.CrossRefGoogle Scholar
  110. 110.
    De Lorgeril, M., Salen, P., Martin, J.-L., Moniaud, I., Delaye, I., and Mamelle, N. (1999) Mediterranean Diet, Traditional Risk Factors and Rate of Cardiovascular Complications After Myocardial Infarction: Final Report of the Lyon Diet Heart Study, Circulation 99, 779–785.PubMedGoogle Scholar
  111. 111.
    GISSI-Prevenzione Investigators (1999) Dietary Supplementation with n-3 Polyunsaturated Fatty Acids and Vitamin E After Myocardial Infarction: Results of the GISSI-Prevenzione Trial, The Lancet 354, 447–455.CrossRefGoogle Scholar
  112. 112.
    Djousse, L., Pankow, J.S., Eckfeldt, J.H., Folsom, A.R., Hopkins, P.N., Province, M.A., Hong, Y., and Ellison, R.C. (2001) Relation Between Dietary Linolenic Acid and Coronary Artery Disease in the National Heart, Lung, and Blood Institute Family Heart Study, Am. J. Clin. Nutr. 74, 612–619.PubMedGoogle Scholar
  113. 113.
    Billman, G.E., Kang, J.X., and Leaf, A. (1999) Prevention of Sudden Cardiac Death by Dietary Pure Omega-3 Polyunsaturated Fatty Acids in Dogs, Circulation 99, 2452–2457.PubMedGoogle Scholar
  114. 114.
    Renaud, S., and Nordoy, A. (1983) “Small Is Beautiful”: α-Linolenic Acid and Eicosapentaenoic Acid in Man, The Lancet (May 21), 1169.Google Scholar
  115. 115.
    Dolecek, T.A. (1992) Epidemiological Evidence of Relationships Between Dietary PUFA and Mortality in the Multiple Risk Factor Intervention Trial, Proc. Soc. Exp. Biol. Med. 200, 177–182.PubMedGoogle Scholar
  116. 116.
    Hu, F.B., Stampfer, M.J., Manson, J.E., Rimm, E.B., Wolk, A., Colditz, G.A., Hennekens, C.H., and Willett, W.C. (1999) Dietary Intake of α-Linolenic Acid and Risk of Fatal Ischemic Heart Disease Among Women, Am. J. Clin. Nutr. 69, 890–897.PubMedGoogle Scholar
  117. 117.
    Ferretti, A., and Flanagan, V.P. (1996) Antithromboxane Activity of Dietary α-Linolenic Acid: A Pilot Study, Prostaglandins Leukot. Essent. Fatty Acids 54, 451–455.PubMedCrossRefGoogle Scholar
  118. 118.
    Appel, L.J., Miller, E.R., 3rd, Seidler, A.J., and Whelton, P.K. (1993) Does Supplementation of Diet with “Marine Omega 3 Oil” Reduce Blood Pressure? A Meta-analysis of Controlled Clinical Trials, Arch. Intern. Med. 153, 1429–1438.PubMedCrossRefGoogle Scholar
  119. 119.
    Nestel, P.J., Pomeroy, S.E., Sasahara, T., Yamashita, T., Liang, Y.L., Dart, A.M., Jennings, G.L., Abbey, M., and Cameron, J.D. (1997) Arterial Compliance in Obese Subjects Is Improved with Dietary Plant n-3 Fatty Acid from Flaxseed Oil Despite Increased LDL Oxidizability, Arterioscler. Thromb. Vasc. Biol. 17, 1163–1170.PubMedGoogle Scholar
  120. 120.
    McLellan, P.L., Abewardena, M.Y., and Charnock, J.S. (1988) Dietary Marine Omega 3 Oil Prevents Ventricular Fibrillation Following Coronary Artery Occlusion and Reperfusion, Am. Heart J. 116, 709–717.CrossRefGoogle Scholar
  121. 121.
    Billman, G.E., Kang, J.X., and Leaf, A. (1997) Prevention of Ischemia-Induced Cardiac Sudden Death by n-3 Polyunsaturated Fatty Acids in Dogs, Lipids 32, 1161–1168.PubMedCrossRefGoogle Scholar
  122. 122.
    Singh, R.B., Dubnov, G., Niaz, M.A., Ghosh, S., Singh, R., Rastogi, S.S., Manor, O., Pella, D., and Berry, E. (2002) Effect of an Indo-Mediterranean Diet on Progression of Coronary Artery Disease in High Risk Patients (Indo-Mediterranean Diet Heart Study): A Randomized Single-Blind Trial, Lancet 360, 1455–1466.PubMedCrossRefGoogle Scholar
  123. 123.
    Giovannucci, E., Rimm, E.B., Colditz, G.A., Stampfer, M., Ascherio, A., Chute, C.C., and Willett, W. (1993) A Prospective Study of Dietary Fat and Risk of Prostate Cancer, J. Natl. Cancer Inst. 85, 1571–1579.PubMedGoogle Scholar
  124. 124.
    De Stéfani, E., Deneo-Pellegrini, H., Boffetta, P., Ronco, A., and Mendilaharsu, M. (2000) α-Linolenic Acid and Risk of Prostate Cancer: A Case-Control Study in Uruguay, Cancer Epidemiol. Biomarkers Prev. 9, 335–338.PubMedGoogle Scholar
  125. 125.
    Ramon, J.M., Ricard, B., Romea, S., Alkiza, M.E., Jacas, M., Ribes, J., and Oromi, J. (2000) Dietary Intake and Prostate Cancer Risk: A Case-Control Study in Spain, Cancer Causes Control 11, 679–685.PubMedCrossRefGoogle Scholar
  126. 126.
    Gann, P.H., Hennekens, C.H., Sacks, F.M., Grodstein, F., Giovannucci, E.L., and Stampfer, M.J. (1994) Prospective Study of Plasma Fatty Acids and Risk of Prostate Cancer, J. Natl. Cancer Inst. 86, 281–286.PubMedGoogle Scholar
  127. 127.
    Harvei, S., Bjerve, K.S., Tretli, S., Jellum, E., Robsahm, T.E., and Vatten, L. (1997) Prediagnostic Level of Fatty Acids in Serum Phospholipids: ω-3 and ω-6 Fatty Acids and the Risk of Prostate Cancer, Int. J. Cancer 71, 545–551.PubMedCrossRefGoogle Scholar
  128. 128.
    Newcomer, L.M., King, I.B., Wicklund, K.G., and Stanford, J.L. (2001) The Association of Fatty Acids with Prostate Cancer, The Prostate 47, 262–268.PubMedCrossRefGoogle Scholar
  129. 129.
    Andersson, S.O., Wolk, A., Bergstrom, R., Giovannucci, E., Lindgren, C., Baron, J., and Adami, H.O. (1996) Energy, Nutrition Intake and Prostate Cancer Risk: A Population-Based Case-Control Study in Sweden, Int. J. Cancer 68, 716–722.PubMedCrossRefGoogle Scholar
  130. 130.
    Alberg, A.J., Kafonek, S., Huang, H.Y., Hoffman, S.C., Comstock, G.W., and Helzlsouer, K.J. (1996) Fatty Acid Levels and the Subsequent Development of Prostate Cancer, Proc. Am. Assoc. Cancer Res. 37, 281.Google Scholar
  131. 131.
    Godley, P.A., Campbell, M.K., Gallagher, P., Martinson, F.E., Mohler, J.L., and Sandler, R.S. (1996) Biomarkers of Essential Fatty Acid Consumption and Risk of Prostatic Carcinoma, Cancer Epidemiol. Biomarkers Prev. 5, 889–895.PubMedGoogle Scholar
  132. 132.
    Schuurman, A.G., van den Brandt, P.A., Dorant, E., Brants, H.A.M., and Goldbohm, R.A. (1999) Association of Energy and Fat Intake with Prostate Carcinoma Risk: Results from the Netherlands Cohort Study, Cancer 86, 1019–1027.PubMedCrossRefGoogle Scholar
  133. 133.
    Freeman, V.L., Meydani, M., Yong, S., Pyle, J., Flanigan, R.C., Waters, B., and Wojcik, E.M. (2000) Prostatic Levels of Fatty Acids and the Histopathology of Localized Prostate Cancer, J. Urology 164, 2168–2172.CrossRefGoogle Scholar
  134. 134.
    Cave, W.T., Jr. (1991) Dietary n-3 (ω-3) Polyunsaturated Fatty Acid Effects on Animal Tumorigenesis, FASEB J. 5, 2160–2166.PubMedGoogle Scholar
  135. 135.
    Liang, T., and Liao, S. (1992) Inhibition of Steroid 5α-Reductase by Specific Aliphatic Unsaturated Fatty Acids, Biochem. J. 285, 557–562.PubMedGoogle Scholar
  136. 136.
    Marshall, L.A., Szczesniewski, A., and Johnston, P.V. (1983) Dietary α-Linolenic Acid and Prostaglandin Synthesis: A Time Course Study, Am. J. Clin. Nutr. 38, 895–900.PubMedGoogle Scholar
  137. 137.
    Klein, V., Chajes, V., Germain, E., Schulgen, G., Pinault, M., Malvy, D., Lefrancq, T., Fignon, A., Le Floch, O., Lhuillery, C., and Bougnoux, P. (2000) Low α-Linolenic Acid Content of Adipose Breast Tissue Is Associated with an Increased Risk of Breast Cancer, Eur. J. Cancer 36, 335–340.PubMedCrossRefGoogle Scholar
  138. 138.
    Maillard, V., Bougnoux, P., Ferrari, P., Jourdain, M.L., Pinault, M., Lavillonniere, F., Body, G., Le Floch, O., and Chajes, V. (2002) n-3 and n-6 Fatty Acids in Breast Adipose Tissue and Relative Risk of Breast Cancer in a Case-Control Study in Tours, France, Int. J. Cancer 98, 78–93.PubMedCrossRefGoogle Scholar
  139. 139.
    Cognault, S., Jourdan, M.L., Germain, E., Pitavy, R., Morel, E., Durand, G., Bougnoux, P. and Lhuillery, C. (2000) Effect of an α-Linolenic Acid-Rich Diet on Rat Mammary Tumor Growth Depends on the Dietary Oxidative Status, Nutr. Cancer 36, 33–41.PubMedCrossRefGoogle Scholar
  140. 140.
    Holman, R.T., Johnson, S.B., and Hatch, T.F. (1982) A Case of Human Linolenic Acid Deficiency Involving Neurological Abnormalities, Am. J. Clin. Nutr. 35, 617–623.PubMedGoogle Scholar
  141. 141.
    Bjerve, K.S., Thoresen, L., and Borsting, S. (1998) Linseed and Cod Liver Oil Induce Rapid Growth in a 7-Year-Old Girl with n-3 Fatty Acid Deficiency, JPEN J. Parenter. Enteral Nutr. 12, 521–525.CrossRefGoogle Scholar
  142. 142.
    NHMRC: Report of Working Party (1992) The Role of Polyunsaturated Fatty Acids in the Australian Diet, Australian Government Publishing Service, Canberra.Google Scholar
  143. 143.
    Simopoulos, A.P., Leaf, A., and Salem, N. (2000) Workshop Statement on the Essentiality of and Recommended Intakes for Omega 6 and Omega 3 Fatty Acids, Prostaglandins Leukot. Essent. Fatty Acids 63, 119–121.PubMedCrossRefGoogle Scholar
  144. 144.
    Lands, W.E.M., Libelt, B., Morris, A., Kramer, N.C., Prewitt, T.E., Bowen, P., Schmeisser, D., and Davidson, M.H. (1992) Maintenance of Lower Proportions of (n-6) Eicosanoid Precursors in Phospholipids of Human Plasma in Response to Added Dietary (n-3) Fatty Acids, Biochim. Biophys. Acta 1180, 147–162.PubMedGoogle Scholar
  145. 145.
    Blank, C., Neumann, M.A., Makrides, M., and Gibson, R.A. (2002) Optimizing DHA Levels in Piglets by Lowering the Linoleic Acid to α-Linolenic Acid Ratio, J. Lipid Res. 43, 1537–1543.PubMedCrossRefGoogle Scholar

Copyright information

© AOCS Press 2002

Authors and Affiliations

  • Andrew J. Sinclair
    • 1
  • Nadia M. Attar-Bashi
    • 1
  • Duo Li
    • 2
  1. 1.Department of Food ScienceRMIT UniversityMelbourneAustralia
  2. 2.Department of Food ScienceHangzhou University of CommerceChina

Personalised recommendations