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.
Similar content being viewed by others
Abbreviations
- ALA:
-
α-linolenic acid
- CE:
-
cholesterol ester
- DPA:
-
docosapentaenoic acid
- PG:
-
prostaglandin
References
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.
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.
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.
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.
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).
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.
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.
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.
Holman, R.T. (1968) Biological Activities of and Requirements for Polyunsaturated Fatty Acids, Prog. Chem. Fats Other Lipids 9, 611–680.
Yamamoto, S., and Smith, W.I. (2002) Molecular Biology of the Arachidonate Cascade (second edition), Prostaglandins Other Lipid Mediat. 68–69, 1 (Preface).
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.
Burr, G.O. (1942) Significance of the Essential Fatty Acids, Fed. Proc. 1, 224–233.
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.
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.
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.
Crawford, M.A., and Sinclair, A.J. (1972) The Limitations of Whole Tissue Analysis to Define Linolenic Acid Deficiency, J. Nutr. 102, 1315–1322.
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.
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.
Fleisler, S.J., and Anderson, R.E. (1983) Chemistry and Metabolism of Lipids in the Vertebrate Retina, Prog. Lipid Res. 22, 79–131.
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.
Sinclair, A.J. (2000) Commentary on the Workshop Statement, Prostaglandins, Leukot. Essent. Fatty Acids 63, 135–137.
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.
Salem, N., Jr., and Ward, G.R. (1993) Are Omega-3 Fatty Acids Essential Nutrients for Mammals? World Rev. Nutr. Dietet. 72, 128–147.
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.
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.
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.
Ahmad, A., Moriguchi, T., and Salem, N., Jr. (2002) Decrease in Neuron Size in Docosahexaenoic Acid-Deficient Brain, Pediatr. Neurol. 26, 210–218.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Mostofsky, D.I., Yehuda, S., Rabinovitz, S., and Carasso, R. (2000) The Control of Blepharospasm by Essential Fatty Acids Neuropsychobiology 41, 154–157.
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.
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.
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.
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.
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.
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.
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.
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.
Rokkones, T. (1953) A Dietary Factor Essential for Hair Growth in Rats, Intern. Z. Vitaminforsch. 25, 86–98.
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.
Fu, Z., and Sinclair, A.J. (2000) Novel Pathway of Metabolism of α-Linolenic Acid in the Guinea Pig, Pediatr. Res. 47, 414–417.
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.
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.
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.
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.
Sinclair, A.J. (1975) Incorporation of Radioactive Polyunsaturated Fatty Acids into Liver and Brain of the Developing Rat, Lipids 10, 175–184.
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.
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.
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.
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.
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.
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.
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.
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.
Lloyd, D.H. (1989) Essential Fatty Acids and Skin Disease, J. Small Anim. Prac. 30, 207–212.
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.
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.
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.
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.
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.
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.
Gerster, H. (1998) Can Adults Adequately Convert α-Linolenic Acid to Eicosapentaenoic Acid and Docosahexaenoic Acid? Internat. J. Vit. Nutr. Res. 68, 159–173.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kang, J.X., and Leaf, A. (2000) Prevention of Fatal Cardiac Arrhythmias by Polyunsaturated Fatty Acids, Am. J. Clin. Nutr. 71, 202S-207S.
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.
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.
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.
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.
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.
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.
Renaud, S., and Nordoy, A. (1983) “Small Is Beautiful”: α-Linolenic Acid and Eicosapentaenoic Acid in Man, The Lancet (May 21), 1169.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Cave, W.T., Jr. (1991) Dietary n-3 (ω-3) Polyunsaturated Fatty Acid Effects on Animal Tumorigenesis, FASEB J. 5, 2160–2166.
Liang, T., and Liao, S. (1992) Inhibition of Steroid 5α-Reductase by Specific Aliphatic Unsaturated Fatty Acids, Biochem. J. 285, 557–562.
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.
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.
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.
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.
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.
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.
NHMRC: Report of Working Party (1992) The Role of Polyunsaturated Fatty Acids in the Australian Diet, Australian Government Publishing Service, Canberra.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Sinclair, A.J., Attar-Bashi, N.M. & Li, D. What is the role of α-linolenic acid for mammals?. Lipids 37, 1113–1123 (2002). https://doi.org/10.1007/s11745-002-1008-x
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-002-1008-x