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The conditional nature of the dietary need for polyunsaturates: a proposal to reclassify ‘essential fatty acids’ as ‘conditionally-indispensable’ or ‘conditionally-dispensable’ fatty acids

Published online by Cambridge University Press:  09 March 2007

Stephen C. Cunnane
Stephen C. Cunnane*
Affiliation:
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto M5S 3E2, Canada.
*
*Corresponding author: Dr S.C. Cunnane, fax +1 416978 5882, email s.cunnane@utoronto.ca
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Abstract

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The term essential fatty acid no longer clearly identifies the fatty acids it was originally used to describe. It would be more informative if the concept of essentiality shifted away from the symptoms arising from the lack of de novo synthesis of linoleate or α-linolenate and towards the adequacy of the capacity for synthesis and conservation of both the parent and the derived long-chain polyunsaturates. For instance, despite the existence of the pathway for synthesis of docosahexaenoate from α-linolenate, the former would be more correctly classified as ‘conditionally indispensable’ because the capacity of the pathway appears insufficient during early development, although it may be sufficient later in life in healthy individuals. Similarly, despite the inability to synthesize linoleate de novo, abundant linoleate stores and its relatively slow turnover in healthy adults probably makes linoleate ‘conditionally dispensable’ for long periods. There are two other anomalies with the terms essential and non-essential fatty acids: (1) under several different experimental circumstances, the C-skeleton of essential fatty acids is avidly used in the synthesis of non-essential fatty acids; (2) to function normally, the brain is required to endogenously synthesize several non-essential fatty acids. As with essential amino acids, which have been reclassified as indispensable or conditionally indispensable, such a change in terminology should lead to an improved understanding of the function and metabolism of polyunsaturates in particular, and long-chain fatty acids in general.

Keywords

PolyunsaturatesEssential fatty acidsLinoleate-Linolenate
Type
Review article
Information
British Journal of Nutrition , Volume 84 , Issue 6 , December 2000 , pp. 803 - 812
Copyright
Copyright © The Nutrition Society 2000

References

Aaes-Jorgensen, E (1961) Essential fatty acids. Physiological Reviews 41, 1–51.Google Scholar
Ackman, RG, Cunnane, SC (1991) Long-chain polyunsaturated fatty acids. In Advances in Applied Lipid Research vol. 1x, pp. 161–215 [Padley, FB editors]. London: JAI Press.Google Scholar
Agostoni, C, Trojan, S, Bellu, R, Riva, E & Giovannini, M (1995) Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: The role of long-chain polyunsaturated fatty acids. Pediatric Research 38, 262–266.Google Scholar
Alfin-Slater, RB & Aftergood, L (1968) Essential fatty acids reinvestigated. Physiological Reviews 48, 758–784.Google Scholar
Arbuckle, LD, MacKinnon, MJ & Innis, SM (1994) Formula 18:2n-6 and 18:3n-3 content and ratio influence long-chain polyunsaturated fatty acids in developing piglet liver and central nervous system. Journal of Nutrition 124, 289–298.Google Scholar
Birch, EE, Hoffman, DR, Uauy, R, Birch, DG & Prestidge, C (1998) Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants. Pediatric Research 44, 201–209.CrossRefGoogle ScholarPubMed
Bjerve, KS, Thoresen, L & Borsting, S (1988) Linseed and cod liver oil induce rapid growth in a 7-year-old girl with n-3 fatty acid deficiency. Journal of Parenteral and Enteral Nutrition 12, 521–525.Google Scholar
Bougnoux, P, Koscielny, S, Chajes, V, Descamps, P, Couet, C & Calais, G (1994) Alpha-linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. British Journal of Cancer 70, 330–334.CrossRefGoogle Scholar
Bourre, J-M, Dumont, O, Clement, ME & Durand, G (1997) Endogenous synthesis cannot compensate for absence of dietary oleic acid in rats. Journal of Nutrition 127, 488–493.CrossRefGoogle ScholarPubMed
Bourre, J-M, Francois, M, Youyou, A, Dumont, O, Piciotti, M, Pascal, G & Durand, G (1989) The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons, and performance of learning tasks in rats. Journal of Nutrition 119, 1880–1892.Google Scholar
Bourre, J-M, Piciotti, M, Dumont, O, Pascal, G & Durand, G (1990) Dietary linoleic acid and polyunsaturated fatty acids in rat brain and other organs. Minimal requirements of linoleic acid. Lipids 25, 465–472.Google Scholar
Brenner, RR (1974) The oxidative desaturation of unsaturated fatty acids in animals. Molecular and Cellular Biochemistry 3, 41–52.Google Scholar
Burr, GO & Burr, MM (1930) The nature and role of fatty acids essential in nutrition. Journal of Biological Chemistry 86, 587–621.Google Scholar
Carnielli, VP, Wattimena, DJL, Luijendijk, IHT, Boerlage, A, Degenhart, HJ & Sauer, PJJ (1996) The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acid from linoleic and α-linolenic acids. Pediatric Research 40, 169–171.Google Scholar
Chen, Z-Y & Cunnane, SC (1993) Refeeding after fasting increases apparent oxidation of n-6 and n-3 fatty acids in pregnant rats. Metabolism 42, 1206–1211.CrossRefGoogle ScholarPubMed
Chiang, C, Litingtung, Y & Lee, E (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407–413.CrossRefGoogle ScholarPubMed
Crawford, MA (1993) The role of essential fatty acids in neural development: implications for perinatal nutrition. American Journal of Clinical Nutrition 57, Suppl. 5, 703S–710S.Google Scholar
Cunnane, SC, (1995) Metabolism and function of α-linolenic acid in humans. In Flaxseed in Human Nutrition, 99–127 [Cunnane, SC and Thompson, LU, editors]. Champaign, IL: American Oil Chemists' Society.Google Scholar
Cunnane, SC (1996) The Canadian Society for Nutritional Sciences 1995 Young Scientist Award Lecture. Recent studies on the synthesis, β-oxidation and deficiency of linoleate and α-linolenate: are essential fatty acids more aptly named indispensable or conditionally dispensable fatty acids?. Canadian Journal of Physiology and Pharmacology 74, 629–639.Google Scholar
Cunnane, SC & Anderson, MJ (1997 a) The majority of dietary linoleate in growing rats is β-oxidized or stored in visceral fat. Journal of Nutrition 127, 146–152.Google Scholar
Cunnane, SC & Anderson, MJ (1997b) Pure linoleate deficiency in the rat: influence on growth, accumulation of n-6 polyunsaturates, and [14C]-linoleate oxidation. Journal of Lipid Research 38, 805–812.Google Scholar
Cunnane, SC, Belza, Z, Anderson, MJ & Ryan, MA (1998) Substantial carbon recycling from linoleate into products of de novo lipogenesis occurs in rat liver even under conditions of extreme dietary linoleate deficiency. Journal of Lipid Research 39, 2271–2276.Google Scholar
Cunnane, SC, Francescutti, V, Brenna, JT & Crawford, MA (2000) Breast-fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula-fed infants not consuming dietary docosahexenoate. Lipids 35, 105–111.Google Scholar
Cunnane, SC, Menard, CR, Likhodii, SS, Brenna, JT & Crawford, MA (1999 a) Carbon recycling into de novo lipogenesis is a major pathway in neonatal metabolism of linoleate and α-linolenate. Prostaglandins, Leukotrienes and Essential Fatty Acids 60, 387–392.Google Scholar
Cunnane, SC, Ross, R, Bannister, JL & Jenkins, DJA (1999 b) Magnetic resonance imaging-based balance analysis of linoleate utilization during weight loss in obese humans. Lipids 34, Suppl., S89–S90.Google Scholar
Cunnane, SC, Ryan, MA, Craig, KA, Brookes, S, Koletzko, B, Demmelmair, H, Singer, J & Kyle, DJ (1995) Synthesis of linoleate and α-linolenate by chain elongation in the rat. Lipids 30, 781–783.Google Scholar
Cunnane, SC and Yang, J (1995) Zinc deficiency impairs whole-body accumulation of polyunsaturates and increases the utilization of [1-14C]linoleate for de novo lipid synthesis in pregnant rats. Canadian Journal of Physiology and Pharmacology 73, 1246–1252.Google Scholar
de Lorgeril, M, Renaud, S, Mamelle, N, Salen, P, Martin, J-L, Monjaud, I, Guidollet, J, Touboul, P & Delaye, J (1994) Mediterranean alpha-linolenic acid rich diet in secondary prevention of coronary heart disease. Lancet 343, 1454–1459.CrossRefGoogle ScholarPubMed
Demmelmair, H, Sauerwald, T, Koletzko, B & Richter, T (1997) New insights in lipid and fatty acid metabolism via stable isotopes. European Journal of Pediatrics 156, Suppl. 1, S70–S74.CrossRefGoogle ScholarPubMed
Dolecek, TA (1992) Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Proceedings of the Society for Experimental Biology and Medicine 200, 177–182.Google Scholar
Edmond, J, Higa, TA, Korsak, RA, Bergner, EA & Lee, WN (1998) Fatty acid transport and utilization for the developing brain. Journal of Neurochemistry 70, 1227–1234.CrossRefGoogle ScholarPubMed
Edmond, J, Korsak, RA, Morrow, JW, Torok-Booth, G & Catlin, DH (1991) Dietary cholesterol and the origin of cholesterol in the brain of developing rats. Journal of Nutrition 121, 1223–1330.CrossRefGoogle ScholarPubMed
Emken, EA, Adlof, RO, Rakoff, H, Rohwedder, WK & Gulley, RM (1992) Human metabolic studies with deuterated α-linolenate. Nutrition 8, 213–217.Google Scholar
Farquharson, J, Cockburn, F, Patrick, WA, Jamieson, EC & Logan, RW (1992) Infant cerebral cortex phospholipid fatty acid composition and diet. Lancet 340, 810–813.Google Scholar
Freese, R & Mutanen, M (1997) α-linolenic acid and marine long-chain n-3 fatty acids differ only slightly in their effects on hemostatic factors in healthy subjects. American Journal of Clinical Nutrition 66, 591–598.Google Scholar
Gavino, GR & Gavino, VC (1991) Rat liver outer mitochondrial carnitine palmitoyltransferase activity towards long-chain polyunsaturated fatty acids and the CoA esters. Lipids 26, 266–270.Google Scholar
Gerster, H (1997) Can adults adequately convert α-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)?. International Journal of Vitamin and Nutrition Research 68, 159–173.Google Scholar
Hansen, HS & Jensen, B (1983) Urinary prostaglandin E2 and vasopressin excretion in essential fatty acid deficient rats. Effect of linolenic acid supplementation. Lipids 18, 682–690.Google Scholar
Hansen, HS & Jensen, B (1986) Apparent in vivo retroconversion of arachidonic acid to linoleic acid. Biochimica et Biophysica Acta 878, 284–287.Google Scholar
Hibbeln, J, Umhau, JC, George, DT & Salem, N (1997) Do plasma polyunsaturates predict hostility and depression?. World Review of Nutrition and Dietetics 82, 175–182.Google Scholar
Hirsch, J, Farquhar, JW, Ahrens, EH, Peterson, ML & Stoffel, W (1960) Studies of adipose tissue in man. A microtechnic for sampling and analysis. American Journal of Clinical Nutrition 8, 499–511.Google Scholar
Holman, RT (1971) Essential fatty acid deficiency. Progress in the Chemistry of Fats and Other Lipids 9, 275–348.Google Scholar
Holman, RT, Johnson, SB & Hatch, TF (1982) A case of human linolenic acid deficiency involving neurological abnormalities. American Journal of Clinical Nutrition 35, 617–623.Google Scholar
Horrobin, DF & Bennett, CN (1999) Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, aging and osteoporosis. Prostaglandins, Leukotrienes and Essential Fatty Acids 60, 217–234.Google Scholar
Hu, FB, Stampfer, MJ, Manson, JE, Rimm, EB, Wolk, A, Colditz, GA, Hennekens, CH & Willett, WC (1999) Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. American Journal of Clinical Nutrition 69, 890–897.CrossRefGoogle ScholarPubMed
Hunter, EJ (1990) n-3 fatty acids from vegetable oils. American Journal of Clinical Nutrition 51, 809–814.Google Scholar
Jensen, CL, Prager, TC, Fraley, JK, Chen, H, Andersen, RE & Heird, WC (1997) Effect of dietary linoleic/α-linolenic acid ratio on growth and visual function of term infants. Journal of Pediatrics 131, 200–209.CrossRefGoogle ScholarPubMed
Jurevics, H & Morell, P (1995) Cholesterol for synthesis of myelin is made locally, not imported into the brain. Journal of Neurochemistry 64, 895–901.Google Scholar
Kromhout, D, Bosschieter, EB & de Lezenne Coulander, C (1985) The inverse relation between consumption and 20 year mortality from coronary heart disease. New England Journal of Medicine 312, 1205–1209.Google Scholar
Lamptey, MS & Walker, BL (1976) A possible role of dietary linolenic acid in the development of the young rat. Journal of Nutrition 106, 86–93.Google Scholar
Lasserre, M, Mendy, F, Spielmann, D & Jacotot, B (1985) Effects of different dietary intakes of essential fatty acids on C20:3n-6 and C20:4n-6 serum levels in human adults. Lipids 20, 227–233.Google Scholar
Leyton, J, Drury, PJ & Crawford, MA (1987) Differential oxidation of saturated and unsaturated fatty acids in vivo in the rat. British Journal of Nutrition 57, 383–393.Google Scholar
Makrides, M, Neumann, MA, Byard, RW, Simmer, K & Gibson, RA (1994) Fatty acid composition of brain, retina and erythrocytes in breast- and formula-fed infants. American Journal of Clinical Nutrition 60, 189–194.Google Scholar
Menard, CR, Goodman, K, Corso, T, Brenna, JT & Cunnane, SC (1998) Recycling of carbon into lipids synthesized de novo is a quantitatively important pathway of [U-13C]-α-linolenate utilization in the developing rat brain. Journal of Neurochemistry 71, 2151–2158.Google Scholar
Neuringer, M, Connor, WE, van Petten, C & Barstad, L (1984) Dietary omega-3 fatty acid deficiency and visual loss in infant Rhesus monkeys. Journal of Clinical Investigation 73, 272–276.Google Scholar
Parsons, HG, O'Loughlin, EV, Forbes, D, Cooper, D & Gall, DG (1988) Supplemental calories improve essential fatty acid deficiency in cystic fibrosis. Pediatric Research 24, 353–356.Google Scholar
Porter, JA, Young, KE & Beachy, PA (1996) Cholesterol modification of Hedgehog signalling proteins in animal development. Science 274, 255–259.Google Scholar
Raiten, DJ, Talbot, JM & Waters, JH (1998) Assessment of nutrient requirements for infant formulas. Journal of Nutrition Suppl. 11, 128 2059S–2293S.Google Scholar
Salem, N Jr, Wegher, B, Mena, P & Uauy, R (1996) Arachidonic and docosahexaenoic acids are biosynthesized from their 18 carbon precursors in human infants. Proceedings of the National Academy of Sciences USA 93, 49–54.CrossRefGoogle ScholarPubMed
Salen, G, Shefer, S & Batta, AK (1996) Abnormal cholesterol biosynthesis in the Smith-Lemli-Optiz syndrome. Journal of Lipid Research 37, 1169–1180.Google Scholar
Sastry, PS (1985) Lipids of nervous tissue. Composition and metabolism. Progress in Lipid Research 24, 69–176.Google Scholar
Sheaff-Greiner, RC, Zhang, Q, Goodman, KJ, Guissini, DA, Nathanielsz, PW & Brenna, JT (1996) Linoleate, α-linolenate and docosahexaenoate recycling into saturated and monounsaturated fatty acids is a major pathway in pregnant or lactating adults and fetal or infant rhesus monkeys. Journal of Lipid Research 37, 2675–2686.Google Scholar
Spector, AA & Yorek, MA (1985) Membrane lipid composition and cellular function. Journal of Lipid Research 26, 1015–1035.Google Scholar
Sprecher, H (1968) The synthesis and metabolism of hexadeca-4,7,10-trienoate, eicosa-8,11,14-trienoate, docosa-10,13,16-trienoate, and docosa-6,9,12,15-tetraenoate in the rat. Biochimica et Biophysica Acta 1, 519–530.Google Scholar
Sprecher, H, Luthria, DL, Mohammed, BS & Baykousheva, SP (1995) Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. Journal of Lipid Research 36, 2471–2477.Google Scholar
Suh, M, Wierzbicki, AA, Lien, E & Clandinin, MT (1996) Relationship between dietary supply of long chain fatty acids and membrane composition of long and very long chain essential fatty acids in developing rat photoreceptors. Lipids 31, 61–64.Google Scholar
Trotti, D; (1998) Comparison of linoleate and essential fatty acid deficiency in the rat. MSc Thesis.Google Scholar
Turley, SD, Burns, D, Rosenfeld, CR & Dietschy, JM (1996) Brain does not utilize low density lipoprotein-cholesterol during fetal and neonatal development in the sheep. Journal of Lipid Research 37, 1953–1961.Google Scholar
van Pelt, CK, Huang, ML, Tschanz, CL & Brenna, JT (1999) The octaene fatty acid - 4,7,10,13,16,19,22,25-octacosaoctadecaenoic acid (28:8n-3) – from marine oils. Journal of Lipid Research 40, 1501–1505.CrossRefGoogle ScholarPubMed
Weinsinger, HS, Vingrys, AJ & Sinclair, AJ (1996) The effect of docosahexaenoic acid on the electroretinogram of the guinea pig. Lipids 31, 65–70.Google Scholar