α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans

J. Thomas Brenna1, Norman Salem2, Andrew J. Sinclair3, Stephen C. Cunnane4
1Division of Nutritional Sciences, Cornell University, Savage Hall, Ithaca, NY 14853, USA
2Martek Biosciences Inc., 6480 Dobbin Road, Columbia, MD 21045, USA
3Deakin University, School of Exercise & Nutrition Sciences & Metabolic Research Unit, 221 Burwood Highway, Burwood, Victoria 3125, Australia
4Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada

Tài liệu tham khảo

Bloedon, 2008, Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial, J. Am. Coll. Nutr., 27, 65, 10.1080/07315724.2008.10719676 Terano, 1983, Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects, Atherosclerosis, 46, 321, 10.1016/0021-9150(83)90181-8 Hirai, 1989, Omega-3 fatty acids: epidemiological and clinical aspects, 229 Goyens, 2006, Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio, Am. J. Clin. Nutr., 84, 44, 10.1093/ajcn/84.1.44 Harper, 2006, Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans, J. Nutr., 136, 83, 10.1093/jn/136.1.83 Grimsgaard, 1997, Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids, Am. J. Clin. Nutr., 66, 649, 10.1093/ajcn/66.3.649 de Groot, 2004, Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome, Am. J. Clin. Nutr., 79, 251, 10.1093/ajcn/79.2.251 Mori, 2000, Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, ldl particle size, glucose, and insulin in mildly hyperlipidemic men, Am. J. Clin. Nutr., 71, 1085, 10.1093/ajcn/71.5.1085 James, 2003, Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids, Am. J. Clin. Nutr., 77, 1140, 10.1093/ajcn/77.5.1140 Park, 2002, EPA, but not DHA, decreases mean platelet volume in normal subjects, Lipids, 37, 941, 10.1007/s11745-006-0984-1 Woodman, 2002, Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension, Am. J. Clin. Nutr., 76, 1007, 10.1093/ajcn/76.5.1007 Finnegan, 2003, Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of ldl to oxidative modification in moderately hyperlipidemic subjects, Am. J. Clin. Nutr., 77, 783, 10.1093/ajcn/77.4.783 Brenna, 2002, Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man, Curr. Opin. Clin. Nutr. Metab. Care, 5, 127, 10.1097/00075197-200203000-00002 Burdge, 2005, Conversion of alpha-linolenic acid to longer chain polyunsaturated fatty acids in human adults, Reprod. Nutr. Dev., 45, 581, 10.1051/rnd:2005047 Burdge, 2004, Alpha-linolenic acid metabolism in men and women: nutritional and biological implications, Curr. Opin. Clin. Nutr. Metab. Care, 7, 137, 10.1097/00075197-200403000-00006 Plourde, 2007, Extremely limited synthesis of long chain polyunsaturates in adults: Implications for their dietary essentiality and use as supplements, Appl. Physiol. Nutr. Metab., 32, 619, 10.1139/H07-034 Sinclair, 2002, What is the role of alpha-linolenic acid for mammals?, Lipids, 37, 1113, 10.1007/s11745-002-1008-x Peet, 2001, Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia, Schizophr. Res., 49, 243, 10.1016/S0920-9964(00)00083-9 Wallace, 2003, Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects, Br. J. Nutr., 89, 679, 10.1079/BJN2002821 Woods, 1996, Is docosahexaenoic acid necessary in infant formula? Evaluation of high linolenate diets in the neonatal rat, Pediatr. Res., 40, 687, 10.1203/00006450-199611000-00007 Francois, 2003, Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk, Am. J. Clin. Nutr., 77, 226, 10.1093/ajcn/77.1.226 Abedin, 1999, The effects of dietary alpha-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig, Lipids, 34, 475, 10.1007/s11745-999-0387-3 Li, 1999, Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men, Am. J. Clin. Nutr., 69, 872, 10.1093/ajcn/69.5.872 Bowen, 2005, Maternal dietary 22: 6n-3 is more effective than 18: 3n-3 in increasing the 22: 6n-3 content in phospholipids of glial cells from neonatal rat brain, Br. J. Nutr., 93, 601, 10.1079/BJN20041390 Ezaki, 1999, Long-term effects of dietary alpha-linolenic acid from perilla oil on serum fatty acids composition and on the risk factors of coronary heart disease in japanese elderly subjects, J. Nutr. Sci. Vitaminol. (Tokyo), 45, 759, 10.3177/jnsv.45.759 Lefkowitz, 2005, Where does the developing brain obtain its docosahexaenoic acid? Relative contributions of dietary alpha-linolenic acid, docosahexaenoic acid, and body stores in the developing rat, Pediatr. Res., 57, 157, 10.1203/01.PDR.0000147572.57627.AE Allman, 1995, Supplementation with flaxseed oil versus sunflowerseed oil in healthy young men consuming a low fat diet: effects on platelet composition and function, Eur. J. Clin. Nutr., 49, 169 Nordstrom, 1995, Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. Safflower seed, Rheumatol. Int., 14, 231, 10.1007/BF00262088 Fu, 2000, Increased alpha-linolenic acid intake increases tissue alpha-linolenic acid content and apparent oxidation with little effect on tissue docosahexaenoic acid in the guinea pig, Lipids, 35, 395, 10.1007/s11745-000-537-7 Cunnane, 1995, Nutritional attributes of traditional flaxseed in healthy young adults, Am. J. Clin. Nutr., 61, 62, 10.1093/ajcn/61.1.62 Mantzioris, 1995, Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites, Am. J. Clin. Nutr., 61, 320, 10.1093/ajcn/61.2.320 Bowen, 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, 10.1007/s11745-000-536-8 Freese, 1994, Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/alpha-linolenic acid ratio on platelet aggregation, Thromb. Haemostasis, 71, 73, 10.1055/s-0038-1642387 Cunnane, 1997, The majority of dietary linoleate in growing rats is beta-oxidized or stored in visceral fat, J. Nutr., 127, 146, 10.1093/jn/127.1.146 Kelley, 1993, Dietary alpha-linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans, Lipids, 28, 533, 10.1007/BF02536085 Cunnane, 2003, Why is carbon from some polyunsaturates extensively recycled into lipid synthesis?, Lipids, 38, 477, 10.1007/s11745-003-1087-8 Chan, 1993, Effect of dietary alpha-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis, Lipids, 28, 811, 10.1007/BF02536235 Lin, 2007, Whole body distribution of deuterated linoleic and alpha-linolenic acids and their metabolites in the rat, J. Lipid Res., 48, 2709, 10.1194/jlr.M700369-JLR200 Mutanen, 1992, Rapeseed oil and sunflower oil diets enhance platelet in vitro aggregation and thromboxane production in healthy men when compared with milk fat or habitual diets, Thromb. Haemostasis, 67, 352, 10.1055/s-0038-1648446 Pawlosky, 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, 10.1016/S0022-2275(20)39949-1 Kwon, 1991, Effects of diets high in saturated fatty acids, canola oil, or safflower oil on platelet function, thromboxane b2 formation, and fatty acid composition of platelet phospholipids, Am. J. Clin. Nutr., 54, 351, 10.1093/ajcn/54.2.351 Rivers, 1975, Inability of the cat to desaturate essential fatty acids, Nature, 258, 171, 10.1038/258171a0 Clark, 1992, Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas, J. Pediatr., 120, S151, 10.1016/S0022-3476(05)81250-8 Heinemann, 2005, Long-chain (n-3) polyunsaturated fatty acids are more efficient than alpha-linolenic acid in improving electroretinogram responses of puppies exposed during gestation, lactation, and weaning, J. Nutr., 135, 1960, 10.1093/jn/135.8.1960 Jensen, 1996, Biochemical effects of dietary linoleic/alpha-linolenic acid ratio in term infants, Lipids, 31, 107, 10.1007/BF02522419 Bauer, 2004, Maternal diet alpha-linolenic acid during gestation and lactation does not increase docosahexaenoic acid in canine milk, J. Nutr., 134, 2035S, 10.1093/jn/134.8.2035S Huang, 1996, Arachidonate and docosahexaenoate added to infant formula influence fatty acid composition and subsequent eicosanoid production in neonatal pigs, J. Nutr., 126, 2199, 10.1093/jn/126.9.2199 de la Presa-Owens, 1998, Addition of triglycerides with arachidonic acid or docosahexaenoic acid to infant formula has tissue- and lipid class-specific effects on fatty acids and hepatic desaturase activities in formula-fed piglets, J. Nutr., 128, 1376, 10.1093/jn/128.8.1376 Arbuckle, 1991, Response of (n-3) and (n-6) fatty acids in piglet brain, liver and plasma to increasing, but low, fish oil supplementation of formula, J. Nutr., 121, 1536, 10.1093/jn/121.10.1536 Huang, 2007, Differential tissue dose responses of (n-3) and (n-6) PUFA in neonatal piglets fed docosahexaenoate and arachidonoate, J. Nutr., 137, 2049, 10.1093/jn/137.9.2049 Su, 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, 10.1007/BF02562339 Su, 1999, Bioequivalence of dietary alpha-linolenic and docosahexaenoic acids as sources of docosahexaenoate accretion in brain and associated organs of neonatal baboons, Pediatr. Res., 45, 87, 10.1203/00006450-199901000-00015 Greiner, 1997, Brain docosahexaenoate accretion in fetal baboons: bioequivalence of dietary alpha-linolenic and docosahexaenoic acids, Pediatr. Res., 42, 826, 10.1203/00006450-199712000-00018 Diau, 2003, Docosahexaenoic and arachidonic acid influence on preterm baboon retinal composition and function, Invest. Ophthalmol. Vis. Sci., 44, 4559, 10.1167/iovs.03-0478 Hsieh, 2007, The influence of moderate and high dietary long chain polyunsaturated fatty acids (LCPUFA) on baboon neonate tissue fatty acids, Pediatr. Res., 61, 537, 10.1203/pdr.0b013e318045bec9 Kothapalli, 2007, Differential cerebral cortex transcriptomes of baboon neonates consuming moderate and high docosahexaenoic acid formulas, PLoS One, 2, e370, 10.1371/journal.pone.0000370 Arterburn, 2006, Distribution, interconversion, and dose response of n-3 fatty acids in humans, Am. J. Clin. Nutr., 83, 1467S, 10.1093/ajcn/83.6.1467S Ghafoorunissa, 2002, Effects of dietary alpha-linolenic acid from blended oils on biochemical indices of coronary heart disease in indians, Lipids, 37, 1077, 10.1007/s11745-002-1003-2 Peet, 2002, A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms, J. Psychiatr. Res., 36, 7, 10.1016/S0022-3956(01)00048-6 Harris, 2008, Stearidonic acid-enriched soybean oil increased the omega-3 index, an emerging cardiovascular risk marker, Lipids, 10.1007/s11745-008-3215-0 Cunnane, 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, 10.1007/s11745-000-0501-6 Innis, 1996, Plasma fatty acid responses, metabolic effects, and safety of microalgal and fungal oils rich in arachidonic and docosahexaenoic acids in healthy adults, Am. J. Clin. Nutr., 64, 159, 10.1093/ajcn/64.2.159 Farquharson, 1992, Infant cerebral cortex phospholipid fatty-acid composition and diet, Lancet, 340, 810, 10.1016/0140-6736(92)92684-8 Makrides, 1994, Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants, Am. J. Clin. Nutr., 60, 189, 10.1093/ajcn/60.2.189 Jamieson, 1999, Infant cerebellar gray and white matter fatty acids in relation to age and diet, Lipids, 34, 1065, 10.1007/s11745-999-0458-5 Lands, 1990, Quantitative effects of dietary polyunsaturated fats on the composition of fatty acids in rat tissues, Lipids, 25, 505, 10.1007/BF02537156 Hibbeln, 2004, Increasing homicide rates and linoleic acid consumption among five western countries, 1961–2000, Lipids, 39, 1207, 10.1007/s11745-004-1349-5 Brenner, 1966, Effect of saturated and unsaturated fatty acids on the desaturation in vitro of palmitic, stearic, oleic, linoleic, and linolenic acids, J. Biol. Chem., 241, 5213, 10.1016/S0021-9258(18)96419-7 Bourre, 1993, Dietary alpha-linolenic acid at 1.3g/kg maintains maximal docosahexaenoic acid concentration in brain, heart and liver of adult rats, J. Nutr., 123, 1313, 10.1093/jn/123.7.1313 Mohrhauer, 1963, Effect of linolenic acid upon the metabolism of linoleic acid, J. Nutr., 81, 67, 10.1093/jn/81.1.67 Arbuckle, 1992, Formula alpha-linolenic (18:3(n-3)) and linoleic (18:2(n-6)) acid influence neonatal piglet liver and brain saturated fatty acids, as well as docosahexaenoic acid (22:6(n-3)), Biochim. Biophys. Acta, 1125, 262, 10.1016/0005-2760(92)90054-Y Blank, 2002, Optimizing DHA levels in piglets by lowering the linoleic acid to alpha-linolenic acid ratio, J. Lipid Res., 43, 1537, 10.1194/jlr.M200152-JLR200 Sanders, 1984, The influence of a maternal diet rich in linoleic acid on brain and retinal docosahexaenoic acid in the rat, Br. J. Nutr., 51, 57, 10.1079/BJN19840009 Su, 1996, Increasing dietary linoleic acid in young rats increases and then decreases docosahexaenoic acid in retina but not in brain, Lipids, 31, 1289, 10.1007/BF02587915 Lands, 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, 10.1016/0925-4439(92)90063-S Hibbeln, 2006, Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity, Am. J. Clin. Nutr., 83, 1483S, 10.1093/ajcn/83.6.1483S Lands, 2008, A critique of paradoxes in current advice on dietary lipids, Prog. Lipid Res., 47, 77, 10.1016/j.plipres.2007.12.001 Sinclair, 1975, Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat, Lipids, 10, 175, 10.1007/BF02534156 Emken, 1990, Metabolism in vivo of deuterium-labelled linolenic and linoleic acids in humans, Biochem. Soc. Trans., 18, 766, 10.1042/bst0180766 Carnielli, 1996, The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids, Pediatr. Res., 40, 169, 10.1203/00006450-199607000-00029 Salem, 1996, Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants, Proc. Natl. Acad. Sci. USA, 93, 49, 10.1073/pnas.93.1.49 Sauerwald, 1997, Intermediates in endogenous synthesis of c22:6 omega 3 and c20:4 omega 6 by term and preterm infants, Pediatr. Res., 41, 183, 10.1203/00006450-199702000-00005 Uauy, 2000, Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth, Pediatr. Res., 47, 127, 10.1203/00006450-200001000-00022 Carnielli, 2007, Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids, Am. J. Clin. Nutr., 86, 1323, 10.1093/ajcn/86.5.1323 Burdge, 2003, Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13c] alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men, Br. J. Nutr., 90, 311, 10.1079/BJN2003901 Burdge, 2002, Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women, Br. J. Nutr., 88, 411, 10.1079/BJN2002689 Pawlosky, 2001, Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans, J. Lipid Res., 42, 1257, 10.1016/S0022-2275(20)31576-5 Vermunt, 2000, Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13c-alpha-linolenic acid, Lipids, 35, 137, 10.1007/BF02664762 Pawlosky, 2003, Effects of beef- and fish-based diets on the kinetics of n-3 fatty acid metabolism in human subjects, Am. J. Clin. Nutr., 77, 565, 10.1093/ajcn/77.3.565 McCloy, 2004, A comparison of the metabolism of eighteen-carbon 13c-unsaturated fatty acids in healthy women, J. Lipid Res., 45, 474, 10.1194/jlr.M300304-JLR200 Hussein, 2005, Long-chain conversion of [13c]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men, J. Lipid Res., 46, 269, 10.1194/jlr.M400225-JLR200 Burdge, 2002, Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*, Br. J. Nutr., 88, 355, 10.1079/BJN2002662 Pawlosky, 2003, n-3 fatty acid metabolism in women, Br. J. Nutr., 90, 993, 10.1079/BJN2003985 Giltay, 2004, Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects, Am. J. Clin. Nutr., 80, 1167, 10.1093/ajcn/80.5.1167 Bakewell, 2006, Polyunsaturated fatty acid concentrations in young men and women consuming their habitual diets, Br. J. Nutr., 96, 93, 10.1079/BJN20061801 Mayes, 2006, Variation in [u-13c] alpha linolenic acid absorption, beta-oxidation and conversion to docosahexaenoic acid in the pre-term infant fed a DHA-enriched formula, Pediatr. Res., 59, 271, 10.1203/01.pdr.0000196372.29648.7a Pawlosky, 2007, Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers, J. Lipid Res., 48, 935, 10.1194/jlr.M600310-JLR200 Hoffman, 2001, Impaired synthesis of DHA in patients with x-linked retinitis pigmentosa, J. Lipid Res., 42, 1395, 10.1016/S0022-2275(20)30271-6 Neuringer, 1986, Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys, Proc. Natl. Acad. Sci. USA, 83, 4021, 10.1073/pnas.83.11.4021 Anderson, 2005, Can prenatal n-3 fatty acid deficiency be completely reversed after birth? Effects on retinal and brain biochemistry and visual function in rhesus monkeys, Pediatr. Res., 58, 865, 10.1203/01.pdr.0000182188.31596.5a Su, 2001, Fetal baboons convert 18:3n-3 to 22:6n-3 in vivo. A stable isotope tracer study,, J. Lipid Res., 42, 581, 10.1016/S0022-2275(20)31167-6