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

Published:August 25, 2009DOI:https://doi.org/10.1016/j.plefa.2009.01.004

      Abstract

      Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.

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      References

        • Bloedon L.T.
        • Balikai S.
        • Chittams J.
        • et al.
        Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial.
        J. Am. Coll. Nutr. 2008; 27: 65-74
        • Terano T.
        • Hirai A.
        • Hamazaki T.
        • et al.
        Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects.
        Atherosclerosis. 1983; 46: 321-331
        • Hirai A.
        • Terano T.
        • Saito H.
        • et al.
        Omega-3 fatty acids: epidemiological and clinical aspects.
        in: Spiller G.A. Scala J. New Protective Roles for Selected Nutrients. Alan R. Liss, New York1989: 229-252
        • Goyens P.L.
        • Spilker M.E.
        • Zock P.L.
        • et al.
        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. 2006; 84: 44-53
        • Harper C.R.
        • Edwards M.J.
        • DeFilipis A.P.
        • et al.
        Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans.
        J. Nutr. 2006; 136: 83-87
        • Grimsgaard S.
        • Bonaa K.H.
        • Hansen J.B.
        • et al.
        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. 1997; 66: 649-659
        • de Groot R.H.
        • Hornstra G.
        • van Houwelingen A.C.
        • et al.
        Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome.
        Am. J. Clin. Nutr. 2004; 79: 251-260
        • Mori T.A.
        • Burke V.
        • Puddey I.B.
        • et al.
        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. 2000; 71: 1085-1094
        • James M.J.
        • Ursin V.M.
        • Cleland L.G.
        Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids.
        Am. J. Clin. Nutr. 2003; 77: 1140-1145
        • Park Y.
        • Harris W.
        EPA, but not DHA, decreases mean platelet volume in normal subjects.
        Lipids. 2002; 37: 941-946
        • Woodman R.J.
        • Mori T.A.
        • Burke V.
        • et al.
        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. 2002; 76: 1007-1015
        • Finnegan Y.E.
        • Minihane A.M.
        • Leigh-Firbank E.C.
        • et al.
        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. 2003; 77: 783-795
        • Brenna J.T.
        Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man.
        Curr. Opin. Clin. Nutr. Metab. Care. 2002; 5: 127-132
        • Burdge G.C.
        • Calder P.C.
        Conversion of alpha-linolenic acid to longer chain polyunsaturated fatty acids in human adults.
        Reprod. Nutr. Dev. 2005; 45: 581-597
        • Burdge G.
        Alpha-linolenic acid metabolism in men and women: nutritional and biological implications.
        Curr. Opin. Clin. Nutr. Metab. Care. 2004; 7: 137-144
        • Plourde M.
        • Cunnane S.C.
        Extremely limited synthesis of long chain polyunsaturates in adults: Implications for their dietary essentiality and use as supplements.
        Appl. Physiol. Nutr. Metab. 2007; 32: 619-634
        • Sinclair A.J.
        • Attar-Bashi N.M.
        • Li D.
        What is the role of alpha-linolenic acid for mammals?.
        Lipids. 2002; 37: 1113-1123
        • Peet M.
        • Brind J.
        • Ramchand C.N.
        • et al.
        Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia.
        Schizophr. Res. 2001; 49: 243-251
        • Wallace F.A.
        • Miles E.A.
        • Calder P.C.
        Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects.
        Br. J. Nutr. 2003; 89: 679-689
        • Woods J.
        • Ward G.
        • Salem Jr., N.
        Is docosahexaenoic acid necessary in infant formula? Evaluation of high linolenate diets in the neonatal rat.
        Pediatr. Res. 1996; 40: 687-694
        • Francois C.A.
        • Connor S.L.
        • Bolewicz L.C.
        • et al.
        Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk.
        Am. J. Clin. Nutr. 2003; 77: 226-233
        • Abedin L.
        • Lien E.L.
        • Vingrys A.J.
        • et al.
        The effects of dietary alpha-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig.
        Lipids. 1999; 34: 475-482
        • Li D.
        • Sinclair A.
        • Wilson A.
        • et al.
        Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men.
        Am. J. Clin. Nutr. 1999; 69: 872-882
        • Bowen R.A.
        • Clandinin M.T.
        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. 2005; 93: 601-611
        • Ezaki O.
        • Takahashi M.
        • Shigematsu T.
        • et al.
        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). 1999; 45: 759-772
        • Lefkowitz W.
        • Lim S.Y.
        • Lin Y.
        • et al.
        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. 2005; 57: 157-165
        • Allman M.A.
        • Pena M.M.
        • Pang D.
        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. 1995; 49: 169-178
        • Nordstrom D.C.
        • Honkanen V.E.
        • Nasu Y.
        • et al.
        Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. Safflower seed.
        Rheumatol. Int. 1995; 14: 231-234
        • Fu Z.
        • Sinclair A.J.
        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. 2000; 35: 395-400
        • Cunnane S.C.
        • Hamadeh M.J.
        • Liede A.C.
        • et al.
        Nutritional attributes of traditional flaxseed in healthy young adults.
        Am. J. Clin. Nutr. 1995; 61: 62-68
        • Mantzioris E.
        • James M.J.
        • Gibson R.A.
        • et al.
        Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites.
        Am. J. Clin. Nutr. 1995; 61: 320-324
        • Bowen R.A.
        • Clandinin M.T.
        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. 2000; 35: 389-394
        • Freese R.
        • Mutanen M.
        • Valsta L.M.
        • et al.
        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. 1994; 71: 73-77
        • Cunnane S.C.
        • Anderson M.J.
        The majority of dietary linoleate in growing rats is beta-oxidized or stored in visceral fat.
        J. Nutr. 1997; 127: 146-152
        • Kelley D.S.
        • Nelson G.J.
        • Love J.E.
        • et al.
        Dietary alpha-linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans.
        Lipids. 1993; 28: 533-537
        • Cunnane S.C.
        • Ryan M.A.
        • Nadeau C.R.
        • et al.
        Why is carbon from some polyunsaturates extensively recycled into lipid synthesis?.
        Lipids. 2003; 38: 477-484
        • Chan J.K.
        • McDonald B.E.
        • Gerrard J.M.
        • et al.
        Effect of dietary alpha-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis.
        Lipids. 1993; 28: 811-817
        • Lin Y.H.
        • Salem Jr., N.
        Whole body distribution of deuterated linoleic and alpha-linolenic acids and their metabolites in the rat.
        J. Lipid Res. 2007; 48: 2709-2724
        • Mutanen M.
        • Freese R.
        • Valsta L.M.
        • et al.
        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. 1992; 67: 352-356
        • Pawlosky R.
        • Barnes A.
        • Salem Jr., N.
        Essential fatty acid metabolism in the feline: relationship between liver and brain production of long-chain polyunsaturated fatty acids.
        J. Lipid Res. 1994; 35: 2032-2040
        • Kwon J.S.
        • Snook J.T.
        • Wardlaw G.M.
        • et al.
        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. 1991; 54: 351-358
        • Rivers J.P.
        • Sinclair A.J.
        • Craqford M.A.
        Inability of the cat to desaturate essential fatty acids.
        Nature. 1975; 258: 171-173
        • Clark K.J.
        • Makrides M.
        • Neumann M.A.
        • et al.
        Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas.
        J. Pediatr. 1992; 120: S151-S158
        • Heinemann K.M.
        • Waldron M.K.
        • Bigley K.E.
        • et al.
        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. 2005; 135: 1960-1966
        • Jensen C.L.
        • Chen H.
        • Fraley J.K.
        • et al.
        Biochemical effects of dietary linoleic/alpha-linolenic acid ratio in term infants.
        Lipids. 1996; 31: 107-113
        • Bauer J.E.
        • Heinemann K.M.
        • Bigley K.E.
        • et al.
        Maternal diet alpha-linolenic acid during gestation and lactation does not increase docosahexaenoic acid in canine milk.
        J. Nutr. 2004; 134: 2035S-2038S
        • Huang M.C.
        • Craig-Schmidt M.C.
        Arachidonate and docosahexaenoate added to infant formula influence fatty acid composition and subsequent eicosanoid production in neonatal pigs.
        J. Nutr. 1996; 126: 2199-2208
        • de la Presa-Owens S.
        • Innis S.M.
        • Rioux F.M.
        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. 1998; 128: 1376-1384
        • Arbuckle L.D.
        • Rioux F.M.
        • Mackinnon M.J.
        • et al.
        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. 1991; 121: 1536-1547
        • Huang M.C.
        • Brenna J.T.
        • Chao A.C.
        • et al.
        Differential tissue dose responses of (n-3) and (n-6) PUFA in neonatal piglets fed docosahexaenoate and arachidonoate.
        J. Nutr. 2007; 137: 2049-2055
        • Su H.M.
        • Bernardo L.
        • Mirmiran M.
        • et al.
        Dietary 18:3n-3 and 22:6n-3 as sources of 22:6n-3 accretion in neonatal baboon brain and associated organs.
        Lipids. 1999; 34: S347-S350
        • Su H.M.
        • Bernardo L.
        • Mirmiran M.
        • et al.
        Bioequivalence of dietary alpha-linolenic and docosahexaenoic acids as sources of docosahexaenoate accretion in brain and associated organs of neonatal baboons.
        Pediatr. Res. 1999; 45: 87-93
        • Greiner R.C.
        • Winter J.
        • Nathanielsz P.W.
        • et al.
        Brain docosahexaenoate accretion in fetal baboons: bioequivalence of dietary alpha-linolenic and docosahexaenoic acids.
        Pediatr. Res. 1997; 42: 826-834
        • Diau G.Y.
        • Loew E.R.
        • Wijendran V.
        • et al.
        Docosahexaenoic and arachidonic acid influence on preterm baboon retinal composition and function.
        Invest. Ophthalmol. Vis. Sci. 2003; 44: 4559-4566
        • Hsieh A.T.
        • Anthony J.C.
        • Diersen-Schade D.A.
        • et al.
        The influence of moderate and high dietary long chain polyunsaturated fatty acids (LCPUFA) on baboon neonate tissue fatty acids.
        Pediatr. Res. 2007; 61: 537-545
        • Kothapalli K.S.
        • Anthony J.C.
        • Pan B.S.
        • et al.
        Differential cerebral cortex transcriptomes of baboon neonates consuming moderate and high docosahexaenoic acid formulas.
        PLoS One. 2007; 2: e370
        • Arterburn L.M.
        • Hall E.B.
        • Oken H.
        Distribution, interconversion, and dose response of n-3 fatty acids in humans.
        Am. J. Clin. Nutr. 2006; 83: 1467S-1476S
        • Ghafoorunissa
        • Vani A.
        • Laxmi R.
        • et al.
        Effects of dietary alpha-linolenic acid from blended oils on biochemical indices of coronary heart disease in indians.
        Lipids. 2002; 37: 1077-1086
        • Peet M.
        • Horrobin D.F.
        A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms.
        J. Psychiatr. Res. 2002; 36: 7-18
        • Harris W.S.
        • Lemke S.L.
        • Hansen S.N.
        • et al.
        Stearidonic acid-enriched soybean oil increased the omega-3 index, an emerging cardiovascular risk marker.
        Lipids. 2008;
        • Cunnane S.C.
        • Francescutti V.
        • Brenna J.T.
        • et al.
        Breast-fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula-fed infants not consuming dietary docosahexaenoate.
        Lipids. 2000; 35: 105-111
        • Innis S.M.
        • Hansen J.W.
        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. 1996; 64: 159-167
        • Farquharson J.
        • Cockburn F.
        • Patrick W.A.
        • et al.
        Infant cerebral cortex phospholipid fatty-acid composition and diet.
        Lancet. 1992; 340: 810-813
        • Makrides M.
        • Neumann M.A.
        • Byard R.W.
        • et al.
        Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants.
        Am. J. Clin. Nutr. 1994; 60: 189-194
        • Jamieson E.C.
        • Farquharson J.
        • Logan R.W.
        • et al.
        Infant cerebellar gray and white matter fatty acids in relation to age and diet.
        Lipids. 1999; 34: 1065-1071
        • Lands W.E.
        • Morris A.
        • Libelt B.
        Quantitative effects of dietary polyunsaturated fats on the composition of fatty acids in rat tissues.
        Lipids. 1990; 25: 505-516
        • Hibbeln J.R.
        • Nieminen L.R.
        • Lands W.E.
        Increasing homicide rates and linoleic acid consumption among five western countries, 1961–2000.
        Lipids. 2004; 39: 1207-1213
        • Brenner R.R.
        • Peluffo R.O.
        Effect of saturated and unsaturated fatty acids on the desaturation in vitro of palmitic, stearic, oleic, linoleic, and linolenic acids.
        J. Biol. Chem. 1966; 241: 5213-5219
        • Bourre J.M.
        • Dumont O.
        • Pascal G.
        • et al.
        Dietary alpha-linolenic acid at 1.3g/kg maintains maximal docosahexaenoic acid concentration in brain, heart and liver of adult rats.
        J. Nutr. 1993; 123: 1313-1319
        • Mohrhauer H.
        • Holman R.T.
        Effect of linolenic acid upon the metabolism of linoleic acid.
        J. Nutr. 1963; 81: 67-74
        • Arbuckle L.D.
        • Rioux F.M.
        • MacKinnon M.J.
        • et al.
        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. 1992; 1125: 262-267
        • Blank C.
        • Neumann M.A.
        • Makrides M.
        • et al.
        Optimizing DHA levels in piglets by lowering the linoleic acid to alpha-linolenic acid ratio.
        J. Lipid Res. 2002; 43: 1537-1543
        • Sanders T.A.
        • Mistry M.
        • Naismith D.J.
        The influence of a maternal diet rich in linoleic acid on brain and retinal docosahexaenoic acid in the rat.
        Br. J. Nutr. 1984; 51: 57-66
        • Su H.M.
        • Keswick L.A.
        • Brenna J.T.
        Increasing dietary linoleic acid in young rats increases and then decreases docosahexaenoic acid in retina but not in brain.
        Lipids. 1996; 31: 1289-1298
        • Lands W.E.
        • Libelt B.
        • Morris A.
        • et al.
        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. 1992; 1180: 147-162
        • Hibbeln J.R.
        • Nieminen L.R.
        • Blasbalg T.L.
        • et al.
        Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity.
        Am. J. Clin. Nutr. 2006; 83: 1483S-1493S
        • Lands B.
        A critique of paradoxes in current advice on dietary lipids.
        Prog. Lipid Res. 2008; 47: 77-106
        • Sinclair A.J.
        Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat.
        Lipids. 1975; 10: 175-184
        • Emken E.A.
        • Adlof R.O.
        • Rakoff H.
        • et al.
        Metabolism in vivo of deuterium-labelled linolenic and linoleic acids in humans.
        Biochem. Soc. Trans. 1990; 18: 766-769
        • Carnielli V.P.
        • Wattimena D.J.
        • Luijendijk I.H.
        • et al.
        The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids.
        Pediatr. Res. 1996; 40: 169-174
        • Salem Jr., N.
        • Wegher B.
        • Mena P.
        • et al.
        Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants.
        Proc. Natl. Acad. Sci. USA. 1996; 93: 49-54
        • Sauerwald T.U.
        • Hachey D.L.
        • Jensen C.L.
        • et al.
        Intermediates in endogenous synthesis of c22:6 omega 3 and c20:4 omega 6 by term and preterm infants.
        Pediatr. Res. 1997; 41: 183-187
        • Uauy R.
        • Mena P.
        • Wegher B.
        • et al.
        Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth.
        Pediatr. Res. 2000; 47: 127-135
        • Carnielli V.P.
        • Simonato M.
        • Verlato G.
        • et al.
        Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids.
        Am. J. Clin. Nutr. 2007; 86: 1323-1330
        • Burdge G.C.
        • Finnegan Y.E.
        • Minihane A.M.
        • et al.
        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. 2003; 90: 311-321
        • Burdge G.C.
        • Wootton S.A.
        Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women.
        Br. J. Nutr. 2002; 88: 411-420
        • Pawlosky R.J.
        • Hibbeln J.R.
        • Novotny J.A.
        • et al.
        Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans.
        J. Lipid Res. 2001; 42: 1257-1265
        • Vermunt S.H.
        • Mensink R.P.
        • Simonis M.M.
        • et al.
        Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13c-alpha-linolenic acid.
        Lipids. 2000; 35: 137-142
        • Pawlosky R.J.
        • Hibbeln J.R.
        • Lin Y.
        • et al.
        Effects of beef- and fish-based diets on the kinetics of n-3 fatty acid metabolism in human subjects.
        Am. J. Clin. Nutr. 2003; 77: 565-572
        • McCloy U.
        • Ryan M.A.
        • Pencharz P.B.
        • et al.
        A comparison of the metabolism of eighteen-carbon 13c-unsaturated fatty acids in healthy women.
        J. Lipid Res. 2004; 45: 474-485
        • Hussein N.
        • Ah-Sing E.
        • Wilkinson P.
        • et al.
        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. 2005; 46: 269-280
        • Burdge G.C.
        • Jones A.E.
        • Wootton S.A.
        Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*.
        Br. J. Nutr. 2002; 88: 355-363
        • Pawlosky R.
        • Hibbeln J.
        • Lin Y.
        • et al.
        n-3 fatty acid metabolism in women.
        Br. J. Nutr. 2003; 90 (discussion 994–995): 993-994
        • Giltay E.J.
        • Gooren L.J.
        • Toorians A.W.
        • et al.
        Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects.
        Am. J. Clin. Nutr. 2004; 80: 1167-1174
        • Bakewell L.
        • Burdge G.C.
        • Calder P.C.
        Polyunsaturated fatty acid concentrations in young men and women consuming their habitual diets.
        Br. J. Nutr. 2006; 96: 93-99
        • Mayes C.
        • Burdge G.C.
        • Bingham A.
        • et al.
        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. 2006; 59: 271-275
        • Pawlosky R.J.
        • Hibbeln J.R.
        • Salem Jr., N.
        Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers.
        J. Lipid Res. 2007; 48: 935-943
        • Hoffman D.R.
        • DeMar J.C.
        • Heird W.C.
        • et al.
        Impaired synthesis of DHA in patients with x-linked retinitis pigmentosa.
        J. Lipid Res. 2001; 42: 1395-1401
        • Neuringer M.
        • Connor W.E.
        • Lin D.S.
        • et al.
        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. 1986; 83: 4021-4025
        • Anderson G.J.
        • Neuringer M.
        • Lin D.S.
        • et al.
        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. 2005; 58: 865-872
        • Su H.M.
        • Huang M.C.
        • Saad N.M.
        • et al.
        Fetal baboons convert 18:3n-3 to 22:6n-3 in vivo. A stable isotope tracer study,.
        J. Lipid Res. 2001; 42: 581-586