α-Linolenic acid metabolism in men and women: Nutritional and biological implications

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 7, Issue 2, 2004, Pages 137-144

  Burdge, Graham ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

Linolenic acid; Oxidation; Docosahexaenoic acid; Gender

Indexed keywords

DOCOSAHEXAENOIC ACID; ICOSAPENTAENOIC ACID; LINOLEIC ACID; POLYUNSATURATED FATTY ACID; CARBON; DOCOSAPENTAENOIC ACID; LINOLENIC ACID; UNSATURATED FATTY ACID;

CELL FUNCTION; CELL STRUCTURE; CONSENSUS; DIET SUPPLEMENTATION; DIETARY INTAKE; FAT INTAKE; FATTY ACID DESATURATION; FATTY ACID METABOLISM; FATTY ACID OXIDATION; FEMALE; HUMAN; LACTATION; LIPID COMPOSITION; MALE; PREGNANCY; REVIEW; ENERGY METABOLISM; METABOLISM; NUTRITIONAL REQUIREMENT; OXIDATION REDUCTION REACTION; PHYSIOLOGY; SEXUAL DEVELOPMENT;

ALPHA-LINOLENIC ACID; CARBON ISOTOPES; EICOSAPENTAENOIC ACID; ENERGY METABOLISM; FATTY ACIDS, UNSATURATED; FEMALE; HUMANS; MALE; NUTRITIONAL REQUIREMENTS; OXIDATION-REDUCTION; SEX CHARACTERISTICS;

EID: 3042680440     PISSN: 13631950     EISSN: None     Source Type: Journal    
DOI: 10.1097/00075197-200403000-00006     Document Type: Review

References (71)

1. Ministry of Agriculture, Fisheries and Food. Dietary intake of iodine and fatty acids. Food Information Surveillance Sheet 127. London: Ministry of Agriculture, Fisheries and Food; 1997.
2. Kris-Etherton PM, Shaffer Taylor D, Yu-Poth S, et al. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 2000; 71:179-188.
3. Uauy R, Hoffman DR, Peirano P, Birch EE. Essential fatty acids in visual and brain development. Lipids 2001; 36:885-895.
4. Mitchell DC, Niu SL, Litman BJ. Enhancement of G protein-coupled signaling by DHA phospholipids. Lipids 2003; 38:437-443. Provides a mechanistic explanation for the adverse effects of low DHA status in retinal function in preferm infants.
5. Jeffrey BG, Weisinger HS, Neuringer M, Mitchell DC. The role of docosahexaenoic acid in retinal function. Lipids 2001; 36:859-871.
6. Sinclair AJ, Attar-Bashi NM, Li D. What is the role of α-linolenic acid for mammals? Lipids 2000; 37:1113-1123.
7. Vinton NE, Heckenlively JR, Laidlaw SA, et al. Visual function in patients undergoing parenteral nutrition. Am J Clin Nutr 1990; 52:895-902.
8. Bretillon L, Chardigny JM, Sebedio JL, et al. Isomerization increases the postprandial oxidation of linoleic acid but not α-linolenic acid in men. J Lipid Res 2001; 42:995-997.
9. DeLany JP, Windhauser MM, Champagne CM, Bray GA. Differential oxidation of individual dietary fatty acids in humans. Am J Clin Nutr 2000; 72:905-911.
10. Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men. Br J Nutr 2002; 88:355-363. This paper shows that conversion of α-LNA to EPA and DHA is very low in men.
11. 13C]α-linolenic acid to longer-chain fatty acids and partitioning towards β-oxidation in older men. Br J Nutr 2003; 90:311-321. Conversion of α-LNA to longer-chain fatty acids is investigated by comparisons in the same individuals before and after modification of n-3 fatty acid consumption.
12. 13C]- α-linolenic acid. Lipids 2000; 35:137-142.
13. Burdge GC, Wootton SA. Conversion of α-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr 2002; 88:411-420. This paper shows higher conversion of α-LNA to EPA and DHA in women than previously reported in men.
14. 13C palmitic acid. Eur J Clin Nutr 1998; 52:22-28.
15. Jones AE, Stolinski M, Smith RD, et al. Effect of fatty acid chain length and saturation on the gastrointestinal handling and metabolic disposal of dietary fatty acids in women. Br J Nutr 1999; 81:37-43.
16. Leyton J, Drury PJ, Crawford MA. Differential oxidation of saturated and unsaturated fatty acids in vivo in the rat. Br J Nutr 1987; 57:383-393.
17. Sheaff Greiner RC, Zhang Q, Goodman KJ, et al. 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. J Lipid Res 1996; 37:2675-2686.
18. Cunnane SC, Ryan MA, Nadeau CR, et al. Why is carbon from some polyunsaturates extensively recycled in lipid synthesis? Lipids 2003; 38:477-484. A useful summary of the literature on carbon recycling from PUFAs in animal models.
19. Burdge GC, Wotton SA. Conversion of α-linolenic acid to palmitic, palmitoleic, stearic and oleic acids in men and women. Prostaglandins Leukot Essent Fatty Acids 2003; 69:283-290. The first report demonstrating carbon recycling from α-LNA in humans.
20. Sprecher H. The roles of anabolic and catabolic reactions in the synthesis and recycling of polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids 2002; 67:79-83. Summarizes the key reactions in PUFA metabolism.
21. D'andrea S, Guillou H, Jan S, et al. The same rat Δ6-desaturase not only acts on 18- but also on 24-carbon fatty acids in very-long-chain polyunsaturated fatty acid biosynthesis. Biochem J 2002; 364:49-55.
22. De Antueno RJ, Knickle LC, Smith H, et al. Activity of human Δ5 and Δ6 desaturases on multiple n-3 and n-6 polyunsaturated fatty acids. FEBS Lett 2001; 509:77-80.
23. Infante JP, Huszagh VA. Analysis of the putative role of 24-carbon polyunsaturated fatty acids in the biosynthesis of docosapentaenoic (22:5nn-6) and docosahexaenoic (22:6n-3) acids. FEBS Lett 1998; 431:1-6.
24. Li Z, Kaplan ML, Hachey DL. Hepatic microsomal and peroxisomal docosahexaenoate biosynthesis during piglet development. Lipids 2000; 35:1325-1333.
25. Harmon SD, Kaduce TL, Manuel TD, Spector AA. Effect of Δ6-desaturase inhibitor SC-26196 on PUFA metabolism in human cells. Lipids 2003; 38:469-476. Directly demonstrates the important of Δ6-desaturase as the rate-limiting enzyme in α-LNA conversion and in the synthesis of the DHA precursor 24:6n-3.
26. Sprecher H. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta 2000; 1486:219-231.
27. Emken EA. Stable isotope approaches, applications and issues related to polyunsaturated fatty acid metabolism studies. Lipids 2001; 36:965-973.
28. Emken EA, Adlof RO, Gulley RM. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta 1994; 1213:277-288.
29. Emken EA, Adlof RO, Duval SM, Nelson GJ. Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope-labeled oleic, linoleic and linolenic acids by male subjects. Lipids 1999; 34:785-798.
30. Salem N, Powlosky R, Wegher B, Hibbeln J. In vivo conversion of linoleic acid to arachidonic acid in human adults. Prostaglandins Leukot Essent Fatty Acids 1999; 60:407-410.
31. Pawlosky RJ, Hibbeln, JR, Novotny JA, Salem N. Physiological compartmental analysis of α-linolenic acid metabolism in adult humans. J Lipid Res 2001; 42:1257-1265.
32. Pawlosky RJ, Hibbeln JR, 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. Detailed kinetic analysis of the effects of altered fatty acid intake on α-LNA metabolism.
33. Dyerberg J, Bang HO, Aagaard O. α-Linolenic acid and eicosapentaenoic acid. Lancet 1980; 1:199.
34. Sanders TA, Roshanai F. The influence of different types of ω3 polyunsaturated fatty acids on blood lipids and platelet function in healthy volunteers. Clin Sci 1983; 64:91-99.
35. Singer P, Berger I, Wirth M, et al. Slow desaturation and elongation of linoleic and α-linolenic acids as a rationale of eicosapentaenoic acid-rich diet to lower blood pressure and serum lipids in normal, hypertensive and hyperlipidaemic subjects. Prostaglandins Leukot Med 1986; 24:173-193.
36. Kestin M, Clifton P, Belling GB, Nestel PJ. n-3 Fatty acids of marine origin lower systolic blood pressure and triglycerides but raise LDL cholesterol compared with n-3 and n-6 fatty acids from plants. Am J Clin Nutr 1990; 51:1028-1034.
37. Kelly DS, Nelson GJ, Love JE, et al. Dietary α-linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans. Lipids 1993; 28:533-537.
38. Chan JK, McDonald BE, Gerrard JM, et al. Effect of dietary α-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis. Lipids 1993; 28:811-817.
39. Freese R, Mutanen M, Valsta LM, Salminen I. Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/α-linolenic acid ratio on platelet aggregation. Thromb Haemost 1994; 71:73-77.
40. Allman MA, Pena MM, Peng D. Supplementation with flaxseed oil versus sunflower oil in healthy young men when consuming a low fat diet: effects on platelet composition and function. Eur J Clin Nutr 1995; 49:169-178.
41. Cunnane SC, Hamadeh MJ, Leide AC, et al. Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr 1995; 61:62-68.
42. Li D, Sinclair A, Wilson A, et al. Effect of dietary α-linolenic acid on thrombotic risk factors in vegetarian men. Am J Clin Nutr 1999; 69:872-882.
43. Mantzioris E, James MJ, Gibson RA, Cleland LG. Dietary substitution with an alpha-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues. Am J Clin Nutr 1994; 59:1304-1309.
44. Mutanen M, Freese R, Valsta LM, 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 Haemost 1992; 67:352-356.
45. Valsta LM, Salminen I, Aro A, Mutanen M. Alpha-linolenic acid in rapeseed oil partly compensates for the effect of fish restriction on plasma long chain n-3 fatty acids. Eur J Clin Nutr 1996; 50:229-235.
46. Ezaki O, Takahashi M, Shigematsu T, et al. Long-term effects of dietary alpha-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 (Tokyo) 1999; 45:759-772.
47. Gerster H. Can adults convert α-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:5n-3)? Int J Vitam Nutr Res 1998; 68:159-173.
48. Finnegan YE, Minihane AM, Leigh-Firbank EC, et al. Plantand 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 hyperlipidaemic subjects. Am J Clin Nutr 2003; 77:783-795. One of series of papers [11asterisk inside a circle sign,49asterisk inside a circle sign,50asterisk inside a circle sign] from a comprehensive comparison of dietary enrichment with α-LNA or EPA and DHA on a wide range of immune and haemostaic functional outcomes in individuals to whom dietary recommendations for n-3 fatty acid intake may be particularly targeted.
49. Kew S, Banerjee T, Minihane AM, et al. Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function. Am J Clin Nutr 2003; 77:1287-1295. Comprehensive study showing that although altered n-3 fatty acid intakes can modify cell membrane composition this is not necessarily associated with alerted function.
50. Finnegan YE, Howarth D, Minihane AM, et al. Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans. J Nutr 2003; 133:2210-2213. Detailed study of the effect of altered n-3 intake on haemostaic factors.
51. Gronn M, Christensen E, Hagve TA, Christophersen BO. Peroxisomal retroconversion of docosahexaenoic acid (22:6(n-3)) to eicosapentaenoic acid (20:5(n-3)) studied in isolated rat liver cells. Biochim Biophys Acta 1991; 1081:85-91.
52. Nelson GJ, Schmidt PC, Bartolini GL, et al. The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 1997; 32:1137-1146.
53. Mori TA, Burke V, Puddey IB, et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidaemic men. Am J Clin Nutr 2000; 71:1085-1094.
54. Grimsgaard S, Bonaa KH, Hansen JB, Nordoy A. 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.
55. Thies F, Nebe-von-Caron G, Powell JR, et al. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects ages >55 years. Am J Clin Nutr 2001; 73:539-548.
56. 13C]22:6n-3-triacylglycerols. Am J Clin Nutr 1996; 64:577-586.
57. Tang C, Cho HP, Nakamura MT, Clarke SD. Regulation of human Δ-6 desaturase gene transcription: identification of a functional direct repeat-1 element. J Lipid Res 2003; 44:686-695. Provides a molecular mechanism by which n-3 fatty acid intake may modify α-LNA desaturation and elongation.
58. Lauritzen L, Hansen HS, Jorgensen MH, Michaelsen KF. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 2001; 40:1-94.
59. Poisson J-P, Dupuy R-P, Sarda P, et al. Evidence that liver microsomes of human neonates desaturate essential fatty acids. Biochim Biophys Acta 1993; 1167:109-113.
60. Salem N, Wegher B, Mena P, Uauy R. Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc Natl Acad Sci U S A 1996; 93:49-54.
61. Sauerwald TU, Hachey DL, Jensen CL, et al. Intermediates in endogenous synthesis of C22:6ω3 and C20:4ω6 by term and preterm infants. Pediatr Res 1997; 41:183-187.
62. Carnielli CP, Wattimena JDL, Luijendijk IHT, et al. The very-low-birth-weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acid from linolenic and linolenic acid. Pediatr Res 1996; 40:169-174.
63. de Gomez Dumm IN, Brenner RR. Oxidative desaturation of alpha-linoleic, linoteic, and stearic acids by human liver microsomes. Lipids 1975; 10:315-317.
64. Postle AD, Al MDM, Burdge GC, Hornstra G. The composition of individual molecular species of plasma phosphatidylcholine in human pregnancy. Early Human Dev 1995; 43:47-58.
65. Gregersen MI, Rawson RA. Blood volume. Physiol Rev 1959; 39:307-342.
66. Smit EN, Fokkema MR, Boersma ER, Muskiet FA. Higher erythrocyte 22:6n-3 and 22:5n-6, and lower 22:5n-3 suggest higher Delta-4-desaturation capacity in women of childbearing age. Br J Nutr 2003; 89:739-740. The first report showing gender differences in plasma DHA concentration.
67. Ottosson UB, Lagrelius A, Rosing U, von Schoultz B. Relative fatty aids composition of lecithin during postmenopausal replacement therapy: a comparison between ethinyl estradiol and estradiol valerate. Gynecol Obstet Invest 1984; 18:296-302.
68. Larque E, Garcia-Ruiz PA, Perez-Llamas F, et al. Dietary trans fatty acids alter the compositions of microsomes and mitochondria and the activities of microsome Δ6-fatty acid desaturase and glucose-6-phosphatase in livers of pregnant rats. J Nutr 2003; 133:2526-2531. Shows for the first time altered Δ6-desaturase activity in pregnancy.
69. Francois CA, Connor SL, Bolewicz LC, Connor WE. Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk. Am J Clin Nutr 2003; 77:226-233. Shows that the contribution of α-LNA conversion is a minor source of longer-chain PUFAs during lactation.
70. Del Prado M, Villalpando S, Elizondo A, et al. Contribution of dietary and newly formed arachidonic acid to human milk lipids in women eating a low-fat diet. Am J Clin Nutr 2001; 74:242-247.
71. Calder PC. N-3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic. Lipids 2003; 38:343-352. Comprehensive review of the clinical role of n-3 fatty acids in modifying the inflammatory response.