Hostname: page-component-745bb68f8f-5r2nc Total loading time: 0 Render date: 2025-01-11T13:54:23.405Z Has data issue: false hasContentIssue false
  • English
  • Français

Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men*

Published online by Cambridge University Press:  09 March 2007

Graham C. Burdge ,
Amanda E. Jones  and
Stephen A. Wootton
Graham C. Burdge*
Affiliation:
Institute of Human Nutrition, Level C, West Wing, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Amanda E. Jones
Affiliation:
Institute of Human Nutrition, Level C, West Wing, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Stephen A. Wootton
Affiliation:
Institute of Human Nutrition, Level C, West Wing, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
*
†Corresponding author:Dr G. C. Burdge, fax +44 23 80794945, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The capacity for conversion of α-linolenic acid (ALNA) to n−3 long-chain polyunsaturated fatty acids was investigated in young men. Emulsified [U−13C]ALNA was administered orally with a mixed meal to six subjects consuming their habitual diet. Approximately 33 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h. [13C]ALNA was mobilised from enterocytes primarily as chylomicron triacylglycerol (TAG), while [13C]ALNA incorporation into plasma phosphatidylcholine (PC) occurred later, probably by the liver. The time scale of conversion of [13C]ALNA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) suggested that the liver was the principal site of ALNA desaturation and elongation, although there was some indication of EPA and DPA synthesis by enterocytes. [13C]EPA and [13C]DPA concentrations were greater in plasma PC than TAG, and were present in the circulation for up to 7 and 14 d, respectively. There was no apparent 13C enrichment of docosahexaenoic acid (DHA) in plasma PC, TAG or non-esterified fatty acids at any time point measured up to 21 d. This pattern of 13C n−3 fatty acid labelling suggests inhibition or restriction of DHA synthesis downstream of DPA. [13C]ALNA, [13C]EPA and [13C]DPA were incorporated into erythrocyte PC, but not phosphatidylethanolamine, suggesting uptake of intact plasma PC molecules from lipoproteins into erythrocyte membranes. Since the capacity of adult males to convert ALNA to DHA was either very low or absent, uptake of pre-formed DHA from the diet may be critical for maintaining adequate membrane DHA concentrations in these individuals.

Keywords

α-Linolenic acidPolyunsaturated fatty acidsMetabolism
Type
Research Article
Information
British Journal of Nutrition , Volume 88 , Issue 4 , October 2002 , pp. 355 - 363
Copyright
Copyright © The Nutrition Society 2002

References

Allman, MA, Pena, MM & Peng, D (1995) Supplementation with flaxseed oil versus sunflower oil in healthy young men when consuming a low fat diet: effects on platelet composition and function. European Journal of Clinical Nutrition 49, 169–178.Google ScholarPubMed
Beitz, J, Mest, HJ & Forster, W (1981) Influence of linseed oil diet on the pattern of serum phospholipids in man. Acta Biologica Medica Germany 40, K31–K35.Google ScholarPubMed
Bennoson, J, Humayun, MA, Jones, AE, Hounslow, A & Wootton, SA (1999) Within-individual variability in the gastrointestinal handling and metabolism of [1,1,1-13C]tripalmitin. Proceedings of the Nutrition Society 58, 25A.Google Scholar
Burdge, GC, Wright, P, Jones, AE & Wootton, SA (2000) A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid phase extraction. British Journal of Nutrition 84, 781–787.CrossRefGoogle ScholarPubMed
Caesar, PA, Wilson, SJ, Normand, ICS & Postle, AD (1988) A comparison of the specificity of phosphatidylcholine synthesis by human fetal lung maintained in either organ or organotypic culture. Biochemical Journal 253, 451–457.CrossRefGoogle ScholarPubMed
Carnielli, CP, Wattimena, JDL, Luijendijk, IHT, Boerlage, A, Dagenhart, HJ & Sauer, PJJ (1996) The very-low-birth-weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acid from linolenic and linolenic acid. Pediatric Research 40, 169–174.CrossRefGoogle Scholar
Chan, JK, McDonald, BE, Gerrard, JM, Bruce, VM, Weaver, BJ & Holub, BJ (1993) Effect of dietary α-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis. Lipids 28, 811–817.CrossRefGoogle ScholarPubMed
Cunnane, SC, Hamadeh, MJ, Leide, AC, Thompson, LU, Wolver, TMS & Jenkins, DJA (1995 a) Nutritional attributes of tradition flaxseed in healthy young adults. American Journal of Clinical Nutrition 61, 62–68.CrossRefGoogle ScholarPubMed
Cunnane, SC, Ryan, MA, Craig, KS, Brookes, S, Koletzko, B, Demmelmair, H, Singer, J & Kyle, DJ (1995 b) Synthesis of linoleate and (-linolenate by chain elongation in the rat. Lipids 30, 781–783.CrossRefGoogle ScholarPubMed
Emken, EA, Adolf, RO, Duval, SM & Nelson, GJ (1999) Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope-labeled oleic, linoleic and linolenic acids by male subjects. Lipids 34, 785–798.CrossRefGoogle ScholarPubMed
Emken, EA, Adolf, RO & Gully, RM (1994) Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochimica Biophysica Acta 1213, 277–288.CrossRefGoogle ScholarPubMed
Ezaki, O, Takahashi, M, Shigematsu, T, Shimamura, K, Kimura, J, Ezaki, H & Gotoh, T (1999) 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. Journal of Nutritional Science and Vitaminology (Tokyo) 45, 759–772.CrossRefGoogle ScholarPubMed
Folch, JL, Lees, M & Sloane-Stanley, GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. Journal of Biological Chemistry 226, 497–509.CrossRefGoogle ScholarPubMed
Freese, R, Mutanen, M, Valsta, LM & Salminen, I (1994) Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/α-linolenic acid ratio on platelet aggregation. Thrombosis and Haemostasis 71, 73–77.Google Scholar
Galli, C, Sirtori, CR, Mosconi, C, Medini, L, Giafranceschi, G, Vaccarino, V & Scolastico, C (1992) Prolonged retention of doubly labelled phosphatidylcholine in human plasma and erythrocytes after oral administration. Lipids 27, 105–1012.CrossRefGoogle ScholarPubMed
Garg, ML, Keelan, M, Thomson, ABR & Clandinin, MT (1992) Desaturation of linoleic acid in the small bowel is increased by short-term fasting and by dietary content of linoleic acid. Biochimica Biophysica Acta 1126, 17–25.CrossRefGoogle ScholarPubMed
Gerster, H (1998) Can adults convert α-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:5n-3)? International Journal of Vitamin and Nutrition Research 68, 159–173.Google Scholar
Irving, CS, Wong, WW, Schulman, RJ, Smith, EO & Klein, PD (1983) [13C]Bicarbonate kinetics in humans: intra- vs. inter-individual variations. American Journal of Physiology 245, R190–R202.Google Scholar
Jones, AE, Stolinski, M, Smith, RD, Murphy, JL & Wootton, SA (1999) Effect of fatty acid chain length and saturation on the gastrointestinal handling and metabolic disposal of dietary fatty acids in women. British Journal of Nutrition 81, 37–43.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Li, D, Sinclair, A, Wilson, A, Nakkote, S, Kelly, F, Abedin, L, Mann, N & Turner, A (1999) Effect of dietary α-linolenic acid on thrombotic risk factors in vegetarian men. American Journal of Clinical Nutrition 69, 872–882.CrossRefGoogle ScholarPubMed
Luthria, DL, Mohammed, S & Sprecher, H (1996) Regulation of the biosynthesis of 4,7,10,13,16,19-docosahexaenoic acid. Journal of Biological Chemistry 271, 16020–16025.CrossRefGoogle Scholar
Ministry of Agriculture, Fisheries and Food (1997) Dietary Intake of Iodine and Fatty Acids. Food Information Surveillance Sheet 127. London: Ministry of Agriculture, Fisheries and Food.Google Scholar
Pawlosky, RJ, Hibbeln, JR, Novotny, JA & Salem, N (2001) Physiological compartmental analysis of α-linolenic acid metabolism in adult humans. Journal of Lipid Research 42, 1257–1265.CrossRefGoogle ScholarPubMed
Redgrave, TG, Roberts, DCK & West, CE (1975) Separation of plasma lipoproteins by density gradient ultracentrifugation. Analytical Biochemistry 65, 42–49.CrossRefGoogle ScholarPubMed
Salem, N, Powlosky, R, Wegher, B & Hibbeln, J (1999) In vivo conversion of linoleic acid to arachidonic acid in human adults. Prostaglandins, Leukotrienes and Essential Fatty Acids 60, 407–410.CrossRefGoogle ScholarPubMed
Salem, N, 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
Sauerwald, TU, Hachey, DL, Jensen, CL, Chen, H, Anderson, RE & Heird, WC (1997) Intermediates in endogenous synthesis of C22:6ω3 and C20:4ω6 by term and preterm infants. Pediatric Research 41, 183–187.CrossRefGoogle Scholar
Sheaff, RC, Zhang, Q, Goodman, KJ, Giussani, 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.CrossRefGoogle Scholar
Sniderman, AD, Cianflone, K, Arner, P, Summers, LKM & Frayn, KN (1998) The adipocyte, fatty acid trapping and atherogenesis. Atheriosclerosis, Thrombosis and Vascular Biology 18, 147–151.CrossRefGoogle ScholarPubMed
Sprecher, H (2000) Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochimica et Biophysica Acta 1486, 219–231.CrossRefGoogle ScholarPubMed
Stolinski, M, Murphy, JL, Jones, AE, Jackson, AA & Wootton, SA (1997) Stable-isotope method for determining the gastrointestinal handling of [1-13C]palmitic acid. Lipids 32, 337–340.CrossRefGoogle ScholarPubMed
Su, HM, Bernardo, L, Mirmiran, M, Ma, XH, Corso, TN, Nathanielsz, PW & Brenna, JT (1999 a) Bioequivalence of dietary alpha-linolenic and docosahexaenoic acids as sources of docosahexaenoate accretion in brain and associated organs of neonatal baboons. Pediatric Research 45, 87–93.CrossRefGoogle ScholarPubMed
Su, HM, Bernardo, L, Mirmiran, M, Ma, XH, Nathanielsz, PW & Brenna, JT (1999 b) 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.CrossRefGoogle Scholar
Valsta, LM, Salminen, I, Aro, A & Mutanen, M (1996) Alpha-linolenic acid in rapeseed oil partly compensates for the effect of fish restriction on plasma long chain n-3 fatty acids. European Journal of Clinical Nutrition 50, 229–235.Google ScholarPubMed
Vermunt, SHF, Mensink, RP, Simonis, AMG & Hornstra, G (1999) Effects of age and dietary n-3 fatty acids on the metabolism of [13C]-α-linolenic acid. Lipids 34, S127 abstr.CrossRefGoogle Scholar
Vermunt, SHF, Mensink, RP, Simonis, AMG & Hornstra, G (2000) Effects of dietary (-linolenic acid on the conversion and oxidation of [13C]-α-linolenic acid. Lipids 35, 137–142.CrossRefGoogle ScholarPubMed
Voss, A, Reinhart, M, Sankarappa, S & Sprecher, H (1991) The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase. Journal of Biological Chemistry 266, 19995–20000.CrossRefGoogle Scholar
Watkins, JB, Klein, PD, Schoeller, DA, Kirschner, BS, Park, R & Perman, JA (1982) Diagnosis and differentiation of fat malabsorption in children using [13C]-labelled lipids: trioctanoin, triolein and palmitic acid breath tests. Gastroenterology 82, 911–917.CrossRefGoogle ScholarPubMed