Advertisement

Validation of an equation predicting highly unsaturated fatty acid (HUFA) compositions of human blood fractions from dietary intakes of both HUFAs and their precursors

      Highlights

      • Omega-3/omega-6 highly unsaturated fatty acids (HUFA) are disease risk biomarkers.
      • Precursor dietary fats are not typically included in estimating n-3 and n-6 HUFAs.
      • Reliable HUFA biomarkers estimates require both dietary precursor fats and HUFAs.

      Abstract

      Proportions of omega-3 (n-3) and omega-6 (n-6) in 20- and 22-carbon highly unsaturated fatty acids with 3 or more double bonds (HUFA) accumulated in tissue HUFA (e.g., the %n-6 in HUFA) are biomarkers reflecting intakes of n-6 and n-3 fatty acids. An empirical equation, referred to here as the Lands’ Equation, was developed previously to use dietary intakes of n-6 and n-3 HUFA and their 18-carbon precursors to estimate the %n-6 in HUFA of humans. From the PubMed database, we identified clinical trials reporting (a) dietary intake of at least linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), and (b) the amounts of at least arachidonic acid (20:4n-6), eicosapentaenoic acid (20:5n-3), and docosahexaenoic acid (22:6n-3) in lipids of plasma, serum, or red blood cell. Linear regression analyses comparing reported and predicted %n-6 in HUFA gave a correlation coefficient of 0.73 (p<0.000000) for 34 studies with 92 subject groups. These results indicate that circulating HUFA compositions can be reliably estimated from dietary intake data that not only includes n-3 and n-6 HUFA consumption, but also includes consumption of 18 carbon n-3 and n-6 precursor fatty acids.

      Abbreviations:

      AA (arachidonic acid), ALA (alpha-linolenic acid), DHA (docosahexaneoic acid), GLA (gamma-linolenic acid), en% (percent of energy), EPA (eicosapentaenoic acid), %EPA+DHA in RBC (percentage of EPA and DHA in total fatty acids of red blood cell), HUFA (highly unsaturated fatty acids), LA (linoleic acid), NR (not reported), n-3 (omega-3), n-6 (omega-6), %n-6 in HUFA (the percentage of omega-6 highly unsaturated fatty acids in total tissue HUFA), P-PL (plasma phospholipids), P-TL (plasma total lipids), PUFA (polyunsaturated fatty acids), RBC (red blood cell), RBC-PL (red blood cell phospholipids), S-PL (serum phospholipids), SDA (stearidonic acid), S-TL (serum total lipids)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Prostaglandins, Leukotrienes and Essential Fatty Acids
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Das U.N.
        Essential fatty acids—a review.
        Curr. Pharm. Biotechnol. 2006; 7: 467-482
        • Khanapure S.P.
        • Garvey D.S.
        • Janero D.R.
        • Letts L.G.
        Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers.
        Curr. Top. Med. Chem. 2007; 7: 311-340
        • Wada M.
        • DeLong C.J.
        • Hong Y.H.
        • Rieke C.J.
        • Song I.
        • Sidhu R.S.
        • Yuan C.
        • Warnock M.
        • Schmaier A.H.
        • Yokoyama C.
        • Smyth E.M.
        • Wilson S.J.
        • FitzGerald G.A.
        • Garavito R.M.
        • de Sui X.
        • Regan J.W.
        • Smith W.L.
        Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products.
        J. Biol. Chem. 2007; 282: 22254-22266
        • Hibbeln J.R.
        • Nieminen L.R.
        • Blasbalg T.L.
        • Riggs J.A.
        • Lands W.E.
        Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity.
        Am. J. Clin. Nutr. 2006; 83: 1483S-1493S
        • Lands B.
        Measuring blood fatty acids as a surrogate indicator for coronary heart disease risk in population studies.
        World Rev. Nutr. Diet. 2009; 100: 22-34
        • Wang D.
        • Dubois R.N.
        Eicosanoids and cancer.
        Nat. Rev. Cancer. 2010; 10: 181-193
        • Calder P.C.
        Polyunsaturated fatty acids, inflammation, and immunity.
        Lipids. 2001; 36: 1007-1024
        • Simopoulos A.P.
        Essential fatty acids in health and chronic disease.
        Am. J. Clin. Nutr. 1999; 70: 560S-569S
        • Phillis J.W.
        • Horrocks L.A.
        • Farooqui A.A.
        Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders.
        Brain Res. Rev. 2006; 52: 201-243
        • Tassoni D.
        • Kaur G.
        • Weisinger R.S.
        • Sinclair A.J.
        The role of eicosanoids in the brain.
        Asia Pac. J. Clin. Nutr. 2008; 17: 220-228
        • Bibus D.
        • Lands B.
        Balancing proportions of competing omega-3 and omega-6 highly unsaturated fatty acids (HUFA) in tissue lipids.
        Prost. Leuko. Ess. Fat. Acids. 2015; 99: 19-23
        • Lands B.
        Omega-3 PUFAs lower the propensity for arachidonic acid cascade overreactions.
        Biomed. Res. Int. 2015; 2015: 285135
        • Lands W.E.M.
        • Libelt B.
        • Morris A.
        • Kramer N.C.
        • Prewitt T.E.
        • Bowen P.
        • Schmeisser D.
        • Davidson M.H.
        • Burns J.H.
        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
        • Mohrhauer H.
        • Holman R.T.
        The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver.
        J. Lipid Res. 1963; 4: 151-159
        • Mohrhauer H.
        • Holman R.T.
        Effect of linolenic acid upon the metabolism of linoleic acid.
        J. Nutr. 1963; 81: 67-74
        • Lands B.
        A critique of paradoxes in current advice on dietary lipids.
        Prog. Lipid Res. 2008; 47: 77-106
        • Lands W.E.M.
        • Morris A.J.
        • Libelt B.
        Quantitative effects of dietary polyunsaturated fats on the composition of fatty acids in rat tissues.
        Lipids. 1990; 5: 505-516
        • Clark K.J.
        • Makrides M.
        • Neumann M.A.
        • Gibson R.A.
        Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas.
        J. Pediatr. 1992; 120: S151-S158
        • Lands W.E.M.
        Functional foods in primary prevention or nutraceuticals in secondary prevention?.
        Curr. Top. Nutraceutical Res. 2003; 1: 113-120
      1. Equation with Revised Constants online: 〈http://efaeducation.org/relating-diets-to-hufa/〉.

        • Chan J.K.
        • McDonald B.E.
        • Gerrard J.M.
        • Bruce V.M.
        • Weaver B.J.
        • Holub B.J.
        Effect of dietary alpha-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis.
        Lipids. 1992; 28: 811-817
        • Finnegan Y.E.
        • Minihane A.M.
        • Leigh-Firbank E.C.
        • Kew S.
        • Meijer G.W.
        • Muggli R.
        • Calder P.C.
        • Williams C.M.
        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
        • Hirota S.
        • Adachi N.
        • Gomyo T.
        • Kawashima H.
        • Kiso Y.
        • Kawabata T.
        Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women.
        Prostaglandins Leukot. Essent. Fat. Acids. 2010; 83: 83-88
        • King I.B.
        • Lemaitre R.N.
        • Kestin M.
        Effect of a low-fat diet on fatty acid composition in red cells, plasma, phospholipids, and cholesterol esters: investigation of a biomarker of total fat intake.
        Am. J. Clin. Nutr. 2006; 83: 227-236
        • Legrand P.
        • Schmitt B.
        • Mourot J.
        • Catheline D.
        • Chesneau G.
        • Mireaux M.
        • Kerhoas N.
        • Weill P.
        The consumption of food products from linseed-fed animals maintains erythrocyte omega-3 fatty acids in obese humans.
        Lipids. 2010; 45: 11-19
        • Olza J.
        • Mesa M.D.
        • Aguilera C.M.
        • Moreno-Torres R.
        • Jiménez A.
        • Pérez de la Cruz A.
        • Gil A.
        Influence of an eicosapentaenoic and docosahexaenoic acid-enriched enteral nutrition fomula on plasma fatty acid composition and biomarkers of insulin resistance in the elderly.
        Clin. Nutr. 2010; 29: 31-37
        • Södergren E.
        • Gustafsson I.B.
        • Basu S.
        • Nourooz-Zadeh J.
        • Nälsén C.
        • Turpeinen A.
        • Berglund L.
        • Vessby B.
        A diet containing rapeseed oil-based fats does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids.
        Eur. J. Clin. Nutr. 2001; 55: 922-993
        • Thies F.
        • Nebe-von-Caron G.
        • Powell J.R.
        • Yaqoob P.
        • Newsholme E.A.
        • Calder P.C.
        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 aged >55 y.
        Am. J. Clin. Nutr. 2001; 73: 539-548
        • 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
        • Dabadie H.
        • Motta C.
        • Peuchant E.
        • LeRuyet P.
        • Mendy F.
        Variations in daily intakes of myristic and alpha-linolenic acids in sn-2 position modify lipid profile and red blood cell membrane fluidity.
        Br. J. Nutr. 2006; 96: 283-289
        • Forsythe C.E.
        • Phinney S.D.
        • Fernandez M.L.
        • Quann E.E.
        • Wood R.J.
        • Bibus D.M.
        • Kraemer W.J.
        • Feinman R.D.
        • Volek J.S.
        Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation.
        Lipids. 2007; 43: 65-77
        • Valsta L.M.
        • 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
        • Almario R.U.
        • Vonghavaravat V.
        • Wong R.
        • Kasim-Karakas S.E.
        Effects of walnut consumption on plasma fatty acids and lipoproteins in combined hyperlipidemia.
        Am. J. Clin. Nutr. 2001; 74: 72-79
        • Bourque C.
        • St-Onge P.
        • Papamandjaris A.A.
        • Cohn J.S.
        • Jones P.J.
        Consumption of an oil composed of medium chain triacylglycerols, phytosterols, and N-3 fatty acids improves cardiovascular risk profile in overweight women.
        Metabolism. 2003; 52: 771-777
        • Goyens P.L.
        • Spilker M.E.
        • Zock P.L.
        • Katan M.B.
        • Mensink R.P.
        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 the ratio.
        Am. J. Clin. Nutr. 2006; 84: 44-53
        • Griel A.E.
        • Kris-Etherton P.M.
        • Hilpert K.F.
        • Zhao G.
        • West S.G.
        • Corwin R.L.
        An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans.
        Nutr. J. 2007; 6: 2
        • Li D.
        • A. Sinclair A.
        • Wilson A.
        • Nakkote S.
        • Kelly F.
        • Abedin L.
        • Mann N.
        • Turner A.
        Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men.
        Am. J. Clin. Nutr. 1999; 69: 872-882
        • Lichtenstein A.H.
        • Matthan N.R.
        • Jalbert S.M.
        • Resteghini N.A.
        • Schaefer E.J.
        • Ausman L.M.
        Novel soybean oils with different fatty acid profiles alter cardiovascular disease risk factors in moderately hyperlipidemic subjects.
        Am. J. Clin. Nutr. 2006; 84: 497-504
        • Raatz S.K.
        • Bibus D.
        • Thomas W.
        • Kris-Etherton P.
        Total fat intake modifies plasma fatty acid composition in humans.
        J. Nutr. 2001; 131: 231-234
        • Seppänen-Laaksoa T.
        • Laakso I.
        • Lehtimäki T.
        • Rontu R.
        • Moilanen E.
        • Solakivi T.
        • Seppo L.
        • Vanhanen H.
        • Kiviranta K.
        • Hiltunen R.
        Elevated plasma fibrinogen caused by inadequate alpha-linolenic acid intake can be reduced by replacing fat with canola-type rapeseen oil.
        Prostaglandins Leukot. Essent. Fat. Acids. 2010; 83: 45-54
        • Thijssen M.A.
        • Mensink R.P.
        Small differences in the effects of stearic acid, oleic acid, and linoleic acid on the serum lipoprotein profile of humans.
        Am. J. Clin. Nutr. 2005; 82: 510-516
        • Vega-López S.
        • Ausman L.M.
        • Jalbert S.M.
        • Erkkilä A.T.
        • Lichtenstein A.H.
        Palm and partially hydrogenated soybean oils adversely alter lipoprotein profiles compared with soybean and canola oils in moderately hyperlipidemic subjects.
        Am. J. Clin. Nutr. 2006; 84: 54-62
        • Astorg P.
        • Bertrais S.
        • Laporte F.
        • Arnault N.
        • Estaquio C.
        • Galan P.
        • Favier A.
        • Hercberg S.
        Plasma n-6 and n-3 polyunsaturated fatty acids as biomarkers of their dietary intakes: a cross-sectional study within a cohort of middle-aged French men and women.
        Eur. J. Clin. Nutr. 2008; 62: 1155-1161
        • 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: 98-99
        • Friesen R.W.
        • Innis S.M.
        Linoleic acid is associated with lower long-chain n-6 and n-3 fatty acids in red blood cell lipids in Canadian pregnant women.
        Am. J. Clin. Nutr. 2010; 91: 23-31
        • Glew R.H.
        • Wold R.S.
        • Herbein J.H.
        • Wark W.A.
        • Martinez M.A.
        • Vanderjagt D.J.
        Low docosahexaenoic acid in the diet and milk of women in New Mexico.
        J. Am. Diet. Assoc. 2008; 108: 1693-1699
        • Kobayashi M.
        • Sasaki S.
        • Kawabata T.
        • Hasegawa K.
        • Akabane M.
        • Tsugane S.
        Single measurement of serum phospholipid fatty acid as a biomarker of specific fatty acid intake in middle-aged men.
        Eur. J. Clin. Nutr. 2001; 55: 643-650
        • Kröger J.
        • Zietemann V.
        • Enzenbach C.
        • Weikert C.
        • Jansen E.H.
        • Döring F.
        • Joost H.G.
        • Boeing H.
        • Schulze M.B.
        Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.
        Am. J. Clin. Nutr. 2011; 93: 127-143
        • Kuriki K.
        • Nagaya T.
        • Imaeda N.
        • Tokudome Y.
        • Fujiwara N.
        • Sato J.
        • Ikeda M.
        • Maki S.
        • Tokudome S.
        Discrepancies in dietary intakes and plasma concentrations of fatty acids according to age among Japanese female dietitians.
        Eur. J. Clin. Nutr. 2002; 56: 524-531
        • Kuriki K.
        • Nagaya T.
        • Tokudome Y.
        • Imaeda N.
        • Fujiwara N.
        • Sato J.
        • Goto C.
        • Ikeda M.
        • Maki S.
        • Tajima K.
        • Tokudome S.
        Plasma concentrations of (n-3) highly unsaturated fatty acids are good biomarkers of relative dietary fatty acid intakes: a cross-sectional study.
        J. Nutr. 2003; 133: 3643-3650
        • Thiébaut A.C.
        • Kasai M.
        • Taguchi N.
        • Lenoir G.M.
        • Boutron-Ruault M.C.
        • Joulin V.
        • Clavel-Chapelon F.
        • Chajès V.
        Correlation between serum phospholipid fatty acids and dietary intakes assessed a few years earlier.
        Nutr. Cancer. 2009; 61: 500-509
        • Yamada T.
        • Strong J.P.
        • Ishii T.
        • Ueno T.
        • Koyama M.
        • Wagayama H.
        • Shimizu A.
        • Sakai T.
        • Malcom G.T.
        • Guzman M.A.
        Atherosclerosis and omega-3 fatty acids in the populations of a fishing village and a farming village in Japan.
        Atherosclerosis. 2000; 153: 469-481
        • Fuhrman B.J.
        • Barba M.
        • Krogh V.
        • Micheli A.
        • Pala V.
        • Lauria R.
        • Chajes V.
        • Riboli E.
        • Sieri S.
        • Berrino F.
        • Muti P.
        Erythrocyte membrane phospholipid composition as a biomarker of dietary fat.
        Ann. Nutr. Metab. 2006; 50: 95-102
      2. Simple Calculator: 〈http://efaeducation.org/omega_foods_apps/dietary-balance/〉.

        • Harris W.S.
        The omega-3 index as a risk factor for coronary heart disease.
        Am. J. Clin. Nutr. 2008; 87: 1997S-2002S
        • Stark K.D.
        The percentage of n-3 highly unsaturated fatty acids in total HUFA as a biomarker for omega-3 fatty acid status in tissues.
        Lipids. 2008; 43: 45-53
        • Murphy M.G.
        • Wright V.
        • Scott J.
        • Timmins A.
        • Ackman R.G.
        Dietary menhaden, seal, and corn oils differentially affect lipid and ex vivo eicosanoid and thiobarbituric acid-reactive substances generation in the guinea pig.
        Lipids. 1999; 34: 115-124
        • Sun Q.
        • Ma J.
        • Campos H.
        • Rexrode K.M.
        • Albert C.M.
        • Mozaffarian D.
        • Hu F.B.
        Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction.
        Am. J. Clin. Nutr. 2008; 88: 216-223
        • Armstrong J.F.
        • Metherel A.H.
        • Stark K.D.
        Direct microwave transesterification of fingertip prick blood samples for fatty acid determinations.
        Lipids. 2008; 43: 187-196
        • Stark K.D.
        • Beblo S.
        • Murthy M.
        • Buda-Abela M.
        • Janisse J.
        • Rockett H.
        • Whitty J.E.
        • Martier S.S.
        • Sokol R.J.
        • Hannigan J.H.
        • Salem N.
        Comparison of bloodstream fatty acid composition from African-American women at gestation, delivery, and postpartum.
        J. Lipid Res. 2005; 46: 516-525
        • Lands B.
        Benefit–risk assessment of fish oil in preventing cardiovascular disease.
        Drug Saf. 2016; 39: 787-799