1 Kris-Etherton, PM, Taylor, DS, Yu-Poth, S, et al. (2000) Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 71, 179S–188S.
2 Harris, WS, Mozaffarian, D, Rimm, E, et al. (2009) Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation 119, 902–907.
3 Simopoulos, AP (2008) The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood) 233, 674–688.
4 Hamazaki, T & Okuyama, H (2003) The Japan Society for Lipid Nutrition recommends to reduce the intake of linoleic acid. A review and critique of the scientific evidence. World Rev Nutr Diet 92, 109–132.
5 Ailhaud, G (2008) Omega-6 fatty acids and excessive adipose tissue development. World Rev Nutr Diet 98, 51–61.
6 Holman, RT (1961) How essential are fatty acids? JAMA 178, 930–933.
7 Williard, DE, Nwankwo, JO, Kaduce, TL, et al. (2001) Identification of a fatty acid delta6-desaturase deficiency in human skin fibroblasts. J Lipid Res 42, 501–508.
8 Moshfegh, A, Goldman, J & Cleveland, L (2005) What we Eat in America: NHANES 2001–2002: Usual Nutrient Intakes from Food Compared to Dietary Reference Intakes. Beltsville, MD: US Department of Agriculture, Agricultural Research Service.
9 Astorg, P, Bertrais, S, Laporte, F, et al. (2008) 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 62, 1155–1161.
10 Poudel-Tandukar, K, Nanri, A, Matsushita, Y, et al. (2009) Dietary intakes of alpha-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men. Nutr Res 29, 363–370.
11 Rosell, MS, Lloyd-Wright, Z, Appleby, PN, et al. (2005) Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men. Am J Clin Nutr 82, 327–334.
12 Baylin, A, Kim, MK, Donovan-Palmer, A, et al. (2005) Fasting whole blood as a biomarker of essential fatty acid intake in epidemiologic studies: comparison with adipose tissue and plasma. Am J Epidemiol 162, 373–381.
13 Astorg, P, Bertrais, S, Laporte, F, et al. (2008) 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 62, 1155–1161.
14 Calder, PC (2007) Dietary arachidonic acid: harmful, harmless or helpful? Br J Nutr 98, 451–453.
15 Kusumoto, A, Ishikura, Y, Kawashima, H, et al. (2007) Effects of arachidonate-enriched triacylglycerol supplementation on serum fatty acids and platelet aggregation in healthy male subjects with a fish diet. Br J Nutr 98, 626–635.
16 Williams, ES, Baylin, A & Campos, H (2007) Adipose tissue arachidonic acid and the metabolic syndrome in Costa Rican adults. Clin Nutr 26, 474–482.
17 Sprecher, H, Luthria, DL, Mohammed, BS, et al. (1995) Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J Lipid Res 36, 2471–2477.
18 Nakamura, MT & Nara, TY (2004) Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu Rev Nutr 24, 345–376.
19 Cunnane, SC, Keeling, PW, Thompson, RP, et al. (1984) Linoleic acid and arachidonic acid metabolism in human peripheral blood leucocytes: comparison with the rat. Br J Nutr 51, 209–217.
20 Demmelmair, H, Iser, B, Rauh-Pfeiffer, A, et al. (1999) Comparison of bolus versus fractionated oral applications of [13C]-linoleic acid in humans. Eur J Clin Invest 29, 603–609.
21 Emken, EA, Adlof, RO & Gulley, RM (1994) Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta 1213, 277–288.
22 Hussein, N, Ah-Sing, E, Wilkinson, P, et al. (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, 269–280.
23 Sarkkinen, ES, Agren, JJ, Ahola, I, et al. (1994) Fatty acid composition of serum cholesterol esters, and erythrocyte and platelet membranes as indicators of long-term adherence to fat-modified diets. Am J Clin Nutr 59, 364–370.
24 NCEP NCaEP (2001)
25 Briel, M, Ferreira-Gonzalez, I, You, JJ, et al. (2009) Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. BMJ 338, b92.
26 Katan, MB, Zock, PL & Mensink, RP (1994) Effects of fats and fatty acids on blood lipids in humans: an overview. Am J Clin Nutr 60, 1017S–1022S.
27 Nichaman, MZ, Sweeley, CC & Olson, RE (1967) Plasma fatty acids in normolipemic and hyperlipemic subjects during fasting and after linoleate feeding. Am J Clin Nutr 20, 1057–1069.
28 Shepherd, J, Packard, CJ, Grundy, SM, et al. (1980) Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man. J Lipid Res 21, 91–99.
29 Mensink, RP, Zock, PL, Katan, MB, et al. (1992) Effect of dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans. J Lipid Res 33, 1493–1501.
30 Mensink, RP, Zock, PL, Kester, AD, et al. (2003) Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr 77, 1146–1155.
31 Clarke, R, Frost, C, Collins, R, et al. (1997) Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ 314, 112–117.
32 Hodson, L, Skeaff, CM & Chisholm, WA (2001) The effect of replacing dietary saturated fat with polyunsaturated or monounsaturated fat on plasma lipids in free-living young adults. Eur J Clin Nutr 55, 908–915.
33 Franceschini, G (2001) Epidemiologic evidence for high-density lipoprotein cholesterol as a risk factor for coronary artery disease. Am J Cardiol 88, 9N–13N.
34 Yusuf, S, Hawken, S, Ounpuu, S, et al. (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet 364, 937–952.
35 Siguel, E (1996) A new relationship between total/high density lipoprotein cholesterol and polyunsaturated fatty acids. Lipids 31, S51–S56.
36 Jakobsen, MU, O'Reilly, EJ, Heitmann, BL, et al. (2009) Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr 89, 1425–1432.
37 Hodson, L, Skeaff, CM & Chisholm, WA (2001) The effect of replacing dietary saturated fat with polyunsaturated or monounsaturated fat on plasma lipids in free-living young adults. Eur J Clin Nutr 55, 908–915.
38 Salonen, JT, Salonen, R, Ihanainen, M, et al. (1988) Blood pressure, dietary fats, and antioxidants. Am J Clin Nutr 48, 1226–1232.
39 Oster, P, Arab, L, Schellenberg, B, et al. (1980) Linoleic acid and blood pressure. Prog Food Nutr Sci 4, 39–40.
40 Grimsgaard, S, Bonaa, KH, Jacobsen, BK, et al. (1999) Plasma saturated and linoleic fatty acids are independently associated with blood pressure. Hypertension 34, 478–483.
41 Simon, JA, Fong, J & Bernert, JT Jr (1996) Serum fatty acids and blood pressure. Hypertension 27, 303–307.
42 Iacono, JM, Dougherty, RM & Puska, P (1982) Reduction of blood pressure associated with dietary polyunsaturated fat. Hypertension 4, III34–III42.
43 Hall, WL (2009) Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function. Nutr Res Rev 22, 18–38.
44 Hornstra, G, Chait, A, Karvonen, MJ, et al. (1973) Influence of dietary fat on platelet function in men. Lancet 1, 1155–1157.
45 Knapp, HR (1997) Dietary fatty acids in human thrombosis and hemostasis. Am J Clin Nutr 65, 1687S–1698S.
46 Thijssen, MA, Hornstra, G & Mensink, RP (2005) Stearic, oleic, and linoleic acids have comparable effects on markers of thrombotic tendency in healthy human subjects. J Nutr 135, 2805–2811.
47 Halliwell, B & Chirico, S (1993) Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr 57, 715S–724S.
48 Steinberg, D, Parthasarathy, S, Carew, TE, et al. (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915–924.
49 Navab, M, Ananthramaiah, GM, Reddy, ST, et al. (2004) The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 45, 993–1007.
50 Abbey, M, Belling, GB, Noakes, M, et al. (1993) Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary linoleate supplementation. Am J Clin Nutr 57, 391–398.
51 Berry, EM, Eisenberg, S, Haratz, D, et al. (1991) Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins – the Jerusalem Nutrition Study: high MUFAs vs high PUFAs. Am J Clin Nutr 53, 899–907.
52 Bonanome, A, Pagnan, A, Biffanti, S, et al. (1992) Effect of dietary monounsaturated and polyunsaturated fatty acids on the susceptibility of plasma low density lipoproteins to oxidative modification. Arterioscler Thromb 12, 529–533.
53 Kleemola, P, Freese, R, Jauhiainen, M, et al. (2002) Dietary determinants of serum paraoxonase activity in healthy humans. Atherosclerosis 160, 425–432.
54 Damsgaard, CT, Frokiaer, H, Andersen, AD, et al. (2008) Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men. J Nutr 138, 1061–1066.
55 Calder, PC & Grimble, RF (2002) Polyunsaturated fatty acids, inflammation and immunity. Eur J Clin Nutr 56, Suppl. 3, S14–S19.
56 Tilley, SL, Coffman, TM & Koller, BH (2001) Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 108, 15–23.
57 De Caterina, R, Liao, JK & Libby, P (2000) Fatty acid modulation of endothelial activation. Am J Clin Nutr 71, 213S–223S.
58 Serhan, CN (2005) Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot Essent Fatty Acids 73, 141–162.
59 Pischon, T, Hankinson, SE, Hotamisligil, GS, et al. (2003) Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 108, 155–160.
60 Ferrucci, L, Cherubini, A, Bandinelli, S, et al. (2006) Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrinol Metab 91, 439–446.
61 Thies, F, Miles, EA, Nebe-von-Caron, G, et al. (2001) Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids 36, 1183–1193.
62 Lewis, CE, McTigue, KM, Burke, LE, et al. (2009) Mortality, health outcomes, and body mass index in the overweight range: a science advisory from the American Heart Association. Circulation 119, 3263–3271.
63 Romero-Corral, A, Somers, VK & Sierra-Johnson, J (2009) Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J 31, 737–746.
64 DiGirolamo, M, Fine, JB, Tagra, K, et al. (1998) Qualitative regional differences in adipose tissue growth and cellularity in male Wistar rats fed ad libitum. Am J Physiol 274, R1460–R1467.
65 Hausman, DB, DiGirolamo, M, Bartness, TJ, et al. (2001) The biology of white adipocyte proliferation. Obes Rev 2, 239–254.
66 Tchoukalova, YD, Sarr, MG & Jensen, MD (2004) Measuring committed preadipocytes in human adipose tissue from severely obese patients by using adipocyte fatty acid binding protein. Am J Physiol Regul Integr Comp Physiol 287, R1132–R1140.
67 Cleary, MP, Phillips, FC & Morton, RA (1999) Genotype and diet effects in lean and obese Zucker rats fed either safflower or coconut oil diets. Proc Soc Exp Biol Med 220, 153–161.
68 Massiera, F, Saint-Marc, P, Seydoux, J, et al. (2003) Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? J Lipid Res 44, 271–279.
69 Gaillard, D, Negrel, R, Lagarde, M, et al. (1989) Requirement and role of arachidonic acid in the differentiation of pre-adipose cells. Biochem J 257, 389–397.
70 Miller, CW, Casimir, DA & Ntambi, JM (1996) The mechanism of inhibition of 3T3-L1 preadipocyte differentiation by prostaglandin F2alpha. Endocrinology 137, 5641–5650.
71 Serrero, G, Lepak, NM & Goodrich, SP (1992) Paracrine regulation of adipose differentiation by arachidonate metabolites: prostaglandin F2 alpha inhibits early and late markers of differentiation in the adipogenic cell line 1246. Endocrinology 131, 2545–2551.
72 Serrero, G, Lepak, NM & Goodrich, SP (1992) Prostaglandin F2 alpha inhibits the differentiation of adipocyte precursors in primary culture. Biochem Biophys Res Commun 183, 438–442.
73 Matsuo, T, Takeuchi, H, Suzuki, H, et al. (2002) Body fat accumulation is greater in rats fed a beef tallow diet than in rats fed a safflower or soybean oil diet. Asia Pac J Clin Nutr 11, 302–308.
74 Okuno, M, Kajiwara, K, Imai, S, et al. (1997) Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down-regulating adipocyte differentiation. J Nutr 127, 1752–1757.
75 Hernandez-Morante, JJ, Larque, E, Lujan, JA, et al. (2009) N-6 from different sources protect from metabolic alterations to obese patients: a factor analysis. Obesity (Silver Spring) 17, 452–459.
76 Shekelle, RB, Shryock, AM, Paul, O, et al. (1981) Diet, serum cholesterol, and death from coronary heart disease. The Western Electric study. N Engl J Med 304, 65–70.
77 Hu, FB, Stampfer, MJ, Manson, JE, et al. (1997) Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 337, 1491–1499.
78 Oh, K, Hu, FB, Manson, JE, et al. (2005) Dietary fat intake and risk of coronary heart disease in women: 20 years of follow-up of the nurses' health study. Am J Epidemiol 161, 672–679.
79 Laaksonen, DE, Nyyssonen, K, Niskanen, L, et al. (2005) Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids. Arch Intern Med 165, 193–199.
80 Harris, WS, Poston, WC & Haddock, CK (2007) Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 193, 1–10.
81 Block, RC, Harris, WS, Reid, KJ, et al. (2008) Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes? Am Heart J 156, 1117–1123.
82 Frantz, ID Jr, Dawson, EA, Ashman, PL, et al. (1989) Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis 9, 129–135.
83 Leren, P (1966) The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Acta Med Scand Suppl 466, 1–92.
84 Woodhill, JM, Palmer, AJ, Leelarthaepin, B, et al. (1978) Low fat, low cholesterol diet in secondary prevention of coronary heart disease. Adv Exp Med Biol 109, 317–330.
85 Rose, GA, Thomson, WB & Williams, RT (1965) Corn oil in treatment of ischaemic heart disease. Br Med J 1, 1531–1533.
86 Turpeinen, O, Karvonen, MJ, Pekkarinen, M, et al. (1979) Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. Int J Epidemiol 8, 99–118.
87 Miettinen, M, Turpeinen, O, Karvonen, MJ, et al. (1983) Dietary prevention of coronary heart disease in women: the Finnish Mental Hospital Study. Int J Epidemiol 12, 17–25.
88 Dayton, S, Pearce, ML, Goldman, H, et al. (1968) Controlled trial of a diet high in unsaturated fat for prevention of atherosclerotic complications. Lancet 2, 1060–1062.
89 Siri-Tarino, PW, Sun, Q, Hu, FB, et al. (2010) Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr 91, 535–546.
90 Kris-Etherton, PM, Innis, S, Ammerican, DA, et al. (2007) Position of the American Dietetic Association and Dietitians of Canada: dietary fatty acids. J Am Diet Assoc 107, 1599–1611.
91 Trumbo, P, Schlicker, S, Yates, AA, et al. (2002) Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc 102, 1621–1630.
92 National Health and Medical Research Council (2006) Nutrient Reference Values for Australia and New Zealand Including Recommended Dietary Intakes. Canberra: ISBN Print.
93 Sasaki, S (2008) Dietary Reference Intakes (DRIs) in Japan. Asia Pac J Clin Nutr 17, Suppl. 2, 420–444.
94 Eurodiet Project (2001) .
95 U.S. Department of Health and Human Services & U.S. Department of Agriculture (2005) Dietary Guidelines for Americans, 6th ed. Washington, DC: U.S. Government Printing Office.
96 Stanley, JC, Elsom, RL, Calder, PC, et al. (2007) UK Food Standards Agency Workshop Report: the effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. Br J Nutr 98, 1305–1310.
97 Harris, WS (2006) The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep 8, 453–459.
98 Katan, MB (2009) Omega-6 polyunsaturated fatty acids and coronary heart disease. Am J Clin Nutr 89, 1283–1284.
99 Tunstall-Pedoe, H (2006) Preventing Chronic Diseases. A Vital Investment: WHO Global Report. Geneva: World Health Organization pp. 200. .
100 McGee, DL, Reed, DM, Yano, K, et al. (1984) Ten-year incidence of coronary heart disease in the Honolulu Heart Program. Relationship to nutrient intake. Am J Epidemiol 119, 667–676.
101 Kushi, LH, Lew, RA, Stare, FJ, et al. (1985) Diet and 20-year mortality from coronary heart disease. The Ireland-Boston Diet-Heart Study. N Engl J Med 312, 811–818.
102 Posner, BM, Cobb, JL, Belanger, AJ, et al. (1991) Dietary lipid predictors of coronary heart disease in men. The Framingham Study. Arch Intern Med 151, 1181–1187.
103 Dolecek, TA (1992) Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Proc Soc Exp Biol Med 200, 177–182.
104 Esrey, KL, Joseph, L & Grover, SA (1996) Relationship between dietary intake and coronary heart disease mortality: lipid research clinics prevalence follow-up study. J Clin Epidemiol 49, 211–216.
105 Ascherio, A, Rimm, EB, Giovannucci, EL, et al. (1996) Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. BMJ 313, 84–90.
106 Pietinen, P, Ascherio, A, Korhonen, P, et al. (1997) Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol 145, 876–887.
107 Medical Research Council (1968) Controlled trial of soya-bean oil in myocardial infarction: report of a research committee to the Medical Research Council. Lancet 292, 693–700.
108 Watts, GF, Lewis, B, Brunt, JN, et al. (1992) Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS). Lancet 339, 563–569.
109 Agence Française de Sécurité Sanitaire des Aliments (2003) .
110 British Nutrition Foundation (2004)