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Low-n-6 and low-n-6 plus high-n-3 diets for use in clinical research

  • Beth A. MacIntosh (a1), Christopher E. Ramsden (a2), Keturah R. Faurot (a3) (a4), Daisy Zamora (a4), Margaret Mangan (a5), Joseph R. Hibbeln (a6) and J. Douglas Mann (a7)...

Abstract

Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; ≤ 2·5 % of energy (en%)) and arachidonic acid ( ≤ 60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA α-linolenic acid (ALA; ≥ 1·5 en%) and EPA+DHA ( ≥ 1000 mg/d). Pre- and intra-intervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to ≤ 2·5 en% (median LA 2·45 (2·1, 3·1); P< 0·001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1·6 en%, (1·3, 2·0), P< 0·001) and EPA+DHA (1482 mg, (374, 2558), P< 0·001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to ≤ 2·5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.

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Corresponding author

*Corresponding author: B. A. MacIntosh, fax +1 919 966 0576, email beth_macintosh@med.unc.edu

References

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1Agricultural Research Service (2010) Nutrient Intakes from Food. Amounts Consumed per Individual, by Gender and Age. What We Eat in America, NHANES 2007–2008 [US Department of Agriculture, editor]. Washington, DC: US Department of Agriculture, Agricultural Research Service.
2Blasbalg, TL, Hibbeln, JR, Ramsden, CE, et al. (2011) Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr 93, 950962.
3Kuipers, RS, Luxwolda, MF, Dijck-Brouwer, DA, et al. (2010) Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet. Br J Nutr 104, 16661687.
4Legrand, P, Schmitt, B, Mourot, J, et al. (2010) The consumption of food products from linseed-fed animals maintains erythrocyte omega-3 fatty acids in obese humans. Lipids 45, 1119.
5Mohrhauer, H & Holman, RT (1963) Alteration of the fatty acid composition of brain lipids by varying levels of dietary essential fatty acids. J Neurochem 10, 523530.
6Mohrhauer, H & Holman, RT (1963) The effect of dietary essential fatty acids upon composition of polyunsaturated fatty acids in depot fat and erythrocytes of the rat. J Lipid Res 4, 346350.
7Mohrhauer, H & Holman, RT (1963) The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver. J Lipid Res 4, 151159.
8Bourre, JM, Piciotti, M, Dumont, O, et al. (1990) Dietary linoleic acid and polyunsaturated fatty acids in rat brain and other organs. Minimal requirements of linoleic acid. Lipids 25, 465472.
9Lands, WE, Libelt, B, Morris, A, et al. (1992) 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 1180, 147162.
10Clark, KJ, Makrides, M, Neumann, MA, et al. (1992) Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas. J Pediatr 120, S151S158.
11Anonymous (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 354, 447455.
12Pradalier, A, Bakouche, P, Baudesson, G, et al. (2001) Failure of omega-3 polyunsaturated fatty acids in prevention of migraine: a double-blind study versus placebo. Cephalalgia 21, 818822.
13Thies, F, Garry, JM, Yaqoob, P, et al. (2003) Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 361, 477485.
14Goldberg, RJ & Katz, J (2007) A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 129, 210223.
15Filion, KB, El Khoury, F, Bielinski, M, et al. (2010) Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 10, 24.
16Ghosh, S, Novak, EM & Innis, SM (2007) Cardiac proinflammatory pathways are altered with different dietary n-6 linoleic to n-3 alpha-linolenic acid ratios in normal, fat-fed pigs. Am J Physiol Heart Circ Physiol 293, H2919H2927.
17Novak, EM, Dyer, RA & Innis, SM (2008) High dietary omega-6 fatty acids contribute to reduced docosahexaenoic acid in the developing brain and inhibit secondary neurite growth. Brain Res 1237, 136145.
18Dayton, S, Hashimoto, S & Pearce, ML (1967) Adipose tissue linoleic acid as a criterion of adherence to a modified diet. J Lipid Res 8, 508510.
19Hodson, L, Skeaff, CM & Fielding, BA (2008) Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res 47, 348380.
20Ramsden, CE, Mann, JD, Faurot, KR, et al. (2011) Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for chronic daily headache: protocol for a randomized clinical trial. Trials 12, 97.
21Headache Classification Subcommittee of the International Headache Society (2004) The International Classification of Headache Disorders: 2nd ed. Cephalalgia 24, Suppl. 1, 9–160.
22Bligh, EG & Dyer, WJ (1959) A rapid method for total lipid extraction and purification. Can J Biochem Physiol 37, 911917.
23Schakel, SF, Sievert, YA & Buzzard, IM (1988) Sources of data for developing and maintaining a nutrient database. J Am Diet Assoc 88, 12681271.
24Simopoulos, 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, 674688.
25Rett, BS & Whelan, J (2011) Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review. Nutr Metab 8, 36.
26Garland, M, Sacks, FM, Colditz, GA, et al. (1998) The relation between dietary intake and adipose tissue composition of selected fatty acids in US women. Am J Clin Nutr 67, 2530.
27Kingsbury, KJ, Paul, S, Crossley, A, et al. (1961) The fatty acid composition of human depot fat. Biochem J 78, 541550.
28Kingsbury, KJ, Heyes, TD, Morgan, DM, et al. (1962) The effect of dietary changes on the fatty acid composition of normal human depot fat. Biochem J 84, 124133.
29Dayton, S, Hashimoto, S, Dixon, W, et al. (1966) Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat. J Lipid Res 7, 103111.
30Katan, MB, Deslypere, JP, van Birgelen, AP, et al. (1997) Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study. J Lipid Res 38, 20122022.
31Rahm, JJ & Holman, RT (1964) Effect of linoleic acid upon the metabolism of linolenic acid. J Nutr 84, 1519.
32Nakamura, MT & Nara, TY (2003) Essential fatty acid synthesis and its regulation in mammals. Prostaglandins Leukot Essent Fatty Acids 68, 145150.
33Kitson, AP, Stroud, CK & Stark, KD (2010) Elevated production of docosahexaenoic acid in females: potential molecular mechanisms. Lipids 45, 209224.
34Friesen, RW & Innis, SM (2010) Linoleic acid is associated with lower long-chain n-6 ad n-3 fatty acids in red blood cell lipids of Canadian pregnant women. Am J Clin Nutr 91, 2331.
35Brenna, JT, Salem, N Jr, Sinclair, AJ, et al. (2009) Alpha-linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 80, 8591.
36Ulven, SM, Kirkhus, B, Lamglait, A, et al. (2011) Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers. Lipids 46, 3746.
37Rossmeisl, M, Jilkova, ZM, Kuda, O, et al. (2012) Metabolic effects of n-3 PUFA as phospholipids are superior to triglycerides in mice fed a high-fat diet: possible role of endocannabinoids. PLoS One 7, e38834.
38Umhau, JC (2011) Docosahexaenoic acid supplementation and Alzheimer disease. JAMA 305, 672, author reply 673.
39Hill, RJ & Davies, PS (2001) The validity of self-reported energy intake as determined using the doubly labelled water technique. Br J Nutr 85, 415430.
40Novotny, JA, Rumpler, WV, Riddick, H, et al. (2003) Personality characteristics as predictors of underreporting of energy intake on 24-hour dietary recall interviews. J Am Diet Assoc 103, 11461151.
41Thompson, FE & Byers, T (1994) Dietary assessment resource manual. J Nutr 124, 2245S2317S.
42Jonnalagadda, SS, Mitchell, DC, Smiciklas-Wright, H, et al. (2000) Accuracy of energy intake data estimated by a multiple-pass, 24-hour dietary recall technique. J Am Diet Assoc 100, 303308, quiz 309–311.
43Tran, KM, Johnson, RK, Soultanakis, RP, et al. (2000) In-person vs telephone-administered multiple-pass 24-hour recalls in women: validation with doubly labeled water. J Am Diet Assoc 100, 777783.
44Trabulsi, J & Schoeller, DA (2001) Evaluation of dietary assessment instruments against doubly labeled water, a biomarker of habitual energy intake. Am J Physiol Endocrinol Metab 281, E891E899.
45Blanton, CA, Moshfegh, AJ, Baer, DJ, et al. (2006) The USDA automated multiple-pass method accurately estimates group total energy and nutrient intake. J Nutr 136, 25942599.
46Moshfegh, AJ, Rhodes, DG, Baer, DJ, et al. (2008) The US Department of Agriculture automated multiple-pass method reduces bias in the collection of energy intakes. Am J Clin Nutr 88, 324332.
47Hebert, JR, Ockene, IS, Hurley, TG, et al. (1997) Development and testing of a seven-day dietary recall. Dietary Assessment Working Group of the Worcester Area Trial for Counseling in Hyperlipidemia (WATCH). J Clin Epidemiol 50, 925937.
48Toobert, DJ, Strycker, LA, Hampson, SE, et al. (2011) Computerized portion-size estimation compared to multiple 24-hour dietary recalls for measurement of fat, fruit, and vegetable intake in overweight adults. J Am Diet Assoc 111, 15781583.

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