Skip to main content
×
×
Home

n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials

  • Christopher E. Ramsden (a1), Joseph R. Hibbeln (a1), Sharon F. Majchrzak (a1) and John M. Davis (a2)
Abstract

Randomised controlled trials (RCT) of mixed n-6 and n-3 PUFA diets, and meta-analyses of their CHD outcomes, have been considered decisive evidence in specifically advising consumption of ‘at least 5–10 % of energy as n-6 PUFA’. Here we (1) performed an extensive literature search and extracted detailed dietary and outcome data enabling a critical examination of all RCT that increased PUFA and reported relevant CHD outcomes; (2) determined if dietary interventions increased n-6 PUFA with specificity, or increased both n-3 and n-6 PUFA (i.e. mixed n-3/n-6 PUFA diets); (3) compared mixed n-3/n-6 PUFA to n-6 specific PUFA diets on relevant CHD outcomes in meta-analyses; (4) evaluated the potential confounding role of trans-fatty acids (TFA). n-3 PUFA intakes were increased substantially in four of eight datasets, and the n-6 PUFA linoleic acid was raised with specificity in four datasets. n-3 and n-6 PUFA replaced a combination of TFA and SFA in all eight datasets. For non-fatal myocardial infarction (MI)+CHD death, the pooled risk reduction for mixed n-3/n-6 PUFA diets was 22 % (risk ratio (RR) 0·78; 95 % CI 0·65, 0·93) compared to an increased risk of 13 % for n-6 specific PUFA diets (RR 1·13; 95 % CI 0·84, 1·53). Risk of non-fatal MI+CHD death was significantly higher in n-6 specific PUFA diets compared to mixed n-3/n-6 PUFA diets (P = 0·02). RCT that substituted n-6 PUFA for TFA and SFA without simultaneously increasing n-3 PUFA produced an increase in risk of death that approached statistical significance (RR 1·16; 95 % CI 0·95, 1·42). Advice to specifically increase n-6 PUFA intake, based on mixed n-3/n-6 RCT data, is unlikely to provide the intended benefits, and may actually increase the risks of CHD and death.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Dr C. E. Ramsden, Tel. +1 301 435 6591, fax +1 301 402 0016, email chris.ramsden@nih.gov
References
Hide All
1 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, 902907.
2 Harris, WS (2008) Linoleic acid and coronary heart disease. Prostaglandins Leukot Essent Fatty Acids 79, 169171.
3 Czernichow, S, Thomas, D & Bruckert, E (2010) n-6 Fatty acids and cardiovascular health: a review of the evidence for dietary intake recommendations. Br J Nutr 104, 19.
4 Kris-Etherton, P & Harris, WS (2009) Dietary omega-6 polyunsaturated fatty acids – important for heart health. Clin Nutr Insight 35, 15.
5 Kris-Etherton, P, Fleming, J & Harris, WS (2010) The debate about n-6 polyunsaturated fatty acid recommendations for cardiovascular health. J Am Diet Assoc 110, 201204.
6 Gordon, D (1995) Lowering cholesterol and total mortality. In Lowering Cholesterol in High Risk Individuals and Populations, pp. 3348 [Rifkin, BM, editor]. New York: Marcel Dekker, Inc.
7 Mozaffarian, D, Micha, R & Wallace, S (2010) Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med 7, e1000252.
8 Katan, MB (2009) Omega-6 polyunsaturated fatty acids and coronary heart disease. Am J Clin Nutr 89, 12831284.
9 Ramsden, C (2009) A misrepresented meta-analysis. Letter to Circulation [serial on the Internet]. CIRCULATIONAHA/2009/865667. http://www.americanheart.org/downloadable/heart/1256648338750Omega6letterswresp.pdf.
10 Ramsden, CE, Hibbeln, JR, Lands, WE (2008) Letter to the Editor re: Linoleic acid and coronary heart disease. Prostaglandins Leukot Essent Fatty Acids, by WS Harris, Prostaglandins Leukot Essent Fatty Acids. 2009 Jan; 80, (1): 77; author reply-8.
11 Ramsden, CE, Faurot, KR, Carrera-Bastos, P, et al. (2009) Dietary fat quality and coronary heart disease prevention: a unified theory based on evolutionary, historical, global and modern perspectives. Curr Treat Options Cardiovasc Med 11, 289301.
12 Katan, MB, Brouwer, IA, Clarke, R, et al. (2010) Saturated fat and heart disease. Am J Clin Nutr 92, 459460.
13 Turpeinen, O (1968) Diet and coronary events. J Am Diet Assoc 52, 209213.
14 Turpeinen, O (1979) Effect of cholesterol-lowering diet on mortality from coronary heart disease and other causes. Circulation 59, 17.
15 Turpeinen, O, Miettinen, M, Karvonen, MJ, et al. (1968) Dietary prevention of coronary heart disease: long-term experiment. I. Observations on male subjects. Am J Clin Nutr 21, 255276.
16 Miettinen, M, Turpeinen, O, Karvonen, MJ, et al. (1972) Effect of cholesterol-lowering diet on mortality from coronary heart-disease and other causes. A twelve-year clinical trial in men and women. Lancet 2, 835838.
17 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, 1725.
18 Burr, ML, Fehily, AM, Gilbert, JF, et al. (1989) Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet ii, 757761.
19 Burr, ML, Fehily, AM, Rogers, S, et al. (1989) Diet and reinfarction trial (DART): design, recruitment, and compliance. Eur Heart J 10, 558567.
20 Fehily, AM, Vaughan-Williams, E, Shiels, K, et al. (1991) Factors influencing compliance with dietary advice: the Diet and Reinfarction Trial (DART). J Hum Nutr Diet 4, 3342.
21 Burr, ML (2001) Reflections on the Diet and Reinfarction Trial (DART). Eur Heart J 3, D75D78.
22 Turpeinen, O, Karvonen, MJ, Pekkarinen, M, et al. (1979) Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. Int J Epidemiol 8, 99118.
23 Reilly, JG, Ayis, SA, Ferrier, IN, et al. (2002) Thioridazine and sudden unexplained death in psychiatric in-patients. Br J Psychiatry 180, 515522.
24 Thornton, CC & Wendkos, MH (1971) EKG T-wave distortions among thioridazine-treated psychiatric inpatients (some correlates of the incidence and severity). Dis Nerv Syst 32, 320323.
25 Rouleau, F, Asfar, P, Boulet, S, et al. (2001) Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome. J Cardiovasc Electrophysiol 12, 6165.
26 Lipscomb, PA (1980) Cardiovascular side effects of phenothiazines and tricyclic antidepressants. A review with precautionary measures. Postgrad Med 67, 189192, 195–196.
27 Allison, DB, Mentore, JL, Heo, M, et al. (1999) Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 156, 16861696.
28 Fehily, AM, Vaughan-Williams, E, Shiels, K, et al. (1989) The effect of dietary advice on nutrient intakes: evidence from the diet and reinfarction trial (DART). J Hum Nutr Diet 2, 225235.
29 Food and Agricultural Organization of the United Nations [database on the Internet] [cited 2010]. http://faostat.fao.org/site/345/default.aspx.
30 Borenstein, M, Hedges, L, Higgins, J, et al. (2006) Comprehensive Meta-analysis version 2. meta-analysis.com2006.
31 Leren, P (1970) The Oslo Diet-Heart Study. Eleven-year report. Circulation 42, 935942.
32 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, 192.
33 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, 563569.
34 Watts, GF, Jackson, P, Burke, V, et al. (1996) Dietary fatty acids and progression of coronary artery disease in men. Am J Clin Nutr 64, 202209.
35 Medical Research Council (1968) Controlled trial of soya-bean oil in myocardial infarction. Lancet ii, 693699.
36 Hiscock, E, Dayton, S, Pearce, ML, et al. (1962) A palatable diet high in unsaturated fat. J Am Diet Assoc 40, 427431.
37 Rose, GA, Thomson, WB & Williams, RT (1965) Corn oil in treatment of ischaemic heart disease. Br Med J 1, 15311533.
38 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, 317330.
39 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, 129135.
40 Executive Committee on Diet and Heart Disease (1968) National Diet-Heart Study Report. Chapter XVII: Faribault Second Study. Circulation 37–38, I.260I.I74.
41 Clarke, JAC, Hedley, E, Marr, JW, et al. (1969) Dietary aspects of a controlled trial of soya-bean oil in myocardial infarction. Int J Food Sci Nutr 23, 136150.
42 U.S. Department of Health and Human Services (2005) Report of the Dietary Guidelines Advisory Committee on Dietary Guidelines for Americans 2005. http://www.health.gov/dietaryguidelines/dga2005/report/ (Accessed 2010).
43 Watts, GF, Jackson, P, Mandalia, S, et al. (1994) Nutrient intake and progression of coronary artery disease. Am J Cardiol 73, 328332.
44 Dayton, S, Pearce, ML, Hashimoto, S, et al. (1962) A controlled clinical trial of a diet high in unsaturated fat. Preliminary observations. N Engl J Med 266, 10171023.
45 Significant Points from the Annual Report of Marrickville Holdings. Sydney Morning Herald (19 November 1965). Sydney, Australia.
46 Woodhill, JM, Palmer, AJ & Blacket, RB (1969) Dietary habits and their modification in a coronary prevention programme for Australians. Food Technol Aust 21, 264271.
47 Woodhill, JM & Bernstein, L (1973) Lowering serum cholesterol levels by dietary modification. A change in food habits, not a special diet. Med J Aust 1, 973979.
48 Blacket, RB, Woodhill, J & Mishkel, MA (1965) Diet, hypercholesterolaemia and coronary heart disease. Med J Aust 1, 5963.
49 Fisher, M (1970) How the ‘Miracle’ was cowed: margarine quotas and politics. Aust Quart 42, 2033.
50 Palmer, J, Woodhill, J & Blacket, R (1969) Strict modified fat diet in coronary heart disease. The problem of nonresponders.. Isr J Med Sci 5, 754759.
51 Fetcher, ES, Foster, N, Anderson, JT, et al. (1967) Quantitative estimation of diets to control serum cholesterol. Am J Clin Nutr 20, 475492.
52 Brewer, ER, Ashman, PL & Kuba, K (1975) The Minnesota Coronary Survey: composition of their diets, adherence, and serum lipid response. Circulation 51 and 52, II-269.
53 Cornfield, J (1942–80) Jerome Cornfield Papers, MS 576. Ames, IA: Special Collections Department, Iowa State University Library. http://www.lib.iastate.edu/spcl/manuscripts/MS576.html.
54 Frantz, ID Jr (PI), Keys, A (Co-I) (1967). R01 HE 0986-03 Research Grant Application: Effect of a Dietary Change on Human Cardiovascular Disease ‘The Minnesota Coronary Survey’.
55 Frantz, ID (1971) Chemical Analysis of Three Week Food Collection in the Control and Treatment Diets for the Minnesota Coronary Survey: Unpublished Data Comparing the Institutional BC Diets at the Seven Individual Hospitals of the MCS.
56 Frantz, ID (PI) (1967). R01 HE 0986-02 Second Supplementary Progress Report: Effect of a Dietary Change on Human Cardiovascular Disease ‘The Minnesota Coronary Survey’.
57 Executive Committee on Diet and Heart Disease (1968) National Diet-Heart Study Report. Chapter IX: assessment of the diets. Circulation 37–38, I.125I.I40.
58 Frantz, ID Jr (1962) Notification and Statement of Grant Award: Diet and Heart Disease. New York: The Minnesota Governor's Council on Developmental Disabilities. http://www.mnddc.org/past/pdf-index.html.
59 Frantz, ID Jr (1963) Summary Progress Report: Feasibility Study – Diet and Heart Disease (closed study at Faribault, Minnesota). New York: The Minnesota Governor's Council on Developmental Disabilities. http://www.mnddc.org/past/pdf-index.html.
60 Moore, RB, Anderson, JT, Taylor, HL, et al. (1968) Effect of dietary fat on the fecal excretion of cholesterol and its degradation products in man. J Clin Invest 47, 15171534.
61 Begg, CB & Mazumdar, M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 10881101.
62 World Health Organization (2003) Diet, Nutrition and the Prevention of Chronic Diseases: Report of a Joint WHO/FAO Expert Consultation. WHO Technical Report Series no. 916. Geneva: WHO.
63 GISSI-Prevenzione Investigators (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.
64 Zittermann, A & Koerfer, R (2008) Vitamin D in the prevention and treatment of coronary heart disease. Curr Opin Clin Nutr Metab Care 11, 752757.
65 Cantwell, MM, Flynn, MA & Gibney, MJ (2006) Acute postprandial effect of hydrogenated fish oil, palm oil and lard on plasma cholesterol, triacylglycerol and non-esterified fatty acid metabolism in normocholesterolaemic males. Br J Nutr 95, 787794.
66 Mozaffarian, D, Aro, A & Willett, WC (2009) Health effects of trans-fatty acids: experimental and observational evidence. Eur J Clin Nutr 63, S5S21.
67 Medical Research Council (1965) Low-fat diet in myocardial infarction: a controlled trial. Lancet ii, 501504.
68 Frantz, ID, Dawson, EA, Kuba, K, et al. (1975) The Minnesota Coronary Survey: effect of diet on cardiovascular events and deaths. American Heart Association Scientific Proceedings. Circulation 52, Suppl. 2, II-14.
69 de Lorgeril, M, Renaud, S, Mamelle, N, et al. (1994) Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 343, 14541459.
70 Renaud, S, de Lorgeril, M, Delaye, J, et al. (1995) Cretan Mediterranean diet for prevention of coronary heart disease.. Am J Clin Nutr 61, Suppl. 6, 1360S1367S.
71 Simopoulos, AP (2001) The Mediterranean diets: what is so special about the diet of Greece? The scientific evidence. J Nutr 131, Suppl. 11, 3065S3073S.
72 de Lorgeril, M, Salen, P, Martin, JL, et al. (1999) Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction – final report of the Lyon Diet Heart Study. Circulation 99, 779785.
73 Begg, CB & Berlin, JA (1988) Publication bias – a problem in interpreting medical data. J R Statist Soc Series A – Statist Soc 151, 419463.
74 Stern, JM & Simes, RJ (1997) Publication bias: evidence of delayed publication in a cohort study of clinical research projects. BMJ 315, 640645.
75 Leren, P (1968) Effect of plasma-cholesterol-lowering diet in male survivors of myocardial infarction – a controlled clinical trial. Bull N Y Acad Med 44, 10121020.
76 Dayton, S, Chapman, JM & Pearce, ML, et al. (1970) Cholesterol, atherosclerosis, ischemic heart disease, and stroke. Ann Intern Med 72, 97109.
77 Dayton, 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.
78 Dayton, S, Hashimoto, S & Pearce, ML (1965) Influence of a diet high in unsaturated fat upon composition of arterial tissue and atheromata in man. Circulation 32, 911924.
79 Dayton, S, Hashimoto, S & Pearce, ML (1967) Adipose tissue linoleic acid as a criterion of adherence to a modified diet. J Lipid Res 8, 508510.
80 Dayton, S & Pearce, ML (1968) Trial of unsaturated-fat diet. Lancet ii, 12961297.
81 Dayton, S & Pearce, ML (1969) Diet high in unsaturated fat. A controlled clinical trial. Minn Med 52, 12371242.
82 Dayton, S & Pearce, ML (1969) Prevention of coronary heart disease and other complications of arteriosclerosis by modified diet. Am J Med 46, 751762.
83 Dayton, S & Pearce, ML (1970) Diet and atherosclerosis. Lancet i, 473474.
84 Dayton, S, Pearce, ML, Goldman, H, et al. (1968) Controlled trial of a diet high in unsaturated fat for prevention of atherosclerotic complications. Lancet ii, 10601062.
85 Pearce, ML & Dayton, S (1971) Incidence of cancer in men on a diet high in polyunsaturated fat. Lancet i, 464467.
86 Burr, ML & Fehily, AM (1991) Fatty fish and heart disease: a randomized controlled trial. World Rev Nutr Diet 66, 306312.
87 Woodhill, JM, Leelarthaepin, B, Blacket, RB, et al. (1975) Efficacy of weight reduction and carbohydrate restriction in moderate type 4 hyperlipidaemia. Cardiac Soc Aust N Z 5, 488.
88 Mozaffarian, D & Clarke, R (2009) Quantitative effects on cardiovascular risk factors and coronary heart disease risk of replacing partially hydrogenated vegetable oils with other fats and oils. Eur J Clin Nutr 63, Suppl. 2, S22S33.
89 National Food Survey [database on the Internet]. Department of Environment, Food and Rural Affairs [cited 2010]. http://www.defra.gov.uk/evidence/statistics/foodfarm/food/familyfood/nationalfoodsurvey/index.htm.
90 USDA (2006) USDA National Nutrient Database for Standard Reference.
91 Greaves, JP & Hollingsworth, DF (1966) Trends in food consumption in the United Kingdom. World Rev Nutr Diet 6, 3489.
92 Ostlund, RE Jr, Racette, SB, Okeke, A, et al. (2002) Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans. Am J Clin Nutr 75, 10001004.
93 Almendingen, K, Jordal, O, Kierulf, P, et al. (1995) Effects of partially hydrogenated fish-oil, partially hydrogenated soybean oil, and butter on serum-lipoproteins and Lp[a] in men. J Lipid Res 36, 13701384.
94 Enig, MG, Atal, S, Keeney, M, et al. (1990) Isomeric trans fatty acids in the U.S. diet. J Am Coll Nutr 9, 471486.
95 Roberts, DC (1991) Dietary factors in the fall in coronary heart disease mortality. Prostaglandins Leukot Essent Fatty Acids 44, 97101.
96 OECD (1954–1985) Food Consumption Statistics. Paris: Organisation for Economic Cooperation and Development.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed