Rajiv Chowdhury, MD, PhD; Samantha Warnakula, MPhil (1); Setor Kunutsor, MD, MSt (1); Francesca Crowe, PhD; Heather A. Ward, PhD; Laura Johnson, PhD; Oscar H. Franco, MD, PhD; Adam S. Butterworth, PhD; Nita G. Forouhi, MRCP, PhD; Simon G. Thompson, FMedSci; Kay-Tee Khaw, FMedSci; Dariush Mozaffarian, MD, DrPH; John Danesh, FRCP (1); Emanuele Di Angelantonio, MD, PhD (1)
* Ms. Warnakula and Dr. Kunutsor contributed equally to this work. Drs. Danesh and Di Angelantonio also contributed equally to this work.
Acknowledgment: The authors thank Drs. Kristiina Nyyssönen, Arja Erkkilä, and Kalevi Pyörälä for kindly providing additional data.
Grant Support: By the British Heart Foundation (RG/13/13/30194), Medical Research Council (MR/K026585/1), Cambridge National Institute for Health Research Biomedical Research Centre, and Gates Cambridge.
Potential Conflicts of Interest: Dr. Franco: Grants: Nestlé and Metagenics. Dr. Butterworth: Grants: Pfizer, Merck Sharp & Dohme, and Novartis; Personal fees: Roche Pharmaceuticals. Dr. Thompson: Grants: Medical Research Council and British Heart Foundation. Dr. Khaw: Grants: Medical Research Council and Cancer Research UK. Dr. Mozaffarian: Personal fees: Bunge, Pollock Institute, Quaker Oats, Life Sciences Research Organization, Foodminds, Nutrition Impact, Amarin, AstraZeneca, Winston & Strawn, Unilever North American Scientific Advisory Board, and UpToDate online chapter. Dr. Danesh: Personal fees: Merck Sharp & Dohme UK Atherosclerosis Advisory Board, Novartis Cardiovascular & Metabolic Advisory Board, Pfizer Population Research Advisory Panel, and Sanofi Advisory Board; Grants: British Heart Foundation; British United Provident Association Foundation; diaDexus; European Research Council; European Union; Evelyn Trust; Fogarty International Centre; GlaxoSmithKline; Merck; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Health Service Blood and Transplant; Novartis; Pfizer; Medical Research Council; University of British Columbia; University of Sheffield; Wellcome Trust; and UK Biobank; Nonfinancial support: Merck Sharp & Dohme UK Atherosclerosis Advisory Board, Novartis Cardiovascular & Metabolic Advisory Board, Pfizer Population Research Advisory Panel, Sanofi Advisory Board, diaDexus, and Roche Pharmaceuticals. Dr. Di Angelantonio: Grant: British Heart Foundation, European Union, National Health Service Blood and Transplant, and Medical Research Council; Royalties: Elsevier (France). Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1788.
Requests for Single Reprints: Rajiv Chowdhury, MD, PhD, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge CB1 8RN, United Kingdom; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Chowdhury, Kunutsor, Butterworth, Thompson, Khaw, Danesh, and Di Angelantonio and Ms. Warnakula: Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge CB1 8RN, United Kingdom.
Dr. Crowe: Cancer Epidemiology Unit, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, United Kingdom.
Dr. Ward: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
Dr. Johnson: Centre for Exercise, Nutrition and Health Sciences, University of Bristol, 8 Priory Road, Bristol BS8 1TZ, United Kingdom.
Dr. Franco: Department of Epidemiology, Erasmus University Medical Center, Office Na 29-16, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
Dr. Forouhi: United Kingdom Medical Research Council Epidemiology Unit, Cambridge Box 285, Addenbrookes Hospital, Cambridge CB2 0QQ, United Kingdom.
Dr. Mozaffarian: Department of Epidemiology, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115.
Author Contributions: Conception and design: R. Chowdhury, K. Khaw, J. Danesh, E. Di Angelantonio.
Analysis and interpretation of the data: R. Chowdhury, S. Warnakula, S. Kunutsor, H.A. Ward, O.H. Franco, S.G. Thompson, J. Danesh, E. Di Angelantonio.
Drafting of the article: R. Chowdhury, E. Di Angelantonio.
Critical revision of the article for important intellectual content: R. Chowdhury, S. Warnakula, S. Kunutsor, F. Crowe, H.A. Ward, L. Johnson, O.H. Franco, A. Butterworth, N.G. Forouhi, S.G. Thompson, K. Khaw, D. Mozaffarian, J. Danesh, E. Di Angelantonio.
Final approval of the article: R. Chowdhury, S. Warnakula, S. Kunutsor, F. Crowe, H.A. Ward, L. Johnson, O.H. Franco, A.S. Butterworth, N.G. Forouhi, S.G. Thompson, K. Khaw, D. Mozaffarian, J. Danesh, E. Di Angelantonio.
Statistical expertise: R. Chowdhury, S. Kunutsor, S.G. Thompson, D. Mozaffarian, E. Di Angelantonio.
Obtaining of funding: K. Khaw, J. Danesh.
Administrative, technical, or logistic support: R. Chowdhury, S. Warnakula, K. Khaw.
Collection and assembly of data: R. Chowdhury, S. Warnakula, S. Kunutsor, K. Khaw, E. Di Angelantonio.
Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, et al. Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis. Ann Intern Med. 2014;160:398-406. doi: 10.7326/M13-1788
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Published: Ann Intern Med. 2014;160(6):398-406.
This article has been corrected. The original version (PDF) is appended to this article as a Supplement.
Guidelines advocate changes in fatty acid consumption to promote cardiovascular health.
To summarize evidence about associations between fatty acids and coronary disease.
MEDLINE, Science Citation Index, and Cochrane Central Register of Controlled Trials through July 2013.
Prospective, observational studies and randomized, controlled trials.
Investigators extracted data about study characteristics and assessed study biases.
There were 32 observational studies (512 420 participants) of fatty acids from dietary intake; 17 observational studies (25 721 participants) of fatty acid biomarkers; and 27 randomized, controlled trials (105 085 participants) of fatty acid supplementation. In observational studies, relative risks for coronary disease were 1.03 (95% CI, 0.98 to 1.07) for saturated, 1.00 (CI, 0.91 to 1.10) for monounsaturated, 0.87 (CI, 0.78 to 0.97) for long-chain ω-3 polyunsaturated, 0.98 (CI, 0.90 to 1.06) for ω-6 polyunsaturated, and 1.16 (CI, 1.06 to 1.27) for trans fatty acids when the top and bottom thirds of baseline dietary fatty acid intake were compared. Corresponding estimates for circulating fatty acids were 1.06 (CI, 0.86 to 1.30), 1.06 (CI, 0.97 to 1.17), 0.84 (CI, 0.63 to 1.11), 0.94 (CI, 0.84 to 1.06), and 1.05 (CI, 0.76 to 1.44), respectively. There was heterogeneity of the associations among individual circulating fatty acids and coronary disease. In randomized, controlled trials, relative risks for coronary disease were 0.97 (CI, 0.69 to 1.36) for α-linolenic, 0.94 (CI, 0.86 to 1.03) for long-chain ω-3 polyunsaturated, and 0.86 (CI, 0.69 to 1.07) for ω-6 polyunsaturated fatty acid supplementations.
Potential biases from preferential publication and selective reporting.
Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.
British Heart Foundation, Medical Research Council, Cambridge National Institute for Health Research Biomedical Research Centre, and Gates Cambridge.
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Cardiology, Coronary Risk Factors, Coronary Heart Disease, Prevention/Screening.
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