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Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies

BMJ 2015; 351 doi: (Published 12 August 2015) Cite this as: BMJ 2015;351:h3978
  1. Russell J de Souza, assistant professor1234,
  2. Andrew Mente, associate professor125,
  3. Adriana Maroleanu, research volunteer2,
  4. Adrian I Cozma, medical student34,
  5. Vanessa Ha, doctoral student134,
  6. Teruko Kishibe, information specialist6,
  7. Elizabeth Uleryk, information specialist7,
  8. Patrick Budylowski, research volunteer4,
  9. Holger Schünemann, professor of medicine and department chair18,
  10. Joseph Beyene, professor of biostatistics12,
  11. Sonia S Anand, professor of medicine and epidemiology1258
  1. 1Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada
  2. 2Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada
  3. 3Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
  4. 4Clinical Nutrition and Risk Factor Modification Center, St Michael’s Hospital, Toronto, ON, Canada
  5. 5Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada
  6. 6Scotiabank Health Sciences Library, St Michael’s Hospital, Toronto, ON, Canada
  7. 7Hospital Library and Archives, Hospital for Sick Children, Toronto, ON, Canada
  8. 8Department of Medicine, McMaster University, Hamilton, ON, Canada
  1. Correspondence to: S Anand, McMaster University, 1280 Main St W, MDCL-3204, Hamilton, ON L8N 3Z5, Canada anands{at}
  • Accepted 15 July 2015


Objective To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes.

Design Systematic review and meta-analysis.

Data sources Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015, supplemented by bibliographies of retrieved articles and previous reviews.

Eligibility criteria for selecting studies Observational studies reporting associations of saturated fat and/or trans unsaturated fat (total, industrially manufactured, or from ruminant animals) with all cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes.

Data extraction and synthesis Two reviewers independently extracted data and assessed study risks of bias. Multivariable relative risks were pooled. Heterogeneity was assessed and quantified. Potential publication bias was assessed and subgroup analyses were undertaken. The GRADE approach was used to evaluate quality of evidence and certainty of conclusions.

Results For saturated fat, three to 12 prospective cohort studies for each association were pooled (five to 17 comparisons with 90 501-339 090 participants). Saturated fat intake was not associated with all cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97, 0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to 1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10). For trans fats, one to six prospective cohort studies for each association were pooled (two to seven comparisons with 12 942-230 135 participants). Total trans fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD mortality (1.28, 1.09 to 1.50), and total CHD (1.21, 1.10 to 1.33) but not ischemic stroke (1.07, 0.88 to 1.28) or type 2 diabetes (1.10, 0.95 to 1.27). Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18 (1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05 to 1.92) v 0.93 (0.73 to 1.18)). Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes (0.58, 0.46 to 0.74). The certainty of associations between saturated fat and all outcomes was “very low.” The certainty of associations of trans fat with CHD outcomes was “moderate” and “very low” to “low” for other associations.

Conclusions Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats. Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats.


  • We are grateful to Viranda Jayalath (University of Toronto) for his assistance developing the data abstraction forms. We thank Paul Knekt, Anthony Hanley, and Ingrid Santaren for providing data, and Hannia Campos, and Kay-tee Khaw for clarifying aspects of their studies; Christine Neilson and Natalie Campbell for their assistance with the literature search; Michael Zulyniak for assistance with preparing the manuscript for publication; and the members of the WHO Nutrition Guidance Advisory Group (NUGAG) Subgroup on Diet and Health for their helpful comments on the draft results. WHO agreed to the publication of this systematic review in a scientific journal because it serves as the background evidence review for updating WHO guidelines on saturated and trans fatty acids and should therefore be available widely. We appreciate the helpful comments of peer reviewers Arne Atrup, Ronald Krauss, JM Chardigny, and Evangeline Mantzioris, which have greatly improved the quality of the manuscript.

  • Contributors: Study concept and design: RJdeS, SSA, JB, AMe. Development and implementation of literature search strategy: EU, TK. Acquisition of data, including review of literature search results and data abstraction: RJdeS, EU, TK, AMe, AMa, AIC, VH, PB. Analysis and interpretation of data: RJdeS, AMe, SSA, JB, HS. Drafting of the manuscript: RJdeS, AMe, VH, AIC. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: RJdeS, JB. Administrative, technical, and material support: EU, TK, AM. Study supervision: SSA, JB. RJdeS is guarantor.

  • Funding: This study was funded by WHO, which defrayed costs associated with preparing the draft manuscript, including information specialist and technical support and article retrieval costs. This systematic review was presented by RJdeS at the 5th Nutrition Guidelines Advisory Group (NUGAG) meeting in Hangzhou, China (4-7 March, 2013), the 6th NUGAG meeting in Copenhagen, Denmark (21-24 Oct, 2013), and the 7th NUGAG meeting in Geneva, Switzerland (9-12 Sept, 2014); and via skype during the 8th NUGAG meeting in Fukuoka, Japan (9-12 June, 2015). WHO covered travel and accommodation costs for RJdeS to attend these meetings. The research questions for the review were discussed and developed by the WHO Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health and the protocol was agreed by the WHO NUGAG Subgroup on Diet and Health; however, neither WHO nor the WHO NUGAG Subgroup on Diet and Health had any role in data collection or analysis.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: RJdeS has received a Canadian Institutes for Health Research (CIHR) postdoctoral fellowship. VH has received a Province of Ontario graduate scholarship and research support from the Canadian Institutes of Health Research (CIHR). AIC has received a Province of Ontario graduate scholarship.

  • Ethical approval: Not required.

  • Transparency statement: RJdeS affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies are disclosed.

  • Data sharing: The full dataset and statistical code are available from the corresponding author.

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