Epidemiology

Omega-3, omega-6 and total dietary polyunsaturated fat on cancer incidence: systematic review and meta-analysis of randomised trials

Abstract

Background

The relationship between long-chain omega-3 (LCn3), alpha-linolenic acid (ALA), omega-6 and total polyunsaturated fatty acid (PUFA) intakes and cancer risk is unclear.

Methods

We searched Medline, Embase, CENTRAL and trials registries for RCTs comparing higher with lower LCn3, ALA, omega-6 and/or total PUFA, that assessed cancers over ≥12 months. Random-effects meta-analyses, sensitivity analyses, subgrouping, risk of bias and GRADE were used.

Results

We included 47 RCTs (108,194 participants). Increasing LCn3 has little or no effect on cancer diagnosis (RR1.02, 95% CI 0.98–1.07), cancer death (RR0.97, 95% CI 0.90–1.06) or breast cancer diagnosis (RR1.03, 95% CI 0.89–1.20); increasing ALA has little or no effect on cancer death (all high/moderate-quality evidence). Increasing LCn3 (NNTH 334, RR1.10, 95% CI 0.97–1.24) and ALA (NNTH 334, RR1.30, 95% CI 0.72–2.32) may slightly increase prostate cancer risk; increasing total PUFA may slightly increase risk of cancer diagnosis (NNTH 125, RR1.19, 95% CI 0.99–1.42) and cancer death (NNTH 500, RR1.10, 95% CI 0.48–2.49) but total PUFA doses were very high in some trials.

Conclusions

The most extensive systematic review to assess the effects of increasing PUFAs on cancer risk found increasing total PUFA may very slightly increase cancer risk, offset by small protective effects on cardiovascular diseases.

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Fig. 1
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Fig. 5: Visual representation of number of additional diagnoses or deaths incurred or avoided per 1000 people increasing their LCn3, ALA or total PUFA intake across cancer and cardiovascular outcomes.

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Acknowledgements

This review is one of a set of reviews conducted by the PUFAH group. The review authors thank all of the authors of primary studies who kindly replied to our queries and where possible provided us with the best set of data available, including: D. Kromhout, Wageningen University (AlphaOmega—ALA; AlphaOmega—EPA + DHA); Emily Chew, NIH (AREDS2 2014); H.S. Black, Veterans Affairs Medical Center, Houston, USA (Black 1994); M.L. Burr, University of Wales and A Ness, University of Bristol (DART fat Burr 1989; DART fish Burr 1989; DART2 Burr 2003); S. Tokudome, National Institute of Health and Nutrition, Japan (DIPP Tukudome 2015); G. Einvik, Akershus University Hospital and H. Arnesen, Oslo University Hospital (DO IT Einvik 2010); A. Sanyal, Virginia Commonwealth University, USA (EPE-A Sanyal 2014); B.G. Feagan, University of Western Ontario, Canada (EPIC-1 2008; EPIC-2 2008); C. Hill, Queen Elizabeth Hospital, Australia (FOSTAR 2016); P.A. Metcalf, University of Aukland, New Zealand (Ley 2004); M. McIllmurray, retired (McIllmurray 1987); J.A. Heady, MRC Statistician (retired) (MRC 1968); D. Nilsen, University of Bergen, Norway (OFAMI Nilsen 2001); S. Schneider, Institut für Herzinfarktforschung, Germany (OMEGA 2009); B.K. Puri, Imperial College London (Puri 2005); C. Roncaglioni and I. Marzona, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Italy (Risk & Prevention 2013); P. Rossing, Steno Diabetes Center, Denmark (Rossing 1996); A. Manni, Penn State College of Medicine, USA (Sandhu 2016); C. von Schacky, Ludwig Maximilians University, Munich (SCIMO von Schacky 1999); M.S. Simon, Wayne State University, USA (Simon 1997); P. Galan, Université Paris (SU.FOL.OM3 Galan 2010); K. Tuttle, Sacred Heart Medical Center, Spokane (THIS DIET 2008); J. Sabaté, Loma Linda University, USA (WAHA 2016).

The PUFAH group

Asmaa Abdelhamid2, Sarah Ajabnoor2, Faye Alabdulghafoor2, Lena Alkhudairy3, Priti Biswas4, Julii Brainard2, Charlene Bridges5, Tracey J Brown2, Katherine Deane4, Daisy Donaldson2, Sarah Hanson4, Lee Hooper2, Oluseyi Florence Jimoh2, Nicole Martin5, Alex O’Brien2, Karen Rees3, Lena Alkhudairy3, Fujian Song2, Gabrielle Thorpe4, Xia Wang2, Lauren Winstanley2

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Contributions

S.H., A.S.A. and L.H. designed the study in consultation with the funder. L.H. and A.S.A. built the search. All authors and other members of the PUFAH consortium screened studies and trial registers for eligibility, extracted data and assessed risk of bias. S.H., G.T., L.W., L.H. and A.S.A. input data into Review Manager software, performed the statistical analysis and interpreted the results. S.H. and L.H. wrote the first draft of the paper. L.H. undertook the GRADE analysis and assembled revisions. All authors have read and approved the final version. All authors had full access to all data (primary publications, trials registry entries, trial author communications, data extractions and assessments of risk of bias, and analyses) and take responsibility for the integrity and accuracy of the data. L.H. is the guarantor.

Corresponding author

Correspondence to Lee Hooper.

Ethics declarations

Ethics approval and consent to participate

No ethical approval was required as this was a systematic review and did not use primary data.

Consent to publish

Not applicable.

Data availability

The dataset for this review was part of our published dataset, and so is publicly available, see ref. 39

Competing interests

S.H., G.T., A.S.A. and L.H. had financial support via the University of East Anglia from the World Health Organization for the submitted work, and L.H. and A.A. were also funded to attend WHO meetings and present review results; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Funding information

The set of reviews was commissioned and funded by the World Health Organization (WHO) Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health, in order to inform their guidance on polyunsaturated fatty acid intake (project number HQNHD1612458). They requested specific inclusion criteria (including duration of trials and outcomes), some sensitivity analyses and subgroups. The results of the reviews, including GRADE assessments, were discussed and reviewed by the WHO NUGAG Subgroup on Diet and Health as part of WHO’s guideline development process. WHO was not otherwise involved in writing this report.

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The members of the PUFAH group are listed above the Acknowledgements.

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Hanson, S., Thorpe, G., Winstanley, L. et al. Omega-3, omega-6 and total dietary polyunsaturated fat on cancer incidence: systematic review and meta-analysis of randomised trials. Br J Cancer 122, 1260–1270 (2020). https://doi.org/10.1038/s41416-020-0761-6

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