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Long-term effects of increasing omega-3, omega-6 and total polyunsaturated fats on inflammatory bowel disease and markers of inflammation: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Background and aim

Effects of long-chain omega-3 (LCn3) and omega-6 fatty acids on prevention and treatment of inflammatory bowel diseases (IBD, including Crohn’s Disease, CD and ulcerative colitis, UC), and inflammation are unclear. We systematically reviewed long-term effects of omega-3, omega-6 and total polyunsaturated fats (PUFA) on IBD diagnosis, relapse, severity, pharmacotherapy, quality of life and key inflammatory markers.

Methods

We searched Medline, Embase, Cochrane CENTRAL, and trials registries, including RCTs in adults with or without IBD comparing higher with lower omega-3, omega-6 and/or total PUFA intake for ≥ 24 weeks that assessed IBD-specific outcomes or inflammatory biomarkers.

Results

We included 83 RCTs (41,751 participants), of which 13 recruited participants with IBD. Increasing LCn3 may reduce risk of IBD relapse (RR 0.85, 95% CI 0.72–1.01) and IBD worsening (RR 0.85, 95% CI 0.71–1.03), and reduce erythrocyte sedimentation rate (ESR, SMD − 0.23, 95% CI − 0.44 to − 0.01), but may increase IBD diagnosis risk (RR 1.10, 95% CI 0.63–1.92), and faecal calprotectin, a specific inflammatory marker for IBD (MD 16.1 μg/g, 95% CI − 37.6 to 69.8, all low-quality evidence). Outcomes for alpha-linolenic acid, omega-6 and total PUFA were sparse, but suggested little or no effect where data were available.

Conclusion

This is the most comprehensive meta-analysis of RCTs investigating long-term effects of omega-3, omega-6 and total PUFA on IBD and inflammatory markers. Our findings suggest that supplementation with PUFAs has little or no effect on prevention or treatment of IBD and provides little support for modification of long-term inflammatory status.

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Acknowledgements

This review is one of a set of reviews conducted by the Polyunsaturated Fats and Health (PUFAH) Group, which includes Asmaa Abdelhamid, Zoya Ahmed, Sarah MA Ajabnoor, Fai K AlAbdulghafoor, Lena Al-Khudairy, Priti Biswas, Julii Suzanne Brainard, Charlene Bridges, Tracey J Brown, Katherine HO Deane, Daisy H Donaldson, Sarah Hanson, Lee Hooper, Oluseyi F Jimoh, Nicole Martin, Katie Maas, Helen J Moore, Alex T O’Brien, Karen Rees, Ruksana Sivakaran, Fujian Song, Carolyn D Summerbell, Gabrielle C Thorpe, Xia Wang, Ailsa Welch, Lauren Winstanley, and Helen V Worthington. 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: YZ Almallah, University of Aberdeen (Almallah 1998); D Kromhout, Wageningen University (AlphaOmega); A Belluzzi, Institute of Clinical Medicine and Gastroenterology, Bologna (Belluzzi 1996); I Dichi, University of Londrina, Brazil (Berbert 2005); l Quanjun, Zhengzhou University, China (Bo 2017); J Brox, University Hospital of North Norway (Brox 2001); GE Lobley, The Rowett Institute of Nutrition and Health, University of Aberdeen (Clark 2016); DA de Luis Román, University of Valladolid (de Luis 2016); G Derosa and P Maffioli, University of Pavia (Derosa 2011 & 2016); PNM Demacker, University Hospital Nijmegen (Deslypere 1992); G Einvik, Akershus University Hospital and H Arnesen, Oslo University Hospital (DO IT 2010); A Sanyal, Virginia Commonwealth University, USA (EPE-A 2014); BG Feagan, University of Western Ontario (EPIC 1 & 2); Vanessa Danthir, CSIRO Human Nutrition, Adelaide (EPOCH 2014); E Lund, University of East Anglia (FishGastro); G Pierce, St Boniface Hospital Resarch Center, Canada (FLAXPAD); S Greenfield, QEII Hospital, Welwyn Garden City (Greenfield 1993); AB Hawthorne, University Hospital Cardif (Hawthorne 1993); P Sparks, University of Melbourne (Kumar 2008); CS Lau, Queen Mary Hospital, Hong Kong (Lau 1993); R Lorenz, Klinikum Universitat Munchen (Loeschke 1996); P Bauer, Medical University of Vienna (Lorenz-Meyer 1996); W Bemelmans, National Institute for Public Health and Environment (RIVM), Bilthoven, the Netherlands (MARGARIN); T Sanders, Kings College London (MARINA); J Mate-Jiminez, Hospital de la Princesa, Madrid (Mate 1991); JA Heady, MRC Social Research Unit (MRC 1968); D Nilsen, University of Bergen, Norway (OFAMI 2001); Y Freund-Levi, Karolinska Institutet, Sweden (Omega-AD); R Zurier, University of Massachusetts (Reed 2014); A Manni, Penn State College of Medicine, USA (Sandhu 2016); B Akesson, University of Lund (Skoldstam 1992); K Tande, Calanus AS, Norway (Tande 2016); K Tuttle, Sacred Heart Medical Center, Spokane (THIS DIET 2008); M Vijayakumar, Amrita Institute of Medical Sciences, India (Vijayakumar 2014).

Funding

This systematic review was one of a set of systematic reviews commissioned by the World Health Organization’s Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health, to inform its guidance on polyunsaturated fatty acid intake. NUGAG 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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Authors and Affiliations

  1. Norwich Medical School, University of East Anglia, Norwich, UK

    Sarah M. Ajabnoor, Asmaa Abdelhamid & Lee Hooper

  2. Clinical Nutrition Department, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80324, Jeddah, 21589, Saudi Arabia

    Sarah M. Ajabnoor

  3. School of Health Sciences, University of East Anglia, Norwich, UK

    Gabrielle Thorpe

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  1. Sarah M. Ajabnoor
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  3. Asmaa Abdelhamid
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Contributions

The authors’ responsibilities were as follows: SMA, GT, AA, and LH designed the study. LH and AA developed and ran the searches. All authors and other members of the PUFAH Group including Zoya Ahmed screened studies and trial registers for eligibility and extracted data. SMA, GT, AA, and LH input data into RevMan, conducted the statistical analysis, and interpreted the results. SMA, GT, AA, and LH wrote the manuscript. LH carried out GRADE assessment. There are no potential conflicts of interest to be declared.

Corresponding author

Correspondence to Sarah M. Ajabnoor.

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Conflict of interest

SMA, GT, AA, and LH had financial support via the University of East Anglia from the World Health Organization (WHO) for the submitted manuscript. 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.

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Ajabnoor, S.M., Thorpe, G., Abdelhamid, A. et al. Long-term effects of increasing omega-3, omega-6 and total polyunsaturated fats on inflammatory bowel disease and markers of inflammation: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr 60, 2293–2316 (2021). https://doi.org/10.1007/s00394-020-02413-y

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  • DOI: https://doi.org/10.1007/s00394-020-02413-y

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