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The Relationship Between Dietary and Supplemental omega-3 Highly Unsaturated Fatty Acid Intake, Blood and Tissue omega-3 Highly Unsaturated Fatty Acid Concentrations, and Colorectal Polyp Recurrence: A Secondary Analysis of the seAFOod Polyp Prevention Trial

Lookup NU author(s): Professor Colin Rees

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2024 The Author(s). Background: The seAFOod randomized controlled trial tested colorectal polyp prevention by the omega-3 (ω-3) highly unsaturated fatty acid (HUFA) eicosapentaenoic acid (EPA) and aspirin. Variable dietary intake of omega-3 HUFAs (also including docosahexaenoic acid [DHA]) and differential EPA capsule compliance could confound analysis of trial outcomes. Objective: The objective of this study was to investigate the relationship between total (diet and capsule) daily omega-3 HUFA intake, red blood cell (RBC), and rectal mucosa omega-3 HUFA concentrations, and colorectal polyp outcomes in a secondary analysis of the seAFOod trial. Methods: Individual-participant dietary omega-3 HUFA intake (mg/d) was derived from food frequency questionnaires using the European Prospective Investigation into Cancer and Nutrition-Norfolk fatty acid nutrient database. Capsule EPA intake (mg/d) was adjusted for compliance (capsule counting). Fatty acids were analyzed by liquid chromatography-tandem mass spectrometry (as % of total fatty acids). HUFA oxidation was measured using the HUFA/saturated fatty acid (SAT) ratio. The colorectal polyp detection rate (PDR; % with ≥1 polyps) and polyp number per participant were analyzed according to the change in RBC EPA concentrations during the trial (ΔEPA), irrespective of treatment allocation. Results: There was a small degree of HUFA degradation over time in RBC samples stored at > −80oC at research sites (r = −0.36, P<0.001 for HUFA/SAT ratio over time), which did not affect analysis of omega-3 HUFA concentrations. Low baseline EPA concentration, as well as allocation to EPA and % compliance, were associated with a high ΔEPA. Individuals with a ΔEPA value >+0.5% points (ΔEPAhigh), irrespective of allocation to EPA or placebo, had a lower PDR than ΔEPAlow individuals (odds ratio: 0.63; 95% confidence interval [CI]: 0.40, 1.01) and reduced colorectal polyp number (incidence rate ratio: 0.74; 95% CI: 0.54, 1.02). Conclusions: Analysis of the seAFOod trial according to the change in EPA concentration, instead of treatment allocation, revealed a protective effect of EPA treatment on colorectal polyp recurrence (ISRCTN05926847).


Publication metadata

Author(s): Sun G, Fuller H, Fenton H, Race AD, Downing A, Rees CJ, Brown LC, Loadman PM, Williams EA, Hull MA

Publication type: Article

Publication status: Published

Journal: Journal of Nutrition

Year: 2025

Pages: Epub ahead of print

Online publication date: 13/12/2024

Acceptance date: 06/12/2024

Date deposited: 04/02/2025

ISSN (print): 0022-3166

ISSN (electronic): 1541-6100

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.tjnut.2024.12.004

DOI: 10.1016/j.tjnut.2024.12.004

Data Access Statement: The biomarker, as well as linked clinical and trial outcomes, datasets described in this report contain identifiable data, which are stored in a secure virtual research environment at the University of Leeds. Data will be anonymized and exported upon request to the Principal Investigator (Professor Hull) and the Study Sponsor (University of Leeds).

PubMed id: 39675479


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Funding

Funder referenceFunder name
Cancer Research UK grant C23434/A24939
Efficacy and Mechanism Evaluation (EME) Programme (funded by MRC and NIHR)

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