The relationship between dietary and supplemental n-3 HUFA intake, blood and tissue n-3 HUFA levels, and colorectal polyp recurrence: A secondary analysis of the seAFOod polyp prevention trial

Ge Sun; Harriett Fuller; Hayley Fenton; Amanda D Race; Amy Downing; Colin J Rees; Louise C Brown; Paul M Loadman; Elizabeth A Williams; Mark A Hull

doi:10.1016/j.tjnut.2024.12.004

The relationship between dietary and supplemental n-3 HUFA intake, blood and tissue n-3 HUFA levels, and colorectal polyp recurrence: A secondary analysis of the seAFOod polyp prevention trial

J Nutr. 2024 Dec 13:S0022-3166(24)01230-6. doi: 10.1016/j.tjnut.2024.12.004. Online ahead of print.

Authors

Affiliations

¹ Leeds Institute of Medical Research, University of Leeds.
² Institute of Cancer Therapeutics, University of Bradford.
³ Population Health Sciences Institute, Newcastle University.
⁴ MRC Clinical Trials Unit at University College, London.
⁵ School of Medicine and Population Health, University of Sheffield.
⁶ Leeds Institute of Medical Research, University of Leeds. Electronic address: M.A.Hull@leeds.ac.uk.

PMID: 39675479
DOI: 10.1016/j.tjnut.2024.12.004

Abstract

Background: The seAFOod randomised controlled trial tested colorectal polyp prevention by the omega-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: To investigate the relationship between total (diet and capsule) daily omega-3 HUFA intake, red blood cell (RBC) and rectal mucosa omega-3 HUFA levels, 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 EPIC-Norfolk fatty acid nutrient database. Capsule EPA intake (mg/d) was adjusted for compliance (capsule counting). Fatty acids were analysed by liquid chromatography-tandem mass spectrometry (as % of total fatty acids). HUFA oxidation was measured as the HUFA/saturated fatty acid (SAT) ratio. The colorectal polyp detection rate [PDR; % with one or more polyps] and polyp number per participant were analysed according to the change in RBC EPA level during the trial (ΔEPA), irrespective of treatment allocation.

Results: There was a small degree of HUFA degradation over time in RBC samples stored at higher than minus 80^oC at research sites (r=-0.36, P<0.001 for HUFA/SAT ratio over time), which did not affect analysis of omega-3 HUFA levels. Low baseline EPA level, as well as allocation to EPA and % compliance, were associated with a high ΔEPA. Individuals with a ΔEPA value >+0.5% points (ΔEPA_high), irrespective of allocation to EPA or placebo, had a lower PDR than ΔEPA_low 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 level, instead of treatment allocation, revealed a protective effect of EPA treatment on colorectal polyp recurrence (ISRCTN05926847).

Keywords: colorectal cancer; compliance; diet; docosahexaenoic acid; eicosapentaenoic acid.