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

Abstract

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 > -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 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 (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 concentration, 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.