N-3 Long Chain Fatty Acids Supplementation, Fatty Acids Desaturase Activity, and Colorectal Cancer Risk: A Randomized Controlled Trial

Abstract

Introduction

n-3 long-chain polyunsaturated fatty acids (LCPUFA) have anti-inflammatory effects and may reduce colorectal cancer risk. The purpose of this study was to evaluate the effects of n-3 LCPUFA supplementation on markers of rectal cell proliferation and apoptosis and examine how genetic variation in desaturase enzymes might modify this effect.

Methods

We conducted a randomized, double-blind, control six-month trial of 2.5 grams of n-3 LCPUFA per day compared to olive oil. Study participants had a history of colorectal adenomas. Randomization was stratified based on the gene variant rs174535 in the fatty acid desaturase 1 enzyme (FADS1). Our primary outcome was change in markers of rectal epithelial proliferation and apoptosis.

Results

A total of 141 subjects were randomized. We found no difference in apoptosis markers between participants randomized to n-3 LCPUFA compared to olive oil (P = 0.41). N-3 LCPUFA supplementation increased cell proliferation in the lower colonic crypt compared to olive oil (P = 0.03) however baseline indexes of proliferation were different between the groups at randomization. We found no evidence that genotype modified the effect.

Conclusions

Our study did not show evidence of a proliferative or pro-apoptotic effect on n-3 LCPUFA supplementation on rectal mucosa regardless of the FADS genotype.

ClinicalTrials.gov Identifier: NCT01661764

Supplemental data for this article is available online at https://dx.doi.org/10.1080/01635581.2021.1955286

Acknowledgments

None.

Disclosure statement

The authors report no conflict of interests to disclose.

Authors’ Contributions

HJM, MJS, WZ, QD, HJM designed research; HJM, MJS, QC, TS, MJH, SSC, conducted research; MNW, HJM analyzed data; HJM, MJS, QC, QD wrote the paper, HJM had primary responsibility for final content. All authors read and approved the final manuscript.

Additional information

Funding

This study was supported through the National Institute of Health grants R01CA160938, R01CA143288, P50CA95103, R01CA97386 and UL1TR000445. Surveys and sample collection, processing, and preparation for this study were conducted by the Survey and Biospecimen Shared Resource, which is supported in part by P30CA068485. Fatty acid analyses were performed by the Vanderbilt Diabetes Research and Training Core Lipid Core lab supported by DK20593. The study was supported in part by the Vanderbilt CTSA grant UL1TR002243. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, National Center for Advancing Translational Sciences, or the National Institutes of Health.