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: NCT01661764Supplemental data for this article is available online at https://dx.doi.org/10.1080/01635581.2021.1955286.

Conflict of interest statement

Disclosure of interest

The authors report no conflict of interests to disclose

Figures

Figure 1:

Flow diagram of trial recruitment and retention

Figure 2:. Baseline percentages of total RBC membrane fatty acids stratified by genotype

ARA = arachidonic acid, LCPUFA = long chain polyunsaturated fatty acids, DGLA = di-homo-γ-linolenic acid, EPA = eicosapentaenoic acid, DPA = docosapentaenoic acid, DHA = docosahexaenoic acid. Values presented as means with S.D., P value difference between baseline RBC membrane fatty acid percentages between genotypes calculated using Wilcoxon rank order sum

Figure 3:. Changes in RBC membrane arachidonic acid and total n-3 long chain polyunsaturated fatty acid percentages stratified by genotype and treatment allocation

ARA = arachidonic acid, LCPUFA = long chain polyunsaturated fatty acids. P values calculated using repeated measures generalized linear models adjusted for age, sex, race, body mass index, physical activity level, and aspirin/NSAID use. P value1 = effect of the intervention on RBC membrane fatty acid ARA percentages; P value2 = effect of genotype on RBC membrane fatty acid ARA percentages; P value3 = effect of the intervention on RBC membrane fatty acid total n-3 LCPUFA percentages; P value4 = effect of the genotype on RBC membrane fatty acid total n-3 LCPUFA percentages