Effect of Supplementation With Marine ω-3 Fatty Acid on Risk of Colorectal Adenomas and Serrated Polyps in the US General Population

Abstract

Marine ω-3 fatty acid has been suggested to protect against colorectal cancer.OBJECTIVE To assess the effect of daily marine ω-3 fatty acid supplementation on the risk of colorectal cancer precursors, including conventional adenomas and serrated polyps. DESIGN, SETTING, AND PARTICIPANTSThis study was a prespecified ancillary study of the placebo-controlled randomized clinical trial VITAL . An intention-to-treat analysis was used to examine the effect of daily marine ω-3 supplements among 25 871 adults in the US general population (including 5106 African American persons) free of cancer and cardiovascular disease at enrollment. Randomization was from November 2011 to March 2014, and intervention ended as planned on December 31, 2017.INTERVENTIONS Marine ω-3 fatty acid, 1 g daily (which included eicosapentaenoic acid, 460 mg, and docosahexaenoic acid, 380 mg) and vitamin D3 (2000 IU daily) supplements. MAIN OUTCOMES AND MEASURESRisk of conventional adenomas (including tubular adenoma, tubulovillous adenoma, villous adenoma, and adenoma with high-grade dysplasia) or serrated polyps (including hyperplastic polyp, traditional serrated adenoma, and sessile serrated polyp). In a subset of participants who reported receiving a diagnosis of polyp on follow-up questionnaires, endoscopic and pathologic records were obtained to confirm the diagnosis. Odds ratios (ORs) and 95% CIs were calculated using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. Secondary analyses were performed according to polyp features and participants' characteristics. RESULTSThe demographic characteristics of participants at randomization were well balanced between the treatment and placebo groups; for example, 50.6% vs 50.5% were women, and 19.7% vs 19.8% were African American persons were included in each group. The mean (SD) age was 67.1 (7.1) years in the placebo group and 67.2 (7.1) in the ω-3 treatment group. During a median follow-up of 5.3 years (range, 3.8-6.1 years), 294 cases of conventional adenomas were documented in the ω-3 group and 301 in the control group (multivariable OR, 0.98; 95% CI, 0.83-1.15) (1:1 ratio between number of cases and number of participants). In addition, 174 cases of serrated polyps were documented in the ω-3 group and 167 in the control group (OR, 1.05; 95% CI, 0.84-1.29). Null associations were found for polyp subgroups according to size, location, multiplicity, or histology. In secondary analyses, marine ω-3 treatment appeared to be associated with lower risk of conventional adenomas among individuals with low plasma levels of ω-3 index at baseline (OR, 0.76; 95% CI, 0.57-1.02; P = .03 for interaction by ω-3 index). A beneficial association of supplementation was also noted in the African American population (OR, 0.59; 95% CI, 0.35-1.00) but not in other racial/ethnic groups (P = .11 for interaction). CONCLUSIONS AND RELEVANCE Supplementation with marine ω-3 fatty acids, 1 g per day, was not associated with reduced risk of colorectal cancer precursors. A...

A prospective study of erythrocyte polyunsaturated fatty acids and risk of colorectal serrated polyps and conventional adenomas

“…Consistent with our findings, several other large prospective studies did not find any association between PUFAs and CRC risk 34‐36 . Recently, a randomized controlled trial study showed that supplementation with marine n−3 PUFA at 1 g/d was not associated with reduced risk of conventional adenomas or serrated polyps in average‐risk US adults 16 . Several previous studies have examined biomarkers of PUFAs in relation to colorectal neoplasm risk.…”

“…[34][35][36] Recently, a randomized controlled trial study showed that supplementation with marine n−3 PUFA at 1 g/d was not associated with reduced risk of conventional adenomas or serrated polyps in averagerisk US adults. 16 Several previous studies have examined biomarkers of PUFAs in relation to colorectal neoplasm risk. Most of these studies assessed plasma PUFAs, which are more susceptible to fasting status and may only reflect dietary intake over several days to weeks compared to erythrocyte PUFAs.…”

“…15 Only a few studies have assessed PUFA intake in relation to serrated polyps, the primary precursors of serrated CRC that include hyperplastic polyp, sessile serrated polyp (SSP) and traditional serrated adenoma. 11,16 We previously reported that higher dietary intake of marine n−3 PUFAs was associated with lower risk of serrated polyps. 11 In contrast to self-reported dietary intake, blood measurements of PUFAs provide an objective assessment of internal PUFA exposures.…”

“…On the other hand, given the close link between inflammation and MSI, tumors arising from the serrated pathway may be more strongly associated with inflammatory factors and processes 15 . Only a few studies have assessed PUFA intake in relation to serrated polyps, the primary precursors of serrated CRC that include hyperplastic polyp, sessile serrated polyp (SSP) and traditional serrated adenoma 11,16 . We previously reported that higher dietary intake of marine n−3 PUFAs was associated with lower risk of serrated polyps 11 …”

Health effects of vitamin and mineral supplements

“…Randomised trials have failed to detect a benefit of vitamin D supplementation, alone or combined with calcium, on cancer risk at either high or low doses2539 despite some evidence suggesting reduced total cancer mortality 2540. The limited evidence on fish oil supplementation suggests it does not reduce cancer risk 2841…”