Efficacy and safety of Omega-3 polyunsaturated fatty acids in adjuvant treatments for colorectal cancer: A meta-analysis of randomized controlled trials

Background: Colorectal cancer (CRC) ranks third globally. There are many adverse reactions to treatments such as surgeries and post-surgical chemotherapy, which affect patients' prognosis and reduce their life quality. Omega-3 polyunsaturated fatty acids (O3FAs) have become an essential part of immune nutrition due to their anti-inflammatory properties, which improve body immunity and have attracted widespread attention. A systematic review focused on the efficacy and safety of O3FAs for patients undergoing surgeries in combination with chemotherapy or a surgery alone is lacking. Objectives: To evaluate the efficacy of O3FAs in the adjuvant treatment of CRC, a meta-analysis was conducted on patients with CRC who underwent surgeries in combination with chemotherapy or a surgery alone. Methods: As of March 2023, publications have been obtained using search terms from digital databases such as PubMed, Web of Science, Embase and Cochrane Library. Only randomized clinical trials (RCTs) evaluating the efficacy and safety of O3FAs following adjuvant treatments for CRC were included in the meta-analysis. Key outcomes were tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1beta (IL-1β), albumin, body mass index (BMI), weight, the rate of infectious and non-infectious complications, the length of hospital stay (LOS), CRC mortality and life quality. Results: After screening 1,080 studies, 19 RCTs (n = 1,556) with O3FAs in CRC were included, in all of which at least one efficacy or safety outcome was examined. Compared to the control group, the level of TNF-α (MD = -0.79, 95% CI: 1.51 to -0.07, p = 0.03) and IL-6 was reduced due to O3FA-enriched nutrition during the perioperative period (MD = -4.70, 95% CI: 6.59 to -2.80, p < 0.00001). It also reduces LOS (MD = 9.36, 95% CI: 2.16 to 16.57, p = 0.01). No significant differences were found in CRP, IL-1β, albumin, BMI, weight, the rate of infectious and non-infectious complications, CRC mortality or life quality. The inflammatory status of patients with CRC undergoing adjuvant therapies decreased after a total parenteral nutrition (TPN) O3FA supplementation (TNF-α, MD = -1.26, 95% CI: 2.25 to -0.27, p = 0.01, I2 = 4%, n = 183 participants). The rate of infectious and non-infectious complications was reduced among patients with CRC undergoing adjuvant therapies after a parenteral nutrition (PN) O3FA supplementation (RR = 3.73, 95% CI: 1.52 to 9.17, p = 0.004, I2 = 0%, n = 76 participants). Conclusion: Our observations suggest that supplementation with O3FAs has little or no effect on patients with CRC undergoing adjuvant therapies and that a prolonged inflammatory state may be modified. To validate these findings, well-designed, large-scale, randomized and controlled studies on homogeneous patient populations are expected.