Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer

Abstract

The majority of evidence linking anti-colorectal cancer (CRC) activity with omega-3 polyunsaturated fatty acids (O3FAs) has focussed on decreased CRC risk (prevention). More recently, preclinical data and human observational studies have begun to make the case for adjuvant treatment of advanced CRC. Herein, we review latest data regarding the effect of O3FAs on post-diagnosis CRC outcomes, including mechanistic preclinical data, evidence that O3FAs have beneficial effects on efficacy and tolerability of CRC chemotherapy, and human epidemiological data linking dietary O3FA intake with CRC outcomes. We also highlight ongoing randomised controlled trials of O3FAs with CRC endpoints and discuss critical gaps in the evidence base, which include limited understanding of the effects of O3FAs on the tumour microenvironment, the host immune response to CRC, and the intestinal microbiome.

Decreased Triacylglycerol Content and Elevated Contents of Cell Membrane Lipids in Colorectal Cancer Tissue: A Lipidomic Study

“…However, other authors found no link between n-3 and n-6 PUFAs and CRC development or treatment outcomes [9]. Furthermore, the available evidence in this matter is insufficient, as most preclinical studies analyzed the direct effects of selected n-3 PUFAs on cancer cells in vitro, rather than in vivo [10]. Some evidence suggests that potential therapeutic effects of n-3 PUFAs, if any, may depend on their dose, concomitant chemotherapy and its regimen [11].…”

Are Long-Chain Polyunsaturated Fatty Acids the Link between the Immune System and the Microbiome towards Modulating Cancer?

“…Although the interaction between gut microbiota and the immune checkpoint pathway has been discovered [ 2 , 3 , 4 ], the mechanism of interaction needs to be elucidated. A strong, direct correlation was observed in several studies between n-3/n-6 PUFA levels and the microbiome [ 18 ], while an inverse correlation was observed for n-3 PUFA levels and inflammation [ 9 ]. Although several studies have demonstrated a direct link between n-3/n-6 levels and the microbiome and independently between n-3/n-6 levels with inflammation, the causal relationship whether n-3/n-6 levels modulate the interaction between the microbiome and the immune system has been circumstantial at best [ 18 , 19 , 20 ].…”

“…A strong, direct correlation was observed in several studies between n-3/n-6 PUFA levels and the microbiome [ 18 ], while an inverse correlation was observed for n-3 PUFA levels and inflammation [ 9 ]. Although several studies have demonstrated a direct link between n-3/n-6 levels and the microbiome and independently between n-3/n-6 levels with inflammation, the causal relationship whether n-3/n-6 levels modulate the interaction between the microbiome and the immune system has been circumstantial at best [ 18 , 19 , 20 ]. This communication hypothesises that higher n-3 PUFA and lower n-6 PUFA levels lower inflammation and promote the growth of favourable gut microbes.…”

“…EPA and DHA could modulate cancer by different mechanisms: (i) apoptosis; (ii) angiogenesis and metastasis; (iii) inflammation; (iv) tumour cell proliferation; (v) epigenetic abnormalities; and (vi) gene expression and cell signalling [ 18 , 19 , 20 ]. In addition, an anti-neoplastic mechanism was recently discovered in endocannabinoid epoxides, n-3 metabolites which have tumour cell-killing capabilities as well anti-angiogenic properties that slow down tumour growth and migration [ 21 ].…”

Complementary and Alternative Treatments for Cancer Prevention and Cure (Part 1)

“…Mortality rates in LMICs were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during . Omega-3s from fish pack a stronger punch than other oils when it comes to cancer prevention [113][114][115]. Seaweeds are specifically used to treat tumors in CHM [116].…”