Randomised controlled trial of the effects of fish oil emulsion in total parenteral nutrition upon tumour vascularity in patients with hepatic colorectal metastases

Tumour growth is dependent on angiogenesis. Angiogenesis often predicts a poorer prognosis in cancer patients and is also associated with the increased development of tumour metastases. Angiogenesis is stimulated by vascular endothelial growth factor, which increases vascular permeability, induces endothelial cell proliferation and promotes endothelial cell survival, which, are pivotal in tumourgenesis. As such angiogenesis and vascular endothelial growth factor inhibitors are now commonplace in the armoury of anti-cancer treatments. In vitro, in-vivo and epidemiological studies have demonstrated that omega-3 fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid have profound anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic properties. Anti-angiogenic actions include a reduction vascular endothelial growth factor concentration and alteration of vascular endothelial growth factor receptor signalling response. Unfortunately only negligible amounts of EPA and DHA can be produced by human metabolism. Omega-3 fatty acids are however synthesised in abundance by algae and plankton and as a consequence fish are the main dietary source of essential omega-3 fatty acids. However even with a balanced diet rich in fish, human plasma concentrations are minimal. In contrast parenteral administration of a fish-oil lipid emulsion leads to a significant and rapid increase in eicosapentaenoic acid and docosahexaenoic acid concentrations in plasma, and platelet and leukocyte membrane phospholipids within hours. There is a large body of work in the scientific literature that supports the theory that omega-3 fish oils have marked anti-angiogenic properties and that plasma concentrations of omega-3 fatty acids can be quickly and safely manipulated with intravenous infusion. I present the findings from a randomised controlled pilot study in patients with hepatic colorectal metastases to assess the response of biomarkers of angiogenesis to intravenous administration of omega-3 fatty acids compared to controls