Bioavailability of Omega-3 Fatty Acid Formulations and Their Effect on the Intestinal Microbiota

Due to their proposed anti-cancer effects, omega-3 fatty acids (O3FA) may have a role to play in both chemoprevention and the adjuvant treatment of colorectal cancer (CRC). Novel O3FA drink formulations may provide a more effective method of delivering O3FA supplementation, although O3FA bioavailability in these preparations compared to traditional capsules has not been ascertained. There is also a lack of research exploring the effects of O3FAs on the colonic microbiota and whether this may have any protective effect on CRC carcinogenesis. This thesis reports the findings of a randomised cross-over trial in healthy volunteers comparing the bioavailability of equivalent doses of O3FA supplementation (2g EPA and 2g DHA daily for 8 weeks) in capsule and drink carton formulations. The trial also explores the effects of O3FA on faecal microbiome profiles. In addition I report the analysis of red blood cell membrane (RBC) EPA levels from the previously reported EMT trial, a Phase II randomised, double-blind, placebo-controlled trial in which patients with colorectal cancer liver metastasis (CRCLM) received EPA (2g daily) prior to surgery. O3FA supplementation provided in a drinks carton supplementation was non-inferior to an equivalent dose of EPA and DHA provided in capsule form. Faecal microbiome profile analysis revealed subtle changes to the colonic microbiota including reversible increases to Lactobacillus and Bifidobacterium. Analysis of RBC samples from the EMT study revealed a positive correlation between RBC membrane and CRCLM tissue EPA levels. Participants with EPA RBC membrane levels of >1.22 also exhibited improved overall survival. This work provides evidence that an O3FA containing drink formulation is of equivalent bioavailability to traditional capsules. Due to their additional nutritional contents they may be of benefit in CRC patients. The effects of O3FAs on faecal microbiome profiles is of significant interest particularly their impact on bacteria associated with anti-CRC effects. Further work is required to elucidate whether O3FAs have a role in CRC chemoprevention or adjuvant treatment via their effects on the colonic microbiota.