A randomised double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis.

The impact of flavonoids on fatigue has not been investigated in relapsing and remitting multiple sclerosis (RRMS). OBJECTIVE: To determine the feasibility and estimate the potential effect of flavonoid-rich cocoa on fatigue and fatigability in RRMS. METHODS: A randomised double-blind placebo-controlled feasibility study in people recently diagnosed with RRMS and fatigue, throughout the Thames Valley, UK (ISRCTN69897291). During a 6-week intervention participants consumed a high or low flavonoid cocoa beverage daily. Fatigue and fatigability were measured at three visits (weeks 0, 3 and 6). Feasibility and fidelity were assessed through recruitment and retention, adherence and a process evaluation. RESULTS: 40 people with multiple sclerosis (10 men, 30 women, age 44±10 years) were randomised and allocated to high (n=19) or low (n=21) flavonoid groups and included in analysis. Missing data were <20% and adherence to intervention of allocated individuals was >75%. There was a small effect on fatigue (Neuro-QoL: effect size (ES) 0.04, 95% CI -0.40 to 0.48) and a moderate effect on fatigability (6 min walk test: ES 0.45, 95% CI -0.18 to 1.07). There were seven adverse events (four control, three intervention), only one of which was possibly related and it was resolved. CONCLUSION: A flavonoid beverage demonstrates the potential to improve fatigue and fatigability in RRMS.

Omega-3 Polyunsaturated Fatty Acids and the Intestinal Epithelium-A Review.

Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for maintaining regulated intestinal absorption and immunological control. Under inflammatory conditions, the intestinal barrier and its component enterocytes become inflamed, leading to changes in barrier histology, permeability, and chemical mediator production. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages. This review aims to assess the current literature detailing the effects of ω-3 PUFAs on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids. Altered inflammatory markers have been attributed to changes in activity and/or expression of proteins involved in inflammatory signalling including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) α and γ, G-protein coupled receptor (GPR) 120 and cyclooxygenase (COX)-2. Effective doses for each ω-3 PUFA are difficult to determine due to inconsistencies in dose and time of exposure between different in vitro models and between in vivo and in vitro models. Further research is needed to determine the anti-inflammatory potential of less-studied ω-3 PUFAs, including docosapentaenoic acid and stearidonic acid.