Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study):study protocol for a randomized, controlled, multicenter, international clinical trial

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017

Activation of human neutrophils by oleic acid involves the production of reactive oxygen species and a rise in cytosolic calcium concentration: a comparison with N-6 polyunsaturated fatty acids

Contains fulltext : 95617.pdf (publisher's version ) (Open Access)BACKGROUND: There is a growing body of evidence showing that dietary constituents and lipids in particular, influence the function of the human immune system. However, although the beneficial effects of oleic acid (OA) are clear, its mechanism of action at the molecular level is poorly understood. AIMS: To evaluate neutrophil activation under the influence of OA and compare this with several n-6 PUFAs. METHODS: Two key aspects of neutrophil activation were investigated: oxygen radical (ROS) production and intracellular Ca(2+) signaling. RESULTS: OA and the n-6 PUFA arachidonic acid (AA) both induced ROS production in a dose-dependent manner, although AA was the more potent stimulus. When looking for the mechanisms behind these effects, we found that both FA induce increases in cytosolic calcium concentration [Ca(2+)](i)), but whereas OA-induced ROS production is totally mediated through Ca2+ signaling, this is not the case for AA since ROS generation by AA is only partly inhibited in BAPTA-treated cells. We also found evidence for the involvement of protein kinase C (PKC) in the OA-induced ROS generation; by contrast, other enzymes apart from PKC seem to be implicated in n-6 PUFA-induced ROS production. In addition, our results argue against the involvement of a pertussis toxin-sensitive receptor activated by OA. CONCLUSIONS: OA differs from the n-6 PUFA AA in the activation of human neutrophils and these differences may be related to their distinct inmunomodulatory properties