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Mechanistic studies of long chain omega-3 fatty acid supplementation and inflammation in metabolic syndrome.

Periodic Reporting for period 2 - PIMS (Mechanistic studies of long chain omega-3 fatty acid supplementation and inflammation in metabolic syndrome.)

Periodo di rendicontazione: 2019-04-01 al 2020-03-31

Chronic inflammation, which describes a state of low but sustained blood levels of proteins that play a role in the response to injury and acute disease, is now indisputably recognized as a key risk factor for heart disease. Obesity is a frequent cause of chronic inflammation, leading to a state of metabolic disorders such as increased blood lipids and hypertension, a state frequently referred to as metabolic syndrome (MetS). The increasing obesity rates worldwide have been paralleled by increases in the prevalence of MetS and associated heart disease risk over the last decades, with unprecedented social and economic impacts on the global health care burden. It therefore becomes of highest priority to investigate strategies to prevent or decrease chronic inflammation among at-risk patients. Nutritional strategies play a major role, especially those based on omega 3 fatty acid dietary supplements. Indeed, omega 3 fatty acids, notably eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), have raised tremendous interest notably for their blood lipid lowering effect and purported anti-inflammatory potential. However, data from rigorously conducted clinical studies supporting anti-inflammatory effects of omega 3 fatty acids are surprisingly lacking. Moreover, almost all studies so far have used a mix of omega 3 fatty acids, notably DHA and EPA together. Therefore, it remains unclear if DHA and EPA have similar or different effects on chronic inflammation, and if so, by which mechanisms. Recent studies suggest that fat accumulation plays a direct role in promoting whole body chronic inflammation. The laboratory of Dr Lamarche has shown previously that DHA is more potent than EPA in reducing some of the blood markers of inflammation in adults at risk of heart disease. In this context, the overarching objective of the present project was to compare and further understand the anti-inflammatory effects of EPA and DHA in men and women at risk of heart disease through innovative physiological and molecular studies. The main results achieved so far suggest that (1) the genes that influence inflammation processes in immune cells do not contribute to the distinct anti-inflammatory effects of high doses of EPA vs. DHA on plasma markers of inflammation, (2) superficial abdominal adipose tissue does not appear to play a role in explaining the difference between EPA and DHA in modulating chronic inflammation, and (3) the stronger anti-inflammatory effects of DHA compared with EPA may be due, in part, to changes in specific bioactive lipid mediators derived from DHA and EPA. No difference between men and women was observed in response to EPA and DHA supplementation regarding the above-mentioned results. Further novel mechanistic studies based on the in vivo tracking of key inflammatory proteins such as C-reactive protein and serum amyloid A are being finalised and will undoubtedly be breakthrough in explaining the anti-inflammatory effects of DHA and EPA.
The impact of EPA vs. DHA supplementation was notably investigated through the study of specific inflammation markers in the bloodstream, immune cells and abdominal adipose tissue of the participants, who received approximately 3g of EPA and 3g of DHA in random order for periods of 10 weeks each. Results revealed that neither immune cells nor superficial abdominal adipose tissue play a significant role in the differential anti-inflammatory effects of DHA and EPA. However, specific lipid mediators derived from DHA may contribute to its greater anti-inflammatory action. All results and findings were presented through oral conferences given at several national and international meetings that gathered thousands of attendees. Such events took place in both non-European and European countries (Canada, USA, Ireland, France, Spain, Sweden).
The project study brings invaluable and timely data, considering that the population is increasingly using DHA and EPA supplements, which represent one of the fastest growing markets in the dietary supplement industry. To date, results of the present project point to specific mechanisms that may explain to the potentially greater anti-inflammatory effects of DHA compared to EPA, although such differences remain small. The present results thus provide competitive future prospects regarding dietary supplement formulation in the dietary and pharmaceutical sector. The comparison examined (DHA vs. EPA) is important given the investments in time and effort in developing separate EPA and DHA supplements. This work also provides new valuable perspectives to pursue in future controlled studies on DHA and EPA. The study of in vivo metabolism of inflammation proteins, which is being finalised, is extremely novel and will bring new insights and added value in the understanding of the anti-inflammatory effects of DHA and EPA. End-users of the results from the project study are: 1) scientists (via papers, conferences), 2) the partnered company ATRIUM Innovations, which continues to use the results of this research for future product development, 3) any other food supplement companies, especially those specialised in omega-3 supplements and 4) the lay public, in conferences given by various members of the research group on a regular basis. Ultimately, this research may provide new evidence to the government, policy makers, health professionals and patients of the importance and proper use of food supplements as potential contributors to metabolic disease prevention.
Summary of results