Effects of Omega-3 Fatty Acids on the Human Gene Expression

Cardiovascular and coronary heart diseases continue to be the leading causes of morbidity and mortality among adults in Europe and North America. Since the number of elderly people and therefore the number of chronic-inflammatory diseases rise, preventive therapies become more important. Within preventive strategies, nutrition plays a central role.

Cross-sectional studies suggested that omega-3 fatty acids, especially the very long-chain fatty acids Eicosapentaenoic acid (EPA, C20:5ω3) and Docosahexaenoic acid (DHA, C22:6ω3), are protective against cardiovascular and coronary heart diseases. Their cardio protective potential is based on their positive effects on blood lipids, vascular tonus and blood clotting. A number of controlled clinical trials have shown that EPA and DHA supplementation lower fasting and postprandial plasma concentrations of triglyceride-rich lipoproteins and their remnants. Biochemical research revealed numerous metabolic effects of EPA and DHA, ranging from their effects on membrane fluidity to the modification of the eicosanoid profile.

However, only a few human clinical trials examined the regulative effects of DHA and EPA supplementation on gene expression. Furthermore, to our knowledge no published research data is available dealing with the effect of these fatty acids on gene expression in subjects with hypertriglyceridemia in comparison to healthy subjects. Such findings are of great concern due to hints that especially people with hypertriglyceridemia benefit from the triglyceride lowering effect of EPA and DHA supplementation. Presently it is not well-established if the gene regulative potential of EPA and DHA in these persons differs from healthy persons. These findings could help to understand the differences in the metabolic effects of EPA and DHA in healthy vs. hypertriglyceridemic persons, which have a greater risk for cardiovascular and coronary diseases. Finally, these data could contribute to a knowledge basis for targeted strategies in preventive therapies with the very long-chain omega-3 fatty acids EPA and DHA.

Inclusion criteria

• males, 20-50 years
• non-smokers
• ethnicity: Caucasians
• no medical treatment
• healthy subjects:

• no documented disease
• normal blood lipids (triglyceride < 150 mg/dl; total cholesterol < 200 mg/dl)
• humans with increased blood lipids (hyperlipidemia)

• documented hypertriglyceridemia or
• triglyceride ≥ 150 mg/dl (≥ 1,7 mmol/l) and
• total cholesterol > 200 mg/dl (5,2 mmol/l)
• written confirmation of the subjects after detailed oral and written explanation about the study contents, - requirements and risks
• ability and willingness of the participants to attend the investigator's orders (compliance of the study conditions, consumption of the study medicaments according to the dosage commendation)

Exclusion criteria

• Body-Mass-Index (BMI) ≥ 35
• smokers
• medical treatment (especially corticosteroids, anti-inflammatory drugs, blood lipids lowering drugs (e.g. statins, fibrates, bile acid exchanger resin, phytosterols)
• taking any supplements with omega-3 fatty acids, phytosterols, polyglucosamines (Chitosan) or other lipid binding ingredients
• daily consumption of omega-3 fatty acids rich fish (salmon, mackerel, herring)
• heavy chronic diseases (tumors, diabetes typ 1, etc.), documented heart disease, documented blood clotting disorders, renal failure, liver diseases
• documented blood clotting disorders and consumption of coagulation-inhibiting drugs (for example Marcumar, ASS)
• allergy or intolerance to fish/fish oil or any of the study ingredients of the test products
• chronic gastro-intestinal diseases (Colitis ulcerosa, Morbus Crohn, pancreatic insufficiency)
• donation of blood in the last 6 weeks
• routine consumption of laxative
• common exclusion criteria like

• alcohol-, drug- and/or medicament dependence
• subjects who are not in agreement with the study conditions
• refusal or rather reset of the consent from the subject
• active participation in other investigational drug or device trial within the last 30 days