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

Effects of Omega-3 Fatty Acids From Fish Oil on the Gene Expression in Healthy Humans and Humans With Hypertriglyceridemia

The aim of this study is to investigate the effects of short- and long-term intervention with EPA and DHA-rich fish oil on gene expression profiles in healthy and hyperlipidemic males.

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.

Dietary Supplement: fish oil capsules (6 per day) 3024 mg n-3 fatty acids daily (1512 mg EPA and 1008 mg DHA) about 3 months

Dietary Supplement: fish oil capsules (6 per day) 3024 mg n-3 fatty acids daily (1512 mg EPA and 1008 mg DHA) about 3 months.

Dietary Supplement: fish oil capsules (6 per day) 3024 mg n-3 fatty acids daily (1512 mg EPA and 1008 mg DHA) about 3 months

Gene expression changes were measured by using whole genome microarrays. The expression values of all genes were compared between baseline and 4 hours, 7 days and twelve weeks after supplementation with FO or CO and differentially expressed genes were detected by standard two-state pooled-variance t-test (p<0,05). The number of differentially expressed genes (regulated genes)compared to the baseline values were determined for every study group in total as well as for every time point (4 hours, 7 days, 12 weeks)in total and specifically.

Fasting venous blood samples were collected and RBC membrane FA composition including the omega-3 index, given as EPA + DHA, was analyzed at baseline and after 12 weeks according to the omega-3 index methodology (Harris & von Schacky, 2004). Results are presented as a percentage of the total identified FAs after response factor correction. The coefficient of variation for EPA + DHA was 5%. Quality was assured according to DIN ISO 15189.

Fasting venous blood samples were collected and blood lipid levels were determined by an external contract laboratory (LADR, Hannover; Germany) at baseline (t0), after one week (t1) and after 12 weeks (t12) of supplementation.

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

Schmidt S, Willers J, Stahl F, Mutz KO, Scheper T, Hahn A, Schuchardt JP. Regulation of lipid metabolism-related gene expression in whole blood cells of normo- and dyslipidemic men after fish oil supplementation. Lipids Health Dis. 2012 Dec 14;11:172. doi: 10.1186/1476-511X-11-172.

Schmidt S, Stahl F, Mutz KO, Scheper T, Hahn A, Schuchardt JP. Different gene expression profiles in normo- and dyslipidemic men after fish oil supplementation: results from a randomized controlled trial. Lipids Health Dis. 2012 Aug 29;11:105. doi: 10.1186/1476-511X-11-105.

Schmidt S, Stahl F, Mutz KO, Scheper T, Hahn A, Schuchardt JP. Transcriptome-based identification of antioxidative gene expression after fish oil supplementation in normo- and dyslipidemic men. Nutr Metab (Lond). 2012 May 23;9(1):45. doi: 10.1186/1743-7075-9-45.