The American Heart Association and the American College of Cardiology (AHA/ACC) recently encouraged "increased consumption of omega-3 fatty acids in the form of fish or capsule form (1 g/day) for risk reduction" and stated that "for treatment of elevated triglycerides, higher doses are usually necessary for risk reduction" (Smith SC et al. Circulation 2006;113:2363-72). These recommendations are based on conflicting evidence about the efficacy of the omega-3 treatment with data derived from single randomized trials or non-randomized studies (Smith SC et al. Circulation 2006;113:2363-72). Much effort has been undertaken to elucidate the role of omega-3 fatty acids in the development of cardiovascular disease, but even recent meta-analyses deliver no clear picture; they either favor (Mozaffarian D Jama 2006;296:1885-99) or reject (Hooper L Bmj 2006;332:752-60) the hypothesis of cardioprotective effects of omega-3 FAs. The objective of the clinical study is to study the effects of fish oil on blood and urinary markers of inflammation and cell stress. By using different permutations of high-dose supplementation of omega-3 and omega-6 fatty acids versus different alimentary omega-3 fish doses and grain alcohol versus different kinds of red wine, this trial will study how omega-3 fatty acids, ethanol and red wine constituents modulate biomarkers of inflammation and cell stress.
This clinical study comprises several parts: Part 1: Single-arm open oral administration of ethanol in n=40 healthy participants. Part 1.1: Single-arm open oral administration of fish oil capsules and ethanol in n=12 healthy participants. Part 2a: Randomized double-blind oral administration of fish oil or safflower oil capsules and ethanol in n=44 healthy participants. Part 2b: Randomized double-blind oral administration of fish foods or control diet and open oral administration of ethanol in n=40 healthy participants. Part 3: Randomized double-blind oral administration of fish foods or control diet and red wine beverages in n=40 healthy participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
Part 1.1: Dose of 9.3 g/day EPA plus 7.5 g/day DHA; Part 2a (run-in phase): Dose of 1 time 2 capsules per day of Lovaza (total of 1.7 g/d ω-3 PUFA consisting of 930 mg/day EPA and 750 mg/day DHA) for 29±1 days; Part 2a (study arm): Dose of 3 times 4 capsules per day of Lovaza (total of 10.1 g/d ω-3 PUFA consisting of 5580 mg/day EPA and 4500 mg/day DHA) for 29±1 days
Part 2a: (Study Arm): Omega-6 polyunsaturated fatty acids 3 times 4 capsules per day (total of 10.2 g/d ω-6 PUFA) for 29±1 days
Part 1 \& Part 1.1: Dose of 0.9 g/kg body weight 98% alcohol solution Part 2a: Doses of 0.4 and 0.9 g/kg body weight 98% alcohol solution and a control placebo drinking solution Part 2b, Part 3: Doses of 0.4, 0.6 and 0.9 g/kg body weight 98% alcohol solution
Part 2b: Alimentary diet delivering ≈ 500 mg/day EPA/DHA,or Alimentary diet delivering ≈ 900-1000 mg/day EPA/DHA, or Alimentary diet delivering ≈ 1500-1800 mg/day EPA/DHA; Part 3: Alimentary diet delivering EPA/DHA in a quantity to be determined by Part 2b.
Part 2b: Control omega-6 fatty acid alimentary diet (\<130 mg/day EPA/DHA)
Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, United States
Urinary isoprostane concentrations
urinary isoprostanes will be analyzed raw (i.e. untransformed, including the Time factor: Baseline vs Peak)
Time frame: Hours and days
Urinary eicosanoid concentrations
Time-dependency of urine eicosanoid and isoprostane formation after acute oral ethanol
Time frame: Hours and days
Plasma eicosanoid concentrations
plasma eicosanoid response after a single oral dose of 0.9 g/kg body weight 98% ethanol.
Time frame: Hours and days
Blood alcohol concentrations
Evaluation of acute toxic alcohol effects
Time frame: Hours and days
Blood fatty acid composition
Oral administration of omega-3 and omega-6 fatty acids
Time frame: Hours to months
Compositional Changes in the Intestinal Microbiome
Collection of stool samples
Time frame: Hours and days
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