Health Beneficial Effects of Krill Oil and Lean and Fatty Fish

Study Overview
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Brief Summary
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Intake of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) from fish oil and fish are associated with significant health benefits in risk of cardiovascular disease. However, both lean and fatty fish have been shown to have beneficial effects suggesting that not all effects are mediated by n-3 PUFAs. Krill oil is an n-3 PUFA supplement on the marked. The n-3 PUFAs from krill oil is in the form of phospholipids, and these fatty acids may be more readily and effectively absorbed after ingestion than n-3 PUFAs in the form of triacylglycerols from fish oil. Fish also contain many other potential health components than n-3 PUFAs such as taurine and vitamin D, iodine, selenium and more unspecified components such as bioactive peptides which can mediate the health beneficial effects observed after intake of fish. The present study aims to elucidate the cardiovascular health beneficial effects after consumption of fish (lean and fatty) and krill oil, with regard to effects on plasma lipids and other markers of cardiovascular health such as inflammatory, haemostatic and endothelial dysfunction markers. The investigators will perform whole genome transcriptome analyses in peripheral blood mononuclear cells (PBMCs) in order to further understand the cardiovascular health benefits and elucidate the mechanisms of action.

Official Title
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Health Beneficial Effects of Krill Oil and Lean and Fatty Fish

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Krill oil
* Other: Lean and fatty fish
* Dietary Supplement: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers (CRP < 10 mg/L) Stable weight (± 5 % of body weight) the last three months BMI 18.5-35 kg/m2 Fasting triglycerides 1.3-4.0 mmol/L Willingness to eat fish Willingness to not take omega-3 or other dietary supplements during the study. Exclusion Criteria: Pregnancy or lactation Any chronic disease, including diabetes type 1 or 2. CVD or cancer past 6 months Elevated thyroid hormones or TSH levels Elevated total cholesterol (>7.8 mmol/L) or fasting triglycerides (>4.0 mmol/L) Use of prescription drugs that may affect triglycerides (e.g. diabetes drugs, Cyclosporin A, Orlistat and Sibutramine), except statins if stable dose past 3 months. Blood pressure > 160/100 mmHg Hormone treatment (except stable doses the past three months of contraceptives or thyroxine) Planned weight loss The use of Vita Proactive or other food items enriched with plant sterols Excessive alcohol consumption (>40 g/day) Habitual fish consumption of more than one serving of fatty fish per week

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Krill group<br>Krill oil capsules. 4 g/day encapsulated krill oil (Rimfrost Sublime) corresponding to  900 mg/day EPA + DHA + DPA for 8 weeks. The participants will be instructed to take the capsules with the breakfast and dinner meals. | Dietary Supplement: Krill oil<br>* The krill group and the control group will be double blinded. The krill oil and placebo capsules will be administered in equal amounts and are of equal size and have the same color.<br>* Other names: Rimfrost Sublime;|
| Experimental: Fish group<br>Lean and fatty fish. Three weekly test-meals, containing two meals of fatty fish and one meal of lean fish for 8 weeks corresponding to  900 mg/day EPA + DHA + DPA. | Other: Lean and fatty fish<br>* The fish group will be open labeled.<br>|
| Placebo Comparator: Control group<br>Placebo capsules. 4 g/day encapsulated high oleic sunflower oil (HOSO) for 8 weeks. The participants will be instructed to take the capsules with the breakfast and dinner meals. | Dietary Supplement: Placebo capsules<br>* The krill group and the control group will be double blinded. The krill oil and placebo capsules will be administered in equal amounts and are of equal size and have the same color.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting triglycerides |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating inflammatory markers | Such as TNFalpha and IL-6 | 8 weeks | 
| Gene expression of inflammatory markers and genes in lipid metabolism | Measured with RT-qPCR | 8 weeks | 
| Plasmamlipids | Such as total- LDL- and HDL-cholesterol | 8 weeks | 
| Lipoprotein subclasses |  | 8 weeks | 
| Plasma fatty acid composition |  | 8 weeks | 
| Blood pressure |  | 8 weeks | 
| Endothelial dysfunction markers | Sush as NOx and ADMA | 8 weeks | 
| Hemostatic markers | Such as vWF and thrombomudulin | 8 weeks | 
| Muscle strength | Measured by hand grip strength and chair stand test | 8 weeks | 
| Whole genome transcriptome analysis in PBMC | Changes in the gene expression profile | 8 weeks | 
| Metabolome profile in blood | In blood | 8 weeks | 
| Metabolome profile in urine | In urine | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Triacylglycerols, Omega-3 fatty acids, Krill oil, Fish, Healthy Volunteers