Omega-3 Fatty Acids on Fasting and Postprandial Triglycerides (TG) Response - a Pilot Study

Study Overview
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Brief Summary
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The aim of this project is to elucidate how repeated exposure with omega-3 fatty acid supplementation for 6 weeks affect mean and individual fasting lipids and inflammatory responses and postprandial TG after a high fat meal with butter (50 g fat) in healthy subjects.

Detailed Description
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The investigators aim to perform a randomized controlled crossover trial where each participant will act as his or her own control. Participants will be randomized to either start to receive fish oil (the omega-3 fatty acid supplement, dose of 2.3 g Eicosapentaenoic acid fatty acids (EPA) + Docosahexaenoic acid fatty acids (DHA) /day) for 6 weeks or a high-oleic sunflower oil (HOSO) containing no omega-3 fatty acids, as control followed by a wash-out period of minimum 12 weeks, before the treatment is changed for 6 weeks. Before and after each intervention period we will take fasting blood samples and collect spot morning urine. At home, the participant will perform a voluntary postprandial meal test with 61 g butter (containing 50 g fat), use DBS to collect fasting (0 h) 2, 4, 6, and 8 h blood samples after intake of the meal to measure TG which has been validated previously. The investigators will use first part of the trial to define fasting and postprandial TG responders and non-responders. The investigators will also monitor at home the postprandial TG response to HOSO to see the participants' postprandial response to a control oil without omega-3 fatty acids. After a 12 week wash-out period, we will then repeat the fish oil intervention period once more for all in order to see if those we defined as responders continue to be defined in the same category in the repeated fish oil intervention (adaptive design). The investigators will collect exposure data, including dietary intake, physical activity, and clinical data such as BMI, body composition (such as fat mass, visceral fat, fat free mass), blood pressure, lipids and glucose and specific single nucleotide polymorphism (SNPs) to understand the impact of these factors on the individual postprandial TG response. In addition, the investigators will collect feces samples before taken before each meal test day for gut microbiota analysis.

Official Title
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Effects of Omega-3 Fatty Acids on Fasting and Postprandial TG Response in Healthy Subjects (Omega-3PT) - a Pilot Study

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Omega- 3
* Dietary Supplement: HOSO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) between 18.5-30 kg/m2 Fasting TG level at ≥0.9 mmol/L Max eating one portion of fatty fish per week. All subjects must be willing to take two capsules with either fish oil or HOSO. They all need to accept to avoid taking omega-3 supplementation. If they use omega-3 supplements, they should wait 12 weeks before starting the study. Exclusion Criteria: Unable to give informed consent BMI <18.5 and >30 kg/m2 Weight change of ± 5 % of body weight in the last three months TG <0.9 mmol/L and > 1.7 mmol/L C reactive protein (CRP) >10 mg/L Total cholesterol >6.9 mmol/L for subjects 30-49 years and >7.8 mmol/L for subjects ≥50 years old Blood pressure >160/100 mm Hg Comorbidities including diabetes type I and II (blood glucose ≥7 mmol/L fasting), Cardiovascular diseases(CVD)/Coronary heart disease (CHD), haemophilia, anaemia (hemoglobin <120 gram/L), gastro intestinal disease, hyperthyroidism (TSH >4 Milliunits per litre (mU/L)) or inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyalgia and other connective tissue diseases. Pregnant or lactating Having CVD/CHD or cancer past 1 year Allergic or intolerant to gluten, milk protein and/or lactose Use of medications affecting lipids and lipid metabolism, blood clotting or inflammation. Unwilling to separate any use of omega-3 fatty acid supplements and other supplements during the study, and fish intake more than one portion per week, 12 weeks prior to and during the study period Hormone treatment (stabile dose of contraception or thyroxin for the last three months excepted) Use of medications affecting lipids and lipid metabolism, blood clotting or inflammation. Stable dose (more than 3 months) of statin, estrogen or blood pressure medications during the trial is allowed. Blood donation two months prior to or during the study period Tobacco smoking and snuff

Ages Eligible for Study
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Minimum Age: 40 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: Crossover Assignment
Interventional Model Description: Start with control oil (HOSO) or start with fish oil, and then change after 12 weeks of wash out.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fish oil (the omega-3 fatty acid supplement)<br>Participants will be randomized to either start to receive fish oil (the omega-3 fatty acid supplement) for 6 weeks. Followed by a wash-out period of a minimum of 12 weeks before the treatment is changed. Once the classical Randomized Controlled Trial (RCT) has finished, all the participants will repeat the fish oil intervention period (adaptive design) to determine if those the investigators defined as responders continue to be defined in the same category. | Dietary Supplement: Omega- 3<br>* In the fish oil supplement period, the participants will receive concentrated fish oil which is equal to in total 2.3 g EPA+DHA per day during 6 weeks.<br>|
| Placebo Comparator: High-oleic sunflower oil (HOSO) containing no omega-3 fatty acids<br>Participants will be randomized to either start to receive high-oleic sunflower oil (HOSO) for 6 weeks. Followed by a wash-out period of minimum 12 weeks, before the treatment is changed. | Dietary Supplement: HOSO<br>* In the HOSO period, the participants will receive similar amount of HOSO per day during 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting TG | Baseline levels of circulating triglycerides | up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial TG | At home, the participant will perform a voluntary postprandial meal test with 61 g butter (containing 50 g fat), use DBS to collect fasting(0 h) 2, 4, 6, and 8 h blood samples after intake of the meal | up to 6 weeks | 
| Fasting cholesterol, free fatty acids (FFA), LDL cholesterol, high-density lipoprotein (HDL) cholesterol, Apo A1, Apo B, Apo B-48 and Apo C-III, and lipoprotein subclasses, glucose and insulin | measure fasting levels -compare fasting levels before and after intake of omega-3 or HOSO | up to 6 weeks | 
| Fasting plasma cytokines, acute phase proteins and soluble adhesion molecules | measure fasting levels of all inflammatory markers before and after intake of omega-3 or HOSO | up to 6 weeks | 
| Fasting whole genome Peripheral Blood Mononuclear Cells (PBMC) transcriptome (mRNA and miRNA) | fasting levels before and after intake of omega-3 or HOSO | up to 6 weeks | 
| Fasting epigenome in PBMCs | fasting levels before and after intake of omega-3 or HOSO | up to 6 weeks | 
| Fasting targeted and non-targeted metabolic profiling in plasma | fasting levels before and after intake of omega-3 or HOSO | up to 6 weeks | 
| Targeted and untargeted metabolomics of spot urine to measure dietary intake biomarkers | Measure food intake metabolites in spot urine | up to 6 weeks | 
| SNPs in whole blood | measure specific SNPs related to omega-3 intake and TG response | Measured once at baseline | 
| Composition of the gut microbiome (both metabolites and bacteria composition) | measure metabolites in blood and feces and bacteria composition in feces | up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers, Postprandial TG response