Clinical trial NCT05621083: Omega-3 Fatty Acids on Fasting and Postprandial Triglycerides (TG) Response - a Pilot Study
Official title: Effects of Omega-3 Fatty Acids on Fasting and Postprandial TG Response in Healthy Subjects (Omega-3PT) - a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Healthy Volunteers
Postprandial TG response
Lead sponsor: University of Oslo
Sponsor class: OTHER
Collaborators: name: Throne-Holst Foundation for Nutrition Research
name: Horizon 2020 - European Commission
name: GC Rieber VivoMega AS
First posted: 2022-11-17
Enrollment: 34
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Start with control oil (HOSO) or start with fish oil, and then change after 12 weeks of wash out.
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Fasting TG
timeFrame: up to 6 weeks
Secondary outcomes:
measure: Postprandial TG
timeFrame: up to 6 weeks
measure: 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
timeFrame: up to 6 weeks
measure: Fasting plasma cytokines, acute phase proteins and soluble adhesion molecules
timeFrame: up to 6 weeks
measure: Fasting whole genome Peripheral Blood Mononuclear Cells (PBMC) transcriptome (mRNA and miRNA)
timeFrame: up to 6 weeks
measure: Fasting epigenome in PBMCs
timeFrame: up to 6 weeks
measure: Fasting targeted and non-targeted metabolic profiling in plasma
timeFrame: up to 6 weeks
measure: Targeted and untargeted metabolomics of spot urine to measure dietary intake biomarkers
timeFrame: up to 6 weeks
measure: SNPs in whole blood
timeFrame: Measured once at baseline
measure: Composition of the gut microbiome (both metabolites and bacteria composition)
timeFrame: up to 6 weeks
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: University of Oslo
Study officials:
References: