Health Effects of Cetoleic Acid (A Randomized Double Blinded Controlled Trial)

Study Overview
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Brief Summary
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In this Randomized Controlled Trial (RCT) we want to study how supplements of cetoleic acid ( C22:n1-11) (intervention) affect the conversion of alpha-linolenic acid (ALA) to EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in healthy subjects, compared to supplements with a low concentration of cetoleic acid (control). Our primary endpoints are changes in the concentration of EPA and DHA in plasma and red blood cells.

Detailed Description
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This is a randomized double-blinded controlled trial ( randomized 1:1). Study population: healthy men and women 20-70 years, BMI 20-35 kg/m2. Study design: 3 weeks run-in-period where all participants consume control capsules every morning. Randomization intervention: control (1:1). All participants consume their capsules (control or intervention) for 4 weeks. The intervention oil consists of a fish oil high in cetoleic acid and the control oil is a mix of different oils and low in cetoleic acid. Power calculation and sample size: It was expected a difference of 15% in n-3 between the groups after the intervention (Østbye et al. 2019, doi:10.1017/S0007114519001478). The level of significance was set to 5% (two-sided) and the power to 80%. A total of thirty-eight subjects were required to participate in the study, but a high dropout rate was expected (20%) and it was considered necessary to include a total of seventy (n=70) subjects (thirty-five per arm).

Official Title
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Health Effects of Cetoleic Acid (Helseeffekter av Ketolinsyre)

Conditions
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Healthy Diet

Intervention / Treatment
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* Dietary Supplement: Cetoleic acid
* Dietary Supplement: Control Oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 20-35kg/m2 opportunity to meet for 3 visits at the Department of Nutrition, University of Oslo, during the study period. Exclusion Criteria: Chronic disease (liver/kidney/metabolism) Alcohol overconsumption (>40g/day) Diabetes and high fasting blood glucose Pregnant/ breastfeeding or planning pregnancy during the study period High fish intake (>3 meals/week). Blood donation during the study period Difficulty following the study protocol. Smoking/snuffing Regularly use of anti-inflammatory drugs Regularly use of omega-3 supplements /cod liver oil.

Ages Eligible for Study
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Minimum Age: 20 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
Interventional Model Description: Randomized double-blinded controlled trial (Randomized 1:1, control:intervention). Run-in period of 3 weeks where all participants receive the control capsules.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention ( Cetoleic acid)<br>6x mackerel oil (cetoleic acid: 16A%, estimated: 135 mg/g (FFA)) capsules every morning for 4 weeks (A%= area percent) | Dietary Supplement: Cetoleic acid<br>* Very long monounsaturated fatty acid ( C22:1n-11)<br>|
| Placebo Comparator: Control oil<br>6x capsules control oil (Control oil= mix of anchovy oil, olive oil, high-oleic sunflower oil, rapeseed oil (cetoleic acid: 0,7 A% estimated: 6 mg/g (FFA)) every morning for 4 weeks (A%= area percent) | Dietary Supplement: Control Oil<br>* Control oil consisting of: mix of anchovy oil, olive oil, high-oleic sunflower oil and rapeseed oil<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EPA and DHA in plasma | EPA and DHA concentration in plasma measured at baseline and and after 4 week intervention (and as a control measurement at the screening visit) | 4 weeks intervention | 
| EPA and DHA in red blood cells | EPA and DHA concentration and omega 3 index (EPA+DHA/total fatty acids) in red blood cells measured at baseline and and after 4 week intervention (and as a control measurement at the screening visit) | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid profile- Triglycerides | Plasma levels of triglycerides measured at baseline and after 4 weeks intervention (and as a control measurement at the screening visit) | 4 weeks | 
| Lipid profile- Cholesterol | Plasma levels of cholesterol (total cholesterol, LDL-cholesterol and HDL-cholesterol) measured at baseline and after 4 weeks intervention (and as a control measurement at the screening visit) | 4 weeks | 
| Lipid profile- Apolipoproteins | Plasma levels of apolipoproteins (apoB and apoA) measured at baseline and after 4 weeks intervention (and as a control measurement at the screening visit) | 4 weeks | 
| Lipid profile- Lipoproteins | Plasma levels of Lp(a) and lipoprotein subclasses measured at baseline and after 4 weeks intervention (and as a control measurement at the screening visit) | 4 weeks | 
| Inflammatory markers | The concentration of circulating levels of inflammatory markers measured at baseline and after 4 weeks intervention ( and as a control measurement at screening) | 4 weeks | 
| Gene expression | Changes in PBMC (peripheral blood mononuclear cell) gene expression profile measured at baseline and after 4 week of intervention | 4 weeks | 
| Pain sensitivity | Measured by cold pressure tests at baseline and after 4 week of intervention ( and as a control measurement at screening) | 4 weeks | 
| Resolvins | Blood levels of resolvins (omega- 3 derivates) concentrations measured at baseline and after 4 week of intervention ( and as a control measurement at screening) | 4 weeks | 
| Metabolome | Changes in metabolome measured at baseline and after 4 week of intervention | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Omega 3 fatty acids, Sustainability, Cetoleic acid, Very long monounsaturated fatty acid, Cardiovascular disease prevention, Antiinflammation