Effects of Cetoleic Acid on Atherosclerosis (Ketolinsyre's Effekt på Aterosklerose)

Effects of Ketolic Acid on Atherosclerosis Markers in High-risk Patients With Metabolic Syndrome (Effekt av Ketolinsyre på aterosklerosemarkører i høyrisikopasienter Med Metabolsk Syndrom)

In this Randomized Controlled Trial (RCT) we want to study the effect of an oil with high concentrations of cetoelic acid (C22:n1-11) (intervention) compared to supplements with a low concentration of cetoleic acid (control), but with equivalent content of EPA og DHA, on plasma levels of epa and dha as well as atherosclerotic markers, glucose, c-peptide and triglycerides in a patient group with a metabolically unfavorable phenotype.

Our primary endpoints are changes in the concentration of EPA and DHA in plasma.

This is a randomized double-blinded controlled trial (randomized 1:1). Study population: men and women 20-70 years with a metabolically unfavorable phenotype defined as: triglycerides > 1.7 mmol/L and waist measurement > 80 cm (women) and > 94 cm (men).

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 is consists of an oil high in cetoleic acid and the control oil is low in cetoleic acid. Both the intervention oil and the control oil are a mix of different oils; fish oils, olive oil, "high-oleic sunflower oil" and rapeseed oil so that the content of EPA, DHA and ALA is similar in the two oils.

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).

Inclusion Criteria:

• Triglycerides > 1.7 mmol/L
• Waist measurement > 80 cm (women) and > 94 cm (men)

Exclusion Criteria:

• Chronic disease (liver/kidney/metabolism)
• Ongoing active cancer treatment
• Excessive alcohol consumption (>40g/day)
• Pregnant/breastfeeding or planned pregnancy during the intervention
• High intake of fish (>3 weekly meals)
• Level of free thyroxine (T4) and triiodothyronine (T3) outside reference ranges.
• Hypertension (≥ 160/ 100 mmHg)
• Total cholesterol > 7.8 mmol/L
• Blood donation during the intervention period
• Difficulty following the protocol
• Smoking or sniffing
• Regular use (> 1 day/week) of anti-inflammatory drugs
• Regular use of omega-3 supplements/cod liver oil
• Drug use other than stable use of statins, hypertension drugs (Ca antagonists, diuretics and beta blockers).
• Hormonal treatment excluding stable use of thyroxine and birth control pills/contraceptive rod