Saturated Fatty Acids and HDL Metabolism

Study Overview
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Brief Summary
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The purpose of this study is to determine whether palmitic acid (C16:0) and stearic acid (C18:0) have different effects on HDL metabolism during the fasted state.

Detailed Description
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Study design: Double blind, randomized, cross-over study with two different diets: one diet will be high in palmitic acid (C16:0) and the other diet will be high in stearic acid (C18:0). Subjects will receive both diets for 4 weeks with a wash-out period of 4-6 weeks in between. Contrast in the intakes of palmitic acid and stearic acid is 6% of energy. A postprandial test will be carried out at the end of each dietary period. Study population: Accounting for a dropout rate of 20%, 40 healthy men and postmenopausal women, aged between 45 and 70 year, having a BMI (body mass index) between ≥ 18.0 and ≤ 30.0 kg/m2 will be recruited.

Official Title
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Effects of C16:0 Versus C18:0 on HDL Metabolism and Other Cardiometabolic Risk Markers: A Dietary Intervention Study in Healthy Normal-weight and Overweight Subjects

Conditions
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Dyslipidemia

Intervention / Treatment
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* Dietary Supplement: Palmitic acid
* Dietary Supplement: Stearic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Apparently healthy men and post-menopausal women (post-menopausal for at least one year) as judged by study physician BMI ≥ 18.0 and ≤ 30.0 kg/m2 Aged between 45 and 70 years Willing to comply to study protocol during study Having a general practitioner Agreeing to be informed about medically relevant personal test-results by a physician Informed consent signed Accessible veins on arms as determined by examination at screening Exclusion Criteria: Having a medical condition which might impact study measurements Use of over-the-counter and prescribed medication, which may interfere with study measurements Use of oral antibiotics in 40 days or less prior to the start of the study; Use of food supplements or plant-sterol/stanol-enriched foods or supplements in the three months prior to the screening and/or during the study; Reported alcohol consumption ≥ 10 units/week (female) or ≥ 14 units/week (male); Reported intense sporting activities ≥ 10 hours/week; Reported weight loss or gain of 3 kg or more during a period of 2 months prior to screening Regular smokers (at least one cigarette (or equivalent) daily or >7 cigarettes (or equivalent) weekly. Smokers who cannot comfortably restrain from smoking for up to 2 days will also be excluded Reported dietary habits: medically prescribed diet, allergy/intolerance to test products that will be provided during the study Blood donation in the past 3 months Drug abuse Reported participation in another nutritional or biomedical trial 3 months prior to screening Fasting triacylglycerol concentrations at screening: ≥ 4.5 mmol/L Serum lipids: treatment recommended according to the Multidisciplinary guidelines Cardiovascular risk management Fasting HbA1c ≥ 48 mmol/mol (or 6.5%)

Ages Eligible for Study
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Minimum Age: 45 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palmitic acid<br>Diet rich in palmitic acid | Dietary Supplement: Palmitic acid<br>* Experimental products are enriched with C16:0<br>|
| Experimental: Stearic acid<br>Diet rich in stearic acid | Dietary Supplement: Stearic acid<br>* Experimental products are enriched with C18:0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cholesterol efflux capacity after dietary period high in palmitic acid compared to dietary period high in stearic acid | J774 Macrophages will be used to measure ex vivo cholesterol efflux capacity of HDL particles after a diet enriched with C16:0 or C18:0. Change in ex vivo cholesterol efflux capacity between the diets will be assessed using a linear mixed model with subject as random factor and day 0 as co-variant. | Cholesterol efflux is measured during fasted state at day 0, day 25 and day 28 of each intervention period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasted lipid metabolism markers between dietary period high in palmitic acid and dietary period high in stearic acid | Markers include fasting LDL-C [mmol/L], HDL-C [mmol/L], total cholesterol [mmol/L], non-HDL cholesterol [mmol/L] and triacylglycerol [mmol/L] concentrations. Change between diets will be assessed using a linear mixed model with subject as random factor and day 0 as co-variant. | Markers for lipid metabolism will be measured during fasted state at day 0, day 14, day 25 and day 28 of each intervention period | 
| Change in fasted lipid ratios between dietary period high in palmitic acid and dietary period high in stearic acid | Markers include fasting total cholesterol to HDL-C ratio and LDL-C to HDL-C ratio. Change between diets will be assessed using a linear mixed model with subject as random factor and day 0 as co-variant. | Markers for lipid metabolism will be measured during fasted state at day 0, day 14, day 25 and day 28 of each intervention period | 
| Change in fasted apolipoproteins between dietary period high in palmitic acid and dietary period high in stearic acid | Apolipoproteins include fasting ApoA1 [μg/mL] and ApoB100 [μg/mL]. Change between diets will be assessed using a linear mixed model with subject as random factor and day 0 as co-variant. | Apolipoproteins will be measured during fasted state at day 0, day 14, day 25 and day 28 of each intervention period | 
| Change in postprandial triacylglycerol levels between dietary period high in palmitic acid and dietary period high in stearic acid | Change between diets will be assessed using a linear mixed model with subject as random factor and day 0 as co-variant. | Triacylglycerol [mmol/L] is measured during postprandial state at day 28 (0 to 480 minutes after meal intake) of each intervention period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palmitic acid, Stearic acid, HDL-metabolism, Human intervention study