Postprandial Response After Intake of Meals With Different Fatty Acid Composition

Study Overview
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Brief Summary
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The aim of the study is to understand more about how different fatty acids modulate postprandial lipid metabolism and inflammatory response.

Official Title
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Postprandial Response After Intake of Meals With Different Fatty Acid Composition in Patients With Familial Hypercholesterolemia and Healthy Subjects

Conditions
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Healthy, Familial Hypercholesterolemia

Intervention / Treatment
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* Dietary Supplement: SFA muffin
* Dietary Supplement: PUFA muffin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 30 years of age Healthy or diagnosed with familial hypercholesterolemia (FH) (mutation in gene coding for LDL-receptor). FH subjects can be included if they are: Untreated Treated with low dose statin (<20 mg atorvastatin, <10-20 mg simvastatin or <5-10 mg rosuvastatin) Treated with high dose statin and willing to use low dose statin during the last 4 weeks prior to both study visits (total 8 week period) Treated with high dose statins and willing to discontinue statin treatment during the last 4 weeks prior to both study visits (total 8 week period) BMI 18.5 - 30 kg/m2 Stabile weight the last three months prior to the first study visit (weight change less than ± 5 % of body weight) Exclusion Criteria: CRP >10 mg/L TG >4 mmol/L Comorbidities including diabetes type I and II, coronary heart disease, haemophilia, anaemia, gastro intestinal disease, renal failure and hyperthyroidism Pregnant or lactating Allergic or intolerant to gluten or egg Not willing to stop using n-3 fatty acid supplements during the last 4 weeks prior to both study visits Using medications affecting lipid metabolism or inflammation, except statins for FH subjects Hormone treatment (except contraception and thyroxin (stabile dose last 3 months)) Donating blood 2 months within or during study period Tobacco smoking Large alcohol consumption (>40g daily)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Familial hypercholesterolemia<br>Subjects diagnosed with familial hypercholesterolemia receive in randomized order muffin with saturated fat (SFA muffin) and polyunsaturated fat (PUFA muffin) at baseline | Dietary Supplement: SFA muffin<br>* Muffin rich in saturated fat.<br>Dietary Supplement: PUFA muffin<br>* Muffin rich in polyunsaturated fat.<br>|
| Active Comparator: Healthy<br>Subjects with no chronic diseases receive in randomized order muffin with saturated fat (SFA muffin) and polyunsaturated fat (PUFA muffin) at baseline | Dietary Supplement: SFA muffin<br>* Muffin rich in saturated fat.<br>Dietary Supplement: PUFA muffin<br>* Muffin rich in polyunsaturated fat.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in levels of circulating triglycerides |  | Measured at baseline and 2,4 and 6 hours after intake of test meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in markers of lipid- and glucose metabolism | Changes in levels of total cholesterol, low-density lipoprotein, high-density lipoprotein, apolipoprotein (apo) B, apo A1, apo CIII, apo B48, lipoprotein (a), free fatty acids, total fatty acid composition, LDL-receptor-related protein with 11 ligand-binding repeats (LR11), HbA1c, glucose, insulin and troponin. | Measured at baseline and 2,4 and 6 hours after intake of test meal | 
| Changes in circulating levels of inflammatory markers | Changes in levels of inflammatory markers in circulation such as i.e. cytokines and hsCRP | Measured at baseline and 2,4 and 6 hours after intake of test meal | 
| Changes in PBMC gene expression levels of markers of inflammation and lipid metabolism | Changes in levels of markers of inflammation and lipid metabolism at PBMC gene expression level | Measured at baseline and 2, 4 and 6 hours after intake of test meal | 
| Changes in lipid classes and lipoprotein size |  | Measured at baseline and 2,4 and 6 hours after intake of test meal | 
| Changes in plasma and urine metabolomics | Changes in metabolites such as glucose, lactate, pyruvate, citrate and amino acids will be measured in plasma and urine. | Measured in plasma at baseline and 2,4 and 6 hours after intake of test meal. Measured in urine at fasting state and during the 6 hour postprandial phase. | 
| Check DNA for single nuclear polymorphisms |  | Measured at baseline and 2,4 and 6 hours after intake of test meal | 
| Changes in PBMC Whole genome transcriptomics |  | Measured at baseline and 4 and 6 hours after intake of test meal |