Clinical trial NCT01735357: Differential Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Platelet, Endothelial and Vascular Function
Official title: Investigation Into Incorporation of (n-3) Polyunsaturated Fatty Acids Into Erythrocyte Membranes and Clearance, and Effects on Platelet Function, Arterial Function and Endothelial Repair
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Eicosapentaenoic acid
Docosahexaenoic acid
Cardiovascular risk
Platelet function
Endothelial function
Vascular function
young males
Lead sponsor: King's College London
Sponsor class: OTHER
First posted: 2012-11-28
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study was to determine whether supplementation with oils enriched with long chain n-3 PUFA, either EPA or DHA, had a differential effect on platelet, endothelial and vascular function.

Detailed description: Relatively few studies have made a head-to-head comparison of DHA (22:6n-3) with EPA (20:5n-3). The understanding of this differential effect may be of great interest in populations with low EPA intake such as vegetarians, who may choose to supplement their dietary intake of long-chain n-3 PUFA in the form of DHA-rich algal oil.

This study aimed to investigate the effect of supplementation with oils rich in either EPA or DHA (3g/day, 6 weeks) in healthy young males on platelet, endothelial and vascular function, as well as other CVD risk factors. The primary outcomes were platelet monocyte aggregates and endothelial progenitor cells - novel markers of platelet and endothelial function, measured by flow cytometry, Secondary outcomes included capillary density, measured by capillaroscopy to assess changes in microvascular function, pulse wave analysis, digital volume pulse and ambulatory blood pressure. Other secondary outcomes included lipid profiles (TAG, cholesterol, NEFA), glycaemic control (HOMA, QUICKI) and oxidative stress (isoprostane). The omega-3 index (erythrocyte EPA+DHA) was used as a marker of compliance.

Eligibility criteria: Inclusion Criteria:

* Healthy males
* No smokers
* Aged 18-45y old
* Able to understand the information sheet and comply with all the trial procedures
* Having given written consent to take part in the study prior to participation.

Exclusion Criteria:

* Reported history of CVD (myocardial infarction, angina, venous thrombosis, stroke, dyslipidemia), diabetes (or fasting glucose ≥ 6.1 mmol/L), cancer, kidney, liver or bowel disease.
* Presence of gastrointestinal disorder or use of drug, which is likely to alter gastrointestinal motility or nutrient absorption.
* Current smokers; history of substance abuse or alcoholism (previous weekly alcohol intake \>60 units/week); current self-reported weekly alcohol intake exceeding 28 units
* Recent use of hypolipidaemic, antihypertensive, antiplatelet or antithrombotic mediations
* Platelet count above or below the normal range or any history indicative of a congenital or acquired platelet or haemostatic defect.
* Allergy or intolerance to any component of study capsules
* Unwilling to restrict consumption of any source of fish oil for the length of the study
* Subjects reporting consumption of \>1 portion oily fish per week
* Weight change of \>3 kg in preceding 2 months; BMI \<18 and \>32 kg/m2
* Blood pressure\>160/90 mmHg
* Fasting blood cholesterol \> 6.5 mmol/L; fasting triacylglycerol concentrations \> 2.0 mmol/L

Primary outcomes:
measure: Platelet Monocyte Aggregates (PMA)
timeFrame: 6 weeks
measure: Endothelial Progenitor Cell (EPC) counts
timeFrame: 6 weeks
Secondary outcomes:
measure: Capillary density
timeFrame: 6 weeks
measure: Arterial stiffness
timeFrame: 6 weeks
measure: Blood Pressure (BP) and Heart Rate (HR)
timeFrame: 6 weeks
measure: Plasma isoprostane concentrations
timeFrame: 6 weeks
measure: Plasma Nitrate and Nitrites (NOx) concentrations
timeFrame: 6 weeks
measure: Serum total cholesterol concentration
timeFrame: 6 weeks
measure: Serum Triacylglycerol concentrations
timeFrame: 6 weeks
measure: Serum high density lipoprotein concentration
timeFrame: 6 weeks
measure: Serum low density lipoprotein concentration
timeFrame: 6 weeks
measure: Serum non esterified fatty acids (NEFA) concentration
timeFrame: 6 weeks
measure: Serum Apolipoprotein B concentration
timeFrame: 6 weeks
measure: Plasma glucose concentration
timeFrame: 6 weeks
measure: Plasma insulin concentration
timeFrame: 6 weeks
measure: Serum adiponectin concentration
timeFrame: 6 weeks
measure: Serum resistin concentration
timeFrame: 6 weeks
measure: Erythrocyte phospholipid fatty acid profiles
timeFrame: 6 weeks
measure: Fatty acid profile of plasma non esterified fatty acid fraction
timeFrame: 6 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Diabetes & Nutritional Sciences Division, King's College London
Study officials:
affiliation: King's College London
name: Wendy L Hall, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cottin SC, Alsaleh A, Sanders TA, Hall WL. Lack of effect of supplementation with EPA or DHA on platelet-monocyte aggregates and vascular function in healthy men. Nutr Metab Cardiovasc Dis. 2016 Aug;26(8):743-51. doi: 10.1016/j.numecd.2016.03.004. Epub 2016 Mar 15.