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OpenTrials
Completed

NCT Number: NCT01735357

Differential Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Platelet, Endothelial and Vascular Function

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.

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Key information

Conditions

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Diabetes & Nutritional Sciences Division, King's College London

London, SE1 9NH, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

EPA-rich triacylglycerol oil

Dietary Supplement

Placebo - olive oil (BP specification)

Dietary Supplement

DHA-rich triacylglycerol oil

Dietary Supplement

Primary outcomes

  1. Platelet Monocyte Aggregates (PMA)

    Time frame: 6 weeks

    The endothelium plays a vital role in the regulation of blood flow, thrombosis and inflammation. Endothelium-derived anti-adhesive and anti-aggregant substances, including prostacyclin and nitric oxide, are known to inhibit platelet activation. Endothelial dysfunction or vessel wall injury lead to the activation of platelets, of which platelet-monocyte-aggregates (PMA) are a sensitive marker, and were shown to inversely correlate with markers of EF in patients with stable CHD. The measurement of PMA by flow cytometry is a method which reduces ex vivo platelet activation to its minimum and is believed to represent platelet activation in vivo.

  2. Endothelial Progenitor Cell (EPC) counts

    Time frame: 6 weeks

    EPCs are a subgroup of circulating progenitor cells that are recruited from the bone marrow to repair the injured vasculature. They have been associated with a reduced CVD risk and may serve as markers of endothelial function because they represent a greater capacity for the endothelium to repair itself. Two populations of EPCs were measured by flow cytometry, described as 'early EPC' (KDR+/CD34+/CD133+) and 'late EPCs' (KDR+/CD34+/CD31+).

Secondary outcomes

  1. Capillary density

    Time frame: 6 weeks

    Capillary rarefaction has been associated to CVD risk factors such as hypertension, smoking and obesity. The cutaneous circulation has emerged as an accessible and representative vascular bed to look at microvascular dysfunction. Capillary density was measured by a Capiscope (kk technologies)

  2. Arterial stiffness

    Time frame: 6 weeks

    Pulse wave analysis (PWA) was used to measure indices of arterial stiffness, including peripheral and central augmentation index, as well as central systolic and diastolic blood pressure. Digital volume pulse (DVP) was used to measure reflection and stiffness indices.

  3. Blood Pressure (BP) and Heart Rate (HR)

    Time frame: 6 weeks

    Resting HR and BP were measured in the seated and supine position after 15 minute rest, on the days of both baseline and endpoint visits. In addition, ambulatory BP and HR (24h, daytime, nighttime) was measured 2-3 days prior to each visit.

  4. Plasma isoprostane concentrations

    Time frame: 6 weeks

    8-iso-prostaglandin-F2α (8-IsoP-F2α), a prostaglandin F2-like compound biosynthesized nonenzymatically by a free-radical oxygenation of arachidonic acid, was measured in plasma in order to assess oxidative stress.

  5. Plasma Nitrate and Nitrites (NOx) concentrations

    Time frame: 6 weeks

    Plasma NOx was measured as a circulating marker of endothelial function.

  6. Serum total cholesterol concentration

    Time frame: 6 weeks

  7. Serum Triacylglycerol concentrations

    Time frame: 6 weeks

  8. Serum high density lipoprotein concentration

    Time frame: 6 weeks

  9. Serum low density lipoprotein concentration

    Time frame: 6 weeks

  10. Serum non esterified fatty acids (NEFA) concentration

    Time frame: 6 weeks

  11. Serum Apolipoprotein B concentration

    Time frame: 6 weeks

  12. Plasma glucose concentration

    Time frame: 6 weeks

  13. Plasma insulin concentration

    Time frame: 6 weeks

  14. Serum adiponectin concentration

    Time frame: 6 weeks

  15. Serum resistin concentration

    Time frame: 6 weeks

  16. Erythrocyte phospholipid fatty acid profiles

    Time frame: 6 weeks

    The EPA and DHA content of erythrocyte lipids were used as a marker of compliance.

  17. Fatty acid profile of plasma non esterified fatty acid fraction

    Time frame: 6 weeks

Sponsors and collaborators

Lead sponsor

King's College London

Other

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2010
Study completion
2010
First posted
Nov 28, 2012
Registry last updated
Sep 16, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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