Fish Oil-derived N-3 Polyunsaturated Fatty Acids and Extracellular Vesicles
Condition: Extracellular Vesicles; Generation and Function
MeSH terms: Blister
Study type: Interventional

Summary: 
      N-3 polyunsaturated fatty acids (n-3 PUFA), which are abundant in oily fish and fish oils,
      have been suggested to play a role in reducing the risk of cardiovascular diseases (CVDs) by
      modifying a wide range of risk factors, such as blood fats, blood clotting, blood vessel
      function and inflammation. Extracellular vesicles (EVs) are small particles released from
      various cells when they are activated or damaged. High numbers of EVs in the blood have been
      associated with a higher risk of CVDs, and it is thought that this is because they carry
      'bioactive' components which can affect many processes involved in CVDs. However, very few
      clinical trials have investigated the relationships between the consumption of n-3 PUFA and
      circulating EVs. This study aims to investigate the effects of dietary n-3 PUFA on the
      generation and functional activities of EVs, which would provide new insight into the
      benefits of n-3 PUFA on cardiovascular health.
    

Detailed description: 
      The proposed study will be a randomised, double-blind, placebo-controlled crossover
      intervention. Subjects (40-70y) at moderate CVDs risk will be supplemented with either fish
      oil (1.8 g/d n-3 PUFA) or placebo (high-oleic safflower oil) for 12 weeks. After a 12-week
      washout and then cross-over to the other intervention for another 12 weeks. Blood samples
      will be collected before and after each intervention. A food frequency questionnaire will be
      administered to assess the subject's habitual intake of n-3 PUFA. Subjects will also be
      expected to maintain a low consumption of n-3 fatty acids, refrain from the use of all
      supplements, and maintain their body weight during the study. The dose is based on our
      previous work, which demonstrated a reduction in numbers of endothelial-derived EVs (EEVs)
      and a trend for reduced numbers of platelet-derived EVs (PEVs), and a dose at which
      beneficial effects of n-3 PUFA on plaque stability are reported. The experimental work will
      follow two main strands. The first strand will examine the influence of n-3 PUFA
      supplementation on the characteristics and functional activities of total EVs from plasma.
      The second strand will examine the influence of n-3 PUFA on the generation of PEVs from
      platelets taken from subjects and stimulated in vitro; the PEVs generated will subsequently
      be assessed for their composition and functional activity. This experimental design will
      allow simultaneous investigation of both the composition and activity of total EVs taken
      directly from blood, and the generation and activity of PEVs. Based on our previous work, 27
      subjects are required to detect a 10% reduction in numbers of EVs following fish oil
      supplementation with a two-sided significance level of 5% and a power of 90%, and 34 subjects
      are required for a power of 95%. Also based on previous data, 22 subjects would give 95%
      power to detect 10% differences in thrombus formation and 30 subjects are required to detect
      a significant effect of n-3 PUFA on platelet aggregation and phosphatidylserine (PS)
      exposure. Allowing for a 15% dropout rate, and aiming for 95% power based on a 10% reduction
      in EVs numbers, we will therefore recruit 40 subjects in total.
    

Intervention name(s): Fish oil capsules; High-oleic safflower oil capsules
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Each serving contains 360mg eicosapentaenoic acid (EPA), 270mg docosahexaenoic acid (DHA) and total supplement is 1.8 g per day n-3 PUFA for 12 weeks; High-oleic safflower oil capsules for 12 weeks
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Fish oil; N-3 polyunsaturated fatty acids