Plasma Diurnal Variation in and Absorption of EPA and DHA
Condition: Lipid Absorption and Metabolism
Study type: Interventional

Summary: 
      This study will evaluate the absorption of two different dietary supplements containing the
      omega 3 fatty acids eicosapentaenoic acid and docosahexaenoic acid over 24 hours via venous
      blood plasma following a single dose taken at bed time. In addition, the circadian rhythm of
      fatty acid metabolism will also be assessed following the placebo intervention.
    

Detailed description: 
      The bioavailability of the omega-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) can be influenced by a number of factors including chemical
      structure of the fatty acid binding form and the food matrix with which the fatty acids are
      consumed. In addition to this, there is evidence from animals that the lipid metabolism
      follows a circadian pattern, although this has yet to be investigated in humans.

      The supplement is produced as a soft gelatine capsule containing fish oil based high
      concentrate omega-3 fatty acids designed to improve bio availability via a self-emulsifying
      drug delivery system (SMEDDS). The in-situ formation of an emulsion occurs spontaneously when
      the capsule erupts in vivo and the SMEDDS solution comes in contact with the
      gastro-intestinal contents. The size of the microdroplets that are formed is in the lower
      micrometer range, the advantage of which is a much larger combined surface area compared to
      drops of oil which results in better access for pancreatic lipases. The resulting free fatty
      acids may then readily be absorbed during its passage through the upper small intestine
      resulting in an effective absorption of the oil.

      Therefore duel objectives of this study are to determine the bioavailability in healthy
      middle aged adults of two formulations of fish oil taken at bed time using SMEDDS and to
      evaluate the diurnal variation in background plasma fatty acids.

      All study visits will take place on the 4th floor of the Northumberland Building, Northumbria
      University within a suite of facilities comprising the Nutrition Kitchen, Sleep Centre,
      Clinical space and the waiting room of the Brain, Performance and Nutrition Research Centre.
      Participants will attend the lab on five separate occasions. The first visit will be a
      screening/introductory visit. The Introductory visit to the laboratory will comprise:
      providing each participant with a 'participant information sheet', briefing them on the
      requirements of the study and signing of the informed consent form and completion of the Case
      Report Form (CRF; including self-reported health screening and collection of demographic
      data). Participants will then attend the lab for four study visits which will be separated by
      at least 6 days, each of which will be identical except for the treatment that they will
      consume. On each of the study visits participants will arrive at the lab at 19:30 having
      consumed nothing but water for at least 2 hours prior to their arrival where their continued
      eligibility will be assessed. A cannula will then be inserted into a vein in the arm of the
      non-dominant hand. The first blood sample will be collected immediately prior to their
      evening meal which will be served at 20:00 and will be followed by a rest period. At 22:00
      participants will consume their evening's treatment. Lights out will be at 22:30. Blood
      samples will be drawn every 2 hours through the night at 00:00, 02:00 and 04:00. Participants
      will be woken up at 06:00 and a blood sample will be taken straight away. Blood samples will
      continue to be collected every two hours until 22:00 when the cannula will be removed. Meals
      will be provided at 07:00, 12:00, 16:00 and 20:00, with the evening meal being exactly the
      same as the previous evening. Participants will have ad libitum access to water throughout
      the study visit. They will also be allowed to consume tea and coffee throughout the day
      however the content and the timing of the hot drinks they consume on the first study visit
      will be replicated for the subsequent visits. Similarly, if they do not eat all of the meals
      that are provided in their entirety, this will be recorded and replicated for the subsequent
      visits. In between meals and blood samples participants will be required to remain within the
      facilities where they will be allowed to read, write, watch television or listen to music.
    

Intervention name(s): Omega-3 oil: DHA enriched; Placebo; Omega-3 oil: EPA enriched
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 3 x 1 g capsules containing a SMEDDS formulation of an DHA-enriched oil: 50% DHA + 15% EPA totalling 900 mg DHA and 270 mg of EPA; 3 x 1 g capsules Placebo: olive oil; 3 x 1 g capsules containing a SMEDDS formulation of an EPA-enriched oil: 50% EPA + 20% DHA totalling 900 mg EPA and 360 mg of DHA
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)