Pharmacokinetics of Omega-3 Monoglycerides
Condition: Healthy
Study type: Interventional

Summary: 
      North American diets have insufficient omega-3 fatty acid (n-3 FA) content. Consequently,
      they display low plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic
      acid (EPA), the two main long chain n-3 FA. A quick and easy way to increase the level of
      dietary n-3 FA is to take supplements. However, people report side effects in using the
      currently available supplements, such as gastrointestinal discomfort, nausea and gastric
      reflux; especially those where EPA and DHA are esterified as ethyl esters (EE). Moreover, EE
      supplements are less absorbed compared to other esterification forms, such as mono-, di- or
      triglycerides. The objective of this study was to test the pharmacokinetics of a new n-3 FA
      supplementation formulation rich in FAs esterified as monoacylglyceride (MAG).
    

Detailed description: 
      The growing presence on the North American as well as European market of food products
      enriched with fish oil as a source of polyunsaturated fatty acids (PUFA) omega-3 in the diet
      requires evaluation and comment. Research exploring health influence of the consumption of
      fish oil started in 1990 years. It was established that long-chain omega-3 PUFA (EPA C20:5
      and DHA C22:6) has beneficial effect on human health. Fish oil is the main dietary source of
      long-chain omega-3 PUFA. Dietary recommendations suggest that the consumption of omega-3 PUFA
      should increase. The European Academy of Nutritional Sciences (EANS) and the United Kingdom
      dietary guidelines recommend a daily average intake of 0.2g of EPA plus DHA. In 2000, the
      Food and Drug Administration stated that the daily intake of EPA and DHA should increase up
      to 3.0 g per person in the form of fish oil, from food and dietary supplements. According to
      the World Health Organization recommendations for preventing cardiovascular diseases, one
      portion of fish should provide an equivalent of 200-500 mg of EPA and DHA. Due to the low
      fish consumption in developed societies, it seems reasonable to introduce fish oil in capsule
      supplement dosage forms and several food products enriched with fish oil that can be an
      additional source of the desirable long-chain omega-3 PUFA in the diet. For this purpose,
      reaching the recommended daily intake may require taking several capsules of fish oil per
      day.

      Several studies have been performed to evaluate the potential health benefits brought by the
      consumption of food enriched with fish oil. Some studies suggest that different amounts of
      long-chain omega-3 - DHA and EPA, provided in a supplement form or added to food products,
      result in the same effect in changes in the blood lipid profile. The development of fish oil
      enriched food must be based on the scientific knowledge of the target function in the body
      and show that the effects are relevant for improved health or reduction of disease risk. The
      physiological effects of the intake of omega-3 fatty acids added to foods may differ
      depending on the quality of the fish oil used and the type of product.

      Fish oil benefits range from decreasing risk of the so-called life-style diseases,
      particularly cardiovascular diseases, to combating depression, bipolar disorder and
      schizophrenia. Fish oil has also prophylaxis effects and treatment effects on inflammation,
      arthritis, anti-aging, age-related macular degeneration and mental health. Most of dietary
      lipids ingested from food consist of triacyglycerols. Prior to passive diffusion into the
      enterocytes, lipid digestion and emulsification are initiated by the action of different
      lipases resulting in the release of 2 free fatty acids and one monoglyceride-linked fatty
      acid. They are incorporated into mixed micelles to facilitate absorption into the
      bloodstream. The process of manufacturing the fish oil determines the quality which also
      depends on the type of fish used and the purity standards followed when refining the oil.
      Emulsified forms of fish oil have led to improved digestion and absorption of EPA and DHA in
      human healthy volunteers.

      Flavored emulsified liquid preparations provide a simplified approach to fish oil delivery;
      emulsion as new approach seems to have advantages in the digestion and absorption of fatty
      acids which will increase the bioavailability. Using a novel approach of fish oil
      emulsification, preliminary results have indicated that both the rate and the extent of
      absorption of the fatty acids, particularly EPA and DHA, may be increased when digested. The
      present study was designed to establish that fish oil pre-emulsified using a novel approach
      will lead to increased absorption of EPA and DHA compared with the non-emulsified form of the
      fish oil.
    

Intervention name(s): Omega-3 + vitamin K2 (monoacylglycerol form); Omega-3 + vitamin K2 (ethyl ester)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The intervention is a randomized double bond cross over design testing the pharmacokinetics of a monoglyceride formulation compared to an ethyl ester form.
Treatments are randomly assigned on days 0 and 7 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours. Each participant will perform the two treatments, with a minimum of 6 days between treatments.; The intervention is a randomized double bond cross over design testing the pharmacokinetics of a monoglyceride formulation compared to an ethyl ester form.
Treatments are randomly assigned on days 0 and 7 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours. Each participant will perform the two treatments, with a minimum of 6 days between treatments.
Intervention MeSH terms: Vitamins; Vitamin K; Vitamin K 2
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double-blind controlled-randomized pharmacokinetic (PK) pilot study with crossover design (10 men and 10 women), with a minimum of 6 days between treatments
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Omega-3 fatty acids; Vitamin K2; Bioavailability; Monoacylglycerol; Pharmacokinetic