Study to Evaluate the Acute Bioavailability of EPA and DHA From a DietarySupplement in Healthy Men and Women

A randomized, controlled two-period crossover study included one screening/baseline visit (visit 1, day -7) with four test visits during Period I (visits 2, 3, 4, and 5; days 0, 1, 2, and 3) and four tests visits during Period II (visits 6, 7, 8, and 9; days 14, 15, 16, and 17) with at least a 7-d washout between test periods. Eighteen healthy adults with fasting TAG concentrations <200 mg/dL were randomly assigned to one of two treatment sequences: receive 8 capsules containing Calanus oil® (Calanus AS, Tromso, Norway) supplying a total of 4 g of oil providing 260 mg EPA and 156 mg/day DHA primarily as wax esters, followed by 1 capsule supplying 1 g of oil providing 465 mg EPA and 375 mg DHA as ethyl esters (Lovaza®, GlaxoSmithKline, Research Triangle Park, NC); or, to receive Lovaza followed by Calanus Oil. Product was dispensed in-clinic with an standardized EPA- and DHA- free breakfast meal (t=0). Blood samples were obtained in-clinic at t= -30 min, and 1, 2, 4, 6, 8, 10 and 12 h timepoints. Subjects were provided a standardized EPA- and DHA-free meal at t=4 h and t=8. Subject were dismissed from the clinic after t-12 h blood draw and returned the morning of days 1, 2 and 3 (days 15, 16 and 17) for a 24 h, 48 h and 72 h fasting blood draw.

Inclusion criteria

• Male or female, 18-59 years of age, inclusive.
• BMI of ≥18.50 and ≤29.99 kg/m2 at visit 1 (day -7).
• Fasting TG <200 mg/dL at visit 1 (day -7).
• Score of 7 to 10 on the Vein Access Scale at visit 1 (day -7).
• No health conditions that would prevent the subject from fulfilling the study requirements as judged by the Investigator on the basis of medical history and routine laboratory test results.
• Willing to refrain from consumption of all fish/seafood (including shellfish), and/or EPA- or DHA-containing foods and supplements 14 d prior to visit 2 (day 0) and throughout the study.
• Willing to limit alcohol consumption to no more than 1 drink/d following visit 1 (day -7) and throughout the study.
• Non-smoker with no plans to change smoking habits during the study period.
• Willing to maintain habitual diet (with the exception of foods to be restricted), physical activity patterns, and body weight throughout the trial.
• Understood the study procedures and signed forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the study Investigator.

Exclusion criteria

• Abnormal laboratory test results of clinical significance at visit 1 (day -7), at the discretion of the Investigator. One re-test was allowed on a separate day prior to visit 2 (day 0) for subjects with abnormal laboratory test results.
• History or presence of clinically important endocrine (including type 1 or 2 diabetes mellitus), cardiovascular (including, but not limited to history of myocardial infarction, peripheral arterial disease, stroke), pulmonary (including uncontrolled asthma), hepatic, renal, hematologic, immunologic, dermatologic, neurologic, psychiatric or biliary disorders.
• History or presence of a GI disorder that, in the judgment of the Investigator, may have disrupted normal digestion and absorption of the study products.
• History of difficulty swallowing tablets/capsules that could have affected ability to consume the study products.
• Extreme dietary habits (e.g., Atkins diet, very high protein, vegetarian), in the opinion of the Investigator.
• Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg) as defined by the blood pressure measured at visit 1 (day -7). One re-test was allowed on a separate day prior to visit 2 (day 0), for subjects whose blood pressure exceeded either of these cut points, in the judgment of the Investigator.
• History or presence of cancer in the prior two years, except for non-melanoma skin cancer.
• Weight loss or gain >4.5 kg in the 3 months prior to visit 1 (day -7).
• Use of medications or dietary supplements known to alter lipid concentrations within 4 weeks of visit 1 (day -7). Dietary supplements included, but were not limited to, the following: sterol/stanol products; dietary fiber supplements (including >1 teaspoon Metamucil® or viscous fiber-containing supplement per day); red rice yeast supplements; garlic supplements; soy isoflavone supplements; or niacin or its analogues at dosages >50 mg/day (or others at the discretion of the Investigator).
• Use of non-study related omega-3-acid ethyl ester drug(s) or dietary supplement(s) with ≥1.0 g/d of EPA, DHA, or a combination of EPA and DHA within 4 months of visit 1 (day -7).
• Known allergy or sensitivity to omega-3 fatty acids, fish, other seafood, or any ingredient in the study product or study meals.
• Active infection or use of antibiotics within 5 d of visits 2 and 6 (days 0 and 14). Subjects that had an active infection and/or were using antibiotics were required to wait at least 5 d after the infection resolved or antibiotic use was complete prior to the first day of each test period (visits 2 and 6, days 0 and 14).
• Female who was pregnant, planning to be pregnant during the study period, lactating, or was of childbearing potential and unwilling to commit to the use of a medically approved form of contraception throughout the study period. The method of contraception was recorded in the source documentation.
• Exposure to any non-registered drug product within 30 d prior to visit 1 (day -7).
• Recent history of (within 12 months of screening; visit 1, day -7) or strong potential for alcohol or substance abuse. Alcohol abuse defined as >14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1½ oz distilled spirits).