Effects of a Self–micro-emulsifying Delivery System Formulation Versus a Standard ω-3 Acid Ethyl Ester Product on the Bioavailability of Eicosapentaenoic Acid and Docosahexaenoic Acid: A Study in Healthy Men and Women in a Fasted State

• Published in: Clinical therapeutics Vol. 40; no. 12; pp. 2065 - 2076
• Main Authors: Maki, Kevin C., Palacios, Orsolya M., Buggia, Mary A., Trivedi, Rupal, Dicklin, Mary R., Maki, Cathleen E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2018; Elsevier Limited
• Subjects: Alcohol; Bioavailability; Blood & organ donations; Blood pressure; Body mass index; Clinical trials; Dietary supplements; Docosahexaenoic acid; Drug dosages; Eicosapentaenoic acid; Family medical history; Fasting; Fatty acids; Fish oils; Hispanic Americans; Laboratories; Mathematics; Smoking; Women; ω-3 self–micro-emulsifying delivery system; ω-3 self–micro-emulsifying delivery system; eicosapentaenoic acid; fish oils; bioavailability; docosahexaenoic acid
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2018.10.014

Intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with several potential health benefits, but standard ethyl ester (EE) formulations of these ω-3 fatty acids require the co-ingestion of fat for adequate absorption. The objective of this research was to assess the relative bioavailability of EPA and DHA administered in a proprietary self–micro-emulsifying delivery system (SMEDS) formulation compared with EPA and DHA in a standard ω-3 acid EE product in healthy men and women in a fasted state. This randomized crossover study investigated the bioavailability of 2 encapsulated formulations of EPA and DHA, a capsule containing 500 mg EPA + DHA administered in a SMEDS formulation (SMEDS treatment), and a capsule containing 840 mg EPA + DHA in a standard ω-3 acid EE formulation (EE treatment). Subjects consumed a single dose of their assigned capsule in a fasting state, and plasma was collected before and for 24 h after dosing. Subjects underwent a ≥14-day washout and were crossed over to the other treatment condition. Plasma concentrations of EPA, DHA, and EPA + DHA were assessed. Twenty-three subjects (11 women, 12 men; mean [SEM] age, 33.8 [2.1] years; and body mass index, 24.9 [0.7] kg/m2) completed the trial. The baseline-adjusted, dose-normalized, arithmetic means (SD) of the incremental (i)-AUC0–24h for EPA + DHA were 543 (266) and 102 (88.2) h · μg/mL/g for the SMEDS and EE formulations, respectively (P < 0.001). The iAUC0–24h least-squares geometric mean ratio (90% CI) for SMEDS:standard EE was 475/58 = 8.2 (4.8–13.9), indicating markedly higher bioavailability of EPA + DHA with the SMEDS formulation compared to the standard EE formulation. This finding was also true for EPA (geometric mean ratio [90% CI], 18.2 [11.3–29.3]) and DHA (geometric mean ratio [90% CI], 4.5 [2.9–7.0]). The SMEDS delivery system markedly enhanced appearance in plasma of EPA and DHA, compared to a standard EE formulation, when ingested in the fasting state. ClinicalTrials.gov identifier: NCT03443076.