Similar eicosapentaenoic acid and docosahexaenoic acid plasma levels achieved with fish oil or krill oil in a randomized double-blind four-week bioavailability study

Lipids Health Dis. 2015 Sep 2;14:99. doi: 10.1186/s12944-015-0109-z.


Background: Long-chain n-3 polyunsaturated fatty acids (LC n-3-PUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) provide multiple health benefits for heart, brain and eyes. However, consumption of fatty fish, the main source of LC n-3-PUFAs is low in Western countries. Intakes of LC n-3-PUFA can be increased by taking dietary supplements, such as fish oil, algal oil, or krill oil. Recently, conflicting information was published on the relative bioavailability of these omega-3 supplements. A few studies suggested that the phospholipid form (krill) is better absorbed than the fish oil ethyl ester (EE) or triglyceride (TG) forms. Yet studies did not match the doses administered nor the concentrations of DHA and EPA per supplement across such comparisons, leading to questionable conclusions. This study was designed to compare the oral bioavailability of the same dose of both EPA and DHA in fish oil-EE vs. fish oil-TG vs. krill oil in plasma at the end of a four-week supplementation.

Methods: Sixty-six healthy adults (n = 22/arm) were enrolled in a double blind, randomized, three-treatment, multi-dose, parallel study. Subjects were supplemented with a 1.3 g/d dose of EPA + DHA (approximately 816 mg/d EPA + 522 mg/d DHA, regardless of formulation) for 28 consecutive days, as either fish oil-EE, fish oil-TG or krill oil capsules (6 caps/day). Plasma and red blood cell (RBC) samples were collected at baseline (pre-dose on Day 1) and at 4, 8, 12, 48, 72, 336, and 672 h. Total plasma EPA + DHA levels at Week 4 (Hour 672) were measured as the primary endpoint.

Results: No significant differences in total plasma EPA + DHA at 672 h were observed between fish oil-EE (mean = 90.9 ± 41 ug/mL), fish oil-TG (mean = 108 ± 40 ug/mL), and krill oil (mean = 118.5 ± 48 ug/mL), p = 0.052 and bioavailability differed by < 24 % between the groups. Additionally, DHA + EPA levels were not significantly different in RBCs among the 3 formulations, p = 0.19, providing comparable omega-3 indexes.

Conclusions: Similar plasma and RBC levels of EPA + DHA were achieved across fish oil and krill oil products when matched for dose, EPA, and DHA concentrations in this four week study, indicating comparable oral bioavailability irrespective of formulation.

Trial registration: identifier NCT02427373.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Animals
  • Biological Availability
  • Dietary Fats, Unsaturated / blood
  • Dietary Fats, Unsaturated / pharmacokinetics*
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage
  • Double-Blind Method
  • Eicosapentaenoic Acid / blood
  • Euphausiacea / chemistry*
  • Fatty Acids / blood
  • Female
  • Fish Oils / blood
  • Fish Oils / pharmacokinetics*
  • Humans
  • Male
  • Phospholipids / blood
  • Therapeutic Equivalency
  • Triglycerides / blood


  • Dietary Fats, Unsaturated
  • Fatty Acids
  • Fish Oils
  • Phospholipids
  • Triglycerides
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid

Associated data