Omega-3 fatty acid exposure with a low-fat diet in patients with past hypertriglyceridemia-induced acute pancreatitis; an exploratory, randomized, open-label crossover study

Lipids Health Dis. 2020 May 30;19(1):117. doi: 10.1186/s12944-020-01295-7.


Background: Omega-3 fatty acids (OM3-FAs) are recommended with a low-fat diet for severe hypertriglyceridemia (SHTG), to reduce triglycerides and acute pancreatitis (AP) risk. A low-fat diet may reduce pancreatic lipase secretion, which is required to absorb OM3-ethyl esters (OM3-EEs), but not OM3-carboxylic acids (OM3-CAs).

Methods: In this exploratory, randomized, open-label, crossover study, 15 patients with SHTG and previous AP were instructed to take OM3-CA (2 g or 4 g) and OM3-EE 4 g once daily for 4 weeks, while adhering to a low-fat diet. On day 28 of each treatment phase, a single dose was administered in the clinic with a liquid low-fat meal, to assess 24-h plasma exposure. Geometric least-squares mean ratios were used for between-treatment comparisons of baseline (day 0)-adjusted area under the plasma concentration versus time curves (AUC0-24) and maximum plasma concentrations (Cmax) for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Results: Before initiating OM3-FA treatment, mean baseline fasting plasma EPA + DHA concentrations (nmol/mL) were 723 for OM3-CA 2 g, 465 for OM3-CA 4 g and 522 for OM3-EE 4 g. At week 4, mean pre-dose fasting plasma EPA + DHA concentrations increased by similar amounts (+ 735 - + 768 nmol/mL) for each treatment. During the 24-h exposure assessment (day 28), mean plasma EPA + DHA increased from pre-dose to the maximum achieved concentration by + 32.7%, + 45.8% and + 3.1% with single doses of OM3-CA 2 g, OM3-CA 4 g and OM3-EE 4 g, respectively. Baseline-adjusted AUC0-24 was 60% higher for OM3-CA 4 g than for OM3-EE 4 g and baseline-adjusted Cmax was 94% higher (both non-significant).

Conclusions: Greater 24-h exposure of OM3-CA versus OM3-EE was observed for some parameters when administered with a low-fat meal at the clinic on day 28. However, increases in pre-dose fasting plasma EPA + DHA over the preceding 4-week dosing period were similar between treatments, leading overall to non-significant differences in baseline (day 0)-adjusted AUC0-24 and Cmax EPA + DHA values. It is not clear why the greater 24-h exposure of OM3-CA versus OM3-EE observed with a low-fat meal did not translate into significantly higher pre-dose fasting levels of DHA + EPA with longer-term use.

Trial registration:, NCT02189252, Registered 23 June 2014.

Keywords: Clinical trials; Docosahexaenoic acid; Eicosapentaenoic acid; Fish oil; Omega-3 carboxylic acids; Omega-3 ethyl esters; Omega-3 fatty acids; Pharmacokinetics; Triglycerides; Viscosity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Area Under Curve
  • Cross-Over Studies
  • Diet, Fat-Restricted*
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / blood
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / blood
  • Fasting / blood
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / blood
  • Female
  • Humans
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / diet therapy*
  • Hypertriglyceridemia / pathology
  • Male
  • Middle Aged
  • Pancreatitis / diet therapy*
  • Pancreatitis / etiology
  • Pancreatitis / pathology
  • Triglycerides / blood


  • Fatty Acids, Omega-3
  • Triglycerides
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid

Associated data