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.
Study Goal
The researchers aimed to compare the effects of OM3-CA and OM3-EE on plasma EPA and DHA levels when administered with a low-fat diet in patients with severe hypertriglyceridemia and previous acute pancreatitis.
Results Summary
The study found that OM3-CA showed greater 24-hour exposure compared to OM3-EE when taken with a low-fat meal, but long-term fasting plasma EPA+DHA levels were similar between treatments, leading to non-significant differences in adjusted AUC and Cmax values.
Population
15 patients with severe hypertriglyceridemia and a history of acute pancreatitis.
Effective Dosage
OM3-CA (2 g or 4 g) and OM3-EE (4 g) once daily.
Duration
4 weeks per treatment phase.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Omega-3 fatty acids (OM3-FAs) with a low-fat diet | decrease | triglycerides and acute pancreatitis (AP) risk | patients with severe hypertriglyceridemia (SHTG) | - | are recommended | #1 |
OM3-CA 2 g | increase | mean pre-dose fasting plasma EPA + DHA concentrations | patients with SHTG and previous AP | + 735 - + 768 nmol/mL | increased | #2 |
OM3-CA 4 g | increase | mean pre-dose fasting plasma EPA + DHA concentrations | patients with SHTG and previous AP | + 735 - + 768 nmol/mL | increased | #3 |
OM3-EE 4 g | increase | mean pre-dose fasting plasma EPA + DHA concentrations | patients with SHTG and previous AP | + 735 - + 768 nmol/mL | increased | #4 |
single dose of OM3-CA 2 g | increase | mean plasma EPA + DHA from pre-dose to the maximum achieved concentration | patients with SHTG and previous AP | + 32.7% | increased | #5 |
single dose of OM3-CA 4 g | increase | mean plasma EPA + DHA from pre-dose to the maximum achieved concentration | patients with SHTG and previous AP | + 45.8% | increased | #6 |
single dose of OM3-EE 4 g | increase | mean plasma EPA + DHA from pre-dose to the maximum achieved concentration | patients with SHTG and previous AP | + 3.1% | increased | #7 |
OM3-CA 4 g | increase | baseline-adjusted AUC0-24 | patients with SHTG and previous AP | 60% higher than for OM3-EE 4 g | was higher | #8 |
OM3-CA 4 g | increase | baseline-adjusted Cmax | patients with SHTG and previous AP | 94% higher than for OM3-EE 4 g | was higher | #9 |
OM3-CA | increase | 24-h exposure | patients with SHTG and previous AP | - | greater 24-h exposure | #10 |
OM3-CA versus OM3-EE | no change | baseline (day 0)-adjusted AUC0-24 and Cmax EPA + DHA values | patients with SHTG and previous AP | - | non-significant differences | #11 |
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: ClinicalTrials.gov, NCT02189252, Registered 23 June 2014.