Pharmacokinetics of Supplemental Omega-3 Fatty Acids Esterified in Monoglycerides, Ethyl Esters, or Triglycerides in Adults in a Randomized Crossover Trial.

BACKGROUND: Omega-3 (n-3) fatty acid (FA) supplements increase blood concentrations of EPA and DHA. Most of the supplements on the market are esterified in triglycerides (TGs) or ethyl esters (EEs), which limits their absorption and may cause gastrointestinal side effects. OBJECTIVE: The objective of this study was to compare the 24-h AUC of the plasma concentrations of EPA, DHA, and EPA+DHA when provided esterified in monoglycerides (MAGs), EEs, or TGs, (primary outcomes) and evaluate their side effects over 24 h (secondary outcome). METHODS: This was a randomized, triple-blind, crossover, controlled clinical trial. Eleven women and 11 men between 18 and 50 y of age ingested, in random order, a single oral dose of ∼1.2 g of EPA and DHA esterified in MAGs, EEs, and TGs with low-fat meals provided during the 24-h follow-up. Eleven blood samples over 24 h were collected from each participant, and the plasma n-3 FAs were quantified. Friedman's paired ANOVA statistical rank test was used for the pharmacokinetic parameters and a chi-square statistical test was used for the side effects. RESULTS: The 24-h AUC of plasma EPA was ∼2 times and ∼1 time higher after the MAG compared with the EE and TG forms of n-3 FAs, respectively (P ≤ 0.0027). Effects of the EE and TG treatments did not differ. The 3 supplements had similar eructation, dysgeusia, abdominal discomfort, nausea, and bloating side effects. CONCLUSIONS: The plasma n-3 FA concentration in adults is greater after acute supplementation with n-3 FAs esterified in MAGs rather than in EEs or TGs, suggesting that with a lower dose of MAG n-3 FAs, the plasma n-3 FA concentrations attained are similar to those after higher doses of n-3 FAs esterified in EEs or TGs. This trial is registered at www.clinicaltrials.gov as NCT03897660.

Comparison of pharmacokinetics of omega-3 fatty acid supplements in monoacylglycerol or ethyl ester in humans: a randomized controlled trial.

BACKGROUND: A diet low in omega-3 fatty acids (n-3 FA) results in low plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two main long chain n-3 FA. n-3 FA supplements on the market are esterified in triglycerides (TG) or ethyl ester (EE); the latter is absorbed less than other esterification forms. The objective of this study was to test and compare the pharmacokinetics of n-3 FA esterified in monoacylglycerides (MAG), a predigested form, with the EE form. METHODS: This study was a randomized, double-blind, crossover, controlled, clinical trial. Ten men and ten women between 18 and 60 years old were recruited. Participants received a single oral dose of 3 g of n-3 FA esterified in EE or MAG. Eleven blood samples were collected over 24 h post-dose. Plasma total lipids were extracted, methylated, and analyzed using gas chromatography. RESULTS: After receiving the MAG form, plasma EPA and DHA peaked at a concentration 3 and 2.5 times higher, respectively, than with the EE form. When provided in MAG form, n-3 FA plasma concentration during the absorption phase was on average 3-5 times higher than in EE form. When n-3 FAs were provided esterified in MAG, their concentration 24 h post-dose was higher than in EE. Males had a lower n-3 FA plasma concentration than females when n-3 FAs were provided in EE but there was no sexe difference when provided in MAG. CONCLUSIONS: Plasma concentration of DHA and EPA was higher when provided in MAG than EE form.