Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers

Abstract

A subject's baseline FA composition may influence the ability of dietary highly unsaturated omega-3 FAs (n3-HUFA) to change circulating profiles of esterified FAs and their oxygenated metabolites. This study evaluates the influence of basal n3-HUFA and n3-oxylipin status on the magnitude of response to n3-HUFA consumption. Blood was collected from fasting subjects (n = 30) before and after treatment (4 weeks; 11 ± 2 mg/kg/day n3-HUFA ethyl esters). Esterified FAs were quantified in erythrocytes, platelets, and plasma by GC-MS. Esterified oxylipins were quantified in plasma by LC-MS/MS. Treatment with n3-HUFAs increased n3-HUFAs and decreased n6-HUFAs in all reservoirs and increased plasma n3-oxylipins without significantly changing n6-oxylipin concentrations. As subject basal n3-HUFAs increased, treatment-associated changes decreased, and this behavior was reflected in the percentage of 20:5n3 + 22:6n3 in red blood cell membrane FAs (i.e., the omega-3 index). To maintain an omega-3 index of 8% and thus reduce cardiovascular disease risk, our analyses suggest a maintenance dose of 7 mg/kg/day n3-HUFA ethyl esters for a 70-kg individual. These results suggest that the basal n3 index may have clinical utility to establish efficacious therapeutic experimental feeding regimens and to evaluate the USDA Dietary Guidelines recommendations for n3-HUFA consumption.

Figures

Fig. 1.

Changes in the mol% composition of platelet, RBC, and plasma lipid pools after 4 g/day n3 FAs ethyl esters. The n6-HUFAs were reduced and n3-HUFAs were enriched in all measured compartments. MUFAs were reduced in plasma and RBCs, and minor but significant changes in platelet stearate (C18:0) were observed. Data are presented as mean ± SEM. Significant changes in composition were assessed with paired two-tailed t-tests and are indicated at *P < 0.05 and **P < 0.001.

Fig. 2.

Changes in the mol% composition of the plasma esterified n6-HUFA (black) and n3-HUFA (white) oxylipins after ingestions of 4 g/day (47 ± 9 mg/kg) n3 FA ethyl esters. The alcohols and ketones (A) of n6-HUFAs were reduced by the P-OM3 challenge, whereas the n3-HUFAs of these oxylipins, as well as the epoxides, diols, and triols (B), were increased. Changes in composition are presented as mean ± SEM. Significant changes in composition were assessed with paired two-tailed t-tests and are indicated at *P < 0.05) and **P < 0.001.

Fig. 3.

Supplementation-dependent changes in representative unsaturated FAs (A), FA alcohols (B), FA epoxides (C), and FA diol (D) expressed as a function of pretreatment concentrations. The magnitudes of concentration changes with treatment decrease as baseline concentrations increase, indicating the presence of a finite and saturable lipid pool. The x-intercepts indicate the population's change threshold (i.e., the apparent baseline concentration of each FA), which would be most likely associated with change in concentration.

Fig. 4.

Changes in the n3 index are influenced by basal n3 status and dose. A: The n3 index achieved after 4 weeks of P-OM3 intake was positively correlated with the product of the initial n3 index and the dose. B: The theoretical dose required to cross an n3 index of 8% given an initial n3 index is estimated from this relationship. The study dose range (35–65 mg/kg/day) is shown in gray.