Increased dietary arachidonic acid enhances the synthesis of vasoactive eicosanoids in humans

Data on the effect of dietary arachidonic acid (AA) (20:4n-6) on the synthesis of thromboxane and prostacyclin (PGl(2)) in humans are lacking. We measured the effect of 1.5 g/d (ca. 0.5 en%) of 20:40-6 added isocalorically to a stabilization (low-AA) diet on the excretion of 11-dehydrothromboxane B-2 (11-DTXB2) and 2,3-dinor-6-oxo-PGF(1 alpha) (PGl(2)-M). In a crossover design, 10 healthy men, living in a metabolic unit, were fed a diet (low-AA) containing 210 mg/d of 20:4n-6 for 65 d and an identical diet (high-AA) that contained 1.5 g/d of additional 20:4n-6 for 50 d. Three-day urine pools were collected at the end of each dietary period and analyzed for eicosanoids by gas chromatography-electron capture negative ion-tandem mass spectrometry. Mean excretion of 11-dehydrothromboxane B-2 was 515 +/- 76, 493 +/- 154, and 696 +/- 144 ng/d (SD; n = 10) during the acclimation (15 d) low-AA diet and high-AA diet periods, respectively (41% increase from low-AA to high-AA diet, P = 0.0037); mean excretion of PGl(2)-M was 125 +/- 40, 151 +/- 36, and 192 +/- 55 ng/d (SD; n = 10) during acclimation (15 d) low-AA and high-AA diets, respectively (27% increase from low-AA to high-AA diets; P = 0.0143). Thus, both the metabolites of thromboxane and PGl(2), increase on the high-AA diet. Furthermore, both indicated changes in metabolite excretion may be associated with measurable effects on several physiologically significant cellular functions, such as platelet aggregation in vivo and inflammation in response to immune challenges.