Stable isotope studies of phytanic acid alpha-oxidation: in vivo production of formic acid

The aim of this study was to test whether formate is formed during alpha-oxidation of phytanic acid in humans. To a healthy volunteer, [1-C-13]phytanic acid was given as an oral substrate in a dose of 15 mg/kg body weight, after which plasma, urine and breath air samples were collected during 35 h. The plasma concentrations of [1-C-13]phytanic acid, 2-hydroxy[1-C-13]phytanic acid, pristanic acid and [C-13]formate were analysed. The [1-C-13]phytanic acid concentration increased within 5-7 h to 105 mu mol/l, then decreased. Formation of 2-hydroxy[1-C-13]phytanic acid increased during the first 11 h after which it decreased during the next 20 h. Pristanic acid increased slightly during the test. In breath air, (CO2)-C-13 enrichment was measured, showing a cumulative output of ca. 30% of the ingested dose after 35 h. In both urine and plasma, enrichment of [C-13]formate, higher than that of (CO2)-C-13 was demonstrated. These findings show that formate is a decarboxylation product in the alpha-oxidation of phytanic acid in vivo.