Isomer-specific effects of conjugated linoleic acid on lipid peroxidation in humans: regulation by α-tocopherol and cyclo-oxygenase-2 inhibitor

We have found previously that supplementation with conjugated linoleic acid (CLA) induces lipid peroxidation and inflammation in humans as indicated by an increase of 8-iso-prostaglandin F_2α (PGF_2α) and 15-keto-dihydro-PGF_2α respectively. The present study was undertaken firstly to study the regulatory mechanisms behind these effects, and secondly to see if these effects are specific to different isomers of CLA. Sixty healthy men and women, divided into six groups, were given a cyclo-oxygenase (COX)-2 inhibitor (rofecoxib; 12 mg/day), α-tocopherol (200 mg/day) or neither treatment (control group) over a period of 6 weeks. During the last 4 weeks, three groups were given a CLA preparation (3.5 g/day) mainly containing the isomers cis-9, trans-11 and trans-10, cis-12 (CLA mix), and the three other groups a CLA preparation mainly containing the isomer trans-10, cis-12 (CLA 1012; 4.0 g/day). Treatment with α-tocopherol or COX-2 inhibitor did not alter the basal urinary levels of either 8-iso-PGF_2α or 15-keto-dihydro-PGF_2α. Both CLA preparations induced an increase in 8-iso-PGF_2α and 15-keto-dihydro-PGF_2α in the urine, with a larger increase being found in the CLA 1012 group. Treatment with the COX-2 inhibitor suppressed the increase in urinary 15-keto-dihydro-PGF_2α in the CLA 1012 group, but not in the CLA mix group. Neither the COX-2 inhibitor nor α-tocopherol had any effect on 8-iso-PGF_2α levels after supplementation with CLA. The CLA-induced production of PGF_2α metabolites is probably partially mediated by COX-2. Levels of the induced lipid peroxidation may be dependent on the isomeric property of CLA.