Lutein accumulates in subcellular membranes of brain regions in adult rhesus macaques: Relationship to DHA oxidation products

Objectives: Lutein, a carotenoid with anti-oxidant functions, preferentially accumulates in primate brain and is positively related to cognition in humans. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), is also beneficial for cognition, but is susceptible to oxidation. The present study characterized the membrane distribution of lutein in brain regions important for different domains of cognitive function and determined whether membrane lutein was associated with brain PUFA oxidation. Methods: Adult rhesus monkeys were fed a stock diet (~2 mg/day lutein or ~0.5 μmol/kg body weight/ day) (n = 9) or the stock diet plus a daily supplement of lutein (~4.5 mg/day or~1 μmol/kg body weight/day) and zeaxanthin (~0.5 mg/day or 0.1 μmol/kg body weight/day) for 6–12 months (n = 4). Nuclear, myelin, mitochondrial, and neuronal plasma membranes were isolated using a Ficoll density gradient from prefrontal cortex (PFC), cerebellum (CER), striatum (ST), and hippocampus (HC). Carotenoids, PUFAs, and PUFA oxidation products were measured using HPLC, GC, and LC-GC/MS, respectively. Results: All-trans-lutein (ng/mg protein) was detected in all regions and membranes and was highly variable among monkeys. Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (P<0.05). In PFC and ST, mitochondrial lutein was inversely related to DHA oxidation products, but not those from arachidonic acid (P <0.05). Discussion: This study provides novel data on subcellular lutein accumulation and its relationship to DHA oxidation in primate brain. These findings support the hypothesis that lutein may be associated with antioxidant functions in the brain.