AbstractThe stability to autoxidation of the polar carotenoids, lutein and zeaxanthin, was compared to that of the less polar carotenoids, β‐carotene and lycopene at physiologically or pathophysiologically relevant concentrations of 2 and 6 μM, after exposure to heat or cigarette smoke. Three methodological approaches were used: 1) Carotenoids dissolved in solvents with different polarities were incubated at 37 and 80°C for different times. 2) Human plasma samples were subjected to the same temperature conditions. 3) Methanolic carotenoid solutions and plasma were also exposed to whole tobacco smoke from 1–5 unfiltered cigarettes. The concentrations of individual carotenoids in different solvents were determined spectrophotometrically. Carotenoids from plasma were extracted and analyzed using high performance liquid chromatography. Carotenoids were generally more stable at 37 than at 80°C. In methanol and dichloromethane the thermal degradation of β‐carotene and lycopene was faster than that of lutein and zeaxanthin. However, in tetrahydrofuran β‐carotene and zeaxanthin degraded faster than lycopene and lutein. Plasma carotenoid levels at 37°C did not change, but decreased at 80°C. The decrease of β‐carotene and lycopene levels was higher than those for lutein and zeaxanthin. Also in the tobacco smoke experiments the highest autoxidation rates were found for β‐carotene and lycopene at 2 μM, but at 6 μM lutein and zeaxanthin depleted to the same extent as β‐carotene. These data support our previous studies suggesting that oxidative stress degrade β‐carotene and lycopene faster than lutein and zeaxanthin. The only exception was the thermal degradation of carotenoids solubilized in tetrahydrofuran, which favors faster breakdown of β‐carotene and zeaxanthin.