The polyphenol quercetin strongly increases homocysteine production in a human hepatoma (Hep G2) cell line

Objective The metabolism of homocysteine is influenced by several dietary factors, including folate, cobalamin and possibly also the intake of polyhydroxylated phenolic compounds (polyphenols), which were shown to increase plasma homocysteine (tHcy) concentration. In order to reveal the cause of the increased plasma tHcy, we have therefore investigated the effects of a polyphenol in cell cultures from human cell lines. Design and methods We have studied the influence of the polyphenol quercetin (Quer) on intra- and extracellular homocysteine concentrations in HeLa and hepatoma cell cultures. Results The main finding is an increased concentration of extracellular homocysteine in the presence of Quer in hepatoma cell cultures, whereas there were no significant changes of homocysteine concentration in HeLa cell cultures. There was no effect on cellular growth, as judged by cell protein. The presence of adenosyl-dialdehyde, an inhibitor of adenosyl-homocysteine hydrolase, abolished the increased extracellular concentration of homocysteine observed in hepatoma cell cultures in the presence of Quer. Conclusion The antioxidative agent Quer strongly increased the extracellular concentration of homocysteine in hepatoma cell cultures probably due to increased cellular methylation. In the human body, the same phenomenon might lead to increased plasma tHcy. Since elevated plasma tHcy is associated with premature vascular disease, high long-lasting dietary intake of polyphenols might be harmful. The interaction between Quer and homocysteine turnover may therefore warrant a re-evaluation of polyphenols as relatively harmless antioxidative food supplements or therapeutic antioxidative agents.