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.     

Dietary polyphenols,metabolic syndrome and cardiometabolic risk factors: An observational study based on the DCH-NG subcohort

Background and aimsPolyphenol-rich foods have beneficial properties that may lower cardiometabolic risk. We aimed to prospectively investigate the relationship between intakes of dietary polyphenols, and metabolic syndrome (MetS) and its components, in 676 Danish residents from the MAX study, a subcohort of the Danish Diet, Cancer and Health–Next Generations (DCH-NG) cohort.Methods and resultsDietary data were collected using web-based 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). The Phenol-Explorer database was used to estimate dietary polyphenol intake. Clinical variables were also collected at the same time point. Generalized linear mixed models were used to investigate relationships between polyphenol intake and MetS. Participants had a mean age of 43.9y, a mean total polyphenol intake of 1368 mg/day, and 75 (11.6%) had MetS at baseline. Compared to individuals with MetS in Q1 and after adjusting for age, sex, lifestyle and dietary confounders, those in Q4 – for total polyphenols, flavonoids and phenolic acids–had a 50% [OR (95% CI): 0.50 (0.27, 0.91)], 51% [0.49 (0.26, 0.91)] and 45% [0.55 (0.30, 1.00)] lower odds of MetS, respectively. Higher total polyphenols, flavonoids and phenolic acids intakes as continuous variable were associated with lower risk for elevated systolic blood pressure (SBP) and low high-density lipoprotein cholesterol (HDL-c) (p < 0.05).ConclusionsTotal polyphenol, flavonoid and phenolic acid intakes were associated with lower odds of MetS. These intakes were also consistently and significantly associated with a lower risk for higher SBP and lower HDL-c concentrations.