Background alpha- and gamma-Tocopherol are vitamin E compounds in human blood and tissues. alpha-CEHC (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman) and gamma-CEHC (2,7,8-trimethyl-2-(2'-carboxyethyl) -6-hydroxychroman) have been identified as water-soluble metabolites which are excreted with the urine in humans. Aim of the study To assess over-time changes of serum levels of alpha- and gamma-CEHC in humans after a single dose of vitamin E from a natural source. Methods Twenty-one healthy subjects ingested a single dose of vitamin E (306 mg of RRR-alpha-tocopherol and 1.77 mg of gamma-tocopherol). Blood was collected before (baseline) and 2,6, 12,24,35,50, and 74 h after ingestion. Serum was separated and levels of alpha- and gamma-tocopherol and alpha- and gamma-CEHC were determined by HPLC. Results After vitamin E ingestion, a statistically significant increase was observed for alpha-tocopherol and alpha-CEHC. Maximum serum levels for both compounds were measured 12 h after application (33.3 +/- 11.1 mumol alpha-tocopherol/L and 42.4 +/- 18.3 nmol alpha-CEHC/L); baseline values were reached again after 72 h. While gamma-tocopherol levels decreased during the study period, an increase in the metabolite gamma-CEHC was observed. The optical isomer formed in the metabolism of RRR-alpha-tocopherol was assigned as S-alpha-CEHC. Conclusions alpha-CEHC levels increase after administration of a single dose of natural vitamin E in humans. The appearance of the metabolite in blood parallels that of the parent compound. The gamma-tocopherol analog appears to be metabolized more efficiently than alpha-tocopherol.