Gamma-tocopherol is largely metabolized to 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC), which has natriuretic activity that is mediated via inhibition of 70 pS ATP-sensitive K+ channels in the thick ascending limb of the loop of Henle. However, the effects of γ-tocopherol administration on edema are unclear. To determine the effects of γ-tocopherol administration on pretibial edema, we measured urinary γ-CEHC concentration by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) after administration of γ-tocopherol. Twenty young women who had a history of pretibial edema due to premenstrual syndrome were randomly divided into two groups. The γ-tocopherol group received 4 "γ-tocopherol capsules" (each containing 100mg of γ-tocopherol), and the control group received 4 "placebo capsules" (each containing 250mg of soybean oil) per day for 7 days. Urinary sodium and potassium secretion and urine volume did not increase after cessation of γ-tocopherol administration, yet the degree of pretibial edema improved in all participants in the γ-tocopherol group. The serum γ-tocopherol concentration significantly increased in the γ-tocopherol group. Urinary excretion of γ-CEHC significantly increased after γ-tocopherol administration. Our results suggest that orally administered γ-tocopherol on renal sodium handling is not apparent, but γ-tocopherol is a precursor of prolonged natriuresis of γ-CEHC and may be effective for edema.