The aim of the present study was to evaluate whether olive oils high in phenolic compounds influence the oxidative/antioxidative status in humans. Healthy men (n = 12) participated in a double-blind, randomized, crossover study in which 3 olive oils with low (LPC), moderate (MPC), and high (HPC) phenolic content were given as raw doses (25 mL/d) for 4 consecutive days preceded by 10-d washout periods. Volunteers followed a strict very low-antioxidant diet the 3 d before and during the intervention periods. Short-term consumption of olive oils decreased plasma oxidized LDL (oxLDL), 8-oxo-dG in mitochondrial DNA and urine, malondialdehyde in urine (P < 0.05 for linear trend), and increased HDL cholesterol and glutathione peroxidase activity (P < 0.05 for linear trend), in a dose-dependent manner with the phenolic content of the olive oil administered. At d 4, oxLDL after MPC and HPC, and 8-oxo-dG after HPC administration (25 mL, respectively), were reduced when the men were in the postprandial state (P < 0.05). Phenolic compounds in plasma increased dose dependently during this stage with the phenolic content of the olive oils at 1, 2, 4, and 6 h, respectively (P < 0.01). Their concentrations increased in plasma and urine samples in a dose-dependent manner after short-term consumption of the olive oils (P < 0.01). In conclusion, the olive oil phenolic content modulated the oxidative/antioxidative status of healthy men who consumed a very low-antioxidant diet.
Despite gamma-hydroxybutyrate (GHB) therapeutic uses and the increasing concern about its toxicity, few studies have addressed GHB dose-related effects under controlled administration and their relationship with its pharmacokinetics. The study design was double-blind, randomized, crossover, and controlled. As a pilot pharmacology phase I study, increasing doses of GHB were given. Single oral sodium GHB doses (40, 50, 60, and 72 mg/kg) were administered to eight volunteers. Plasma and urine were analyzed for GHB by gas chromatography-mass spectrometry. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB produced dose-related changes in subjective effects as measured by questionnaires and VAS. GHB showed a mixed stimulant-sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild-moderate symptoms of sedation with impairment of performance and balance. Mean peak GHB plasma concentrations were 79.1, 83.1, 113.5, and 130.1 mug/L for 40, 50, 60, and 72 mg/kg, respectively. GHB-mediated physiological and subjective effects were dose dependent and related to GHB plasma concentrations. GHB urinary excretion was mainly related to administered doses. GHB-mediated subjective and physiological effects seem dose dependent and related to GHB plasma concentrations. Results suggest a high abuse liability of GHB in the range of dose usually consumed.
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