Context: There is a paucity of data describing the impact of type of beverage (coffee versus energy drink), different rates of consumption and different temperature of beverages on the pharmacokinetic disposition of caffeine. Additionally, there is concern that inordinately high levels of caffeine may result from the rapid consumption of cold energy drinks. Objective: The objective of this study was to compare the pharmacokinetics of caffeine under various drink temperature, rate of consumption and vehicle (coffee versus energy drink) conditions. Materials: Five caffeine (dose = 160 mg) conditions were evaluated in an open-label, group-randomized, crossover fashion. After the administration of each caffeine dose, 10 serial plasma samples were harvested. Caffeine concentration was measured via liquid chromatography–mass spectrometry (LC–MS), and those concentrations were assessed by non-compartmental pharmacokinetic analysis. The calculated mean pharmacokinetic parameters were analyzed statistically by one-way repeated measures analysis of variance (RM ANOVA). If differences were found, each group was compared to the other by all pair-wise multiple comparison. Results: Twenty-four healthy subjects ranging in age from 18 to 30 completed the study. The mean caffeine concentration time profiles were similar with overlapping SDs at all measured time points. The ANOVA revealed significant differences in mean C max and V d ss/F, but no pair-wise comparisons reached statistical significance. No other differences in pharmacokinetic parameters were found. Discussion: The results of this study are consistent with previous caffeine pharmacokinetic studies and suggest that while rate of consumption, temperature of beverage and vehicle (coffee versus energy drink) may be associated with slightly different pharmacokinetic parameters, the overall impact of these variables is small. Conclusion: This study suggests that caffeine absorption and exposure from coffee and energy drink is similar irrespective of beverage temperature or rate of consumption.

Background: Reduced glutathione (GSH) is an endogenously synthesized tripeptide depleted early in the course of Parkinson’s disease (PD) and GSH augmentation has been proposed as a therapeutic strategy in PD.Objective: This Phase IIb study was designed to evaluate whether a Phase III study of intranasal GSH, (in)GSH, for symptomatic relief is warranted and to determine the most appropriate trial design for a disease-modification study.Methods: This was a double-blind, placebo-controlled trial of 45 individuals with Hoehn & Yahr Stage 1–3 PD. Participants were randomized to receive intranasal placebo (saline), 100 mg GSH, or 200 mg GSH thrice daily for three months, and were observed over a one-month washout period.Results: All cohorts improved over the intervention period, including placebo. The high-dose group demonstrated improvement in total Unified PD Rating Scale (UPDRS) (–4.6 (4.7), P = 0.0025) and UPDRS motor subscore (–2.2 (3.8), P = 0.0485) over baseline, although neither treatment group was superior to placebo. One participant in the high-dose GSH cohort developed cardiomyopathy.Conclusions: Although predicted improvements in PD total and motor scores were observed, these data do not suggest (in)GSH is superior to placebo after a three month intervention. The symptomatic effects are sufficient to warrant a delayed-start or wash-out design study for disease-modification trials. Whether long-term use of (in)GSH leads to clinical improvements that are sustained and significantly different than placebo will require appropriately-powered longer-duration studies in larger cohorts. The improvement in the placebo arm was more robust than has been observed in previous PD studies and warrants further investigation.

Objectives. Oxidative stress contributes to Parkinson's disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity. Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross-sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman's rank-order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient-Reported Outcomes in PD (PRO-PD) were used to rate disease severity using regression analysis. Results. Blood measures of Glu decreased with age, although there was no age-related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (P = 0.02, 95% CI: −13.96, −1.14) and the PRO-PD (P = 0.01, 95% CI: −0.83, −0.11) scores. Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes.