Gary H. Kamimori

Caffeine reversal of sleep deprivation effects on alertness and mood

This study assessed the ability of high doses of caffeine to reverse changes in alertness and mood produced by prolonged sleep deprivation. Fifty healthy, nonsmoking males between the ages of 18 and 32 served as volunteers. Following 49 h without sleep, caffeine (0, 150, 300, or 600 mg/70 kg, PO) was administered in a double-blind fashion. Measures of alertness were obtained with sleep onset tests, the Stanford Sleepiness Scale (SSS), and Visual Analog Scales (VAS). Sleep deprivation decreased onset to sleep from a rested average of 19.9 min to 7 min. Following the highest dose of caffeine tested, sleep onset averaged just over 10 min; sleep onset for the placebo group averaged 5 min. Scores on the SSS increased from a rested mean of 1.6–4.8 after sleep deprivation. Caffeine reduced this score to near rested values. Caffeine reversed sleep deprivation-induced changes in three subscales of the POMS (vigor, fatigue, and confusion) and produced values close to fully rested conditions on several VAS. Serum caffeine concentrations peaked 90 min after ingestion and remained elevated for 12 h. This study showed that caffeine was able to produce significant alerting and long-lasting beneficial mood effects in individuals deprived of sleep for 48 h.

The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers

OBJECTIVE The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert chewing gum and capsule formulation. METHODS This was a double blind, parallel, randomized, seven treatment study. The treatment groups were: 50, 100, and 200 mg gum, 50, 100, and 200 mg capsule, and a placebo. Subjects consisted of 84 (n=12 per group); healthy, non-smoking, males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were randomly assigned to the treatment groups. Blood samples were collected pre-dose and at 5, 15, 25, 35, 45, 55, 65, 90 min and 2, 3, 4, 6, 8, 12, 16 and 29 h post administration. Plasma caffeine levels were analyzed by a validated UV-HPLC method. RESULTS Mean Tmax for the gum groups ranged from 44.2 to 80.4 min as compared with 84.0-120.0 min for the capsule groups. The Tmax, for the pooled data was significantly lower (P<0.05) for the gum groups as compared with the capsule groups. Differences in Tmax were significant for the 200 mg capsule versus 200 mg gum (P<0.05). The mean ka values for the gum group ranged from 3.21 to 3.96 h-1 and for the capsule groups ranged from 1.29 to 2.36 h-1. Relative bioavailability of the gum formulation after the 50, 100 and 200 mg dose was 64, 74 and 77%, respectively. When normalized to the total drug released from the gum (85%), the relative bioavailability of the 50, 100 and 200 mg dose were 75, 87, and 90%, respectively. No statistical differences were found for Cmax and AUCinf for comparisons of the gum and capsule formulations at each dose. Within each dose level, there were no significant formulation related differences in Cmax. No significant differences were observed in the elimination of caffeine after the gum or capsule. CONCLUSIONS The results suggest that the rate of drug absorption from the gum formulation was significantly faster and may indicate absorption via the buccal mucosa. In addition, for the 100 and 200 mg groups, the gum and capsule formulations provide near comparable amounts of caffeine to the systemic circulation. These findings suggest that there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation, which is advantageous in situations where the rapid reversal of alertness and performance deficits resulting from sleep loss is desirable.

Caffeine effects on risky decision making after 75 hours of sleep deprivation

INTRODUCTION Recent research indicates that sleep deprivation impairs decision making. However, it is unknown to what extent such deficits are exacerbated in a dose-response manner by increasing levels of sleepiness, and the extent to which such sleep-loss-induced deficits can be reversed by caffeine. METHODS At three time points, 26 healthy subjects completed alternate forms of the Iowa Gambling Task (IGT): rested baseline, 51 h awake, and 75 h awake. Every 2 h each night, 12 volunteers also received 4 200-mg doses of caffeine, with the last dose occurring 3 h prior to the IGT. RESULTS At baseline, volunteers readily learned to avoid disadvantageous high-risk card decks while progressively choosing more frequently from advantageous low-risk card decks. When sleep deprived, however, these same subjects showed impaired performance, choosing more frequently from the disadvantageous high-risk card decks, particularly during the latter half of the game. Contrary to expectations, the severity of performance impairment did not increase significantly from 51 to 75 h of wakefulness, and caffeine had no significant effects on IGT performance during sleep deprivation. DISCUSSION AND CONCLUSIONS As a provisional extension of our previous study, these preliminary findings further suggest that the ability to integrate emotion with cognition to guide decision making, a capacity believed to be mediated by the ventromedial prefrontal cortex, may be particularly vulnerable to sleep loss. Moreover, these capacities may not be significantly improved by moderate doses of caffeine, suggesting that they may function separately from simple arousal and alertness systems.

Catecholamine response to maximal exercise in persons with Down syndrome.

Individuals with Down syndrome (DS) exhibit low peak aerobic capacities and heart rates. Although autonomic modulation is attenuated in individuals with DS at rest, the exercise response appears normal. This suggests that mechanisms other than autonomic control influence the low aerobic capacity, such as catecholamine responsiveness to exercise. The purpose of this study was to determine catecholamine responses to a peak treadmill test in a group of subjects with DS compared with a nondisabled group. Epinephrine and norepinephrine concentrations were measured at rest and immediately after graded exercise tests on a treadmill in 20 subjects with DS (mean age, 24 +/- 7 years) and 21 nondisabled subjects (mean age, 26 +/- 6 years). Catecholamines increased significantly with peak exercise in the control group (p <0.05), with little to no change in subjects with DS. In conclusion, the different catecholamine responses to peak exercise, in particular the lack of a response in individuals with the DS, may be a primary mechanism to explain the reduced peak heart rates and low work capacities observed in this population.

Caffeine protects against increased risk‐taking propensity during severe sleep deprivation

Previous research suggests that sleep deprivation is associated with declines in metabolic activity within brain regions important for judgement and impulse control, yet previous studies have reported inconsistent findings regarding the effects of sleep loss and caffeine on risk‐taking. In this study, 25 healthy adults (21 men, four women) completed the Balloon Analog Risk Task (BART) and Evaluation of Risks (EVAR) scale at regular intervals to examine behavioral and self‐reported risk‐taking propensity during 75 h of continuous sleep deprivation. Participants received either four double‐blind administrations of 200 mg caffeine (n = 12) or indistinguishable placebo (n = 13) gum bi‐hourly during each of the 3 nights of sleep deprivation. No significant effects of drug group or sleep deprivation were evident on the BART or EVAR when measured at 51 h of wakefulness. However, by 75 h, the placebo group showed a significant increase in risk‐taking behavior on the cost–benefit ratio and total number of exploded balloons on the BART, whereas the caffeine group remained at baseline levels. On the EVAR, several factors of self‐reported risk‐taking propensity, including total risk, impulsivity and risk/thrill seeking, were reduced among subjects receiving caffeine across the 3 days of sleep deprivation, but remained at baseline levels for the placebo group. These results suggest that 3 nights of total sleep deprivation led to a significant increase in behavioral risk‐taking but not self‐reported perception of risk‐propensity. Overnight caffeine prevented this increase in risky behavior.

The trait of Introversion-Extraversion predicts vulnerability to sleep deprivation.

According to Eysenck’s theory of Introversion–Extroversion (I–E), introverts demonstrate higher levels of basal activity within the reticular‐thalamic‐cortical loop, yielding higher tonic cortical arousal than Extraverts, who are described conversely as chronically under‐aroused and easily bored. We hypothesized that higher scores on the trait of Extraversion would be associated with greater declines in psychomotor vigilance performance during prolonged wakefulness. We evaluated the relationship between I–E and overnight psychomotor vigilance performance during 77 h of continuous sleep deprivation in a sample of 23 healthy adult military personnel (19 men; four women), ranging in age from 20 to 35 years. At baseline, volunteers completed the Revised NEO Personality Inventory (NEO PI‐R) and completed psychomotor vigilance testing at approximately 10‐min intervals from 00:15 to 08:50 hours over three nights of continuous sleep deprivation. In addition, 12 participants received four repeated administrations of caffeine (200 mg) every 2 h each night. Analysis of covariance and stepwise multiple regression analyses showed that, above and beyond the effects of caffeine, higher Extraversion was significantly related to more extensive declines in speed of responding and more frequent attentional lapses, but only for the first overnight testing session. Sub‐factors of Extraversion, including Gregariousness and higher Activity level were most predictive of these changes following sleep loss. These findings are consistent with Eysenck’s cortico‐reticular activation theory of I–E and suggest that individual differences in the trait of Extraversion confer some vulnerability/resistance to the adverse effects of sleep loss on attention and vigilance.

The effect of the menstrual cycle on the pharmacokinetics of caffeine in normal, healthy eumenorrheic females

Abstract  Objective: Hormonal fluctuations of estrogen and progesterone in eumenorrheic women may be capable of altering the pharmacokinetics of certain agents. The objective of this study was to determine the effect of the luteal, ovulatory and follicular phases of the menstrual cycle on the pharmacokinetics of caffeine, a low clearance, flow-independent drug. Methods: Subjects were ten healthy, non-smoking, eumenorrheic females who were not pregnant and had not used oral contraceptives for a minimum of 3 months prior to the study. Blood samples were collected during one menstrual cycle for the determination of estradiol and progesterone concentrations during the follicular (days 2–6 post-onset of menses), ovulatory (days 13–16 post-onset of menses) and luteal (days 22–26 post-onset of menses) phases. Caffeine was administered over a single menstrual cycle during the follicular, ovulatory and luteal phases. Each subject was administered a single oral dose of caffeine (300 mg) in 100 ml of lemonade during each phase of the menstrual cycle. A venous catheter was used to collect blood samples at pre-dose and at the following time points: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 and 24 h. Plasma caffeine concentrations were determined using a validated ultraviolet high-performance liquid chromatography method. Results: There were no significant (P < 0.05) differences in the pharmacokinetic parameters of caffeine across the menstrual cycle phases. The average area under the plasma concentration–time curve (AUCinf) was 93.01 mg l−1.h and the absorption rate constant (ka) was 2.88 h−1 during the ovulatory phase, 83.0 mg l−1 h and 2.06 h−1, respectively, during the luteal phase and 84.7 mg l−1.h and 1.84 h−1, respectively, during the follicular phase. Conclusions: These findings suggest that the menstrual cycle does not significantly alter the pharmacokinetics of caffeine.

Automated Neuropsychological Assessment Metrics: Repeated Assessment with Two Military Samples

INTRODUCTION U.S. military troops deploying to war zones are currently administered the Automated Neuropsychological Assessment Metrics (ANAM4) Traumatic Brain Injury (TBI) Battery to establish individual neurocognitive performance baselines. In part, the utility of the ANAM4 TBI Battery baseline measurement depends on test-retest reliability of this instrument. The purpose of this report was to evaluate performance following multiple administrations of the ANAM4 TBI Battery: does performance in a repeated measures paradigm constitute a stable, interpretable indication of baseline neurocognitive ability? METHODS The data presented here are from the ANAM4 TBI Battery administered four times to a group of U.S. Marines in Study 1 and eight times to a group of New Zealand Defence Force personnel in Study 2. RESULTS The results show practice effect in five of six performance subtests in both Study 1 and Study 2. DISCUSSION Results are consistent with expectations that multiple test sessions are required to reach stable performance on some computerized tasks. These results have implications for taking ANAM4 TBI Battery practice effects into account in test administration and in data interpretation.

Substrate oxidation is altered in women during exercise upon acute altitude exposure

PURPOSE The purpose of this study was to determine whether substrate oxidation during submaximal exercise in women is affected by an acute exposure to 4300-m altitude and menstrual cycle phase. METHODS Eight female lowlanders (mean +/- SD; 33 +/- 3 yr, 58 +/- 6 kg, 163 +/- 8 cm) completed a peak oxygen uptake (VO2peak) and submaximal exercise to exhaustion (EXH) test at 70% of their altitude-specific VO2peak at sea level (SL) and during an acute altitude (AA) exposure to 4300 m in a hypobaric chamber (446 mm Hg) in their early-follicular and midluteal menstrual cycle phase. The respiratory exchange ratio (RER) was calculated from oxygen uptake and carbon dioxide output measurements made during the EXH tests, and used to estimate the percent contribution of fat and carbohydrate to energy metabolism. Blood samples were taken at rest and every 15 min during the EXH tests. Blood samples were evaluated for glucose, lactate, glycerol, free fatty acids, insulin, growth hormone, cortisol, glucagon, epinephrine, norepinephrine, estradiol, and progesterone concentrations. RESULTS Despite increased (P < 0.05) estradiol and progesterone levels in the midluteal phase, substrate oxidation, energy substrates, and metabolic hormones were not affected by cycle phase at SL or AA. However, free fatty acids and cortisol were increased (P < 0.05) whereas RER was decreased (P < 0.05) during exercise upon AA exposure compared with SL in both cycle phases. CONCLUSIONS These data suggest that substrate oxidation is altered in women during exercise at AA compared with SL but is not affected by cycle phase. Whether increased fat or protein oxidation accounts for the lower RER values during the AA exposure cannot be determined from this study but warrants further investigation.

Cardiorespiratory responses of firefighters to a computerized fire strategies and tactics drill during physical activity.

Firefighters are subjected to a combination of physical and mental challenges in the course of their occupational responsibilities. However, due to the ecological factors involved with firefighting, it makes it extremely difficult to examine physiological and psychological changes that occur as a result of these combined challenges. The purpose of this study was to examine the efficacy of a computer-based Fire Strategies and Tactics Drill (FSTD) in eliciting psychological and physiological measures of stress in professional firefighters. In one session, participants exercised at 60% VO(2max) for 37 min (exercise alone condition, EAC), and in the other session the firefighter exercised for an equal amount of time and responded to the FSTD (dual challenge condition; DCC) while exercising. Cardiorespiratory (heart rate [HR], respiration rate [RR], minute ventilation [V(E)], oxygen consumption [VO(2)], ventilatory efficiency [V(E)/VO(2)], and respiratory exchange ratio [RER]) and psychometric measures (State Anxiety Inventory [SAI] and Ratings of Perceived Exertion [RPE]) were obtained throughout the experimental protocols. The NASA Task Load Index was used to assess perceived physical and mental load during each condition. The results demonstrated that the participants perceived overall workload to be higher in the DCC. Repeated measures ANOVAs revealed no differences between the EAC and DCC for VO(2) or RER, but the DCC did elicit significantly greater elevations in HR, RR, V(E), and V(E)/VO(2) compared to the EAC. These results suggest that the FSTD utilized in this study provides an effective method for examining the physiological and psychological responses of firefighters in a research laboratory environment.