Olivier Coste

Slow release caffeine and prolonged (64‐h) continuous wakefulness: effects on vigilance and cognitive performance

Some long work or shift work schedules necessitate an elevated and prolonged level of vigilance and performance but often result in sleep deprivation (SD), fatigue and sleepiness, which may impair efficiency. This study investigated the effects of a slow‐release caffeine [(SRC) at the daily dose of 600 mg] on vigilance and cognitive performance during a 64 h continuous wakefulness period. Sixteen healthy males volunteered for this double‐blind, randomised, placebo controlled, two‐way crossover study. A total of 300‐mg SRC or placebo (PBO) was given twice a day at 21:00 and 9:00 h during the SD period. Vigilance was objectively assessed with continuous electroencephalogram (EEG), the multiple sleep latency tests (MSLT) and wrist actigraphy. Cognitive functions (information processing and working memory), selective and divided attention were determined with computerised tests from the AGARD‐NATO STRES Battery (Standardised Tests for Research with Environmental Stressors). Attention was also assessed with a symbol cancellation task and a Stroop’s test; alertness was appreciated from visual analogue scales (VAS). Tests were performed at the hypo (02:00–04:00 h, 14:00–16:00 h) and hypervigilance (10:00–12:00 h, 22:00–00:00 h) periods during SD. Central temperature was continuously measured and safety of treatment was assessed from repeated clinical examinations. Compared with PBO, MSLT showed that SRC subjects were more vigilant from the onset (P=0.001) to the end of SD (P < 0.0001) whereas some cognitive functions were improved till the thirty third of SD but others were ameliorated through all the SD period and alertness was better from the thirteenth hour of SD, as shown by Stroop’s test (P=0.048). We showed that 300‐mg SRC given twice daily during a 64‐h SD is able to antagonize the impairment produced on vigilance and cognitive functions.

Effects of Zolpidem and Zaleplon on Sleep, Respiratory Patterns and Performance at a Simulated Altitude of 4,000 m

The effects of zolpidem or zaleplon on sleep architecture, respiratory patterns and performance were assessed at a simulated altitude of 4,000 m. Twelve male healthy subjects spent 4 nights in a decompression chamber, 1 at sea level (baseline), 3 at 4,000 m to test zolpidem (10 mg), zaleplon (10 mg) and placebo, given 15 min before switching the lights off. Sleep and respiratory patterns were analysed using polysomnography. Cognitive and physical performance was examined the next morning at sea level conditions. The study demonstrates that both zolpidem and zaleplon improved slow wave sleep at altitude, with zolpidem showing more marked effects than zaleplon. Both agents did not adversely affect respiration at altitude during the night, or cognitive or physical performance the next morning at the dosages used in this study. Thus, climbers may safely use both hypnotic agents.

Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry.

OBJECTIVE Intensive physical training may have a sport-dependent effect on bone mass acquisition. This cross-sectional study evaluated bone mass acquisition in girls practicing sports that put different mechanical loads on bone. MATERIALS/METHODS Eighty girls from 10.7 to 18.0 years old (mean 13.83 ± 1.97) were recruited: 20 artistic gymnasts (AG; high-impact activity), 20 rhythmic gymnasts (RG; medium-impact activity), 20 swimmers (SW, no-impact activity), and 20 age-matched controls (CON; leisure physical activity <3h/wk). Areal bone mineral density (aBMD) was determined using DEXA. Hip structural analysis applied at the femur evaluated cross-sectional area (CSA, cm(2)), section modulus (Z, cm(3)), and buckling ratio. Bone turnover markers and OPG/RANKL levels were analyzed. RESULTS AG had higher aBMD than SW and CON at all bone sites and higher values than RG in the lumbar spine and radius. RG had higher aBMD than SW and CON only in the femoral region. CSA and mean cortical thickness were significantly higher and the buckling ratio was significantly lower in both gymnast groups compared with SW and CON. In RG only, endocortical diameter and width were reduced, while Z was only increased in AG compared with SW and CON. Reduced bone remodeling was observed in RG compared with AG only when groups were subdivided according to menarcheal status. All groups showed similar OPG concentrations, while RANKL concentrations increased with age and were decreased in SW. CONCLUSION High-impact activity clearly had a favorable effect on aBMD and bone geometry during the growth period, although the bone health benefits seem to be more marked after menarche.

Recovery after Prolonged Sleep Deprivation: Residual Effects of Slow-Release Caffeine on Recovery Sleep, Sleepiness and Cognitive Functions

A long work schedule often results in sleep deprivation, sleepiness, impaired performance and fatigue. We investigated the residual effects of slow-release caffeine (SRC) on sleep, sleepiness and cognitive performance during a 42-hour recovery period following a 64-hour continuous wakefulness period in 16 healthy males, according to a double-blind, randomised, placebo-controlled, crossover study. Three hundred milligrams of SRC or placebo was given twice a day at 21:00 and 9:00 during the first 48 h of wakefulness. Recovery sleep was analysed with electroencephalography (EEG) and wrist actigraphy, daytime sleepiness with continuous EEG, sleep latency tests and actigraphy and cognitive functions with computerized tests from the NATO AGARD STRES battery. Both drug groups exhibited almost the same sleep architecture with a rebound of slow-wave sleep during both recovery nights and of REM sleep during the second night. Wakefulness level and cognitive functions were similarly impaired in both groups on the first day of recovery and partially returned to baseline on the second. To conclude, SRC appears to have no unwanted side-effects on recovery sleep, wakefulness and cognitive performance after a long period of sleep deprivation and might therefore be a useful choice over other psychostimulants for a long work schedule.

Hypoxic alterations of cortisol circadian rhythm in man after simulation of a long duration flight

Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurisation may be involved in this effect through disruption of circadian rhythms, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the circadian rhythm of plasma cortisol, a marker of the circadian time structure. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 h (08:00-16:00 h) to 8000 ft, followed 4 weeks later to 12,000 ft. Plasma cortisol was assayed during two 24-h cycles (control and hypoxic exposure) every 2h in all subjects. We found a significant change in the pattern of cortisol secretion during both hypoxic exposures, with an initial fall in cortisol followed by a transient rebound, whereas the phase and the 24-h mean level remained unchanged. The change in cortisol pattern followed the alterations in autonomic balance assessed by heart rate variability (HRV) spectral analysis. The normalised high frequencies and the low-to-high frequencies ratio showed a significant shift toward sympathetic dominance with some differences in time course for both altitudes studied. HRV analysis improved the interpretation of cortisol 24-h profiles. Our data, which strongly suggest that prolonged mild hypoxia alters the expression of cortisol circadian rhythm, should be taken into account to interpret secretory rhythm changes after transmeridian flights.

Prolonged mild hypoxia modifies human circadian core body temperature and may be associated with sleep disturbances.

Fatigue is often reported after long-haul airplane flights. Hypobaric hypoxia, observed in pressurized cabins, may play a role in this phenomenon by altering circadian rhythms. In a controlled cross-over study, we assessed the effects of two levels of hypoxia, corresponding to cabin altitudes of 8000 and 12,000 ft, on the rhythm of core body temperature (CBT), a marker of circadian rhythmicity, and on subjective sleep. Twenty healthy young male volunteers were exposed for 8 h (08:00–16:00 h) in a hypobaric chamber to a cabin altitude of 8000 ft and, 4 weeks later, 12,000 ft. Each subject served as his own control. For each exposure, CBT was recorded by telemetry for two 24 h cycles (control and hypoxic exposure). After filtering out nonphysiological values, the individual CBT data were fitted with a five-order moving average before statistical group analysis. Sleep latency, sleep time, and sleep efficiency were studied by sleep logs completed every day in the morning. Our results show that the CBT rhythm expression was altered, mainly at 12,000 ft, with a significant increase of amplitude and a delay in the evening decline in CBT, associated with alterations of sleep latency. Mild hypoxia may therefore alter circadian structure and result in sleep disturbances. These results may explain in part the frequent complaints of prolonged post-flight fatigue after long flights, even when no time zones are crossed.

Maximal oxygen uptake and power of lower limbs during a competitive season in triathletes

Background: In order to study the effect of a competitive triathlon season on maximal oxygen uptake (VO2max), aerobic power (AeP) and anaerobic performance (AnP) of the lower limbs, eight triathletes performed exercise tests after: (1) a pre‐competition period (Pre‐COMP) (2) a competitive period (COMP), and (3) a low (volume and intensity) training period (Post‐COMP). The tests were a vertical jump‐and‐reach test and an incremental exercise test on a cycle ergometer. Ventilatory data were collected every minute during the incremental test with an automated breath‐by‐breath system and the heart‐rate was monitored using a telemetric system.

Disruption of the circadian system by environmental factors: Effects of hypoxia, magnetic fields and general anesthetics agents

The biological clock of mammals is under the control of external factors, social life and the environment, and of internal genetic factors. When the biological clock of an individual is no longer in phase with its environment, either because there is no longer any harmony (desynchronization) between the two systems (shift work, night work, and transmeridian flights...) or because the perception of signals in the environment is defective (blindness) or because of a pathology, disorders of the biological clock occur resulting in persistent fatigue, sleep disorders leading to chronic insomnia and mood disturbances that can cause depression. We review here new groups of factors that have been recently studied and that can be considered as potential disruptors of the circadian time structure. These factors are hypoxia, magnetic fields and anesthetic agents whose importance has to be considered.

Hypoxic depression of melatonin secretion after simulated long duration flights in man.

Abstract:  Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurization may be involved in this effect through disruption of circadian rhythms, independent of the number of time zones crossed. In this controlled crossover study we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the rhythm of plasma melatonin concentrations, a marker of circadian rhythmicity. Sixteen healthy young male volunteers (23–39 years) were exposed in a hypobaric chamber for 8 hr (08:00–16:00 hours) to 8000 ft, followed 4 wk later by 12,000 ft. Plasma melatonin was assayed over two 24‐hr cycles (control and hypoxic exposure) every 2 hr in all subjects. We found a significant decrease in the nocturnal melatonin peak after hypoxic exposure at both altitudes, and we found that this effect was age dependent for the 12,000‐ft exposure: the decrease was only seen in the younger subjects (23–28 years). Analysis of heart rate variability allowed us to demonstrate that the older and less trained subjects (29–39 yr) in our study exhibited a far greater increase in sympathetic tone than the younger subjects during the 12,000‐ft exposure. These results show that hypoxic depression of melatonin secretion may be influenced by individual factors such as age, physical fitness and sympathetic reactivity to hypoxia. Our findings suggest that hypoxia may by itself contribute at least in part to postflight fatigue after long duration flights, and to the clinical disorders of jet lag in transmeridian flights through its effects on the circadian system.

Bone mass acquisition in female rhythmic gymnasts during puberty: no direct role for leptin

Objectives  Although hypoleptinaemia has been reported in female peripubertal athletes, data are lacking on leptin and bone mass variations in puberty and the effects of leptin on bone mineralization during this period. This study therefore investigated the variations in leptin level and bone mineral density (BMD) in young elite female rhythmic gymnasts (FRG) according to pubertal stage. The effects of leptin, IGF‐1 and sex hormones on bone mineral acquisition were also evaluated.