Changes of gut microbiota and immune markers during the complementary feeding period in healthy breast-fed infants.

INTRODUCTION: Little is known about changes in intestinal microbiota during the important period of complementary feeding (weaning). This descriptive study investigated changes of selected gut microbiota and markers of gut permeability and the immune system in breast fed infants during the complementary feeding period. METHODS: 22 healthy, exclusively breast fed infants (from birth to 4 months) with no antibiotic intake during the month prior to the study, were followed from 4 to 9 months of age. Faecal and saliva samples were collected at the start of the study (V0) and at monthly intervals (V1-V5) for measurement of selective gut microbiota (bifidobacteria, lactobacilli, vancomycin-insensitive lactobacilli, enterobacteria, enterococci, Clostridium perfringens) using semi-selective media. Immune markers (alpha-1-antitrypsin, eosinophil cationic protein (ECP), secretory IgA and TNF-alpha were measured in saliva and secretory IgA and TNF-alpha in faecal samples. RESULTS: High stool bifidobacteria counts at the start of the study (7.99 1 1.95 log10 CFU/g faeces) remained stable throughout the 5 months of complementary feeding while counts of enterobacteria and enterococci increased with age (P < 0.05 and P = 0.02 respectively). Vancomycin-insensitive lactobacilli increased significantly during weaning for V0 to V3 (P < 0.01), and then decreased slightly (V4). Faecal Clostridium perfringens remained below the detection limit during the study and parameters measured in saliva did not change. Faecal ECP decreased significantly from 1.011.4 (V0) to 0.510.9 mg/mg protein (V5) P = 0.03. CONCLUSION: Age and/or diet modifications during complementary feeding had no impact on faecal bifidobacteria counts but increased those of enterobacteria and enterococci. Transient increases in faecal lactobacilli and vancomycin-insensitive lactobacilli counts were observed. The reduction in faecal ECP may indicate a decrease in gut permeability (reinforcement of gut mucosa integrity) during the weaning period with age [corrected]

Caffeine or melatonin effects on sleep and sleepiness after rapid eastward transmeridian travel.

We measured the effects of slow-release caffeine (SRC) and melatonin (Mlt) on sleep and daytime sleepiness after a seven-time zone eastbound flight. In a double-blind, randomized, placebo-controlled study, each of three groups of nine subjects was given either 300 mg SRC on recovery day 1 (D1) to D5 (0800) or 5 mg Mlt on preflight D-1 (1700), flight day D0 (1600), and from D1 to D3 (2300), or placebo (Pbo) at the same times. Nighttime sleep was evaluated by polysomnography and daytime sleepiness from measurements of sleep latencies and continuous wrist actigraphy. Compared with baseline, we found a significant rebound of slow-wave sleep on night 1 (N1) to N2 under Pbo and Mlt and a significant decrease in rapid eye movement sleep on N1 (Pbo) and N1-N3 (Mlt). Sleepiness was objectively increased under Pbo (D1-D6) and Mlt (D1-D3). SRC reduced sleepiness but also tended to affect sleep quality until the last drug day. In conclusion, both drugs have positive effects on some jet lag symptoms after an eastbound flight: SRC on daytime sleepiness, and Mlt on sleep.

Resynchronization of hormonal rhythms after an eastbound flight in humans: effects of slow-release caffeine and melatonin.

The aim of this work was to investigate the potential chronobiotic properties of slow-release caffeine, in comparison with melatonin, on resynchronization of endogenous melatonin and cortisol secretions after an eastbound flight by jet incurring a time loss of 7 h. A group of 27 reservists of the US Air Force received either slow-release caffeine (300 mg), melatonin (5 mg) or placebo before, during and/or after the transmeridian flight. Saliva and urine were sampled before the flight in the United States (from day -2 to day 0) and after the flight in France (from day 1 to day 10). Saliva was collected once a day on waking to determine saliva melatonin and cortisol concentrations. In addition, concentrations of caffeine in saliva were determined three times a day and of 6-sulphatoxymelatonin in urine collected overnight to check that the treatment regimes had been complied with. From day 3 to day 5, post-flight saliva melatonin concentrations were significantly different from control values in the placebo group only. During treatment with melatonin, the mean urinary 6-sulphatoxymelatonin concentration in the melatonin group was more than twice as high as in the two other groups. In the slow-release caffeine group and the melatonin group, mean saliva cortisol concentrations were significantly lower than control from day 2 to day 5, whereas the placebo group had a mean saliva cortisol concentration significantly lower than the control value from day 2 to day 9. In conclusion, these results indicate that administration of slow-release caffeine, as well as of melatonin, allows a faster resynchronization of hormone rhythms during the 4 days following an eastbound flight incurring the loss of 7 h.

Evaluation of pharmacological aids on physical performance after a transmeridian flight.

PURPOSE: The purpose of this study was to evaluate physical performance (static and dynamic) of U.S. Air Force reservists after an eastbound air travel across seven time zones and to estimate the pharmacological aids slow-release caffeine and melatonin versus placebo in attempt to overcome the decline in performance. METHODS: 27 American volunteers were randomly divided into three groups: caffeine 300 mg, melatonin 5 mg, and placebo (lactose capsules). Two days before the flight and 10 d after, three tests were performed: hand grip strength test (static performance), squat jump test (maximal height), and multiple jump test (power and endurance). All measures were repeated twice a day: morning and afternoon. RESULTS: In placebo conditions, the static performance of the dominant hand decreased significantly during the first three mornings and tended to decrease the fourth morning. Simultaneously, the caffeine group's static performance increased significantly, whereas the melatonin group maintained its levels. No significant differences were observed the afternoons. No statistical differences appeared for the nondominant hand in the mornings or afternoons. Dynamic capacities presented no significant degradation after the travel. In the placebo group, for the squat jump test, performance increased from the fourth day. No real explanation can be given about this result. CONCLUSIONS: We demonstrated that slow-release caffeine and melatonin might be used to compensate for jet-lag troubles and particularly for the static physical performance decrease. The slow-release caffeine seems to be the best treatment, but its effects are only demonstrated on previously damaged performance. These preliminary results need further investigation, but we are the first to report a beneficial effect of slow-release caffeine and melatonin on physical performances after jet-lag.

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.

Slow-release caffeine: a new response to the effects of a limited sleep deprivation.

STUDY OBJECTIVES: The aim of this study is to assess the interest of the intake of a new galenic form of caffeine called "slow-release" caffeine (SR caffeine) during a decrease of vigilance due to a limited sleep deprivation. DESIGN: The controlled method used compared three doses of SR caffeine (150, 300 and 600 mg) with a placebo. Tests were performed 2, 9 and 13 hours after each treatment. Wakefulness level was assessed subjectively through questionnaires and analog visual scales, and objectively with the Multiple Sleep Latency Test. Performance level was also assessed regularly with an attention test, a grammatical reasoning test, a spatial recognition test, a mathematical processing test, a visual tracking test, a memory search test, and a dual task. The motor activity was evaluated by wrist actimeter and safety of treatment was observed by regular clinical examination. SETTING: NA. PARTICIPANTS: Twenty-four young and healthy volunteers (12 men and 12 women) participated in a 32-hour sleep deprivation. INTERVENTIONS: NA. RESULTS: The results show a significant effect of slow-release caffeine vs. placebo, and on vigilance and performance when subjects became tired. The effects of SR caffeine lasted 13 hours after treatment. SR caffeine 300 and 600 mg are efficacious doses but the optimal dose (maximum effect without any side effects) for both men and women is after all 300 mg. Globally, there is no difference between placebo and caffeine during the recovery night period. CONCLUSIONS: SR caffeine (300 mg) seems to be an efficient and safety substance to maintain a good level of vigilance and performance during limited sleep deprivation.

The effects of 600 mg of slow release caffeine on mood and alertness.

BACKGROUND: Caffeine is the most widely used psychostimulant. PURPOSE: This study evaluated the pharmacokinetics and effects of mood and alertness of a single oral administration of 600 mg of a slow release caffeine (SRC) on a large group of healthy subjects. METHOD: In this double-blind, parallel-group study, 120 young adult males were randomly assigned to either a caffeine group (CG, n = 100) or a placebo group (PC, n = 20). After a normal sleep, each subject took 600 mg of a SRC or a placebo. Circulating caffeine was determined by salivary caffeine assays after acetylation phenotype categorization. Mood, alertness and nocturnal sleep were evaluated by visual analog scales (VAS). RESULTS: This SRC was well tolerated probably due to its relative low plasmatic Cmax (10.37 micrograms.ml-1). Between CG and PG, there were no differences for alertness, contentedness and sleep quality of the night after treatment (N2) compared to the previous night (N1). VAS scores showed a decrease in calmness in the CG (p < 0.01). Sleep latency in N2 was significantly increased with caffeine (p < 0.01). Calmness, sleep onset latency, quality of sleep onset and overall rating of N2 compared to N1 were correlated with caffeine levels, which were only influenced by tobacco consumption. CONCLUSIONS: Although a single oral dose of 600 mg of a SRC is well tolerated, further evaluation must be done on alertness and pharmacokinetics with fatigued subjects and with females using oral contraceptives.

Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man.

The effect of an aqueous extract of valerian (Valeriana officinalis L.) root on subjectively rated sleep measures was studied on 128 people. Each person received 9 samples to test (3 containing placebo, 3 containing 400 mg valerian extract and 3 containing a proprietary over-the-counter valerian preparation). The samples, identified only by a code number, and presented in random order, were taken on non-consecutive nights. Valerian produced a significant decrease in subjectively evaluated sleep latency scores and a significant improvement in sleep quality: the latter was most notable among people who considered themselves poor or irregular sleepers, smokers, and people who thought they normally had long sleep latencies. Night awakenings, dream recall and somnolence the next morning were relatively unaffected by valerian. With the proprietary valerian-containing preparation, the only change was a significant increase in reports of feeling more sleepy than normal the next morning. Thus the questionnaire, simple to use and non-invasive, provides a sensitive means for detecting the effects of mild sedatives on different aspects of sleep in man. It also allows identification within the test population of the subgroups most affected.

Plasma amino acid responses in humans to evening meals of differing nutritional composition.

The effect of a carbohydrate or a 20% protein (HP) or a carbohydrate + 0.4% tryptophan (TRP) evening meal on plasma amino acids and on plasma neutral amino acid (NAA) ratios was studied in eight healthy men. After consumption of the protein meal, plasma amino acids rose after 1 h and remained at the same level at 2 h. The dietary profile of the essential amino acids, except for TRP, was retained in the plasma. The plasma profile of nonessential amino acids was not related to the dietary pattern. Glutamic acid and aspartic acid increased several-fold less and alanine several-fold more than would be expected from their dietary concentrations. The tyrosine/NAA and phenylalanine/NAA ratios were not altered by any of the meals and the TRP/NAA ratio was increased only by the carbohydrate + 0.4% TRP meal. The leucine/NAA and isoleucine/NAA ratios were decreased by the carbohydrate and carbohydrate + TRP and increased by the 20% protein meals, while valine/NAA was decreased by the carbohydrate + TRP and HP but increased by the carbohydrate meal. From these data it is concluded that if brain neurotransmitter synthesis is controlled by the same mechanisms as in rats, then the evening meal containing added TRP was the only one of the meals likely to affect brain neurotransmitter (serotonin) synthesis.

Quantifying the effects of mild sedatives.

In quantifying the effects of mild sedatives both physiological and subjective aspects of sleep must be taken into account. A questionnaire analysis on a mild sedative (400 mg of an aqueous extract of Valeriana officinalis L.) showed that by subjective criteria it is sedative (i.e. it significantly decreased perceived sleep latencies and night awakenings, and improved sleep quality). In an EEG study on the same preparation the pattern of results tended to confirm the subjective evaluation (i.e. shorter mean sleep latency, increased mean latency to first awakening) but the changes did not reach statistical significance. The discussion critically examines some of the approaches used to test putative mild sedatives and suggests a rational approach to analysing their effects.