Salivary Melatonin Levels Research Articles

Non-surgical periodontal therapy influences salivary melatonin levels

Melatonin is a hormone, which is involved in the control of the circadian rhythm, but also acts as an antioxidant and immune modulator. Previous studies reported decreased salivary and serum melatonin levels in periodontitis. This prospective cohort trial assessed the effect of non-surgical periodontal therapy on melatonin levels. Salivary and serum samples of 60 participants (30 patients suffering from a severe generalized form of periodontitis, 30 healthy controls) were collected at baseline and 19 samples of periodontitis patients after treatment. Salivary and serum melatonin levels were determined by a commercially available ELISA kit and serum C-reactive protein (CRP) by a routine laboratory test. At baseline, periodontitis patients showed significantly increased serum CRP values and significantly decreased salivary melatonin levels compared to the control group. Clinical periodontal parameters significantly correlated with salivary melatonin levels and serum CRP. Periodontal therapy resulted in a recovery of the decreased salivary melatonin levels and a negative correlation was detected for the changes of salivary melatonin and the inflammatory parameter bleeding on probing. Serum melatonin levels showed no significant differences. Salivary melatonin levels recovered after periodontal therapy and correlated with a decrease of local periodontal inflammation. This may imply the local involvement of melatonin in the pathogenesis of periodontitis due to its antioxidant abilities. However, the exact role of melatonin in periodontal disease remains to be investigated in future trials. The present results suggest salivary melatonin as a risk indicator for the severity of periodontal disease.

CYP1A2 polymorphisms in slow melatonin metabolisers: a possible relationship with autism spectrum disorder?

In some of our patients with intellectual disabilities (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment. In these patients melatonin levels at noon were extremely high (>50 pg/ml). We hypothesise that the disappearing effectiveness is associated with slow metabolisation of melatonin because of a single nucleotide polymorphism (SNP) of CYP1A2. In this pilot study we analysed DNA extracted from saliva samples of 15 consecutive patients with disappearing effectiveness of melatonin. Saliva was collected at noon and 4 pm for measuring melatonin levels. In all patients' salivary melatonin levels at noon were >50 or melatonin half time was > 5 h. A SNP was found in eight of 15 patients. The allele 1C was found in two patients and in six patients the 1F allele was found. Of 15 patients with disappearing effectiveness of melatonin, seven were diagnosed with autism spectrum disorder, and in four of them a SNP was found. The other eight patients were known with a genetic syndrome. In six of them behaviour was considered to be autistic-type and in three of them a SNP was found. This finding may give a new direction for research into the genetic background of autism.

Post-exercise cold water immersion: effect on core temperature and melatonin responses

To study the effect of post-exercise cold water immersion (CWI) on core temperature and melatonin responses, 10 male cyclists completed two evening (~1800hours) cycling trials followed by a 15-min CWI (14°C) or warm water immersion (WWI; 34°C), and were then monitored for 90 min post-immersion. The exercise trial involved 15min at 75% peak power, followed by a 15min time trial. Core (rectal) temperature was not different between the two conditions pre-exercise (~37.4°C), post-exercise (~39°C) or immediately post-immersion (~37.7°C), but was significantly (p<0.05) below pre-exercise levels at 60 and 90min post-immersion in both conditions. Core temperature was significantly lower after CWI than WWI at 30min (36.84±0.24 vs. 37.42±0.40°C, p<0.05) and 90min (36.64±0.24 vs. 36.95±0.43°C, p<0.05) post-immersion. Salivary melatonin levels significantly increased (p<0.05) from post-exercise (~5pM) to 90min post-immersion (~8.3pM), but were not different between conditions. At 30 and 90min post-immersion heart rate was significantly lower (~5-10bpm, p<0.01) after CWI than WWI. These results show that undertaking either CWI or WWI post-exercise in the evening lowers core temperature below baseline for at least 90min; however, the magnitude of decrease is significantly greater following CWI. The usual evening increase in melatonin is unaffected by exercise or post-exercise water immersion undertaken between ~1800 and ~2000hours.

Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels

Attention-deficit hyperactivity disorder (ADHD) in adults is associated with impaired sleep, and it has been postulated that this impairment may contribute to the psychopathology of this common condition. One key driver of sleep/wake cycles is the circadian system, which at the molecular level consists of a series of transcriptional feedback loops of clock genes, which in turn produce endocrine, physiological and behavioural outputs with a near 24 h periodicity. We set out to examine circadian rhythms at the behavioural, endocrine and molecular levels in ADHD. Adults with ADHD as well as age- and sex-matched controls were recruited. Circadian rhythms were measured by means of actigraphy for the determination of gross motor patterns, by self-sampling of oral mucosa for assessment of rhythmic expression of the clock genes BMAL1 and PER2, and by estimation of salivary cortisol and melatonin levels. Actigraphic analysis revealed significant diurnal and nocturnal hyperactivity in the ADHD group, as well as a significant shorter period of best fit for the locomotor circadian rhythm in ADHD. BMAL1 and PER2 showed circadian rhythmicity in controls with this being lost in the ADHD group. Cortisol rhythms were significantly phase delayed in the ADHD group. These findings indicate that adult ADHD is accompanied by significant changes in the circadian system, which in turn may lead to decreased sleep duration and quality in the condition. Further, modulation of circadian rhythms may represent a novel therapeutic avenue in the management of ADHD.

Salivary cortisol and melatonin levels in children with frequent episodic tension‐type headache do not differ from healthy children

To investigate the differences in cortisol and melatonin concentrations between children with frequent episodic tension-type headache (FETTH) and healthy children. Forty-four children, 12 boys/32 girls (age: 9 ± 2 years) with FETTH associated to peri-cranial tenderness and 44 age- and sex- matched healthy children participated. Both salivary cortisol and melatonin concentrations were collected from non-stimulated saliva following standardized guidelines. A headache diary for 4 weeks was used for collecting intensity, frequency and duration of headache. No significant differences for cortisol (t = -0.431; p = 0.668), and melatonin (z = -1.564; p = 0.118) concentrations and salivary flow rate (z = -1.190; p = 0.234) were found between both groups. No significant effect of age or gender was found. In addition, no significant association between cortisol-melatonin concentrations and between cortisol-melatonin concentrations and headache clinical parameters were found. These results suggest that children with FETTH, at first instance, do not present deficits in the secretion of these cortisol and melatonin. Prospective longitudinal studies are needed to further elucidate the direction of current findings, particularly the synchronism of cortisol and melatonin and the course of the headache.

Relationship between circadian salivary melatonin levels and sleep–wake behavior in infants

There have been calls for more aggressive intervention for infants with failure in development of a sleep-wake rhythm. If development of the 'biological clock' in infants can be assessed by measuring melatonin, this may provide a useful indicator of the sleep-wake rhythm development. Thus, we investigated relationship between circadian salivary melatonin concentrations and sleep-wake behavioral parameters in infants. Sixty-seven mothers who had infants aged 3-15 months were requested to record sleep-wake behavior of their baby for 2 days, and to collect their baby's saliva four times daily in the morning (06:00-09:00 h), noon (11:00-13:00 h), evening (16:00-18:00 h), and night (19:00-22:00 h) for measurement of melatonin concentrations by ELISA. The mean melatonin concentrations of the saliva were: morning 40 ± 4 pg/mL, noon 14 ± 3 pg/mL, evening 15 ± 3 pg/mL, and night 23 ± 4 pg/mL. The melatonin concentrations, at each measurement point, were highest in infants aged 3-5 months, and decreased as age increased. Morning melatonin concentrations showed a negative correlation with nocturnal sleep duration (P<0.05). Increased morning concentrations were related to early waking time (P<0.05). In infants with open air baths on most days, evening and night melatonin concentrations were significantly lower (P<0.05). Salivary melatonin concentrations in infants between 06:00 and 22:00 decreased by age, and elevation of morning values may indicate an immature sleep-wake rhythm. Frequent open air baths may contribute to decreased melatonin levels.

Non-Visual Effects of Light on Melatonin, Alertness and Cognitive Performance: Can Blue-Enriched Light Keep Us Alert?

BackgroundLight exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range. Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance.MethodsSixteen healthy young men were studied in a balanced cross-over design with light exposure of 3 different light settings (compact fluorescent lamps with light of 40 lux at 6500K and at 2500K and incandescent lamps of 40 lux at 3000K) during 2 h in the evening.ResultsExposure to light at 6500K induced greater melatonin suppression, together with enhanced subjective alertness, well-being and visual comfort. With respect to cognitive performance, light at 6500K led to significantly faster reaction times in tasks associated with sustained attention (Psychomotor Vigilance and GO/NOGO Task), but not in tasks associated with executive function (Paced Visual Serial Addition Task). This cognitive improvement was strongly related with attenuated salivary melatonin levels, particularly for the light condition at 6500K.ConclusionsOur findings suggest that the sensitivity of the human alerting and cognitive response to polychromatic light at levels as low as 40 lux, is blue-shifted relative to the three-cone visual photopic system. Thus, the selection of commercially available compact fluorescent lights with different colour temperatures significantly impacts on circadian physiology and cognitive performance at home and in the workplace.

Detection of Nighttime Melatonin Level in Chinese Original Quiet Sitting

Some research has shown that melatonin levels increase after meditation practices, but other research has shown that they do not. In our previous functional magnetic resonance imaging study, we found positive activation of the pineal body during Chinese Original Quiet Sitting (COQS). To find other supporting evidence for pineal activation, the aim of this study was to evaluate the effect of COQS on nighttime melatonin levels. Twenty subjects (11 women and 9 men, aged 29-64 years) who had regularly practiced daily meditation for 5-24 years participated in this study. All subjects served alternately as participants in the mediation and control groups. COQS was adopted in this study. Tests were performed during two nighttime sessions. Saliva was sampled at 0, 10, 20, 30, 45, 60 and 90 minutes after COQS and tested for level of melatonin. Time period effect analysis and mixed effect model analysis were preceded by paired t test analysis. In the meditation group (n = 20), the mean level of melatonin was significantly higher than the baseline level at various times post-meditation (p < 0.001). Within the control group (n = 20), the mean level of melatonin at various times was not significantly different compared with baseline (p>0.05). These results suggested that the melatonin level was statistically elevated in the meditation group and almost unchanged in the control group after nighttime meditation. The urine serotonin levels detected by measuring 5-hydroxy-indole-3-acetic acid levels were also studied, but no detectable difference between the groups was found. Our results support the hypothesis that meditation might elevate the nighttime salivary melatonin levels. It suggests that COQS can be used as a psychophysiological stimulus to increase endogenous secretion of melatonin, which in turn, might contribute to an improved sense of well-being.

Loss of response to melatonin treatment is associated with slow melatonin metabolism

In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this loss of response is associated with slow melatonin metabolism. In this study, we determined melatonin clearance in two female (aged 61 and 6 years) and one male (aged 3 years) patients who had chronic insomnia, late melatonin onset and mild ID, and whose sleep quality worsened a few weeks after initial good response to melatonin treatment, suggesting melatonin tolerance. After a 3-week washout period, patients received melatonin 1.0, 0.5 or 0.1 mg, respectively. Salivary melatonin level was measured just before melatonin administration, and 2 and 4 h thereafter. After this melatonin clearance test, melatonin treatment was resumed with a considerably lower dose. In all patients melatonin concentrations remained >50 pg/mL at 2 and 4 h after melatonin administration. After resuming melatonin treatment sleep problems disappeared. The same procedure was followed in three patients who did not show loss of response to melatonin after 6 months of treatment. In all patients in the control group melatonin concentrations decreased between 2 and 4 h after melatonin administration with a mean of 83%. We hypothesise that loss of response to melatonin treatment can be caused by slow metabolisation of exogenous melatonin. As melatonin is metabolised in the liver almost exclusively by cytochrome P450 enzyme CYP1A2, this slow melatonin metabolism is probably due to decreased activity/inducibility of CYP1A2. In patients with loss of response to melatonin, a melatonin clearance test should be considered and a considerably dose reduction is advised.

Positive Relationship between Endogenous Melatonin and Core Temperature Responses to Exercise

At rest, circadian variation in the vaso-active substance, melatonin, is inversely related to that of core body temperature (Tcore). Although ingestion of exogenous melatonin has been reported to lower Tcore by approximately 0.2°C during subsequent exercise (Atkinson et al. 2005, J Pineal Res, 39, 353-9), the relationship between endogenous melatonin and Tcore has not been investigated during and after exercise at different times of the day. PURPOSE: To examine the relationship between exercise-related responses of salivary melatonin and Tcore measured at different sites in the morning and afternoon. METHODS: At 08:00 and 17:00 h, seven male subjects (mean±SD age: 27±5 y) completed 30 min of cycling at 70% peak oxygen uptake followed by 30 min recovery. Salivary melatonin levels were measured at baseline, 15 min into the exercise, immediately post-exercise and following 30 min recovery. Oesophageal (Tes), rectal (Trec), intestinal (Tit), and skin (Tskin) temperature were monitored during trials. Data were analysed using time of day × time general linear models and within-subjects correlation analysis. RESULTS: Melatonin was generally higher at 08:00 than 17:00 h (P=0.059) whilst Tcore was significantly lower during the morning trials compared to the afternoon (P=0.003). This difference was much smaller for Tes compared to Tit and Trec. Melatonin, Tcore and Tskin all increased with exercise but the standardised effects of exercise were smaller for melatonin (0.64-1.03) than for Tcore (2.23-5.26) and Tskin (2.22-4.18). The within-subject correlation between Tes and melatonin was 0.65 and 0.67 in the morning and afternoon respectively (P=0.001). Correlations between Tcore and melatonin were also positive for the other core temperature sites, irrespective of time of day. The correlation between Tskin and melatonin was 0.40 (P=0.065) in the morning and 0.65 (P=0.001) in the afternoon. CONCLUSION: These data indicate that, although circadian rhythms in endogenous melatonin and core temperature are inversely related at rest, exercise mediates a parallel acute increase in both variables. It seems that the effects of exercise are relatively more pronounced on core body temperature than on melatonin, adding weight to the notion that melatonin is a more stable marker of circadian timing.

THERMOREGULATORY EFFECT IN HUMANS OF SUPPRESSED ENDOGENOUS MELATONIN BY PRE-SLEEP BRIGHT-LIGHT EXPOSURE IN A COLD ENVIRONMENT

This study investigated the physiological function of suppressed melatonin through thermoregulation in a cold environment. Interactions between thermoregulation directly affected by exposure to a cold environment and indirectly affected by endogenous melatonin suppression by bright-light exposure were examined. Ten male subjects were exposed to two different illumination intensities (30 and 5000 lux) for 4.5 h, and two different ambient temperatures (15 and 27°C) for 2 h before sleep under dark and thermoneutral conditions. Salivary melatonin level was suppressed by bright light (p < 0.001), although the ambient temperature condition had no significant effect on melatonin. During sleep, significant effects of pre-sleep exposure to a cold ambient temperature (p < 0.001) and bright light (p < 0.01) on rectal temperature (Tre) were observed. Pre-sleep, bright-light exposure led to an attenuated fall in Tre during sleep. Moreover, Tre dropped more precipitously after cold exposure than thermoneutral conditions (cold: −0.54 ± 0.07°C/h; thermoneutral: −0.16 ± 0.03°C/h; p < 0.001). Pre-sleep, bright-light exposure delayed the nadir time of Tre under thermoneutral conditions (p < 0.05), while cold exposure masked the circadian rhythm with a precipitous decrease in Tre. A significant correlation between the Tre nadir and melatonin level (r = −0.774, p < 0.05) indicated that inter-individual differences with higher melatonin levels lead to a reduction in Tre after cold exposure. These results suggest that suppressed endogenous melatonin inhibits the downregulation of the body temperature set-point during sleep. (Author correspondence: ishibasi@design.kyushu-u.ac.jp)

Utility of salivary melatonin measurements in the assessment of the pineal physiology in newborn infants

Subjects The aim of this study was to assess whether salivary melatonin could be used as a reliable alternative to serum melatonin to study the pineal physiology in newborn infants. Design and methods The 95 newborn infants were allocated to four groups according to the time of sampling (09–11 am, 03–05 pm, 09–11 pm, and 03–05 am). Results The median melatonin levels in serum and saliva were not significantly different between groups: median (interquartile range), 18.4 pg/mL (13.9–26.0 pg/mL) and 10.6 pg/mL (7.5–14.9 pg/mL); 13.3 pg/mL (11.5–19.0 pg/mL) and 9.1 pg/mL (7.8–14.2 pg/mL); 16.0 pg/mL (12.4–18.7 pg/mL) and 12.3 pg/mL (8.2–16.8 pg/mL); 13.0 pg/mL (8.8–27.4 pg/mL) and 11.2 pg/mL (7.7–16.6 pg/mL) for groups 1, 2, 3, and 4, respectively ( p > 0.05). The results revealed a highly significant correlation between the serum and salivary melatonin levels (Pearson's correlation coefficient, r = 0.763; P < 0.001). Conclusion Melatonin levels in saliva reflect those in serum at any time of the day and like serum melatonin levels do not increase at night.

Delayed Circadian Rhythm in Adults with Attention-Deficit/Hyperactivity Disorder and Chronic Sleep-Onset Insomnia

Previous studies suggest circadian rhythm disturbances in children with attention-deficit/hyperactivity disorder (ADHD) and sleep-onset insomnia (SOI). We investigate here sleep and rhythms in activity and melatonin in adults with ADHD. Sleep logs and actigraphy data were collected during 1 week in 40 adults with ADHD, of whom 31 reported SOI. Salivary melatonin levels were assessed during 1 night. Sleep measures, circadian activity variables, and dim light melatonin onset were compared between groups of ADHD adults with and without SOI and with matched healthy control subjects. Compared with control subjects, both groups of ADHD adults had longer sleep-onset latency and lower sleep efficiency. Adults with ADHD and SOI showed a delayed start and end of their sleep period and a delayed melatonin onset compared with adults with ADHD without SOI (p = .006; p = .023; p = .02) and compared with healthy control subjects (p = .014; p = .019; p = .000). Adults with ADHD and SOI also showed an attenuated 24-hour amplitude in their rest-activity pattern, in contrast to those without SOI, who showed a higher day-to-day stability. These findings demonstrate diurnal rhythm deviations during everyday life in the majority of adults with ADHD that have SOI and suggest that potential benefits of rhythm-improving measures should be evaluated.

Salivary and Gingival Crevicular Fluid Melatonin in Periodontal Health and Disease

Melatonin, with its antioxidant properties, plays a pertinent role in influencing the pathogenesis of periodontal disease. This study aims to detect the presence of melatonin in gingival crevicular fluid (GCF) and to assess the levels of salivary and GCF melatonin in periodontal disease and show the correlation between salivary and GCF melatonin. Forty-five subjects, based on the gingival and Russell periodontal indexes, were grouped as 15 healthy subjects (group 1), 15 subjects with gingivitis (group 2), and 15 subjects with periodontitis (group 3). Saliva and GCF samples were collected from all subjects. Melatonin levels were assessed using an enzyme-linked immunosorbent assay. The paired-sample test was used to correlate between saliva and GCF. Melatonin was present in GCF (mean: 1.54 pg/ml) with significantly less concentration compared to that of saliva (mean: 2.17 pg/ml). Salivary and GCF melatonin levels were reduced to the lowest concentrations in patients with chronic periodontitis (salivary melatonin: 0.07 pg/ml; GCF melatonin: 0.06 pg/ml; P <0.05), which were inversely proportional to the clinical indices. There was no significant correlation between salivary and GCF melatonin levels (P >0.05). Melatonin was expressed in GCF. Salivary and GCF melatonin levels varied from clinically healthy subjects (group 1) to subjects with periodontitis (group 3). Both salivary and GCF melatonin levels decreased in group 3 subjects compared to group 1 subjects, indicating that melatonin may have a protective role against periodontal disease, although further research is required to validate this hypothesis.

Evaluation of melatonin levels in saliva in periodontal health and disease: A clinico-biochemical study

Background: Melatonin, a secretory product of the vertebrate pineal gland, activates several elements of the immune system that reduce tissue destruction during the inflammatory response, either directly by scavenging free radical, reactive oxygen species and reactive nitrogen species or indirectly by modulating the action of agents such as cytokines and adhesion molecules, which contribute to the advance of cell damage. Aim: The aim of this study was to evaluate melatonin levels in saliva in periodontal health and disease. Materials and Methods: This study was conducted on a total of 20 patients with healthy periodontium and 20 patients each with mild, moderate and severe periodontitis who were patients in the Department of Periodontics, Rural Dental College and Hospital, Loni. The salivary levels of melatonin were assayed using ELISA, a competitive immunoassay using a capture antibody technique. Results: We observed that the periodontitis sufferers had a significantly lower melatonin level than the healthy subjects. Conclusion: Consequently, the reduction in the saliva production with higher age and the decreased melatonin production in older adults reflected in low salivary melatonin levels predispose these individuals to an increased risk of developing oral and periodontal disease.

Diagnostic utility of daytime salivary melatonin levels in Smith–Magenis syndrome

An inverted circadian rhythm of melatonin (MT) likely contributes to the sleep disturbance in patients with Smith-Magenis syndrome (SMS). Plasma MT levels have documented this altered rhythm, but daytime levels of salivary MT has not been determined. Daytime measures of salivary MT might have utility in home/outpatient settings for assessing MT levels in undiagnosed patients with clinical features of SMS. The objective of this study was to determine the utility of daytime salivary MT as a diagnostic test in SMS. Thirty individuals with confirmed SMS [28 with del 17p11.2 and 2 with the retinoic acid induced 1 (RAI1) gene mutation] and five controls were studied. Single or serial daytime salivary MT levels were measured. The mean midday salivary MT level was 79.0 pg/ml in SMS patients, compared with 16.3 pg/ml in controls, with nine patients having values similar to controls. The median MT level in SMS patients was 49.0 pg/ml (first and third quartile values = 15.5 and 106.8 pg/ml). Twenty-six (90%) of 29 patients had at least one MT value >15.5 pg/ml, including 70 (78%) of 90 samples from patients with del 17p11.2 and one (20%) of five samples from the two patients with the RAI1 mutation. Neither the pattern of medication use nor age had an effect on daytime salivary MT levels. Although most SMS patients had elevated daytime salivary MT levels, multiple sampling appears necessary to distinguish patients with SMS from other conditions.

LIGHT INTENSITY EXPOSURE, SLEEP DURATION, PHYSICAL ACTIVITY, AND BIOMARKERS OF MELATONIN AMONG ROTATING SHIFT NURSES

Long-term, night shiftwork has been identified as a potential carcinogenic risk factor. It is hypothesized that increased light at night exposure during shiftwork reduces melatonin production, which is associated with increased cancer risk. Sleep duration has been hypothesized to influence both melatonin levels and cancer risk, and it has been suggested that sleep duration could be used as a proxy for melatonin production. Finally, physical activity has been shown to reduce cancer risk, and laboratory studies indicate it may influence melatonin levels. A cross-sectional study of light exposure, sleep duration, physical activity, and melatonin levels was conducted among 61 female rotating shift nurses (work schedule: two 12 h days, two 12 h nights, five days off). Light intensity was measured using a light-intensity data logger, and sleep duration and physical activity were self-reported in a study diary and questionnaire. Melatonin concentrations were measured from urine and saliva samples. The characteristics of nurses working day and night shifts were similar. Light intensity was significantly higher during sleep for those working at night (p< 0.0001), while urinary melatonin levels following sleep were significantly higher among those working days (p = 0.0003). Mean sleep duration for nurses working during the day (8.27 h) was significantly longer than for those working at night (4.78 h, p< 0.0001). An inverse association (p = 0.002) between light exposure and urinary melatonin levels was observed; however, this was not significant when stratified by shift group. There was no significant correlation between sleep duration and melatonin, and no consistent relationship between physical activity and melatonin. Analysis of salivary melatonin levels indicated that the circadian rhythms of night workers were not altered, meaning peak melatonin production occurred at night. This study indicates that two nights of rotating shift work may not change the timing of melatonin production to the day among those working at night. Additionally, in this study, sleep duration was not correlated with urinary melatonin levels, suggesting it may not be a good proxy for melatonin production. (Author correspondence: anne.grundy@queensu.ca)

Indirect blue light does not suppress nocturnal salivary melatonin in humans in an automobile setting

In 2007, the International Agency for Research on Cancer (IARC) classified shift work that involves circadian disruption as being probably carcinogenic to humans (Group 2A). In this context, light exposure during the night plays a key role because it can suppress nocturnal melatonin levels when exposures exceed a certain threshold. Blue light around 464 nm is most effective in suppressing melatonin because of the spectral sensitivity of melanopsin, a recently discovered photopigment in retinal ganglion cells; the axons of these cells project to the suprachiasmatic nucleus, a circadian master clock in the brain. Due to advances in light technologies, normal tungsten light bulbs are being replaced by light-emitting diodes which produce quasi-monochromatic or white light. The objective of this study was to assess whether the light-melanopsin-melatonin axis might be affected in automobiles at night which employ the new generation diodes. To this end, we have tested in an experimental automobile setting whether indirect blue light (lambda(max) = 465 nm) at an intensity of 0.22 or 1.25 lx can suppress salivary melatonin levels in 12 male volunteers (age range 17-27 years) who served as their own controls. Daytime levels were low (2.7 +/- 0.5 pg/mL), and night-time levels without light exposure were high (14.5 +/- 1.1 pg/mL), as expected. Low-intensity light exposures had no significant effect on melatonin levels (0.22 lx: 17.2 +/- 2.8 pg/mL; P > 0.05; 1.25 lx: 12.6 +/- 2.0 pg/mL; P > 0.05). It is concluded that indirect blue light exposures in automobiles up to 1.25 lx do not cause unintentional chronodisruption via melatonin suppression.

Saliva as a valid alternative in monitoring melatonin concentrations in newborn infants

Background and aims Pineal physiology is not completely elucidated in newborn infants. As melatonin in pharmacological doses has been reported to reduce oxidative stress in neonates with asphyxia, respiratory distress syndrome, or sepsis, there is the need to better understand the physiological role of melatonin in the neonatal period. The aim of this study was to evaluate a new saliva sampling method suitable for newborn infants and to assess whether salivary melatonin could be used as a reliable, non-invasive, pain-free alternative to serum melatonin to study the pineal physiology in newborn infants. Subjects and methods In 86 healthy term newborn infants, a serum sample was collected by venipuncture after 36 h of life during blood sampling for newborn screening, immediately after a saliva sample had been collected. Results Of the 86 saliva samples, 62 were ‘ideal’ samples for the analysis. The median serum and salivary melatonin levels of the 62 newborns were 14.4 pg/mL (11.5–20.5 pg/mL) and 10.8 pg/mL (7.5–16.1 pg/mL), respectively. There was no significant difference between serum and salivary melatonin levels. The results revealed a highly significant correlation between the serum and salivary melatonin levels (Pearson's correlation coefficient, r = 0.793; p < 0.001). Linear regression analysis showed that the equation for the relationship between serum ( x) and saliva ( y) was y = 1.12 x − 5.58 pg/mL. Conclusion To study pineal function in newborn infants, saliva collection using cotton buds and measurement of melatonin in saliva offers a valid, non-invasive, pain-free and practical alternative to blood sampling and determination of serum melatonin.

BLUE LIGHT Exposure Reduces Objective Measures of Sleepiness during Prolonged Nighttime Performance Testing

This study examined the effects of nocturnal exposure to dim, narrowband blue light (460 nm, ∼1 lux, 2 µW/cm2), compared to dim broad spectrum (white) ambient light (∼0.2 lux, 0.5 µW/cm2), on subjective and objective indices of sleepiness during prolonged nighttime performance testing. Participants were also exposed to a red light (640 nm, ∼1 lux, 0.7µW/cm2) placebo condition. Outcome measures were driving simulator and psychomotor vigilance task (PVT) performance, subjective sleepiness, salivary melatonin, and electroencephalographic (EEG) activity. The study had a repeated-measures design, with three counterbalanced light conditions and a four-week washout period between each condition. Participants (n = 8) maintained a regular sleep-wake schedule for 14 days prior to the ∼14 h laboratory study, which consisted of habituation to light conditions followed by neurobehavioral performance testing from 21:00 to 08:30 h under modified constant-routine conditions. A neurobehavioral test battery (2.5 h) was presented four times between 21:00 and 08:30 h, with a 30 min break between each. From 23:30 to 05:30 h, participants were exposed to blue or red light, or remained in ambient conditions. Compared to ambient light exposure, blue light exposure suppressed EEG slow wave delta (1.0–4.5 Hz) and theta (4.5–8 Hz) activity and reduced the incidence of slow eye movements. PVT reaction times were significantly faster in the blue light condition, but driving simulator measures, subjective sleepiness, and salivary melatonin levels were not significantly affected by blue light. Red light exposure, as compared to ambient light exposure, reduced the incidence of slow eye movements. The results demonstrate that low-intensity, blue light exposure can promote alertness, as measured by some of the objective indices used in this study, during prolonged nighttime performance testing. Low intensity, blue light exposure has the potential to be applied to situations where it is desirable to increase alertness but not practical or appropriate to use bright light, such as certain occupational settings.