The influence of intermittent fasting on the circadian pattern of melatonin while controlling for caloric intake, energy expenditure, light exposure, and sleep schedules: A preliminary report.
ABSTRACT: We hypothesized that if we control for food composition, caloric intake, light exposure, sleep schedule, and exercise, intermittent fasting would not influence the circadian pattern of melatonin. Therefore, we designed this study to assess the effect of intermittent fasting on the circadian pattern of melatonin.Eight healthy volunteers with a mean age of 26.6 ± 4.9 years and body mass index of 23.7 ± 3.5 kg/m2 reported to the Sleep Disorders Center (the laboratory) on four occasions: (1) adaptation, (2) 4 weeks before Ramadan while performing Islamic intermittent fasting for 1 week (fasting outside Ramadan [FOR]), (3) 1 week before Ramadan (nonfasting baseline [BL]), and (4) during the 2nd week of Ramadan while fasting (Ramadan). The plasma levels of melatonin were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00 h. The light exposure, meal composition, energy expenditure, and sleep schedules remained the same while the participants stayed at the laboratory.The melatonin levels followed the same circadian pattern during the three monitoring periods (BL, FOR, and Ramadan). The peak melatonin level was at 02:00 h and the trough level was at 11:00 h in all studied periods. Lower melatonin levels at 22:00 h were found during fasting compared to BL. Cosinor analysis revealed no significant changes in the acrophase of melatonin levels.In this preliminary report, under controlled conditions of light exposure, meal composition, energy expenditure, and sleep-wake schedules, intermittent fasting has no significant influence on the circadian pattern of melatonin.
Project description:BACKGROUND:Levels of cortisol, melatonin, ghrelin, and leptin are highly correlated with circadian rhythmicity. The levels of these hormones are affected by sleep, feeding, and general behaviors, and fluctuate with light and dark cycles. During the fasting month of Ramadan, a shift to nighttime eating is expected to affect circadian rhythm hormones and, subsequently, the levels of melatonin, cortisol, ghrelin, and leptin. The present study aimed to examine the effect of diurnal intermittent fasting (DIF) during Ramadan on daytime levels of ghrelin, leptin, melatonin, and cortisol hormones in a group of overweight and obese subjects, and to determine how anthropometric, dietary, and lifestyle changes during the month of Ramadan correlate with these hormonal changes. METHODS:Fifty-seven overweight and obese male (40) and female (17) subjects were enrolled in this study. Anthropometric measurements, dietary intake, sleep duration, and hormonal levels of serum ghrelin, leptin, melatonin, and salivary cortisol were assessed one week before the start of Ramadan fasting and after 28 days of fasting at fixed times of the day (11:00 am-1:00 pm). RESULTS:At the end of Ramadan, serum levels of ghrelin, melatonin, and leptin significantly (P<0.001) decreased, while salivary cortisol did not change compared to the levels assessed in the pre-fasting state. CONCLUSIONS:DIF during Ramadan significantly altered serum levels of ghrelin, melatonin, and serum leptin. Further, male sex and anthropometric variables were the most impacting factors on the tested four hormones. Further studies are needed to assess DIF's impact on the circadian rhythmicity of overweight and obese fasting people.
Project description:INTRODUCTION:The impact of Ramadan fasting, a type of intermittent fasting, on the management of diabetes has not been well investigated. Physical activity, sleep duration, and time of sleep are susceptible to alterations during Ramadan due to the changes in the times and numbers of meals. This study compared physical activity and sleep patterns of individuals with type 2 diabetes mellitus (T2DM) during and after Ramadan using the international physical activity questionnaire (IPAQ) and a Fitbit Flex 2 accelerometer. METHODS:Saudi individuals (n?=?36) with T2DM completed a self-reported questionnaire and wore a Fitbit device for seven consecutive days during and after Ramadan. Fitbit generated weekly step counts, activity intensities, sedentary time, and sleep durations and times. IPAQ was used to estimate the physical activity and sitting time of participants in each period. Sleep patterns were assessed in each period by a self-reported questionnaire. RESULTS:Both Fitbit and IPAQ indicated a high prevalence of low physical activity among the participants with non-significant variances between the during and after Ramadan periods. Also, a significant short daily total sleeping hours and daily night-time sleeping hours was seen during the Ramadan period. The duration of night-time sleep was observed to be low in each period. CONCLUSIONS:This is the first study to use a Fitbit device to monitor individuals with T2DM who chose to fast during Ramadan. The study shows a high prevalence of low physical activity among Saudi individuals with T2DM in each period, and short sleep durations in the during Ramadan period compared to after Ramadan period. A high prevalence of short night-time sleep duration and excessive daytime sleeping was observed in both periods and significantly in the during Ramadan period. A larger study is needed in the future covering before, during, and after Ramadan to evaluate the impact of lifestyle changes related to Ramadan fasting on type 2 diabetes.
Project description:A neural network model was previously developed to predict melatonin rhythms accurately from blue light and skin temperature recordings in individuals on a fixed sleep schedule. This study aimed to test the generalizability of the model to other sleep schedules, including rotating shift work. Ambulatory wrist blue light irradiance and skin temperature data were collected in 16 healthy individuals on fixed and habitual sleep schedules, and 28 rotating shift workers. Artificial neural network models were trained to predict the circadian rhythm of (i) salivary melatonin on a fixed sleep schedule; (ii) urinary aMT6s on both fixed and habitual sleep schedules, including shift workers on a diurnal schedule; and (iii) urinary aMT6s in rotating shift workers on a night shift schedule. To determine predicted circadian phase, center of gravity of the fitted bimodal skewed baseline cosine curve was used for melatonin, and acrophase of the cosine curve for aMT6s. On a fixed sleep schedule, the model predicted melatonin phase to within ± 1 hour in 67% and ± 1.5 hours in 100% of participants, with mean absolute error of 41 ± 32 minutes. On diurnal schedules, including shift workers, the model predicted aMT6s acrophase to within ± 1 hour in 66% and ± 2 hours in 87% of participants, with mean absolute error of 63 ± 67 minutes. On night shift schedules, the model predicted aMT6s acrophase to within ± 1 hour in 42% and ± 2 hours in 53% of participants, with mean absolute error of 143 ± 155 minutes. Prediction accuracy was similar when using either 1 (wrist) or 11 skin temperature sensor inputs. These findings demonstrate that the model can predict circadian timing to within ± 2 hours for the vast majority of individuals on diurnal schedules, using blue light and a single temperature sensor. However, this approach did not generalize to night shift conditions.
Project description:Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the metabolic pathways involved in sleep/wake regulation processes. Twelve healthy young female participants remained in controlled laboratory conditions for ~92 hr with respect to posture, meals and environmental light (18:00-23:00 hr and 07:00-09:00 hr <8 lux; 23:00-07:00 hr 0 lux (sleep opportunity) or <8 lux (continuous wakefulness); 09:00-18:00 hr ~90 lux). Regular blood samples were collected for 70 hr for plasma melatonin and cortisol, and targeted liquid chromatography-mass spectrometry metabolomics. Timepoints between 00:00 and 06:00 hr for day 1 (baseline sleep), day 2 (sleep deprivation) and day 3 (recovery sleep) were analysed. Cosinor analysis and MetaCycle analysis were performed for detection of rhythmicity. Night-time melatonin levels were significantly increased during sleep deprivation and returned to baseline levels during recovery sleep. No significant differences were observed in cortisol levels. Of 130 plasma metabolites quantified, 41 metabolites were significantly altered across the study nights, with the majority decreasing during sleep deprivation, most notably phosphatidylcholines. In cosinor analysis, 58 metabolites maintained their rhythmicity across the study days, with the majority showing a phase advance during acute sleep deprivation. This observation differs to that previously reported for males. Our study is the first of metabolic profiling in females during sleep deprivation and recovery sleep, and offers a novel view of human sleep/wake regulation and sex differences.
Project description:Many adolescents fall asleep too late to get enough sleep (8-10 h) on school nights. Morning bright light advances circadian rhythms and could help adolescents fall asleep earlier. Morning bright light treatment before school, however, is difficult to fit into their morning schedule; weekends are more feasible. We examined phase advances in response to morning light treatment delivered over one weekend. Thirty-seven adolescents (16 males; 14.7-18.0 years) who reported short school-night sleep (?7 h) and late bedtimes (school-nights ?23:00; weekend/non-school nights ?24:00) slept as usual at home for ?2 weeks ("baseline") and then kept a fixed sleep schedule (baseline school-night bed and wake-up times ±30 min) for ?1 week before living in the lab for one weekend. Sleep behavior was measured with wrist actigraphy and sleep diary. On Saturday morning, we woke each participant 1 h after his/her midpoint of baseline weekend/non-school night sleep and 1 h earlier on Sunday. They remained in dim room light (?20 lux) or received 1.5 or 2.5 h of intermittent morning bright light (?6000 lux) on both mornings. The dim light melatonin onset (DLMO), a phase marker of the circadian timing system, was measured on Friday and Sunday evenings to compute the weekend circadian phase shift. The dim room light and 1.5-h bright light groups advanced the same amount (0.6 ± 0.4 and 0.6 ± 0.5 h). The 2.5-h bright light group advanced 1.0 ± 0.4 h, which was significantly more than the other groups. These data suggest that it is possible to phase advance the circadian clock of adolescents who have late bedtimes and short school-night sleep in one weekend using light that begins shortly after their sleep midpoint.
Project description:The timing of the internal circadian clock shows large inter-individual variability across the lifespan. Although the sleep-wakefulness pattern of most toddlers includes an afternoon nap, the association between napping and circadian phase in early childhood remains unexplored. This study examined differences in circadian phase and sleep between napping and non-napping toddlers. Data were collected on 20 toddlers (34.2±2.0 months; 12 females; 15 nappers). Children followed their habitual napping and non-napping sleep schedules (monitored with actigraphy) for 5 days before an in-home salivary dim light melatonin onset (DLMO) assessment. On average, napping children fell asleep during their nap opportunities on 3.6±1.2 of the 5 days before the DLMO assessment. For these napping children, melatonin onset time was 38 min later (p = 0.044; d = 0.93), actigraphically-estimated bedtime was 43 min later (p = 0.014; d = 1.24), sleep onset time was 59 min later (p = 0.006; d = 1.46), and sleep onset latency was 16 min longer (p = 0.030; d = 1.03) than those not napping. Midsleep and wake time did not differ by napping status. No difference was observed in the bedtime, sleep onset, or midsleep phase relationships with DLMO; however, the wake time phase difference was 47 min smaller for napping toddlers (p = 0.029; d = 1.23). On average, nappers had 69 min shorter nighttime sleep durations (p = 0.006; d = 1.47) and spent 49 min less time in bed (p = 0.019; d = 1.16) than non-nappers. Number of days napping was correlated with melatonin onset time (r = 0.49; p = 0.014). Our findings indicate that napping influences individual variability in melatonin onset time in early childhood. The delayed bedtimes of napping toddlers likely permits light exposure later in the evening, thereby delaying the timing of the clock and sleep. Whether the early developmental trajectory of circadian phase involves an advance associated with the decline in napping is a question necessitating longitudinal data as children transition from a biphasic to monophasic sleep-wakefulness pattern.
Project description:BACKGROUND:Peripartum major depression (MD) disables mothers and impairs emotional and neurocognitive development of offspring. We tested the hypothesis that critically-timed wake therapy (WT) relieves peripartum MD by altering melatonin and sleep timing, differentially, in antepartum vs. postpartum depressed patients (DP). METHODS:In a university clinical research center, we initially randomized 50 women - 26 antepartum (17 healthy comparison-HC, 9 DP) and 24 postpartum (8 HC, 16 DP) - to a cross-over trial of one night of early-night wake therapy (EWT: sleep 3:00-7:00 am) vs. late-night wake therapy (LWT: sleep 9:00 pm-01:00 am). Ultimately, we obtained mood, overnight plasma melatonin and polysomnography for: 15 antepartum women receiving EWT, 18 receiving LWT; 15 postpartum women receiving EWT, 14 receiving LWT. RESULTS:EWT improved mood more in antepartum vs. postpartum DP in conjunction with reduced (normalized) melatonin-sleep phase-angle differences (PADs) due to delayed melatonin onsets and advanced sleep onsets, and increased (from baseline) total sleep times (TST). LWT improved mood more in postpartum vs. antepartum DP in conjunction with increased TST. LIMITATIONS:Small samples potentially rendered the study underpowered to detect group differences, making confirmation with larger samples essential. Sufficient follow-up data were not available in most women to document the duration of the mood response to wake therapy. CONCLUSIONS:EWT benefitted antepartum DP more by realigning melatonin and sleep timing, whereas LWT benefitted postpartum DP more by increasing TST. Thus, consistent with precision medicine aims, maximum mood benefits accrue from timing sleep/wake interventions to specific peripartum circadian pathophysiologies.
Project description:<h4>Background</h4>During the fasting month of Ramadan, practicing Saudis develop severe disturbances in sleeping and feeding patterns. Concomitantly, cortisol circadian rhythm is abolished, diurnal cortisol levels are elevated and circulating levels of several adipokines are altered favouring insulin resistance.<h4>Aim</h4>To examine changes in the expression of CLOCK and glucocorticoid-controlled genes, such as DUSP1 and IL-1? in Saudi adults before and during Ramadan, and to investigate possible associations with selected cardiometabolic risk factors.<h4>Methods</h4>Healthy young volunteers (5 females, 18 males; mean age +SEM = 23.2 +1.2 years) were evaluated before Ramadan and two weeks into it. Blood samples were collected at 9 am (±1 hour) and twelve hours later for determination of serum lipid profile, high sensitivity CRP (hsCRP), and adiponectin. The expression of CLOCK, DUSP1 and IL-1? was evaluated in circulating leukocytes.<h4>Results</h4>Mean levels of GGT and morning adiponectin decreased, while those of LDL-c/ HDL-c and atherogenic index (AI) increased significantly in Ramadan compared to Shabaan. There was no significant difference between morning and evening adiponectin during Ramadan, while the diurnal rhythm of hsCRP was lost. CLOCK gene expression mean was significantly higher in morning than in evening during Shabaan. Mean morning and evening DUSP1 mRNA levels showed significant increase during Ramadan compared to Shabaan, however, its diurnal rhythm was maintained. Morning IL-1? mRNA expression remained significantly higher than in the evening during Ramadan, but was markedly decreased compared to Shabaan.<h4>Discussion</h4>Ramadan fasting in Saudi Arabia is associated with improvements in some cardiometabolic risk factors, such as circulating GGT and hsCRP and leukocyte expression of IL-1? mRNA, suggesting that intermittent fasting might have a beneficial component. These benefits may be offset by the previously reported dysregulation in the circadian rhythm, excess glucocorticoid levels and action, and insulin resistance, explaining increased prevalence of cardiometabolic disorders and type 2 diabetes mellitus.
Project description:CONTEXT:To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS. OBJECTIVE:To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI. DESIGN:Cross-sectional study. PARTICIPANTS:Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33). OUTCOME MEASURES:Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis. RESULTS:All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing. CONCLUSION:Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.
Project description:We examined the effects of an advanced sleep/wake schedule and morning short wavelength (blue) light in 25 adults (mean age±SD=21.8±3 years; 13 women) with late sleep schedules and subclinical features of delayed sleep phase disorder (DSPD).After a baseline week, participants kept individualized, fixed, advanced 7.5-h sleep schedules for 6days. Participants were randomly assigned to groups to receive "blue" (470nm, ?225lux, n=12) or "dim" (<1lux, n=13) light for 1h after waking each day. Head-worn "Daysimeters" measured light exposure; actigraphs and sleep diaries confirmed schedule compliance. Salivary dim light melatonin onset (DLMO), self-reported sleep, and mood were examined with 2×2 ANOVA.After 6days, both groups showed significant circadian phase advances, but morning blue light was not associated with larger phase shifts than dim-light exposure. The average DLMO advances (mean±SD) were 1.5±1.1h in the dim light group and 1.4±0.7h in the blue light group.Adherence to a fixed advanced sleep/wake schedule resulted in significant circadian phase shifts in young adults with subclinical DSPD with or without morning blue light exposure. Light/dark exposures associated with fixed early sleep schedules are sufficient to advance circadian phase in young adults.