A randomized, sham-controlled trial of a novel near-infrared phototherapy device on sleep and daytime function.

STUDY OBJECTIVES: Near-infrared light exhibits several therapeutic properties, but little is known about the benefits to sleep and daytime function. The purpose of this study was to investigate the effects of red and near-infrared exposure before bed on sleep and next-day function. METHODS: Thirty adults (30-60 y) with a self-reported sleep complaint but without a sleep disorder participated in a randomized, sham-controlled study for a duration of 5 weeks. After a 2-week baseline period, participants wore either a cervical red light/near-infrared-emitting collar (combined: 660 nm, 740 nm, 810 nm, and 870 nm) or sham device every other night before bed for 3 weeks. Sleep was measured using actigraphy and sleep diaries. Mood and performance were assessed using weekly self-reported surveys and debrief interviews. RESULTS: Objective sleep parameters, as measured by actigraphy, did not differ between the active or sham groups, but improved self-reported sleep, as well as perceived improvements in relaxation and mood, were observed among active but not sham users. Both active and sham users improved in Insomnia Severity Index score by the end of the trial. CONCLUSIONS: Red and near-infrared exposure to the head and neck before bed may offer potential therapeutic benefits to sleep and daytime function, but further work needs to be done to determine optimal dose parameters, wavelengths, and milliwatt power level. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Phase II Study-Trial of a Phototherapy Light Device to Improve Sleep Health (PHOTONS); URL: https://clinicaltrials.gov/ct2/show/NCT05116358; Identifier: NCT05116358. CITATION: Kennedy KER, Wills CCA, Holt C, Grandner MA. A randomized, sham-controlled trial of a novel near-infrared phototherapy device on sleep and daytime function. J Clin Sleep Med. 2023;19(9):1669-1675.

The effects of caffeinated products on sleep and functioning in the military population: A focused review.

Military personnel rely on caffeinated products such as coffee or energy drinks (ED) to maintain a maximal level of vigilance and performance under sleep-deprived and combat situations. While chronic caffeine intake is associated with decreased sleep duration and non-restful sleep in the general population, these relationships are relatively unclear in the military personnel. We conducted a focused review of the effects of caffeinated products on sleep and the functioning of military personnel. We used a pre-specified search algorithm and identified 28 peer-reviewed articles published between January 1967 and July 2019 involving military personnel. We classified the findings from these studies into three categories. These categories included descriptive studies of caffeine use, studies evaluating the association between caffeinated products and sleep or functioning measures, and clinical trials assessing the effects of caffeinated products on functioning in sleep-deprived conditions. Most of the studies showed that military personnel used at least one caffeine-containing product per day during active duty and coffee was their primary source of caffeine. Their mean caffeine consumption varied from 212 to 285 mg/day, depending on the type of personnel and their deployment status. Those who were younger than 30 years of age preferred ED use. Caffeine use in increasing amounts was associated with decreased sleep duration and increased psychiatric symptoms. The consumption of caffeinated products during sleep deprivation improved their cognitive and behavioral outcomes and physical performance. Caffeine and energy drink consumption may maintain some aspects of performance stemming from insufficient sleep in deployed personnel, but excessive use may have adverse consequences.

A Randomized, Double-Blind, Placebo-Controlled Trial of a Polyphenol Botanical Blend on Sleep and Daytime Functioning.

Despite the high prevalence of subclinical sleep disturbances, existing treatments are either potent prescription medications or over-the-counter supplements with minimal scientific support and numerous side effects. However, preliminary evidence shows that polyphenols such as rosmarinic acid and epigallocatechin gallate can support healthy sleep without significant side effects. Therefore, the present study examined whether a polyphenol botanical blend (PBB) could improve sleep and/or daytime functioning in individuals with subclinical sleep disturbances. A total of 89 individuals completed a double-blind, randomized trial of daily treatment with PBB (n = 43) or placebo (n = 46) 30 min before bed for 30 days. Participants were monitored for changes in sleep (by sleep diary and an activity tracker), mood, and neurocognitive functioning. After 30 days, PBB improved diary sleep quality (p = 0.008) and reduced insomnia severity (p = 0.044) when compared to placebo. No other changes in sleep outcomes were observed. Additionally, PBB did not impair neurocognitive functioning, and some improvement was noted in vigilant attention, working memory, and risk assessment. Among individuals with subclinical sleep disturbances, PBB improved sleep quality, insomnia severity, and neurocognitive functioning over placebo. These findings indicate that polyphenol compounds may be useful for improving certain aspects of sleep without compromising neurocognitive functioning.

Meta-analysis of light and circadian timekeeping in rodents.

We conducted a meta-analysis of papers published over the past half-century (1964-2017) that quantified the phase-shifting effects of timed light exposure on rodent locomotor rhythms. Descriptive statistics were tabulated in order to explore the extent to which these studies were generalizable across species, sex, age, circadian timing, and light sources. Attempts at understanding photic resetting were primarily targeted at younger male animals, with particular emphases placed on characterizing the pacemaker systems of C57BL/6 mice and Syrian hamsters during the parts of their subjective night most sensitive to delivery of white-fluorescent light. With subsequent analyses restricted to these rodent models, we then assessed the relationship between luminous exposure (via broadspectrum emission) and phase-shifting through a series of linear regressions. Monotonically increasing illuminance-response functions were noted at most circadian times surveyed. In the aggregate, our results show that previous research conducted on light's regulation of circadian timekeeping has been skewed in design with respect to several important biological variables. This bias might limit translation of phototherapy-relevant data to women and older individuals.

Disassembling insomnia symptoms and their associations with depressive symptoms in a community sample: the differential role of sleep symptoms, daytime symptoms, and perception symptoms of insomnia.

OBJECTIVE: Insomnia and depression are closely related. However, few studies have investigated whether certain insomnia symptoms differentially relate to certain depressive symptoms. The present study aimed to examine relationship between specific types of insomnia symptoms (sleep symptoms, daytime symptoms, and perception symptoms) and specific symptoms of depression. DESIGN: Cross-sectional, observational study data from the Sleep, Health, Activity, Diet and Environment and Social Factors (SHADES) Survey. SETTING: Community-level population. PARTICIPANTS: A total of 1003 community-based adults aged 22-60 from the Philadelphia area. MEASUREMENTS: Insomnia symptoms were represented by scores of sleep symptoms, daytime symptoms and perception symptoms, derived from the Insomnia Severity Index (ISI). Depression symptoms were assessed with the items of the Patient Health Questionnaire 9 (PHQ-9). RESULTS: A Confirmatory Factor Analysis (CFA) supported the three-factor model based on ISI data. Binary logistic regressions examined independent associations between the three insomnia symptom types and individual depression symptoms. Sleep symptoms were more strongly associated with physiological aspects of depressive symptoms (appetite symptoms, psychomotor symptoms, and suicidal ideation). The daytime symptoms, on the other hand, were significantly associated with almost all depressive symptoms, except for appetite. Moreover, daytime symptoms were exclusively related to cognitive symptoms of depression (eg, trouble concentrating). The perception symptoms were independently associated with mood symptoms, tiredness, appetite, and judgment of oneself as a failure, but not with psychomotor, cognitive and suicidal ideation symptoms. CONCLUSION: Daytime symptoms and perception symptoms of insomnia were more strongly associated with a full range of depressive symptoms than sleep symptoms. The sleep symptoms were mainly associated with more physiological symptoms of depression, implicating more biological mechanisms. Further research is needed regarding how these types of insomnia symptoms differentially related to multiple health consequences.

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer.

Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

Sleep symptoms associated with intake of specific dietary nutrients.

Sleep symptoms are associated with weight gain and cardiometabolic disease. The potential role of diet has been largely unexplored. Data from the 2007-2008 National Health and Nutrition Examination Survey (NHANES) were used (n = 4552) to determine which nutrients were associated with sleep symptoms in a nationally representative sample. Survey items assessed difficulty falling asleep, sleep maintenance difficulties, non-restorative sleep and daytime sleepiness. Analyses were adjusted for energy intake, other dietary factors, exercise, body mass index (BMI) and sociodemographics. Population-weighted, logistic regression, with backwards-stepwise selection, examined which nutrients were associated with sleep symptoms. Odds ratios (ORs) reflect the difference in odds of sleep symptoms associated with a doubling in nutrient. Nutrients that were associated independently with difficulty falling asleep included (in order): alpha-carotene (OR = 0.96), selenium (OR = 0.80), dodecanoic acid (OR = 0.91), calcium (OR = 0.83) and hexadecanoic acid (OR = 1.10). Nutrients that were associated independently with sleep maintenance difficulties included: salt (OR = 1.19), butanoic acid (0.81), carbohydrate (OR = 0.71), dodecanoic acid (OR = 0.90), vitamin D (OR = 0.84), lycopene (OR = 0.98), hexanoic acid (OR = 1.25) and moisture (OR = 1.27). Nutrients that were associated independently with non-restorative sleep included butanoic acid (OR = 1.09), calcium (OR = 0.81), vitamin C (OR = 0.92), water (OR = 0.98), moisture (OR = 1.41) and cholesterol (OR = 1.10). Nutrients that were associated independently with sleepiness included: moisture (OR = 1.20), theobromine (OR = 1.04), potassium (OR = 0.70) and water (OR = 0.97). These results suggest novel associations between sleep symptoms and diet/metabolism, potentially explaining associations between sleep and cardiometabolic diseases.

Short wavelength light administered just prior to waking: a pilot study.

Bright light in the blue-green range, administered in the early morning hours (prior to waking) may be particularly effective in shifting circadian rhythms and may increase gonadotropin production. Accordingly, we tested the feasibility and utility of a mask that emits bright blue/green light (compared to a similar mask that emitted a dim red light) towards the end of sleep in a randomized, placebo-controlled pilot study. The study included a 3-day baseline period, immediately followed by a 12-day intervention period. Subjects were 30 healthy young men with minimal-mild depression. The bright light masks were well-tolerated and demonstrated adequate safety and feasibility. Following the intervention, those who wore the bright light mask demonstrated altered sleep timing suggestive of an earlier sleep period, and excreted a slight increase in follicle-stimulating hormone. Overall, light masks may prove useful in future studies of bright light therapy.

Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults.

Melatonin is increasingly used for the treatment of sleep disorders. Surge-sustained formulations consisting of combined immediate release and controlled release dosing may mimic the endogenous melatonin physiologic profile. However, relatively little is known about the pharmacokinetic properties of low-dose (<0.5mg) and high-dose (>2mg) melatonin in a combined immediate release/controlled release dose, especially in older adults who may also exhibit altered melatonin disposition. To assess this, we conducted a randomized, double-blind, placebo-controlled study of low-dose (0.4mg) and high-dose (4.0mg) melatonin (25% immediate release+75% controlled release) in 27 older adults with insomnia complaints and low endogenous melatonin levels to determine whether melatonin pharmacokinetic properties differ between these two doses. The time to maximum level (1.3hrs versus 1.5hrs), elimination half-life (1.8hrs versus 2.1hrs), and apparent total clearance (379L/hr versus 478L/hr) did not differ significantly between the low- and high-dose arms, respectively. The maximum concentration was 405 ±93pg/mL for the low-dose arm and 3999±700pg/mL for the high-dose arm, both of which are substantially higher than physiologic melatonin levels for this age group. In addition, subjects in the high-dose arm maintained melatonin levels >50pg/mL for an average of 10hrs, which could result in elevated melatonin levels beyond the typical sleep period. Renal and liver function parameters remained stable after 6wks of treatment. The linear pharmacokinetic behavior of melatonin observed in the elderly can form the basis for future studies exploring a wider range of dosing scenarios to establish exposure-response relationships for melatonin-mediated sleep outcomes.

Light exposure is related to social and emotional functioning and to quality of life in older women.

While there are data supporting the use of light in clinical populations, there has been less investigation of relationships among light and psychological variables in non-clinical samples. Subjects were 459 ethnically diverse women (mean age 67.68) recruited as part of the Women's Health Initiative. Light exposure and sleep were measured with an Actillume wrist actigraph. Subjects completed questionnaires, investigating Social Support, Social Functioning, Social Strain, Quality of Life, Satisfaction with Life, Emotional Well-being, Optimism, Negative Emotional Expressiveness, and Role Limitation Due to Emotional Problems. Significant partial correlations (controlling for age, education and ethnicity) were found between mesor light exposure and Social Functioning, Quality of Life, Satisfaction with Life, and Emotional Well-Being. Quality of Life and Satisfaction with Life were also found to be significantly correlated with morning light. The most parsimonious model to account for the variance shared between mesor light and the predictors included only Quality of Life. The variance shared between mesor light exposure and social and emotional functioning could be subsumed under the variance shared between mesor light exposure and Quality of Life. Increased light exposure is related to improved quality of life and social and emotional functioning.

Bright light treatment of depression for older adults [ISRCTN55452501].

BACKGROUND: The incidence of insomnia and depression in the elder population is significant. It is hoped that use of light treatment for this group could provide safe, economic, and effective rapid recovery. METHODS: In this home-based trial we treated depressed elderly subjects with bright white (8,500 Lux) and dim red (<10 Lux) light for one hour a day at three different times (morning, mid-wake and evening). A placebo response washout was used for the first week. Wake treatment was conducted prior to the initiation of treatment, to explore antidepressant response and the interaction with light treatment. Urine and saliva samples were collected during a 24-hour period both before and after treatment and assayed for aMT6s and melatonin respectively to observe any change in circadian timing. Subjects wore a wrist monitor to record light exposure and wrist activity. Daily log sheets and weekly mood (GDS) and physical symptom (SAFTEE) scales were administered. Each subject was given a SCID interview and each completed a mood questionnaire (SIGH-SAD-SR) before and after treatment. Also, Hamilton Depression Rating (SIGH-SAD version) interviews were conducted by a researcher who was blind to the treatment condition. A control group of healthy, age-matched, volunteers was studied for one day to obtain baseline data for comparison of actigraphy and hormone levels. RESULTS: Eighty-one volunteers, between 60 and 79 years old, completed the study. Both treatment and placebo groups experienced mood improvement. Average GDS scores improved 5 points, the Hamilton Depression Rating Scale (HDRS) 17 scores (extracted from the self-rated SIGH-SAD-SR) improved 6 points. There were no significant treatment effects or time-by-treatment interactions. No significant adverse reactions were observed in either treatment group. The assays of urine and saliva showed no significant differences between the treatment and placebo groups. The healthy control group was active earlier and slept earlier but received less light than the depressed group at baseline. CONCLUSION: Antidepressant response to bright light treatment in this age group was not statistically superior to placebo. Both treatment and placebo groups experienced a clinically significant overall improvement of 16%.

Bright green light treatment of depression for older adults [ISRCTN69400161].

BACKGROUND: Bright white light has been successfully used for the treatment of depression. There is interest in identifying which spectral colors of light are the most efficient in the treatment of depression. It is theorized that green light could decrease the intensity duration of exposure needed. Late Wake Treatment (LWT), sleep deprivation for the last half of one night, is associated with rapid mood improvement which has been sustained by light treatment. Because spectral responsiveness may differ by age, we examined whether green light would provide efficient antidepressant treatment in an elder age group. METHODS: We contrasted one hour of bright green light (1,200 Lux) and one hour of dim red light placebo (<10 Lux) in a randomized treatment trial with depressed elders. Participants were observed in their homes with mood scales, wrist actigraphy and light monitoring. On the day prior to beginning treatment, the participants self-administered LWT. RESULTS: The protocol was completed by 33 subjects who were 59 to 80 years old. Mood improved on average 23% for all subjects, but there were no significant statistical differences between treatment and placebo groups. There were negligible adverse reactions to the bright green light, which was well tolerated. CONCLUSION: Bright green light was not shown to have an antidepressant effect in the age group of this study, but a larger trial with brighter green light might be of value.