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1.
The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review.
Prono, F, Bernardi, K, Ferri, R, Bruni, O
International journal of molecular sciences. 2022;23(3)
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Vitamin D deficiency or insufficiency is a global epidemic, estimated to affect over one billion people worldwide, including children. The main function of vitamin D is the regulation of bone homeostasis but it is also involved in many other conditions such as cardiovascular disease, cancer, diabetes mellitus and autoimmune disorders. Recent studies show that sufficient levels of vitamin D seem to be necessary to maintain sleep and low vitamin D levels have been associated with shorter sleep duration. This systematic review is the first to assess the association between Vitamin D and sleep disorders in children, 14 articles were included. Vitamin D deficiency in children is associated with decreased sleep duration and poorer sleep efficiency, as well as with delayed bedtimes. Children with reduced vitamin D serum levels have a higher risk of excessive daytime sleepiness (EDS). Since vitamin D levels influence sleep duration, sleep duration can also influence vitamin D serum concentration suggesting a bidirectional relationship. Evidence is scarce and so further high-quality prospective cohort studies and well-designed randomized controlled trials (RCTs) are needed to determine the effect of vitamin D supplementation in children with sleep disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Vitamin D plays an important role in the sleep quality of children. Healthcare practitioners may wish to establish vitamin D status in children presenting with sleep disturbances.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Vitamin D levels have been associated with improved sleep in adults, but few studies have concentrated on the paediatric population. In order to identify if vitamin D plays a role regulating sleep in children and adolescents the paper reviewed studies, which looked at vitamin D in relation to sleep duration and quality of sleep. This included the following sleep disorders: obstructive sleep apnoea (OSA), restless leg syndrome (RLS) and insomnia.
Methods
- A broad systematic review following the PRISMA guidelines and using PubMed and Cochrane databases
- Search identified 748 papers. After exclusions for non-relevance, incorrect age group, or lack of data on sleep, 14 papers were included
- Due to the shortage of papers on this topic none of these papers were excluded, regardless of quality
- The participants in each study varied from 39 to 5289.
Results
The results highlighted:
- Plasma levels of vitamin D affect sleep duration and quality of sleep in children. Data taken from 5 studies
- Vitamin D cord blood levels were correlated to sleep in preschool children. Partly this was due to the mother’s vitamin D level during pregnancy affecting the level of vitamin D available to the foetus. Venous blood vitamin D level was linked to the sleep wake cycle of children. Data taken from 2 studies
- OSA was more likely to develop in children who had low vitamin D levels with a risk of 14.16% compared to a control group of 5.83% (1 study)
- Vitamin D supplementation was found to reduce neuron damage caused by hypoxia (1 study)
- An association exists between parental vitamin D insufficiency and their child’s vitamin D status (1 study). Data taken from 5 studies
- Vitamin D levels in specific diseases, such as coeliac disease (CD) showed a negative correlation with RLS
- For familial Mediterranean fever (FMF) vitamin D deficiency reduced sleep quality (36.5%). Data taken from 2 studies.
Conclusion
Notwithstanding the small number of studies, the review shows vitamin D deficiency, defined as <20 ng/mL, is associated with an increased risk for sleep disorders in children.
Clinical practice applications:
- Due to the role vitamin D plays in sleep in children, establishing vitamin D status may be useful for children presenting with sleep disturbances
- Adequate vitamin D levels during pregnancy are important to establish a vitamin D pool in the foetus
- Vitamin D supplementation is something to rule out in the case of OSA and associated hypoxia, metabolic dysfunction and systemic inflammation in children
- Due to the negative impact poor sleep has on the body, improving sleep quality at a young age could form an important part of preventative health care.
Considerations for future research:
- Additional studies are required to support the conclusion in this study
- Due to the low number of studies, any additional research should be of a high standard and include prospective cohort studies and randomised control trials.
Abstract
This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS.
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Melatonin: Roles in influenza, Covid-19, and other viral infections.
Anderson, G, Reiter, RJ
Reviews in medical virology. 2020;30(3):e2109
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Viruses like influenza and coronaviruses change quickly, making it challenging to develop effective treatments and vaccines in a short time frame. Consequently, the use of generic substances that limit viral effects are of high interest. In this paper, the authors summarize a range of mechanisms in which melatonin can alter the impact of virus infections and infection-associated inflammatory overdrive aka cytokine storm. Melatonin, the sleep hormone, is well known for its potent antioxidant and anti-inflammatory action. It seems highly likely that melatonin can modulate the cellular function of all cells, mostly via mitochondrial function. This is particularly relevant in immune cells. For example, the daytime variance in immune function seems to be closely linked with mitochondrial activity and energy production. Other relevant mechanisms described are the antiviral role of melatonin-induced sirtuins - proteins that regulate cellular health-, the impact of viruses on cell coordinating microRNA, the role of the gut microbiome and gut permeability, as well as sympathetic nervous system activation and the protective effects of parasympathetic activation. Also considered are pre-existing health conditions and conditions that are linked with a decline in melatonin along with ageing, all being groups in which severity of viral infections is felt. This paper may be of interest to those who like to explore in more depth the mechanisms behind melatonin and its ability to influence viral disease progression.
Abstract
There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian "resetting" of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl-CoA is a necessary cosubstrate for arylalkylamine N-acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus- and cytokine-storm-driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus-and cytokine storm-driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid-19 and other viral infections.
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Bridging the Reciprocal Gap between Sleep and Fruit and Vegetable Consumption: A Review of the Evidence, Potential Mechanisms, Implications, and Directions for Future Work.
Noorwali, E, Hardie, L, Cade, J
Nutrients. 2019;11(6)
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Both sleep disruption and a low intake of fruit and vegetables (FV) are associated with higher rates of premature death and chronic disease. This review looked at previous studies in order to determine whether there is a link between sleep and FV consumption. A recent meta-analysis found that shorter sleep duration is consistently associated with low fruit and vegetable intake in children, but in adults the association is less clear. Studies looking at the effect of sleep on FV intake had variable results. Tart cherries and kiwi fruits were the most commonly studied fruits for their effect on sleep measures. Observational studies tended to find that both short- and long-sleepers tend to eat less FV than those that sleep for 7-8 hours. A lot of evidence shows that people who go to sleep later (‘owls’) tend to consume unhealthier diets with lower intakes of FV than people who go to bed earlier (‘larks’). The researchers also looked at potential mechanisms for the association between sleep and FV intake. Polyphenols in FV may influence sleep by increasing neurotransmitters via the gut-brain axis, improving energy metabolism and through alterations in circadian rhythms and the CLOCK genes. Ways in which disrupted sleep may affect FV consumption included changes in hunger hormones, emotional stress and impaired decision making. With further research, interactions between sleep measures and FV consumption may be clarified and potentially reduce the burden of chronic diseases and premature deaths.
Abstract
A substantial burden of disease and mortality globally is attributable to both sleep disruption and low intakes of fruit and vegetable (FV) and there is increasing mechanistic and epidemiological evidence to support a reciprocal relationship between the two. This review provides an overview of experimental and observational studies assessing the relations between sleep and FV consumption from 52 human adult studies. Experimental studies are currently limited and show inconsistent results. Observational studies support a non-linear association with adults sleeping the recommended 7-9 hours/day having the highest intakes of FV. The potential mechanisms linking sleep and FV consumption are highlighted. Disrupted sleep influences FV consumption through homeostatic and non-homeostatic mechanisms. Conversely, FV consumption may influence sleep through polyphenol content via several potential pathways. Few human experimental studies have examined the effects of FV items and their polyphenols on sleep and there is a need for more studies to address this. An appreciation of the relationship between sleep and FV consumption may help optimize sleep and FV consumption and may reduce the burden of chronic diseases. This review provides implications for public health and directions for future work.
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A systematic review and meta-analysis of cognitive and behavioral interventions to improve sleep health in adults without sleep disorders.
Murawski, B, Wade, L, Plotnikoff, RC, Lubans, DR, Duncan, MJ
Sleep medicine reviews. 2018;40:160-169
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Sleep is important for good health but more than a quarter of the adult population reports poor quality sleep. This review and meta-analysis looked at cognitive and behavioural interventions in adults who report poor sleep but are not diagnosed with a clinical sleep disorder. The most commonly used interventions were stress management/relaxation, meditation, controlled breathing and stimulus control. A meta-analysis showed a medium improvement of overall sleep quality and a small but significant improvement of subjective sleep quality and duration with cognitive and behavioural interventions. The effects were bigger when sleep at baseline was worse. Effects of mode of delivery, study duration and the inclusion of a relaxation component were not assessed, due to insufficient numbers. The authors conclude that there is room for improvements of cognitive and behavioural interventions and call for more investigations into this.
Abstract
Many adults without a diagnosed sleep disorder report poor sleep health, which is defined by dissatisfactory levels of sleep duration, sleep quality, or the timing of sleep. No previous review has summarized and described interventions targeting poor sleep health in this population. This meta-analysis aimed to quantify the efficacy of behavioral and cognitive sleep interventions in adults with poor sleep health, who do not have a sleep disorder. Electronic databases (Medline, Embase, PsycInfo, Cinahl) were searched with restrictions for age (18-64 y) and English language full-text, resulting in 18,009 records being screened and 592 full-texts being assessed. Eleven studies met inclusion criteria, seven of which reported a measure of overall sleep health (Pittsburgh sleep quality index [PSQI]). Following appraisal for risk of bias, extracted data were meta-analyzed using random-effects models. Meta-analyses showed interventions had a medium effect on sleep quality (Hedge's g = -0.54, [95% confidence interval (CI)] -0.90 to -0.19, p < 0.01). Baseline sleep health was the only significant effect moderator (p = 0.01). The most frequently used intervention components were stress management and relaxation practice, stimulus control, sleep hygiene, and exercise. Interventions targeting cognitive and behavioral self-regulation improve sleep quality in adults without clinical sleep disorder.
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Shared Dysregulation of Homeostatic Brain-Body Pathways in Depression and Type 2 Diabetes.
Hoogendoorn, CJ, Roy, JF, Gonzalez, JS
Current diabetes reports. 2017;17(10):90
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Depression and type 2 diabetes (T2D) appear to have a bidirectional relationship, with the two diseases possibly being linked through emotional and biological changes. This review paper aimed to discuss this bidirectional relationship and in particular the biological changes that may be involved. The authors started by stating that two biological systems may be influenced in depression and T2D, the hypothalamic-pituitary-adrenal axis (HPA), which is responsible for many systems in the body involved in the stress response and emotional and physical health. The second is the brain-gut-microbiome axis (BGM), which is related to the microorganisms in the gut and how they communicate with the brain. The immune system, sleep and blood sugar balance may be influenced by the HPA and BGM and are all dysregulated in both depression and T2D indicating a link between the two diseases. However causal relationships need further research. Dietary and lifestyle changes may be of benefit in these individuals. It was concluded that the disruption of shared biological systems in T2D and depression may be an important target for treatments, however further research is warranted. This study could be used by healthcare practitioners to understand the relationship between T2D and depression and the potential therapeutic areas to target. However, although research is optimistic, it is still in its infancy.
Abstract
PURPOSE OF REVIEW The purpose of this review is to provide an overview of shared dysregulation of the hypothalamic-pituitary-adrenal (HPA) and brain-gut-microbiome (BGM) axes associated with depression and type 2 diabetes (T2D). Clinical implications and future research are also discussed. RECENT FINDINGS Both depression and T2D are associated with dysregulation of the HPA and BGM axes. These pathways regulate immune function, glucose metabolism, and sleep, which are altered in both illnesses. Dysregulation of homeostatic brain-body pathways may be positively influenced through different therapeutic actions, including psychotherapy, healthy eating, physical activity, sleep promotion, and certain anti-inflammatory or antidepressant medications. While the causal nature of the relationship between depression and T2D remains unclear, these conditions share dysregulation of homeostatic brain-body pathways that are central to mental and physical health. Better understanding of this dysregulation may provide opportunities for interventions that could benefit both conditions. Future research should examine the additive burden of depression and T2D on HPA and BGM dysregulation and better differentiate depression from emotional distress.
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The microbiome: A key regulator of stress and neuroinflammation.
Rea, K, Dinan, TG, Cryan, JF
Neurobiology of stress. 2016;4:23-33
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This study discusses the concept of intestinal microbiota as the key regulator involved in energy regulation, gut barrier function, protection from pathogens, and immune system function amongst others. The gut microbiota is the complex community of microorganisms that lives in the digestive tracts of humans. The main aim of this study is to summarise the role of gastrointestinal microbiota in fundamental physiological and pathophysiological processes and thereafter to understand and treat a range of stress and immune-related disorders. This review outlines the numerous complex relationships between gastrointestinal microbiota, stress and immune responses at the three critical stages of life The authors concluded that the evidence from this study suggests that resilience to stress and immune-related disorders and dysfunction of stress and immune systems may be dependent on the diversity and complexity of gastrointestinal microbiota. However, gut microbiota mediated relationship to stress and neuro-inflammation is still unconfirmed as previous studies mostly, have largely been, preclinical and further studies are warranted.
Abstract
There is a growing emphasis on the relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiota) and health/disease, including brain health and disorders of the central nervous system. The microbiota-gut-brain axis is a dynamic matrix of tissues and organs including the brain, glands, gut, immune cells and gastrointestinal microbiota that communicate in a complex multidirectional manner to maintain homeostasis. Changes in this environment can lead to a broad spectrum of physiological and behavioural effects including hypothalamic-pituitary-adrenal (HPA) axis activation, and altered activity of neurotransmitter systems and immune function. While an appropriate, co-ordinated physiological response, such as an immune or stress response are necessary for survival, a dysfunctional response can be detrimental to the host contributing to the development of a number of CNS disorders. In this review, the involvement of the gastrointestinal microbiota in stress-mediated and immune-mediated modulation of neuroendocrine, immune and neurotransmitter systems and the consequential behaviour is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in stress-related disorders as a consequence of neuroinflammatory processes.
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Circadian Rhythms, Metabolism, and Chrononutrition in Rodents and Humans.
Johnston, JD, Ordovás, JM, Scheer, FA, Turek, FW
Advances in nutrition (Bethesda, Md.). 2016;7(2):399-406
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Chrononutrition is an emerging field that links the body’s metabolism to its endogenous circadian rhythm. It is now recognised that numerous circadian clocks are found within all major tissues and most cells of the body. This complex network of clocks influences a wide range of biological processes including neuronal, endocrine, metabolic and behavioural function. When there is a disruption in a single circadian clock, whole-organism homeostasis can be impacted, potentially resulting in the development of disease. This review explains the potential mechanisms by which circadian clocks influence biological processes through transgenic animal studies, and how they are being translated to human genetics and metabolomics. The principles of chrononutrition are clinically significant factors that should be considered when managing and treating metabolic disease, as well as maintaining health in the general population.
Abstract
Chrononutrition is an emerging discipline that builds on the intimate relation between endogenous circadian (24-h) rhythms and metabolism. Circadian regulation of metabolic function can be observed from the level of intracellular biochemistry to whole-organism physiology and even postprandial responses. Recent work has elucidated the metabolic roles of circadian clocks in key metabolic tissues, including liver, pancreas, white adipose, and skeletal muscle. For example, tissue-specific clock disruption in a single peripheral organ can cause obesity or disruption of whole-organism glucose homeostasis. This review explains mechanistic insights gained from transgenic animal studies and how these data are being translated into the study of human genetics and physiology. The principles of chrononutrition have already been demonstrated to improve human weight loss and are likely to benefit the health of individuals with metabolic disease, as well as of the general population.
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Short sleep duration and dietary intake: epidemiologic evidence, mechanisms, and health implications.
Dashti, HS, Scheer, FA, Jacques, PF, Lamon-Fava, S, Ordovás, JM
Advances in nutrition (Bethesda, Md.). 2015;6(6):648-59
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Short sleep duration is associated with various cardio-metabolic parameters that contribute to chronic disease. While the underlying mechanism is multifactorial, the link may be mediated through changes in dietary intake. This review provides an overview of the relationship between chronic short sleep duration and dietary intake. This review indicates that short sleep duration is associated with higher total caloric intake, higher fat intake and diets with relatively higher fat and lower protein composition. Further epidemiological studies are required to better establish the relationship between chronic short sleep and dietary patterns, and improvements in sleep should be an added factor in weight management programmes.
Abstract
Links between short sleep duration and obesity, type 2 diabetes, hypertension, and cardiovascular disease may be mediated through changes in dietary intake. This review provides an overview of recent epidemiologic studies on the relations between habitual short sleep duration and dietary intake in adults from 16 cross-sectional studies. The studies have observed consistent associations between short sleep duration and higher total energy intake and higher total fat intake, and limited evidence for lower fruit intake, and lower quality diets. Evidence also suggests that short sleepers may have irregular eating behavior deviating from the traditional 3 meals/d to fewer main meals and more frequent, smaller, energy-dense, and highly palatable snacks at night. Although the impact of short sleep duration on dietary intake tends to be small, if chronic, it may contribute to an increased risk of obesity and related chronic disease. Mechanisms mediating the associations between sleep duration and dietary intake are likely to be multifactorial and include differences in the appetite-related hormones leptin and ghrelin, hedonic pathways, extended hours for intake, and altered time of intake. Taking into account these epidemiologic relations and the evidence for causal relations between sleep loss and metabolism and cardiovascular function, health promotion strategies should emphasize improved sleep as an additional factor in health and weight management. Moreover, future sleep interventions in controlled studies and sleep extension trials in chronic short sleepers are imperative for establishing whether there is a causal relation between short sleep duration and changes in dietary intake.