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Impact of Melatonin Supplementation on Sports Performance and Circulating Biomarkers in Highly Trained Athletes: A Systematic Review of Randomized Controlled Trials.
Celorrio San Miguel, AM, Roche, E, Herranz-López, M, Celorrio San Miguel, M, Mielgo-Ayuso, J, Fernández-Lázaro, D
Nutrients. 2024;16(7)
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Melatonin (N-acetyl-5 methoxytryptamine) is an indolic neurohormone known for its antioxidant, anti-inflammatory, and immunoregulatory properties. Highly demanding training exponentially increases physical and biochemical demands, particularly in the skeletal muscle and the liver. This study aimed to critically review the effects of melatonin supplementation on sports performance and circulating biomarkers in highly trained athletes. This study was a systematic review of twenty-one randomised controlled trials. The dose of melatonin supplemented in the trials ranged from 5 mg to 100 mg, administered before or after exercise. Results showed that melatonin supplementation improved antioxidant status and inflammatory response. Additionally, it reversed liver and muscle damage, and moderate effects were also observed in modulating glycaemia, total cholesterol, triglycerides, and creatinine. Authors concluded that melatonin has a high safety profile. In fact, melatonin supplementation could act indirectly to improve performance by preventing tissue damage, reduce inflammation caused by reactive oxygen and nitrogen species, and restore circulating biomarkers in highly trained athletes during demanding exercises.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Diet and lifestyle modifications should always be made first to ensure that athletes have sufficient melatonin levels.
- Adequate light exposure at appropriate times and specific foods which contain melatonin may help.
- During periods of intense training, supplementation may be needed to reach adequate levels and to aid recovery.
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
- High-intensity exercise can disrupt inflammatory and immune processes within the body resulting in inflammation, poor immune function, and poor recovery.
- Melatonin is a neurohormone that has anti-inflammatory and antioxidant properties, and has the potential to be of benefit to recovery following strenuous exercise.
- This systematic review of randomised control trials aimed to determine the effect of melatonin on sports performance and circulating health biomarkers.
Methods
- This was a systematic review of randomised control trials (RCTs).
- The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.
- Studies that were included looked at the use of melatonin by trained sports professional and athletes.
Results
- 21 RCTs were included in the review.
- Melatonin doses ranged from 5mg to 100mg in the studies.
- Melatonin was administered either acutely or for periods of 3 to 30 days pre and post exercise.
- None of the studies were rated low risk of bias.
- Seven studies had a high risk of bias.
- There was a high degree of heterogeneity, which prevented a meta-analysis being performed.
- The study showed that melatonin supplementation had some effect on white blood cell count levels and immunoglobulins but results were conflicting.
- Moderate effects were seen on blood glucose, cholesterol, triglycerides, and phospholipids but did not affect high density lipoprotein or low-density lipoprotein.
- Improvements were seen in antioxidant status and inflammation.
- Reversal of kidney and liver damage was reported following supplementation.
- Promising effects were seen on sports performance with some studies reporting improvements in aerobic capacity, agility, and sprint performance.
- No effects were apparent on hormonal response of cortisol, testosterone, or growth hormone.
- No adverse effects were seen following melatonin supplementation.
Conclusion
- Melatonin supplementation may mitigate some of the damaging effects of extreme exercise.
- However, it is unclear as to how this might occur.
Clinical practice applications:
- Sufficient melatonin levels may be necessary in highly trained athletes.
- This may limit inflammation and oxidative stress and help prevent tissue damage and aid recovery.
- During periods of intense training or when quick recovery is needed, melatonin supplementation may be of benefit.
Considerations for future research:
- More studies on the mechanisms through which melatonin may be supporting athletic performance and preventing liver and kidney damage are needed.
- Studies on the effects of melatonin on mitochondrial function may be of benefit.
Abstract
Melatonin (N-acetyl-5 methoxytryptamine) is an indolic neurohormone that modulates a variety of physiological functions due to its antioxidant, anti-inflammatory, and immunoregulatory properties. Therefore, the purpose of this study was to critically review the effects of melatonin supplementation in sports performance and circulating biomarkers related to the health status of highly trained athletes. Data were obtained by performing searches in the following three bibliography databases: Web of Science, PubMed, and Scopus. The terms used were "Highly Trained Athletes", "Melatonin", and "Sports Performance", "Health Biomarkers" using "Humans" as a filter. The search update was carried out in February 2024 from original articles published with a controlled trial design. The PRISMA rules, the modified McMaster critical review form for quantitative studies, the PEDro scale, and the Cochrane risk of bias were applied. According to the inclusion and exclusion criteria, 21 articles were selected out of 294 references. The dose of melatonin supplemented in the trials ranged between 5 mg to 100 mg administered before or after exercise. The outcomes showed improvements in antioxidant status and inflammatory response and reversed liver damage and muscle damage. Moderate effects on modulating glycemia, total cholesterol, triglycerides, and creatinine were reported. Promising data were found regarding the potential benefits of melatonin in hematological biomarkers, hormonal responses, and sports performance. Therefore, the true efficiency of melatonin to directly improve sports performance remains to be assessed. Nevertheless, an indirect effect of melatonin supplementation in sports performance could be evaluated through improvements in health biomarkers.
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The effect of melatonin on irritable bowel syndrome patients with and without sleep disorders: a randomized double-blinded placebo-controlled trial study.
Faghih Dinevari, M, Jafarzadeh, F, Jabbaripour Sarmadian, A, Abbasian, S, Nikniaz, Z, Riazi, A
BMC gastroenterology. 2023;23(1):135
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Previous research has shown that the use of melatonin by individuals with irritable bowel syndrome (IBS) has improved symptoms and quality of life (QoL) but did not affect sleep. This research has been shown to have some limitations in that it has been conducted in a small number of individuals and did not use the latest IBS diagnostic criteria. This randomised control trial aimed to determine in 136 individuals with IBS with and without sleep disorders the effects of melatonin on IBS score, gastrointestinal (GI) symptoms, QoL, and sleep. The results showed that compared to placebo, the use of melatonin for 8 weeks resulted in improved IBS score and GI symptoms in individuals with and without sleep disorders. Severity and frequency of abdominal pain, satisfaction with bowel habits, disease impacts on life, and stool consistency were all improved, however frequency of defecations was unaffected. Sleep was improved in those with sleep disorders, but not those without. It was concluded that melatonin can be used to improve IBS and QoL in individuals with or without sleep disorders and may also improve sleep in those with sleep disorders and IBS. This study could be used by healthcare professionals to recommend the use of melatonin to individuals with IBS to improve symptoms and QoL.
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is one of the world's most common gastrointestinal (GI) disorders, and current treatments do not meet patients' demands. This study aimed to investigate melatonin's therapeutic effects on IBS score, GI symptoms, quality of life, and sleep parameters in both groups of IBS patients with and without sleep disorders. METHODS In this randomized double-blinded placebo-controlled trial study, 136 patients with a diagnosis of IBS based on ROME IV criteria were enrolled and then divided into two groups respecting having sleep disorders or not. Patients of each group were randomized in a 1:1 ratio to receive melatonin 6 mg daily (3 mg fasting and 3 mg at bedtime) for 2 months (8 weeks). Blocked randomization was used in this process. All patients were evaluated both at the beginning and the end of the trial regarding IBS score, GI symptoms, quality of life, and sleep parameters through valid questionnaires. RESULTS In both groups of patients with and without sleep disorders, a significant improvement was observed in IBS score and GI symptoms, including the severity and the frequency of abdominal pain, the severity of abdominal bloating, satisfaction with bowel habits, disease's impact on patient's life, and stool consistency; however, there was no significant improvement in the frequency of defecations per week. In patients with sleep disorders, significant improvement in sleep parameters, including subjective sleep quality, sleep latency, sleep duration, sleep efficiency, and daytime dysfunction, was observed, while in patients without sleep disorders, there was no significant improvement in sleep parameters. In addition, quality-of-life improvement was observed in a significant number of melatonin recipients compared to placebo in both groups of patients. CONCLUSION Melatonin can be considered an effective treatment for improving IBS score, GI symptoms, and quality of life in IBS patients with and without sleep disorders. It is also effective to improve sleep parameters in IBS patients with sleep disorders. TRIAL REGISTRATION This study has been registered to the Iranian Registry of Clinical Trials (IRCT) with the approval number IRCT20220104053626N2 on the date of 13/02/2022.
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The efficacy of exogenous melatonin supplement in ameliorating irritable bowel syndrome severity: A meta-analysis of randomized controlled trials.
Chen, KH, Zeng, BY, Zeng, BS, Sun, CK, Cheng, YS, Su, KP, Wu, YC, Chen, TY, Lin, PY, Liang, CS, et al
Journal of the Formosan Medical Association = Taiwan yi zhi. 2023;122(3):276-285
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Irritable bowel syndrome (IBS) is characterised by abdominal distension, change in stool consistency, sensation of incomplete evacuation, or pain relieved with defecation. This study's aim was to provide more evidence and directly address the efficacy of exogenous melatonin supplement in improving IBS severity. This study was a meta-analysis of four randomised controlled trials with a total of 115 participants. Results showed that daily melatonin supplement was associated with significantly better improvement in overall IBS severity, IBS pain severity, and quality of life, but not in abdominal distension or sleep quality. Furthermore, melatonin supplement was not associated with a significantly different safety profile compared to placebo. Authors concluded that their findings provided evidence for the potential benefit of exogenous melatonin supplementation in IBS management, including overall IBS severity, IBS pain severity, and quality of life.
Abstract
BACKGROUND Irritable bowel syndrome (IBS) was found in 11% of the general population worldwide. The current pharmacologic management of IBS was unsatisfactory, and it was accompanied by a number of adverse events. Melatonin was found to play an important role in gastrointestinal smooth muscle motility. Dysregulation of endogenous melatonin secretion has been found in IBS patients. Exogenous melatonin supplement has become one alternative treatment for IBS, but the evidence is inconclusive. The current meta-analysis sought to determine the efficacy of exogenous melatonin supplement in improving IBS severity in IBS patients. METHODS We included randomized controlled trials (RCTs) that investigated the efficacy of exogenous melatonin supplement in ameliorating IBS severity in IBS patients. This meta-analysis was conducted using a random effects model. The primary target outcomes were changes in IBS severity associated with melatonin or placebo. RESULTS This meta-analysis of 4 RCTs and 115 participants revealed that exogenous melatonin supplement was associated with significantly better improvement in overall IBS severity than placebo (k = 4, Hedges' g = 0.746, 95% confidence intervals = 0.401-1.091, p < 0.001). The subgroup without concurrent medication had the same result (p < 0.001). In addition, exogenous melatonin supplement was also associated with significantly better improvement in IBS pain severity (p < 0.001) and quality of life (p = 0.007) than placebo, but not in abdominal distension (p = 0.111) or sleep quality (p = 0.142). Finally, melatonin was associated with similar safety profiles with placebo. CONCLUSION This meta-analysis provides evidence for the use of exogenous melatonin in IBS patients to ameliorate overall IBS severity, IBS pain severity, and quality of life. TRIAL REGISTRATION PROSPERO CRD42021269451.
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Exercise-based interventions on sleep quality in patients with fibromyalgia syndrome: An umbrella and mapping review with meta-analysis.
Cuenca-Martínez, F, Suso-Martí, L, Fernández-Carnero, J, Muñoz-Alarcos, V, Sempere-Rubio, N
Seminars in arthritis and rheumatism. 2023;61:152216
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Fibromyalgia syndrome (FMS) is a chronic condition characterised by widespread pain and fatigue, often accompanied by sleep disturbances. This study's aim was to evaluate the effectiveness of exercise-based interventions (EBIs) on sleep quality in patients with FMS. This study was an umbrella and mapping review with meta-analysis of nine systematic reviews. Results showed a moderate statistically significant effect of EBIs on improving sleep quality. Furthermore, the subgroup analyses indicated that body-mind exercises and combined exercises had a significant effect, whereas aerobic and strength exercises in isolation did not. Authors concluded that EBIs are effective in improving sleep quality in FMS patients compared to minimal intervention, no intervention, or usual care, with a low certainty of evidence. Mind-body and combined exercises were identified as the most beneficial.
Abstract
The main aim of this umbrella review was to assess the impact of exercise-based interventions (EBIs) on sleep quality in patients with fibromyalgia syndrome (FMS). We searched systematically in PubMed, PEDro, EMBASE, CINAHL, SPORTDiscus and Google Scholar. Methodological quality was analyzed using AMSTAR and ROBIS scale, and the strength of evidence was established according to GRADE. Nine systematic reviews were included. Meta-analysis (MA) of primary studies (n = 42) were performed with a random-effects model. The MA revealed a moderate statistically significant effect of EBIs (SMD=-0.46 [-0.69 to -0.23]). Subgroup analyses by type of exercise showed significant effect of body-mind exercises (SMD=-0.55 [-0.86 to -0.23]) and combined exercises (SMD=-1.11 [-2.12 to -0.11]) but not for aerobic (SMD=-0.04 [-0.15 to 0.07]) or strength (SMD=-0.52 [-1.14 to 0.1]) exercises in isolation. The results obtained showed that EBIs were effective in improving sleep quality compared to minimal intervention, no intervention or usual care, with a low certainty of evidence. Subgroup analyses showed that mind-body and combined exercises elicited the strongest effect, while aerobic and strength exercise in isolation did not show significant effects.
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Dietary supplements in neurological diseases and brain aging.
Naureen, Z, Dhuli, K, Medori, MC, Caruso, P, Manganotti, P, Chiurazzi, P, Bertelli, M
Journal of preventive medicine and hygiene. 2022;63(2 Suppl 3):E174-E188
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The rate of neurodegenerative diseases (ND) is increasing at a concerning rate. The condition is characterized by the progressive decline of neuron function in the brain, eventually leading to cognitive impairment and motorneuron disorders. This process appears to be mediated by the complex interplay of factors. The brain is extremely sensitive to oxidative stress, and oxidative stress and inflammation of the nervous tissue appear to be a common denominator in all neurodegenerative diseases. One of the challenges of ND for prevention as well as treatment and treatment development, is that the initial disease progression usually goes unnoticed, with symptoms only becoming apparent in the more advanced stages when irreversible damage has occurred. Diet quality has a significant impact on brain health and hence can also influence ND development. For example, the Mediterranean diet (MedDiet) has demonstrated many valuable attributes that can reduce ND incidences and improve cognitive function. This review looked at dietary components, natural compounds and medicinal plants that have shown to be beneficial for brain health in ND. The authors discussed the MedDiet followed by a brief review of dietary supplements, including N-acetylcysteine (NAC), phospholipids (Phosphatidylserine, Phosphatidylcholine), Gamma-aminobutyric acid, melatonin, omega-3 fatty acids, neurotropic vitamin B (B1, B6 and B12), S-adenosyl methionine (SAMe), the amino acid tryptophan, magnesium and various polyphenols. Several medicinal plants are reviewed that have demonstrated positive effects on preventing or alleviating neurological diseases. This includes Withania somnifera (Ashwagandha), Baccopa monnieri (Brahmi), Acorus calamus (Calamus) and Hypericum perforatum (St. Johns Wort). The review concluded that many bioactive compounds and plant constituents that can be obtained from a qualitative diet, as well as certain medicinal plants and supplements, can help preserve and promote brain health and prevent the onset of ND. Large clinical trials are needed to assess their suitability for their wider use.
Abstract
A healthy diet shapes a healthy mind. Diet quality has a strong association with brain health. Diet influences the onset and consequences of neurological diseases, and dietary factors may influence mental health at individual and population level. The link between unhealthy diet, impaired cognitive function and neurodegenerative diseases indicates that adopting a healthy diet would ultimately afford prevention and management of neurological diseases and brain aging. Neurodegenerative diseases are of multifactorial origin and result in progressive loss of neuronal function in the brain, leading to cognitive impairment and motoneuron disorders. The so-called Mediterranean diet (MedDiet) with its healthy ingredients rich in antioxidant, anti-inflammatory, immune, neuroprotective, antidepressant, antistress and senolytic activity plays an essential role in the prevention and management of neurological diseases and inhibits cognitive decline in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. The MedDiet also modulates the gut-brain axis by promoting a diversity of gut microbiota. In view of the importance of diet in neurological diseases management, this review focuses on the dietary components, natural compounds and medicinal plants that have proven beneficial in neurological diseases and for brain health. Among them, polyphenols, omega-3 fatty acids, B vitamins and several ayurvedic herbs have promising beneficial effects.
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The effect of Melatonin on Improving the benign Prostatic Hyperplasia Urinary Symptoms, a Randomized Clinical Trial.
Fotovat, A, Samadzadeh, B, Ayati, M, Nowroozi, MR, Momeni, SA, Yavari, S, Nasseri, A, Sharifi, L
Urology journal. 2022;19(5):406-411
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Benign prostatic hyperplasia (BPH) is a common issue in men older than 40. BPH is accompanied by irritating and obstructive symptoms that sometimes lead to surgery due to lack of recovery. Tamsulosin is an alpha-receptor blocker that is considered a standard treatment for patients. The aim of this study was to investigate the effect of melatonin [a hormone secreted by the pineal gland at night that regulates the sleep-wake cycle] along with standard treatment on improving the BPH urinary symptoms as well as patients’ quality of life due to their urinary problems. This study is a single centre, parallel group randomised, double-blind clinical trial with balanced randomisation. Patients (n = 108) were randomly allocated to one of the two groups. Results show the combination of melatonin and tamsulosin was significantly effective in treating the symptoms of frequency and nocturia in patients with BPH. Authors conclude that their findings can be used to pave the way to improving the symptoms of patients with BPH.
Abstract
PURPOSE to investigate the effect of melatonin along with tamsulosin in improving BPH urinary symptoms. MATERIALS AND METHODS A total of 108 men with BPH symptoms, age of ≥ 50 years, and International Prostate Symptom Score (IPSS) ≥ 8 entered into the parallel group randomized, double-blind clinical trial with balanced randomization. The treatment group received of 3mg melatonin plus 0.4mg tamsulosin and the control group received placebo plus 0.4mg tamsulosin. Patients and physicians were concealed by sealed and opaque envelopes. Symptoms were assessed at baseline and 1 month after treatment. Finally all scores at the initial and end of the study were compared and analyzed using SPSS software. RESULTS This study showed that adding melatonin to the classic treatment of BPH patients with tamsulosin could significantly reduce the likelihood of nocturia by 2.39 times (95% CI: 1.07-5.32, OR = 2.39, p = 0.033) and could also reduce the frequency of urination by 2.59 times (95% CI: 1.15-5.84, OR = 2.59, p = 0.021). There was no statistically significant difference between the two groups in IPSS, intermittency, incomplete emptying, straining, urgency, and weak stream. CONCLUSION Melatonin plus tamsulosin treatment is associated with a significant improvement of nocturia and frequency in patients with benign proststic hyperplasia. However, it is necessary to do more studies.
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Evidence for the Benefits of Melatonin in Cardiovascular Disease.
Tobeiha, M, Jafari, A, Fadaei, S, Mirazimi, SMA, Dashti, F, Amiri, A, Khan, H, Asemi, Z, Reiter, RJ, Hamblin, MR, et al
Frontiers in cardiovascular medicine. 2022;9:888319
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Cardiovascular disease (CVD) encompasses a group of disorders involving blood vessels or the heart. The beneficial effects of melatonin [hormone] in treating various human diseases have been broadly investigated. Melatonin is an indoleamine-derived molecule, which is synthesised at night. The aim of this review was to point out therapeutic potentials of melatonin in the treatment of CVDs with an emphasis on the molecular mechanisms of action. This review shows that: - nearly all the studies have reported positive effects of melatonin on cardiovascular physiology, and the prevention of damage to the myocardium after heart attack, reperfusion injury, or sepsis. - melatonin can help blood pressure and heart arrhythmia. - some clinical trials indicated that the utilization of melatonin in CVDs is associated with more inconsistencies regarding its cardioprotective effects. Authors conclude that further preclinical and clinical studies are required to better delineate the cardiovascular benefits of melatonin.
Abstract
The pineal gland is a neuroendocrine gland which produces melatonin, a neuroendocrine hormone with critical physiological roles in the circadian rhythm and sleep-wake cycle. Melatonin has been shown to possess anti-oxidant activity and neuroprotective properties. Numerous studies have shown that melatonin has significant functions in cardiovascular disease, and may have anti-aging properties. The ability of melatonin to decrease primary hypertension needs to be more extensively evaluated. Melatonin has shown significant benefits in reducing cardiac pathology, and preventing the death of cardiac muscle in response to ischemia-reperfusion in rodent species. Moreover, melatonin may also prevent the hypertrophy of the heart muscle under some circumstances, which in turn would lessen the development of heart failure. Several currently used conventional drugs show cardiotoxicity as an adverse effect. Recent rodent studies have shown that melatonin acts as an anti-oxidant and is effective in suppressing heart damage mediated by pharmacologic drugs. Therefore, melatonin has been shown to have cardioprotective activity in multiple animal and human studies. Herein, we summarize the most established benefits of melatonin in the cardiovascular system with a focus on the molecular mechanisms of action.
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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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Endocrine and metabolic aspects of the COVID-19 pandemic.
Marazuela, M, Giustina, A, Puig-Domingo, M
Reviews in endocrine & metabolic disorders. 2020;21(4):495-507
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Endocrine and metabolic related diseases such as diabetes and obesity may increase the risk of developing severe Covid-19 and as a result these diseases could be severely affected by Covid-19 infection. This very large review paper looked at over 100 studies and outlined the interrelationship between Covid-19 infection and several endocrine diseases. Diabetes, obesity, pituitary-hypothalamic function, thyroid function, Cushing's syndrome and adrenal function were all reviewed. No aim was stated. Data on individuals with obesity and diabetes indicated an increased risk for severe Covid-19 infection, hospitalisation and mortality. Data surrounding pituitary-hypothalamic function, thyroid function, Cushing's syndrome and adrenal function was less abundant, however neurological issues in Covid-19 patients suggested an involvement of the pituitary and hypothalamus. In lieu of sufficient data the author commented on the possible similarities between severe acute respiratory syndrome coronavirus with the Covid-19 virus. A number of management strategies were discussed such as the use of vitamin D, oxytocin and melatonin, however the authors commented on the lack of data regarding oxytocin and melatonin in Covid-19 patients, but mechanistic data suggested they might be of use. No overall conclusions were drawn on the findings. Clinicians could use this paper to understand how patients with pre-existing endocrine and metabolic conditions may be at a higher risk of more severe Covid-19 and if contracted could exacerbate their pre-existing condition. These patients could require constant monitoring and additional measures to avoid contracting Covid-19. Supplements such as vitamin D, oxytocin or melatonin could be therapeutic, however more data needs to be reviewed.
Abstract
COVID-19 infection has tremendously impacted our daily clinical practice as well as our social living organization. Virtually all organs and biological systems suffer from this new coronavirus infection, either because the virus targets directly specific tissues or because of indirect effects. Endocrine diseases are not an exception and some of endocrine organs are at risk of direct or indirect lesion by COVID-19. Although there is still no evidence of higher predisposition to contract the infection in patients with diabetes and/or obesity, the coexistence of these conditions contributes to a worse prognosis because both conditions confer an impaired immunologic system. Cytokines storm can be amplified by these two latter conditions thereby leading to multisystemic failure and death. Glycaemic control has been demonstrated to be crucial to avoiding long hospital stays, ICU requirement and also prevention of excessive mortality. Endocrine treatment modifications as a consequence of COVID-19 infection are required in a proactive manner, in order to avoid decompensation and eventual hospital admission. This is the case of diabetes and adrenal insufficiency in which prompt increase of insulin dosage and substitutive adrenal steroids through adoption of the sick day's rules should be warranted, as well as easy contact with the health care provider through telematic different modalities. New possible endocrinological targets of COVID-19 have been recently described and warrant a full study in the next future.
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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.