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Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle interventions: secondary analyses of the "MIMOSA" randomized clinical trial.
Georgoulis, M, Yiannakouris, N, Kechribari, I, Lamprou, K, Perraki, E, Vagiakis, E, Kontogianni, MD
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2022;18(5):1251-1261
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Plain language summary
Obstructive sleep apnoea (OSA) represents one of the most common and serious sleep-related breathing disorders. Excess body weight has emerged as the strongest modifiable predictor of the onset and severity of OSA. The aim of this study was to explore the dose-response relationship between the degree of weight loss and improvements in OSA severity. This study is a secondary analysis of the Mediterranean diet/lifestyle Intervention for the Management of Obstructive Sleep Apnea (MIMOSA) study, which was designed as a single-centre, single-blind, parallel, randomised, controlled clinical trial. Results show that respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Authors conclude that their findings indicate a dose-response relationship between the degree of weight loss and improvement in OSA severity and symptoms. However, further research is needed to gather more data on the optimal degree of weight loss and appropriate weight-loss interventions for managing the wide spectrum of OSA severity to guide clinical practice.
Expert Review
Conflicts of interest:
None
Take Home Message:
Important from a public health perspective:
- This study has confirmed that even a small degree of weight loss can have a beneficial effect on respiratory events and oxygen desaturation in moderate-to-severe OSA, but clinicians should preferably aim at a ≥ 5% weight loss, and ideally a ≥ 10% weight loss, to achieve clinically meaningful reductions in OSA severity.
Evidence Category:
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X
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
OSA represents one of the most common and serious sleep-related breathing disorders, with a high worldwide prevalence of almost 1 billion people. OSA has numerous well-established cardiometabolic consequences.
The authors highlight that weight loss is essential for obstructive sleep apnea (OSA) management. However, the optimal degree of weight loss for improving OSA severity or eliminating sleep-disordered breathing has not been extensively studied. The aim of this study was to explore the dose-response relationship between the degree of weight loss and improvements in OSA severity.
Methods
This is a secondary analysis of the Mediterranean diet/lifestyle Intervention for the Management of Obstructive Sleep Apnea (MIMOSA) study. This study was designed as a single-center, single-blind, parallel, randomised, controlled clinical trial to evaluate the effectiveness of a weight-loss Mediterranean dietary/lifestyle intervention on managing OSA.
This 6-month long clinical trial included 180 adult, overweight/obese moderate-to-severe OSA patients (45 patients per study group plus a 29% dropout rate). All patients were prescribed the standard of care continuous positive airway pressure (CPAP) therapy and were randomised to 3 arms: standard care; Mediterranean diet; Mediterranean lifestyle
Based on percent change in weight at 6 months, participants were categorised into a weight-stable/gain (WS/GG) group or one of 3 weight-loss groups (WLG): < 5%WLG; 5%–10%WLG; ≥ 10%WLG. Polysomnographic data and OSA symptoms were also evaluated preintervention and postintervention.
Results
Results confirm a dose-response relationship between the degree of weight loss achieved through a dietary/lifestyle intervention and improvements in OSA severity.
- Respiratory events and oximetry indices improved only in patients who lost weight. Improvements were proportional to the degree of weight loss.
- Median percent change in apnea-hypopnea index (AHI) was −11.7%, − 37.9%, and − 49.3% in the < 5%WLG, 5%–10%WLG, and ≥ 10%WLG, respectively (P < .001).
- Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use–adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23–0.87) in the 5%–10%WLG and 0.32 (0.17–0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22–0.82]).
- Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss.
- The dose-response relationship between weight loss and improvement in OSA severity was evident regardless of self-reported CPAP use.
Conclusions
The authors conclude that even a < 5% weight loss was sufficient for improvements in respiratory events and oximetry indices, but the prevalence of severe OSA reduced only after a ≥ 5% weight loss, and patients achieving a ≥ 10% weight loss exhibited the greatest benefits compared to weight-stable/gain patients.
Clinical practice applications:
These findings might be useful for Nutritional Therapists and Clinical Practitioners:
- Clinicians should aim for a ≥ 5% weight loss, and ideally a ≥ 10% weight loss, to achieve clinically meaningful reductions in OSA severity.
- Improvements after weight loss were significant even though a healthy body weight was not achieved.
Considerations for future research:
- The study sample consisted of predominantly male, overweight, otherwise healthy patients with moderate-to-severe OSA. Therefore, findings cannot be generalised to the whole OSA population and further research is required with broader, diverse, study samples.
- 6 months is a short duration period, therefore longer trials are required.
- Self-reported CPAP use by participants is a limitation of this study. Further robust analysis methods should be considered for future trials.
- Participants were advised to abstain from CPAP therapy for 2 days prior to the follow-up PSG but this was not evaluated or confirmed in this study and should be in future research.
Abstract
STUDY OBJECTIVES Lifestyle-induced weight loss is a complementary therapeutic approach for obstructive sleep apnea (OSA). We aimed at identifying the dose-response relationship between weight loss and OSA severity improvement. METHODS This is a secondary analysis of a 6-month clinical trial in 180 adult, overweight/obese moderate-to-severe OSA patients. Participants were randomized to a standard care, a Mediterranean diet, or a Mediterranean lifestyle arm. All patients were prescribed with continuous positive airway pressure (CPAP), while intervention arms additionally participated in a weight-loss dietary/lifestyle intervention. Based on percent change in weight at 6 months, participants were categorized into a weight-stable/gain (WS/GG) group or 3 weight-loss groups (WLG): < 5%WLG, 5%-10%WLG, and ≥ 10%WLG. Polysomnographic data and OSA symptoms were evaluated preintervention and postintervention. RESULTS Respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Median percent change in apnea-hypopnea index (AHI) was -11.7%, - 37.9%, and - 49.3% in the < 5%WLG, 5%-10%WLG, and ≥ 10%WLG, respectively (P < .001). Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use-adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23-0.87) in the 5%-10%WLG and 0.32 (0.17-0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22-0.82]). Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss. CONCLUSIONS Even a < 5% weight loss can reduce respiratory events, but a ≥ 5% and ideally ≥ 10% weight loss is necessary for reducing the prevalence of severe OSA. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Name: Mediterranean Diet/Lifestyle Intervention in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02515357; Identifier: NCT02515357. CITATION Georgoulis M, Yiannakouris N, Kechribari I, et al. Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle intervention: secondary analyses of the "MIMOSA" randomized clinical trial. J Clin Sleep Med. 2022;18(5):1251-1261.
2.
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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Plain language summary
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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X
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.
3.
Effect of sleep duration on dietary intake, desire to eat, measures of food intake and metabolic hormones: A systematic review of clinical trials.
Soltanieh, S, Solgi, S, Ansari, M, Santos, HO, Abbasi, B
Clinical nutrition ESPEN. 2021;45:55-65
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Plain language summary
Adequate sleep is crucial to health. Yet, sleep disturbances have become very common in modern societies. A lack of sleep is linked to increased risk for several chronic diseases such as diabetes, high blood pressure, metabolic syndrome and cardiovascular disease. Furthermore, appetite-regulating hormones can be disrupted by sleep shortages, which is thought to drive chronic overeating, leading to weight gain, obesity and its associated health consequences. This review examined the relationship between sleep duration and food consumption and energy intake, whilst also monitoring changes in body weight and appetite-regulating hormones. The review encompassed 50 randomized controlled trials (RCTs) with 3387 participants, including 1079 children and adolescents and 2308 adults. The findings suggested that sleep shortages contribute to significant increases in calorie intake, fat intake, increased body weight, appetite, hunger, more frequent eating and bigger portion sizes. In this review lack of sleep did not change protein and carbohydrate intake. Nor did lack of sleep make people exert more or less energy overall, however, a variance amongst ethnic groups was observed here. There was not enough evidence for changes in metabolic rate, so the review assumed no significant effect. When viewed collectively, the appetite-regulating hormones of leptin and ghrelin, the stress hormone cortisol and the sugar-regulating hormone insulin were not significantly influenced by sleep duration. However, there seemed to be a wide variance of outcomes when looking at individual studies' results. In conclusion, the authors reiterated the importance of sleep for health maintenance, advocating for a minimum of 7 hours of sleep per day for adults and that, despite busy modern lifestyles, sleep optimisation strategies should be prioritised. Less than 6 hours of sleep per day increases the risk of health consequences, like weight gain and metabolic disorders and sleep management should be considered part of their treatment protocols.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Reduced sleep duration may serve as a mediator for weight gain in part due to increased appetite, increased fat intake and disruptions to energy balance.
- Enhancing sleep quality may serve to support weight loss protocols.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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
Short sleep duration and disruptions to circadian rhythm have been associated with being overweight and obese. It has been suggested that sleep restriction may interfere with appetite regulating hormones leading to increased appetite and disrupted energy balance.
This study aimed to systematically review studies exploring the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics and appetite-regulating hormones.
Methods
This systematic review included 50 randomised controlled trials including 3,387 participants.
Results
Energy intake
- 13 out of 30 the included studies found that short sleep conditions led to higher energy intake.
- 1 study identified that sleep restriction resulted in a 15.3% and 9.2% increase in energy intake in both women and men.
- 3 studies noted that prolonging sleep duration led to a reduction in energy intake.
- 1 study reported a reduction in energy intake after sleep restriction (P=0.031).
Fat consumption
- 9 studies out of 22 identified a significant association between short sleep and increased fat consumption.
- 7 studies did not identify a difference between groups.
- 3 studies noted a decrease in fat consumption following prolonged sleep (P<0.001, P<0.05, P=0.04).
Hunger and appetite
- 11 studies out of 17 observed that sleep restriction resulted in increased hunger ratings.
- 3 studies found an increase in appetite following sleep restriction (P<0.01) with 3 finding no difference..
- 1 study reported a decrease in appetite following sleep restriction.
- 2 studies noted that portion sizes increased as a result of sleep restriction (P<0.01).
- 1 study reported an increase in eating occasions following restricted sleep compared to habitual sleep (6.08 vs 4.96).
Body weight
- 6 studies out of 14 found no effect of sleep loss on body weight.
- 4 studies identified that sleep restriction led to weight gain (P<0.001, P<0.05, P=0.14, P=0.031).
- 2 studies reported weight loss following increased sleep duration (P<0.001).
Ghrelin and leptin
- Leptin and ghrelin levels were generally not found to be influenced by sleep duration, with the exception of a few studies.
Clinical practice applications:
Reduced sleep duration may promote weight gain by:
- Increasing energy intake.
- Increasing fat consumption.
- Increasing hunger and appetite.
- Increasing portion sizes and eating occasions.
Prolonging sleep duration may support weight loss by:
- Reducing energy intake.
- Reducing fat intake.
Considerations for future research:
- Mixed results on the influence of sleep restriction on appetite regulating hormones, leptin and ghrelin.
- Some studies noted the negative impact of sleep restriction on leptin and ghrelin concentrations, collectively shortened sleep duration did not appear to influence these hormones.
- Further sleep restriction studies exploring additional appetite regulating hormones and neuropeptides and the reward system may provide a more definitive understanding of the underlying mechanism for reduced sleep duration to disrupt the appetite and energy balance and promote weight gain.
Abstract
BACKGROUND AND AIMS Sleep, as well as diet and physical activity, plays a significant role in growth, maturation, health, and regulation of energy homeostasis. Recently, there is increasing evidence indicating a possible causal association between sleep duration and energy balance. We aimed to examine the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics, and appetite-regulating hormones by randomized controlled trials (RCTs). METHODS Electronic literature searches were conducted on Medline, Web of Science, and Google Scholar until July 2020. The search was conducted with the following words: "Sleep Duration", "Circadian Rhythm", "Sleep Disorders" in combination with "Obesity", "Overweight", "Abdominal Obesity", "Physical Activity", "Energy Intake", "Body Mass Index", "Lipid Metabolism", "Caloric Restriction", Leptin, "Weight Gain", and "Appetite Regulation" using human studies.methods RESULTS After screening 708 abstracts, 50 RCTs (7 on children or adolescents and 43 on adults) were identified and met the inclusion criteria. In general, the findings suggested that sleep restriction may leads to a significant increment in energy intake, fat intake, body weight, appetite, hunger, eating occasions, and portion size, while protein and carbohydrate consumption, total energy expenditure, and respiratory quotient remained unaffected as a result of sleep restriction. Serum leptin, ghrelin, and cortisol concentrations were not influenced by sleep duration as well. CONCLUSION Insufficient sleep can be considered as a contributing factor for energy imbalance, weight gain, and metabolic disorders and it is suggested that to tackle disordered eating it may be necessary to pay more attention to sleep duration.