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Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial.
Irwin, MR, Olmstead, R, Bjurstrom, MF, Finan, PH, Smith, MT
Pain. 2023;164(5):1128-1137
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Sleep disturbance is associated with elevated levels of inflammation. Experimental studies have found that even a modest amount of sleep loss activates inflammatory processes. Experimental sleep disruption also induces alterations in sleep architecture including loss of slow wave or N3 sleep and loss of rapid eye movement sleep. The aim of this study was to clarify whether changes in the amount of N3 sleep and cellular inflammation mediate thermal pain sensitivity (i.e., heat pain threshold) in response to experimental sleep disruption. This study was a secondary analysis (assessor-blind) of a randomised controlled trial. The enrolled participants were randomised to 1 of 2 groups: 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA). Participants underwent 2 consecutive nights of US (or FA), followed by a 2-week washout interval in their home environment, and then completed 2 consecutive nights of the opposing sleep condition FA (or US). Results showed that in healthy adults, experimental disruption of sleep due to the administration of FA induced a significant decrease in heat pain threshold, as compared with responses after US. Experimental manipulation of sleep with FA also led to disturbance in sleep continuity and changes in sleep architecture, including loss of N3 sleep. Moreover, in the morning after FA, there was a robust activation of cellular inflammation Authors conclude that the differential loss of N3 sleep and increases in cellular inflammation may be important drivers of pain sensitivity in response to sleep disruption.
Abstract
Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep ( P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α ( P = 0.03), and decreases in hPTH ( P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=-0.15; 95% confidence interval, -0.30 to -0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption.Clinical Trials Registration: NCT01794689.
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Sleep-Opt-In: A Randomized Controlled Pilot Study to Improve Sleep and Glycemic Variability in Adults With Type 1 Diabetes.
Martyn-Nemeth, P, Duffecy, J, Quinn, L, Steffen, A, Baron, K, Chapagai, S, Burke, L, Reutrakul, S
The science of diabetes self-management and care. 2023;49(1):11-22
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Insufficient sleep (insufficient total sleep time) and irregular sleep timing (variability in the occurrence of sleep within a 24-hour period) are increasingly recognized as important contributors to glycaemic control and variability in type 1 diabetes (T1D). The aims of this study were to evaluate the feasibility and acceptability of a sleep intervention (Sleep-Opt-In) targeted for adults with type 1 diabetes with short or irregular sleep and to examine the effects of Sleep-Opt-In on sleep duration and regularity, glucose indices, and patient-reported outcomes. This study was a randomised controlled parallel trial design. Participants (n=14) were randomly assigned to either the Sleep-Opt-In intervention or a Healthy Living attention control group. Results showed that: - Sleep-Opt-In was feasible and acceptable to the target population. - participants with objectively confirmed short or irregular sleep, sleep irregularity improved by 25 minutes on average, whereas sleep duration improved only negligibly (8 minutes). - the control group experienced an increase in sleep duration but no change in sleep regularity. Authors conclude that Sleep-Opt-In is feasible, acceptable, and promising for further evaluation to improve sleep duration or regularity, glucose parameters and important patient reported outcomes of diabetes distress, daytime sleepiness, fatigue and depressive mood in the T1D population.
Abstract
PURPOSE The purpose of this study was to evaluate the feasibility and acceptability of a technology-assisted behavioral sleep intervention (Sleep-Opt-In) and to examine the effects of Sleep-Opt-In on sleep duration and regularity, glucose indices, and patient-reported outcomes. Short sleep duration and irregular sleep schedules are associated with reduced glycemic control and greater glycemic variability. METHODS A randomized controlled parallel-arm pilot study was employed. Adults with type 1 diabetes (n = 14) were recruited from the Midwest and randomized 3:2 to the sleep-optimization (Sleep-Opt-In) or Healthy Living attention control group. Sleep-Opt-In was an 8-week, remotely delivered intervention consisting of digital lessons, sleep tracker, and weekly coaching phone calls by a trained sleep coach. Assessments of sleep (actigraphy), glucose (A1C, continuous glucose monitoring), and patient-reported outcomes (questionnaires for daytime sleepiness, fatigue, diabetes distress, and depressive mood) were completed at baseline and at completion of the intervention. RESULTS Sleep-Opt-In was feasible and acceptable. Those in Sleep-Opt-In with objectively confirmed short or irregular sleep demonstrated an improvement in sleep regularity (25 minutes), reduced glycemic variability (3.2%), and improved time in range (6.9%) compared to the Healthy Living attention control group. Patient-reported outcomes improved only for the Sleep-Opt-In group. Fatigue and depressive mood improved compared to the control. CONCLUSIONS Sleep-Opt-In is feasible, acceptable, and promising for further evaluation as a means to improve sleep duration or regularity in the population of people with type 1 diabetes.
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Changes in objectively measured sleep after a multidisciplinary lifestyle intervention in children with abdominal obesity: A randomized trial.
Catalán-Lambán, A, Ojeda-Rodríguez, A, Marti Del Moral, A, Azcona-Sanjulian, C
Sleep medicine. 2023;109:252-260
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The main factors that contribute to obesity are genetics, excessive energy intake, decreased physical activity, and sedentarism. Sleep duration, sleep timing and chronotype have also recently been recognised as possible risk factors for obesity in children. The aim of this study was to assess the effectiveness of an intervention (usual care vs. intervention group) on sleep quality and its relationship with changes in biochemical and metabolic syndrome related anthropometric parameters. This study was a randomised controlled trial. The multidisciplinary intervention consisted of a two-year program that comprised a 2-month intensive phase with individual and group sessions and a follow-up period at 12 and 24 months. Subjects were randomly assigned to the usual care or intervention group at a ratio of 1:3. Results showed that a lifestyle intervention improved most sleep parameters in children and adolescents with abdominal obesity. In fact, the lifestyle intervention showed a reduction in anthropometric indexes and several biochemical parameters, and improved sleep quality at 2, 12, and 24 months of follow-up. Decreasing sleep latency, awakenings duration and wakefulness after sleep onset (WASO) also accompanied improved sleep efficiency. Authors conclude that their findings add to the growing body of research on the relationship between sleep and metabolic health outcomes in children, emphasizing the need to consider multiple dimensions of sleep beyond just sleep duration.
Abstract
BACKGROUND/OBJECTIVE childhood obesity and sleep disorders have a well-established cross-sectional association, but lifestyle interventions' effects on sleep quality remain under-researched. This study aimed to evaluate the sleep quality of 122 participants (7-16 years) with abdominal obesity after a 2-year necessary lifestyle intervention. PATIENTS/METHODS participants were assigned to either the intervention group (moderate hypocaloric Mediterranean Diet) or the usual care group (standard recommendations on a healthy diet). Sleep was objectively assessed using triaxial accelerometry, and sleep parameters analyzed included latency, efficiency, wake after sleep onset, total time in bed, total sleep time, number of awakenings, and awakening duration. RESULTS AND CONCLUSIONS the results showed that the intervention group significantly improved sleep latency at 12 and 24 months and improved sleep efficiency at 2 and 12 months, compared to the usual care group. Wake after sleep onset and the number of awakenings were significantly reduced at 24 months in the intervention group. Wake after sleep onset and leptin levels were positively associated in all participants. Total time in bed was inversely associated with triglycerides and metabolic score, and total sleep time was inversely associated with leptin, triglycerides, and metabolic score after the 2-month intervention. Triglyceride levels were inversely associated with total time in bed and total sleep time at one year, while the metabolic score was directly associated with wake after sleep onset and the number of awakenings and inversely associated with efficiency. In conclusion, the multidisciplinary intervention in children and adolescents with abdominal obesity reduced anthropometric parameters and improved sleep habits.
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Late, but Not Early, Night Sleep Loss Compromises Neuroendocrine Appetite Regulation and the Desire for Food.
Meyhöfer, S, Chamorro, R, Hallschmid, M, Spyra, D, Klinsmann, N, Schultes, B, Lehnert, H, Meyhöfer, SM, Wilms, B
Nutrients. 2023;15(9)
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Sleep loss has become common in modern societies. In parallel, the prevalence of obesity and metabolic comorbidities, such as type 2 diabetes, are rising worldwide. The aim of this study was to investigate the impact of the specific timing of sleep loss compared to regular sleep on appetite regulation and desire for foods. This study was a randomised, balanced, crossover design on three conditions spaced at least three and at maximum five weeks apart. Fifteen healthy young male participants were included. All participants had a regular sleep–wake cycle during the last four weeks before the experiments, with a minimum of 7 hours sleep per night. Results showed that ‘late-night sleep loss’, but not ‘early-night sleep loss’, elevated ghrelin concentrations, as well as feelings of hunger and appetite, and desire for food during the subsequent morning. Leptin concentrations were not affected by acute sleep loss per se, nor timing of sleep loss. Authors conclude that their findings could be of clinical interest to healthcare practitioners working with sleep deprived individuals, regarding sleep hygiene and appropriate sleep recommendations.
Abstract
OBJECTIVE There is evidence that reduced sleep duration increases hunger, appetite, and food intake, leading to metabolic diseases, such as type 2 diabetes and obesity. However, the impact of sleep timing, irrespective of its duration and on the regulation of hunger and appetite, is less clear. We aimed to evaluate the impact of sleep loss during the late vs. early part of the night on the regulation of hunger, appetite, and desire for food. METHODS Fifteen normal-weight ([mean ± SEM] body-mass index: 23.3 ± 0.4 kg/m2) healthy men were studied in a randomized, balanced, crossover design, including two conditions of sleep loss, i.e., 4 h sleep during the first night-half ('late-night sleep loss'), 4 h sleep during the second night-half ('early-night sleep loss'), and a control condition with 8h sleep ('regular sleep'), respectively. Feelings of hunger and appetite were assessed through visual analogue scales, and plasma ghrelin and leptin were measured from blood samples taken before, during, and after night-time sleep. RESULTS Ghrelin and feelings of hunger and appetite, as well as the desire for food, were increased after 'late-night sleep loss', but not 'early-night sleep loss', whereas leptin remained unaffected by the timing of sleep loss. CONCLUSIONS Our data indicate that timing of sleep restriction modulates the effects of acute sleep loss on ghrelin and appetite regulation in healthy men. 'Late-night sleep loss' might be a risk factor for metabolic diseases, such as obesity and type 2 diabetes. Thereby, our findings highlight the metabolic relevance of chronobiological sleep timing.
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Intake of Lactiplantibacillus plantarum HEAL9 Improves Cognition in Moderately Stressed Subjects: A Randomized Controlled Study.
Önning, G, Montelius, C, Hillman, M, Larsson, N
Nutrients. 2023;15(15)
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It is thought that there is a bidirectional communication pathway between the gut microbiota and the brain, known as the gut-brain axis. Stress, anxiety and low mood and the hormones produced when experiencing these have been shown to be improved by the introduction of healthy gut microbiota through probiotic use. As such, the use of probiotics may be of benefit to mental health problems. This randomised control trial of 129 individuals with moderate stress aimed to determine the effect of one probiotic strain Lactoplantibacillus plantarum HEAL9 (LPHEAL9) on the gut-brain axis. The results showed that following supplementation for 12 weeks, cognitive function was significantly improved compared to placebo and there was an improvement in the feelings of confusion, anger, and depression. There was a trend for improved sleep for individuals given LPHEAL9, however this was not significantly better than individuals given placebo. There were no benefits to perceived stress following LPHEAL9 supplementation. It was concluded that LPHEAL9 improved cognitive function compared to placebo and this may be due to improved mood and sleep. This study could be used by healthcare professionals to specifically recommend LPHEAL9 to individuals with stress, anxiety, and low mood.
Abstract
BACKGROUND The usage of probiotics has expanded beyond the areas of gut and immune health improvement. Several studies have shown the positive impact associated between probiotics and stress, cognition, and mood; a relationship referred to as the gut-brain axis. METHOD The aim of this exploratory study was to evaluate the effect of the probiotic strain Lactiplantibacillus plantarum HEAL9 (LPHEAL9) on the gut-brain axis in subjects with moderate stress. One hundred and twenty-nine subjects aged 21-52 years completed the study, randomized to consume either LPHEAL9 (n = 65) or placebo (n = 64) for 12 weeks. RESULTS Perceived stress and awakening cortisol were significantly reduced over time in both groups. A significant improvement in four cognition tests after consumption of LPHEAL9 compared to placebo was observed (rapid information processing test, numeric working memory test, paired associated learning, and word recall, p < 0.05). There was a tendency for a significantly better improvement in the LPHEAL9 group for three mood subscales (Confusion-Bewilderment, Anger-Hostility, and Depression-Dejection) and for fewer subjects with poor sleep in the LPHEAL9 group compared to placebo (p < 0.10). CONCLUSIONS Intake of LPHEAL9 significantly improved cognitive functions compared to the placebo, potentially by ameliorating aspects of mood and sleep.
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Probiotic intervention benefits multiple neural behaviors in older adults with mild cognitive impairment.
Fei, Y, Wang, R, Lu, J, Peng, S, Yang, S, Wang, Y, Zheng, K, Li, R, Lin, L, Li, M
Geriatric nursing (New York, N.Y.). 2023;51:167-175
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Mild cognitive impairment (MCI) is an intermediate stage between the normal cognitive changes associated with aging and dementia. Recent research shows that probiotic supplementation can regulate the balance of the intestinal flora and improve self-care ability and cognition in older adults. The aim of this study was to explore the effects and the underlying mechanisms of probiotic supplementation on MCI older adults. This study was a pilot randomised controlled trial (RCT) to investigate the effects of 12 weeks of probiotic supplementation in patients with MCI. Participants were randomly assigned to the probiotic group or control group. Results demonstrated the beneficial effects of probiotic supplementation intervention on multiple neural behaviours by regulating the homeostasis of the gut microbiota in older MCI patients. Authors conclude that this study provided new insights into nutrition interventions in older MCI patients. However, further trials with larger cohorts should be conducted to confirm the effects of probiotic intervention in MCI patients and provide more clinical evidence for its preventive and therapeutic effects.
Abstract
Probiotic supplements were shown to improve cognitive function in Alzheimer's disease (AD) patients. However, it is still unclear whether this applies to older individuals with mild cognitive impairment (MCI). We aimed to explore the effects of probiotic supplementation on multiple neural behaviors in older adults with MCI. Forty-two MCI patients (age > 60 years) were randomly divided into two groups and consumed either probiotics (n=21) or placebo (n=21) for 12 weeks. Various scale scores, gut microbiota measures and serological indicators were recorded pre- and posttreatment. After 12 weeks of intervention, cognitive function and sleep quality were improved in the probiotic group compared with those in the control group, and the underlying mechanisms were associated with changes in the intestinal microbiota. In conclusion, our study demonstrated that probiotic treatment enhanced cognitive function and sleep quality in older MCI patients, thus providing important insights into the clinical prevention and treatment of MCI.
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Essential Hypertension and Oxidative Stress: Novel Future Perspectives.
Franco, C, Sciatti, E, Favero, G, Bonomini, F, Vizzardi, E, Rezzani, R
International journal of molecular sciences. 2022;23(22)
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High blood pressure is one of the main risk factors for cardiovascular disease and a significant contributor to the development of strokes, heart attacks, and heart and kidney failure leading to early disability and reduced life expectancy. Essential or primary hypotension makes up 95% of high blood pressure cases, which is abnormally elevated blood pressure that is not a result of any other medical condition. Essential hypertension arises from various factors such as diet, lifestyle, environmental and genetic influences. Despite many available medications, not all patients attain well-managed blood pressure levels. Unmanaged high blood pressure can, over time, lead to narrowing and stiffening of the blood vessels and ultimately to structural and functional changes in the blood tissues. In part, this is mediated by oxidative stress, changes in antioxidant capacity and chronic low-grade inflammation, which damage the blood vessels' endothelial tissue and result in vascular stiffness. Melatonin is one of the most potent antioxidants found in nature and has been studied in short-term trials for its blood pressure lowering, antioxidant and vascular protective effects. This small open-label randomised study sought to get a better understanding of the long-term use of melatonin. Initially, the study assessed endothelial tissue damage, oxidative status and vascular stiffness in patients with high blood pressure. Subsequently, some of the participants received a low-dose melatonin supplement (1 mg/day) for one year, whilst being monitored for clinical and structural vascular changes. The study included 23 patients and 14 in the final analysis. After one year, the results showed a significant improvement in arterial stiffness in the melatonin group (11) and an improvement in endothelial tissue function, though the latter was not at statistically significant levels. Improvement in arterial stiffness seemed to be linked to a reduction in total antioxidant capacity (TAC). These findings suggest that melatonin can contribute to restoring oxidative balance in blood plasma, which reflects improved arterial stiffness. The study also demonstrated that besides being a well-tolerated intervention, melatonin also has clinical benefits even when administered at lower doses than normal.
Abstract
Among cardiovascular diseases, hypertension is one of the main risk factors predisposing to fatal complications. Oxidative stress and chronic inflammation have been identified as potentially responsible for the development of endothelial damage and vascular stiffness, two of the primum movens of hypertension and cardiovascular diseases. Based on these data, we conducted an open-label randomized study, first, to evaluate the endothelial damage and vascular stiffness in hypertense patients; second, to test the effect of supplementation with a physiological antioxidant (melatonin 1 mg/day for 1 year) in patients with essential hypertension vs. hypertensive controls. Twenty-three patients of either gender were enrolled and randomized 1:1 in two groups (control and supplemented group). The plasmatic total antioxidant capacity (as a marker of oxidative stress), blood pressure, arterial stiffness, and peripheral endothelial function were evaluated at the beginning of the study and after 1 year in both groups. Our results showed that arterial stiffness improved significantly (p = 0.022) in supplemented patients. The endothelial function increased too, even if not significantly (p = 0.688), after 1 year of melatonin administration. Moreover, the supplemented group showed a significative reduction in TAC levels (p = 0.041) correlated with the improvement of arterial stiffness. These data suggest that melatonin may play an important role in reducing the serum levels of TAC and, consequently, in improving arterial stiffness.
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Resistance Training Improves Sleep and Anti-Inflammatory Parameters in Sarcopenic Older Adults: A Randomized Controlled Trial.
de Sá Souza, H, de Melo, CM, Piovezan, RD, Miranda, REEPC, Carneiro-Junior, MA, Silva, BM, Thomatieli-Santos, RV, Tufik, S, Poyares, D, D'Almeida, V
International journal of environmental research and public health. 2022;19(23)
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Sleep is a behavioural state that is characterised by relative immobility and reduced responsiveness and can be distinguished from coma or anaesthesia by its rapid reversibility. Sleep has a number of functions, which include metabolism modulation and the repair of organic tissue. The aim of this study was to investigate the effects of a 12-week resistance exercise training (RET) protocol on subjective and objective sleep parameters in older individuals with sarcopenia and the possible role of inflammation status in this process. This study was a randomised, placebo-controlled, parallel-group study. Participants were randomly assigned to one of the two groups; RET group or control group. Results showed that a 12-week RET protocol simultaneously improved muscle strength. In addition to the increase in overall subjective sleep quality, there was also a reduction in sleep latency, apnoea-hypopnea index, and insomnia severity, as well as an increase in deeper stage 3 sleep (slow-wave sleep) in the RET group in comparison with the CTL group. Authors conclude that future studies are necessary to elucidate how different age groups and genders, with and without sarcopenia, can present specific muscle and sleep responses to potentially anti-inflammatory interventions, such as physical exercise.
Abstract
Sleep and exercise have an important role in the development of several inflammation-related diseases, including sarcopenia. Objective: To investigate the effects of 12 weeks of resistance exercise training on sleep and inflammatory status in sarcopenic patients. Methods: A randomized controlled trial comparing resistance exercise training (RET) with a control (CTL) was conducted. Outcomes were obtained by physical tests, polysomnography, questionnaires, isokinetic/isometric dynamometry tests, and biochemical analysis. Results: Time to sleep onset (sleep latency) was reduced in the RET group compared to the CTL group (16.09 ± 15.21 vs. 29.98 ± 16.09 min; p = 0.04) after the intervention. The percentage of slow-wave sleep (N3 sleep) was increased in the RET group (0.70%, CI: 7.27−16.16 vs. −4.90%, CI: 7.06−16.70; p = 0.04) in an intention to treat analysis. Apnea/hour was reduced in the RET group (16.82 ± 14.11 vs. 7.37 ± 7.55; p = 0.001) and subjective sleep quality was improved compared to the CTL (−1.50; CI: 2.76−6.14 vs. 0.00; CI: 1.67−3.84 p = 0.02) in an intention-to-treat analysis. Levels of interleukin-10 (IL-10) (2.13 ± 0.80 vs. 2.51 ± 0.99; p < 0.03) and interleukin-1 receptor antagonist (IL-1ra) (0.99 ± 0.10 vs. 0.99 ± 0.10 ng/mL; p < 0.04; delta variation) were increased in the RET group. Conclusions: RET improves sleep parameters linked to muscle performance, possibly due to an increase in anti-inflammatory markers in older sarcopenic patients.
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Effect of Docosahexaenoic Acid and Eicosapentaenoic Acid Supplementation on Sleep Quality in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial.
Yokoi-Shimizu, K, Yanagimoto, K, Hayamizu, K
Nutrients. 2022;14(19)
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Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are unsaturated Omega-3 fatty acids, primarily found in fish and seafood. The fatty acids fulfil many vital roles in the body, such as creating cell membranes, supporting brain functions and being associated with many disease-protective benefits. These fatty acids also influence sleep in children and young adults, but less is known about their effect in older people. Hence, this Japanese study investigated the impact of EPA and DHA on sleep quality in people above the age of ≥ 45. 66 males and females with poor sleep participated in this randomized, placebo-controlled, double-blinded, parallel-grouped study. They either received 860 mg of combined DHA/EPA per day (576 mg DHA/284 mg EPA) or a placebo of corn oil for 12 weeks. The outcome was assessed subjectively via sleep quality and mood questionnaires, as well as objectively with a sleep scanner and blood samples. Blood samples and blood pressure where also monitored as a safety measure. Upon completion of the study there was a subjective improvement, which was backed-up by the results of the sleep scanner. This study confirmed that DHA/EPA improves sleep quality in the middle aged and older population and does so at doses lower than those administered in previous studies. The authors had set the daily minimum intake of DHA/EPA at 860 mg/day for this trial, as previous research showed no effects at lower doses. They also noted that poor responders tended to be people with pre-existing conditions or those who were pregnant. This population may require higher dosages of DHA/EPA than healthy patients. Overall, the intervention was well tolerated. Ensuring adequate DHA and EPA levels and intake could be part of nutritional strategies for sleep support.
Abstract
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-omega-3 fatty acids with various functions-influence sleep in children and young adults. However, only limited studies on their effects on sleep in middle- and old-aged adults have been reported. Therefore, we investigated the effects of DHA and EPA on sleep quality in subjects aged ≥ 45 years. We performed a randomized, placebo-controlled, double-blinded, parallel-grouped study, in which we randomly assigned 66 healthy Japanese males and females. Each individual received six 480 mg capsules containing 576 mg DHA and 284 mg EPA per day (DHA/EPA group, n = 33), or corn oil (placebo group, n = 33), for 12 weeks. Before and after the intervention, the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA) and the sleep state test were conducted. In the DHA/EPA group, factor III (frequent dreaming) scores among the OSA-MA scores were significantly improved compared to the placebo group. Additionally, sleep state tests revealed that sleep efficiency improved in the DHA/EPA group. To our knowledge, this study is the first to report that DHA/EPA improves sleep quality in middle- and old-aged individuals, even at doses lower than those administered in previous studies.
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Sleep Disturbance Affects Immune Factors in Clinical Liver Cancer Patients.
Wang, Z, Wang, Y, Huang, J, Xu, J, Chen, F, Zhu, Z, Gao, L, Qin, J, Liu, B, Liang, C
Current oncology (Toronto, Ont.). 2022;29(10):7943-7952
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Many studies have shown that sleep disorders promote tumor growth and can impair immunity at the cellular level. There is however a lack of research in patients with liver cancer. The aim of this study was the asses the quality of sleep and the prevalence of disturbed sleep in patients with liver cancer and to explore whether sleep quality influences immune factors. 210 patients with liver cancer were randomly divided into 2 groups: HBV (Hepatitis B virus) cirrhosis and non-HBV cirrhosis. Their sleep quality was evaluated using a questionnaire and then the patients were divided into 2 groups according to these scores. The association between sleep disturbances and immune factors was analysed by logistic regression models. Over half the patient experienced poor sleep quality. Sleep disturbances were higher in patients with liver cancer of non-HBV cirrhosis than with that coming from the HBV virus. A rise in CD3+ T cells and a reduction in NK cells are associated with sleep disturbances in patients with non-HBV cirrhosis liver cancer. Medicines that can promote sleep and therefore improve immune function might be beneficial. Non-pharmacological sleep interventions to improve sleep quality, should be a safer choice where there are complex drug side effects.
Abstract
BACKGROUND Sleep-wake disturbance is prevalent in patients with liver cancer, but there is no direct evidence of its association and related biological mechanisms. Our study was to assess quality of sleep and to describe prevalence of sleep disturbances in patients with different etiologies of liver cancer, especially to explore whether sleep quality influences immune factors. METHODS A total of 210 patients with liver cancer from August 2015 to December 2015 were randomly divided into two groups including HBV cirrhosis and non-HBV cirrhosis. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate their sleep quality, and then 202 patients enrolled in this study were divided into two groups according to their PSQI scores: PSQI ≤ 5 and PSQI > 5. The association between sleep disturbances and immune factors was analyzed by logistic regression models. RESULTS A total of 56.9% of liver cancer patients experienced poor sleep quality (PSQI > 5). The prevalence of sleep disturbances was significantly higher in patients with liver cancer of non-hepatitis B virus (HBV) cirrhosis than with that evolving from HBV cirrhosis (66.7% vs. 50%, p = 0.018). In non-HBV cirrhosis liver cancer patients, the PSQI > 5 group had a higher percentage of CD3+ T cells (71.06 ± 11.07 vs. 63.96 ± 14.18, p = 0.014) and lower natural killer (NK) cells (14.67 ± 9.65 vs. 20.5 ± 10.77, p = 0.014) compared with patients with PSQI ≤ 5. Logistic regression further confirmed that liver cancer patients without HBV cirrhosis are more prone to experience poor sleep with increased CD3+ T cells (OR = 1.07, 95% CI = 1.01-1.13, p = 0.030) and decreased NK cells (OR = 0.92, 95% CI = 0.85-0.98, p = 0.014). Our results indicate that increased CD3+ T cells and decreased NK cells are both associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis. CONCLUSIONS Most liver cancer patients suffer from sleep disturbances, especially evolving from non-HBV cirrhosis. A rise in CD3+ T cells and a reduction in NK cells are associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis.