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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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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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Usefulness of a Lifestyle Intervention in Patients With Cardiovascular Disease.
Broers, ER, Gavidia, G, Wetzels, M, Ribas, V, Ayoola, I, Piera-Jimenez, J, Widdershoven, JWMG, Habibović, M
The American journal of cardiology. 2020;125(3):370-375
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Modifiable (behavioural) risk factors such as sedentary lifestyle and low sleep efficiency, are associated with increased mortality risk and disease progression in individuals with cardiovascular disease. The main aim of this study was to evaluate changes in objectively measured lifestyle and health data derived from wearable devices. This study was part of an international, multicenter randomized controlled trial, the Do Cardiac Health Advanced New Generation Ecosystem 2 study. Only the participants (n=70) randomised to the intervention group were analysed. The participants received the devices to monitor their lifestyle and health parameters. Results indicate significant changes over time in the number of steps and activity level. No significant improvement over time was observed in other outcome measures (i.e., blood pressure, weight, and sleep efficiency). Secondary analysis showed demographic (gender, nationality, marital status), clinical (co-morbidities, heart failure), and psychological (anxiety, depression) profiles that were associated with lifestyle measures. Authors conclude that a personalised approach might be the way forward in order to improve health outcomes in the future.
Abstract
The importance of modifying lifestyle factors in order to improve prognosis in cardiac patients is well-known. Current study aims to evaluate the effects of a lifestyle intervention on changes in lifestyle- and health data derived from wearable devices. Cardiac patients from Spain (n = 34) and The Netherlands (n = 36) were included in the current analysis. Data were collected for 210 days, using the Fitbit activity tracker, Beddit sleep tracker, Moves app (GPS tracker), and the Careportal home monitoring system. Locally Weighted Error Sum of Squares regression assessed trajectories of outcome variables. Linear Mixed Effects regression analysis was used to find relevant predictors of improvement deterioration of outcome measures. Analysis showed that Number of Steps and Activity Level significantly changed over time (F = 58.21, p < 0.001; F = 6.33, p = 0.01). No significant changes were observed on blood pressure, weight, and sleep efficiency. Secondary analysis revealed that being male was associated with higher activity levels (F = 12.53, p < 0.001) and higher number of steps (F = 8.44, p < 0.01). Secondary analysis revealed demographic (gender, nationality, marital status), clinical (co-morbidities, heart failure), and psychological (anxiety, depression) profiles that were associated with lifestyle measures. In conclusion results showed that physical activity increased over time and that certain subgroups of patients were more likely to have a better lifestyle behaviors based on their demographic, clinical, and psychological profile. This advocates a personalized approach in future studies in order to change lifestyle in cardiac patients.