Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis. Melatonin reduces oxidative stress in surgical neonates. Short- but Not Long-Term Melatonin Administration Reduces Central Levels of Brain-Derived Neurotrophic Factor in Rats with Inflammatory Pain Analgesic and antihyperalgesic effects of melatonin in a human inflammatory pain model: a randomized, double-blind, placebo-controlled, three-arm crossover study The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial Melatonin Supplementation May Improve the Outcome of Patients with Hemorrhagic Stroke in the Intensive Care Unit Effects of blackcurrant-based juice on atherosclerosis-related biomarkers in cultured macrophages and in human subjects after consumption of a high-energy meal. Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study. Efficacy of melatonin in the treatment of endometriosis: A phase II, randomized, double-blind, placebo-controlled trial Pain in neonatal intensive care: role of melatonin as an analgesic antioxidant. Supplementation With Fatty Acids Influences the Airway Nitric Oxide and Inflammatory Markers in Patients With Cystic Fibrosis A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women. Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury Utility of melatonin to treat surgical stress after major vascular surgery--a safety study. Effect of vitamin D supplementation on inflammation: protocol for a systematic review Neurocognitive performance, subjective well-being, and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder: a randomized clinical trial of add-on melatonin versus placebo Soft gel capsules improve melatonin’s bioavailability in humans Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease. The effects of L-tryptophan and melatonin on selected biochemical parameters in patients with steatohepatitis. Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases. Circulating fibronectin to C-reactive protein ratio and mortality: a biomarker in COPD? Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. Anti-inflammatory and antioxidant effect of ginger in tuberculosis
Multiple sclerosis ( MS ) is a chronic inflammatory disease , which leads to focal plaques of demyelination and tissue injury in the central nervous system ( CNS ) . Neuroinflammation and oxidative stress are involved in the pathogenesis of MS , promoting tissue damage and demielinization . Current research findings suggest that melatonin has antioxidant and neuroprotective effects . The aim of this study was to evaluate the efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing-remitting multiple sclerosis ( RRMS ) . 36 patients diagnose with RRMS treated with Interferon β-1b ( IFNβ-1b ) were enrolled in a double bind , r and omized , placebo controlled trial . The experimental group received orally 25 mg/d of melatonin for 6 months . After melatonin administration , we observed a significant decrease in serum concentration of pro-inflammatory cytokines and oxidative stress markers ; 18 % for TNF-α ( p < 0.05 ) , 34.8 % for IL-1β ( p < 0.05 ) , 34.7 % for IL-6 ( p < 0.05 ) , 39.9 % for lipoperoxides ( LPO ) ( p < 0.05 ) and 24 % for nitric oxide catabolites ( NOC ) levels ( p < 0.05 ) , compared with placebo group . No significant difference in clinical efficacy outcomes were found between groups . Melatonin treatment was well tolerated and we did not observe significant differences in rates of side effects between the two groups . We concluded that melatonin administration during 6 months period is effective in reducing levels of serum pro-inflammatory cytokines and oxidative stress markers in patients with RRMS . These data support future studies evaluating the safety and effectiveness of melatonin supplementation in RRMS patients BACKGROUND / PURPOSE Cytokines are inflammatory mediators found in the circulation after surgery . Newborns have less protection against oxidation and are very susceptible to free radical oxidative damage . Melatonin has been reported recently to reduce oxidative stress in neonates with sepsis , asphyxia , and respiratory distress . The aim of this study has been to determine if melatonin would lower interleukin (IL)-6 , IL-8 , tumor necrosis factor alpha ( TNF-alpha ) and nitrite/nitrate ( NOx ) levels and modify serum inflammation parameters , improving the clinical course of surgical neonates . METHODS Ten newborns ( group 1 ) , 5 with surgical malformations and respiratory distress ( group 1a ) and 5 with isolated abdominal surgical malformations ( group 1b ) received a total of 10 doses of melatonin ( 10 mg/kg ) at defined times interval for 72 hours . The treatment was started within 3 hours after the end of surgery . Ten surgical neonates ( group 2 ) , did not receive melatonin .  Twenty healthy neonates ( group 3 ) served as control . Blood sample s were collected at the end of operation ; before treatment with the antioxidant ; and 24 hours 72 hours , and 7 days after start of treatment with melatonin or placebo , respectively . RESULTS Postoperative value of cytokines and NOx levels of groups 1 and 2 were significantly higher than group 3 . Compared with group 1b , group 2 displayed significantly higher cytokines and NOx levels at 24 hours , 72 hours , and at 7 days . In group 1a the immediate postoperative values of cytokines were significantly higher than group 1b and group 2 , but a significant improvement was observed after administration of melatonin with significantly lower levels of IL-6 and IL-8 with respect to group 2 . An improvement of clinical outcome was observed by progressive reduction of clinical parameters of inflammation . CONCLUSIONS Melatonin reduces cytokines and NOx levels showing potent antioxidant properties with improvement in clinical outcome . Further studies are warranted to define , on larger numbers , the role of melatonin in surgical patients Objective : To evaluate the effect of short- and long-term administration of melatonin on central brain-derived neurotrophic factor ( BDNF ) levels in rats with acute and chronic inflammatory pain . Methods : The animals were allocated to one of two experiments : experiment 1 or experiment 2 . In experiment 1 , all animals were injected with complete Freund 's adjuvant ( CFA ) to induce inflammation and were r and omly allocated to receiving melatonin ( 60 mg/kg ) or vehicle . Injections were administered 1 h after CFA and once daily for 2 more days ( for a total of 3 days of melatonin administration ) . In experiment 2 , fifteen days after CFA injection , the animals were treated with melatonin ( 50 mg/kg ) or vehicle for 8 days . The animals were killed by decapitation 24 h after the last melatonin or vehicle administration , and an ELISA assay was performed to detect BDNF expression in the spinal cord , brainstem , and prefrontal cortex of the rats in both groups . Data were analyzed using Student 's t test and the results are expressed as means ± SEM . Results : In the first experiment , the BDNF levels of the melatonin group were reduced in the prefrontal cortex ( Student 's t test , p = 0.01 ) and increased in the spinal cord ( Student 's t test , p = 0.04 ) . In experiment 2 , BDNF levels were similar in both groups for all structures ( Student 's t test , p > 0.00 for all ) . A two-way ANOVA reveled a significant effect of structures ( p = 0.0001 ) but not of treatment ( p > 0.05 ) . The prefrontal cortex presented higher BDNF levels than other structures ( ANOVA/Student-Newman-Keuls test , p = 0.0001 ) . Considering the relationship between BDNF levels in all three structures , we found an effect of central nervous system structures ( p = 0.01 ) and an interaction between treatment and structures ( p = 0.04 ) . Conclusion : The high spinal cord BDNF levels and the low prefrontal cortical BDNF levels observed in rats with acute CFA-induced inflammation  following short-term melatonin administration may be related to the pain-modulating and neuroprotective effects of this protein . Long-term melatonin administration did not alter BDNF levels in chronic inflammation Abstract Antinociceptive effects of melatonin have been documented in a wide range of experimental animal models . The aim of this study was to investigate the analgesic , antihyperalgesic , and anti-inflammatory properties of melatonin using a vali date d burn injury ( BI ) model in healthy male volunteers . The design was a r and omized , double-blind , placebo-controlled , three-arm crossover study . Each volunteer participated in 3 identical study sessions with intravenous administration of placebo , melatonin 10 mg , or melatonin 100 mg . Sixty minutes after bolus injection of study medication , a BI was induced by a computerized contact thermode ( 47.0 ° C , 420 seconds , 5.0 × 2.5 cm2 ) . Pain ratings during the BI and quantitative sensory testing at baseline and at 1 , 2 , 4 , and 6 hours after the BI were performed . Quantitative sensory testing included assessment s of secondary hyperalgesia areas , mechanical and thermal thresholds in the BI area , and pressure algometry . Furthermore , markers of inflammation , skin-reflectance spectrophotometry , and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area . Pain during the BI and secondary hyperalgesia areas were defined as primary outcomes . Twenty-nine volunteers were r and omized and completed the study . While the BI induced large secondary hyperalgesia areas and significantly increased the markers of inflammation , no significant effects of melatonin were observed with respect to primary or secondary outcomes , compared with placebo . The administration of melatonin was not associated with any adverse effects . Melatonin did not demonstrate any analgesic , antihyperalgesic , or anti-inflammatory properties in the BI model Background Diabetes mellitus ( DM ) and periodontitis are two common chronic diseases with bidirectional relationship . Oxidative stress plays a key role in the pathogenesis of these two diseases . The aim of this study was to investigate the effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status , serum melatonin and inflammatory markers in type 2 DM patients with chronic periodontitis ( CP ) . Material s and methods In this double-blind clinical trial study , 50 type 2 DM patients with CP were r and omly allocated to the intervention and control groups . The intervention and control groups received either 6 mg melatonin or placebo ( 2 tablets ) once a day . Serum levels of melatonin , tumor necrosis factor-alpha ( TNF-α ) , interleukin-6 ( IL-6 ) , hs-C-reactive protein ( hs-CRP ) , clinical attachment loss ( CAL ) , pocket depth ( PD ) , bleeding on probing ( BOP ) and plaque index were evaluated in all subjects pre- and post-intervention . Results Melatonin supplementation significantly increased the mean serum levels of melatonin after intervention . The mean changes of melatonin were significantly higher in intervention group compared with control group . IL-6 and hs-CRP levels were significantly ( p = 0.008 and p = 0.017 , respectively ) reduced in the intervention group . The mean changes of IL-6 were significantly lower in the intervention group compared with the control group ( p = 0.04 ) . In the intervention group , PD and CAL were significantly decreased after intervention ( p < 0.001 ) . There were significant differences in the mean change of PD and CAL between the intervention and control groups after intervention ( p < 0.001 ) . Conclusions Melatonin supplementation in adjunct with non-surgical periodontal therapy might improve inflammatory and periodontal status in T2DM with CP Objective : Although mechanical ventilation is frequently a life-saving therapy , its use can result in unwanted side effects . It has been well documented that the choice of sedating agent may influence the duration of mechanical ventilation .  Melatonin is a sedative and analgesic agent without any respiratory depressant effect which makes it an attractive adjuvant for sedation in the intubated patients . The aim of this study is to evaluate the effect of melatonin on the duration of mechanical ventilation in patients with hemorrhagic stroke . Methods : Forty adult intubated patients with hemorrhagic stroke , who were admitted to the Intensive Care Unit ( ICU ) within 24 h of onset , were enrolled in this r and omized double-blind study . Subjects in the melatonin group received 30 mg of melatonin every night throughout the nasogastric tube .  Length of ICU stay , mortality , and duration of mechanical ventilation were recorded for all patients . Findings : The duration of mechanical ventilation and length of ICU stay were shorter in patients who received melatonin in comparison with the control group , and this difference was statistically significant for the length of ICU stay and marginally significant for the duration of mechanical ventilation . Although not statistically significant , the mortality rate of the control group was 30 % , almost double that of the study group ( 15 % ) . Conclusion : Melatonin possesses hypnotic , analgesic , anti-inflammatory , and anti-oxidative properties that distinguish it as an attractive adjuvant in patients under mechanical ventilation . In conclusion , the administration of melatonin may facilitate the weaning process through decreasing the consumption of sedatives with respiratory depressant properties as well as preventing ventilator-associated lung injury Regular consumption of fruit and vegetables may be associated with decreased CVD risk . In the present study , we investigated the effects of blackcurrant ( BC ) juice , rich in polyphenols and ascorbic acid , on oxidative and inflammatory biomarkers in cultured macrophages in vitro and in human subjects with an atherosclerosis-prone phenotype ( after consumption of a high-energy meal ) . In cultured macrophages ( RAW264.7 ) , BC treatment significantly inhibited lipopolysaccharide-induced inflammation as indicated by lower mRNA levels of TNF-α , IL-1β and inducible NO synthase ( iNOS ) and lower nuclear p65 levels indicating decreased NF-κB activity . iNOS protein levels were lower and haem oxygenase 1 levels higher in BC-treated cells when compared with untreated controls . Subjects given a high-energy meal had elevated serum glucose and insulin levels with no significant difference between the BC-based juice and placebo treatment groups . TAG following meal ingestion tended to be attenuated after the BC treatment . Plasma ascorbic acid and radical-scavenging capacity were decreased following placebo meal consumption ; however , BC significantly elevated both parameters compared with baseline and placebo ingestion . Plasma oxidised LDL , α-tocopherol and paraoxonase activity were unchanged in both treatment groups . Furthermore , production of TNF-α and IL-1β was not significantly changed by BC meal consumption . The present results suggest potential antioxidative and anti-inflammatory properties of BC in vitro in cultured macrophages . Although the observations were not directly transferable to a postpr and ial in vivo situation , the present results show that BC juice consumption may improve postpr and ial antioxidant status as indicated by higher ascorbic acid levels and free radical-scavenging capacity in plasma BACKGROUND Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer 's disease ( AD ) . Omega-3 fatty acids ( ω-3 FAs ) found in fish and fish oil have several biological properties that may be beneficial in AD . However , they may also auto-oxidize and induce in vivo lipid peroxidation . OBJECTIVE The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA . METHODS Forty patients with moderate AD were r and omized to receive 1.7 g DHA ( 22:6 ) and 0.6 g EPA ( 20:5 ) or placebo for 6 months . Urinary sample s were collected before and after supplementation . The levels of the major F2-isoprostane , 8-iso-PGF2α , a consistent in vivo biomarker of oxidative stress , and 15-keto-dihydro-PGF2α , a major metabolite of PGF2α and biomarker of inflammatory response , were measured . RESULTS F2-isoprostane in urine increased in the placebo group after 6 months , but there was no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2α . At baseline , the levels of 15-keto-dihydro-PGF2α showed negative correlative relationships to ω-3 FAs , and a positive correlation to linoleic acid . 8-iso-PGF2α correlated negatively to the ω-6 FA arachidonic acid . CONCLUSION The findings indicate that supplementation of ω-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F2-isoprostane or cyclooxygenase-mediated formation of prostagl and in F2α . The correlative relationships to FAs indicate a potential role of FAs in immunoregulation & NA ; Melatonin reduced pain scores and analgesic use , and improved sleep quality in endometriosis‐associated chronic pelvic pain . Melatonin modulates the secretion of brain‐derived neurotrophic factor independently of its analgesic effect in endometriosis . & NA ; Endometriosis‐associated chronic pelvic pain ( EACPP ) presents with an intense inflammatory reaction . Melatonin has emerged as an important analgesic , antioxidant , and antiinflammatory agent . This trial investigates the effects of melatonin compared with a placebo on EACPP , brain‐derived neurotrophic factor ( BDNF ) level , and sleep quality . Forty females , aged 18 to 45 years , were r and omized into the placebo ( n = 20 ) or melatonin ( 10 mg ) ( n = 20 ) treatment groups for a period of 8 weeks . There was a significant interaction ( time vs group ) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on daily pain , dysmenorrhea , dysuria , and dyschezia ( analysis of variance , P < 0.01 for all analyses ) . Post hoc analysis showed that compared with placebo , the treatment reduced daily pain scores by 39.80 % ( 95 % confidence interval [ CI ] 12.88–43.01 % ) and dysmenorrhea by 38.01 % ( 95 % CI 15.96–49.15 % ) . Melatonin  improved sleep quality , reduced the risk of using an analgesic by 80 % , and reduced BNDF levels independently of its effect on pain . This study provides additional evidence regarding the analgesic effects of melatonin on EACPP and melatonin ’s ability to improve sleep quality . Additionally , the study revealed that melatonin modulates the secretion of BDNF and pain through distinct mechanisms Endotracheal intubation is a common painful procedure in newborn care . Neonates are more sensitive to pain than older infants , children , and adults , and this hypersensitivity is further exacerbated in preterm neonates . The aim of this study was to evaluate the analgesic activity of melatonin during endotracheal intubation of the newborn by using the Neonatal Infant Pain Scale ( NIPS ) and Premature Infant Pain Profile ( PIPP ) score . Secondary outcome was an evaluation of melatonin as inflammatory responses . This was performed by measuring the levels of pro- and anti-inflammatory cytokines implicated in the pain . Sixty preterm infants were enrolled in the study and were r and omly divided into two groups : 30 infants treated with melatonin plus common sedation and analgesia recommended by Italian Society of Neonatology ( group 1 ) and 30 infants treated with only common sedation and analgesia .  The sedative and analgesic drugs included atropine , fentanyl , and vecuronium . The reduction in pain score ( NIPS ) was similar in both groups at an early phase , while it ( PIPP score ) was lower in melatonin-treated group infants than the other newborns at a late phase , during intubation and mechanical ventilation . The differences were statistically significant at 12 , 24 , 48 , and 72 hr ( P < 0.001 ) . Pro-inflammatory and anti-inflammatory cytokines ( IL-6 , IL-8 , IL-10 and IL-12 ) were higher in the common sedation and analgesia group than in melatonin-treated infants at 24 , 48 , 72 hr and 7 days ( P < 0.001 ) . This study suggests the use of melatonin as an adjunct analgesic therapy during procedural pain , especially when an inflammatory component is involved Objectives : To obtain a balance in the fatty acid ( FA ) metabolism is important for the inflammatory response and of special importance in cystic fibrosis ( CF ) , which is characterized by impaired FA metabolism , chronic inflammation , and infection in the airways . Nitric oxide ( NO ) has antimicrobial properties and low nasal ( nNO ) and exhaled NO ( FENO ) , commonly reported in CF that may affect bacterial status . The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF . Patients and Methods : Forty-three patients with CF and “ severe ” mutations were consecutively enrolled in a r and omized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo .  FENO , nNO , serum phospholipid concentrations of FA , and biomarkers of inflammation were measured before and after 3 months of supplementation . Results : Thirty-five patients in clinical ly stable condition completed the study . The serum phospholipid FA pattern changed significantly in all 3 groups . An increase of the n-6 FA , arachidonic acid , was associated with a decrease of FENO and nNO . The inflammatory biomarkers , erythrocyte sedimentation rate , and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA . Conclusions : This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF . FENO and nNO were influenced by changes in the arachidonic acid concentration , supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways Obesity , the global epidemic health problem , results in chronic disorders . Melatonin supplementation may prevent the adverse health consequences of obesity . The aim of this study was to assess the effects of melatonin supplementation on inflammatory and oxidative stress parameters in obese women . In r and omized , double-blind , placebo-controlled trial , 44 obese women were r and omly assigned to melatonin ( n=22 ) and placebo ( n=22 ) groups . Subjects were supplemented with a daily dose of 6 mg melatonin or placebo with low calorie diet for 40 days . Serum TNF-α , IL-6 , hsCRP , TAC , and MDA levels were assessed before and after intervention . In the melatonin group , mean serum TNF-α , IL-6 , hsCRP , and MDA levels decreased significantly ( p<0.05 ) from 3.52±0.72 pg/ml , 27.12±6.32 pg/ml , 2.54±0.49 mg/l , and 3.81±0.29 nmol/l to 1.73±0.07 , 16.34±6.32 , 1.67±0.27 , and 2.79±0.29 , respectively . Whilst in the placebo group the decrease in values were not statistically significant . Mean TAC level increased slightly ( from 1.11±0.30 to 1.14±0.45 mmol/l ) in the melatonin group whereas it decreased slightly ( from 1.13±0.15 to 1.08±0.21 nmol/l ) in the placebo group . Significant differences were observed only for TNF-α ( p=0.02 ) and IL-6 ( p=0.03 ) between the 2 study groups . Considering the improvements in inflammatory and oxidative stress factors in obese women , it seems that melatonin supplementation may provide beneficial effects in obesity treatment by ameliorating some of its complications . However , further studies are needed to make concise conclusions Spinal cord injury ( SCI ) results in the loss of function below the lesion . Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death . Methylprednisolone ( MP ) , by reducing edema and protecting the cell membrane against peroxidation , is the only pharmacological agent with a proven clinical ly beneficial effect on SCI . Melatonin , known as a free radical scavenger , has been shown to have an effect on lipid peroxidation following experimental SCI . The purpose of this study was to examine the effect of MP and melatonin on neurological , ultrastructural , and electrophysiological recovery .  Female albino rats weighing 200–250 g were r and omized into five groups of 18 rats each and six rats for the control group . Weight-drop trauma was performed for each group and a 30-mg/kg single dose of MP for rats in group 1 , a 10-mg/kg single dose of melatonin for rats in group 2 , and MP and melatonin in the same doses for rats in group 3 were administered immediately after trauma . The rats in group 4 were the vehicle group ( treated with ethanol ) and group 5 was the trauma group . The motor and somatosensory evoked potentials were recorded at the 4th hour , the 24th hour , and on the 10th day of the study for six rats in each group . Posttraumatic neurological recovery was recorded for 10 days using “ motor function score ” and inclined plane test . After electrophysiological study the rats were terminated for an analysis of lipid peroxidation level of the injured site of the spinal cord . Electron microscopic studies were performed to determine the effects of melatonin , MP , and the combined treatment with MP and melatonin on axons , neurons , myelin , nucleus , and intracytoplasmic edema . The groups treated with MP , melatonin , and a combination of both had significantly enhanced electrophysiological , biochemical , and neurological recovery and also showed better ultrastructural findings than the trauma and vehicle groups . Although combined treatment was significantly more effective on lipid peroxidation than melatonin or MP treatments alone , at the 10th day , neurobehavioral , electrophysiological , and ultrastructural recovery were at the same level . In conclusion , MP , melatonin , and MP and melatonin combined treatment modalities improved functional recovery at the same level . Future studies involving different doses of melatonin and different dose combinations with MP could promise better results since each drug has a different antioxidative mechanism of action Surgery for abdominal aortic aneurysm is associated with elevated oxidative stress . As an antioxidant in animal and human studies , melatonin has the potential of ameliorating some of this oxidative stress , but melatonin has never been administered to adults during surgery for the purpose of reducing oxidative damage . The aim of this pilot study was to evaluate the safety of various doses of melatonin administered during or after surgery and to monitor the changes in biomarkers of oxidative stress and inflammation during the pre- , intra- , and postoperative period . Six patients undergoing aortic surgery received 10 ( n = 2 ) , 30 ( n = 2 ) or 60 ( n = 2 ) mg melatonin intravenously in the intraoperative phase and 10 mg orally for three nights after surgery . Patients were monitored for hemodynamic parameters during and after surgery . Any unexpected events during the hospitalization were registered . Blood sample s were collected preoperatively and at 5 min , 6 hr and 24 hr after clamp removal or after re-circulation of the first leg and the sample s were analyzed for malondialdehyde ( MDA ) , ascorbic acid ( AA ) , dehydroascorbic acid ( DHA ) , and interleukin-6 ( IL-6 ) . Troponin I ( TpI ) and C-reactive protein ( CRP ) were also measured for 4 days after surgery . Melatonin administration did not change hemodynamic parameters ( mean arterial pressure or pulse rate ) during surgery ( P = 0.499 and 0.149 , respectively ) , but oxidative stress parameters ( MDA and AA ) decreased significantly ( P = 0.014 and 0.001 , respectively ) . There was a significant increase in the inflammatory parameters ( IL-6 and CRP ) ( P = 0.001 and 0.001 , respectively ) and an increase in TpI ( P = 0.009 ) as a consequence of surgery . These were not influenced by melatonin treatment . Treatment of patients undergoing major aortic surgery with melatonin intravenously up to 60 mg in the intraoperative phase was safe and without complications . Melatonin may decrease oxidative damage result ing from surgery , but r and omized clinical trials are required before definitive conclusions can be drawn regarding the clinical benefit of melatonin in surgical situations Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 Chronic benzodiazepine use is common in patients with mental illness and is associated with cognitive impairment . It is unclear whether benzodiazepine-induced cognitive impairment is reversible . Amelioration of cognitive dysfunction may be facilitated during benzodiazepine tapering by add-on melatonin due to its anti-inflammatory and neuroprotective properties . We examined how melatonin and benzodiazepine withdrawal affect cognition , subjective well-being , and psychosocial functioning .  Eighty patients with schizophrenia or bipolar disorder were r and omized to add-on treatment once daily with either prolonged-release melatonin or placebo in a 24-week , double-blind clinical trial . All participants gradually tapered usual benzodiazepine dosage in a closely monitored treatment setting . We used the Brief Assessment of Cognition in Schizophrenia ( BACS ) to assess neurocognitive performance with additional assessment s of subjective well-being and psychosocial functioning . BACS composite and subscale scores ( except motor speed ) significantly improved in parallel with benzodiazepine dose reduction , but there was no additional effect of melatonin . Cognitive performance was still markedly impaired post-tapering compared with normative data . Neither benzodiazepine withdrawal nor treatment group affected subjective well-being or psychosocial functioning . In conclusion , add-on melatonin does not seem to affect cognition , well-being , or psychosocial functioning in patients with severe mental illness . The observed improvement in cognitive performance could not be distinguished from retest effects , which may in turn have been facilitated by the benzodiazepine tapering Objective : Oral bioavailability is one of the most important properties in drug design and development . A poor oral bioavailability can result in low efficacy and unpredictable response to a drug . Several dosages of melatonin have been used for various investigations to clarify its bioavailability in humans . Aim ing to search for a pharmaceutical form , which is better absorbed , the pharmacokinetic ( PK ) profile of the new manufactured melatonin soft gelatin ( soft gel ) capsule form has been evaluated and compared with the commercially available melatonin powder . Research design and methods : A total of 60 healthy volunteers received 1 , 3 mg of melatonin powder and 1 mg of melatonin in soft gel capsules . PK profiles were obtained by analysis of melatonin plasma concentration , and the respective melatonin bioavailability was compared . Results : Melatonin soft gel capsule form showed similar PK parameters compared with the highest doses of melatonin in powder form , but its bioavailability was improved . Conclusions : Soft gel capsules improved the bioavailability of melatonin in humans even when administered dose was reduced . Considering the number of conditions in which melatonin supplementation is recommended , this evidence could support a broader use of melatonin in clinical practice Disturbed sleep is common in chronic obstructive pulmonary disease ( COPD ) . Conventional hypnotics worsen nocturnal hypoxemia and , in severe cases , can lead to respiratory failure . Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions . This r and omized , double-blind , placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD . Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study . None of the participants had a history of disease exacerbation 4 weeks prior to the study , obstructive sleep apnea , mental disorders , current use of oral steroids , methylxanthines or hypnotic-sedative medication , nocturnal oxygen therapy , and shift work . Patients received 3 mg melatonin ( N = 12 ) or placebo ( N = 13 ) , orally in a single dose , 1 h before bedtime for 21 consecutive days . Sleep quality was assessed by the Pittsburgh Sleep Quality Index ( PSQI ) and daytime sleepiness was measured by the Epworth Sleepiness Scale . Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test , respectively . Twenty-five patients completed the study protocol and were included in the final analysis . Melatonin treatment significantly improved global PSQI scores ( P = 0.012 ) , particularly sleep latency ( P = 0.008 ) and sleep duration ( P = 0.046 ) . No differences in daytime sleepiness , lung function and functional exercise level were observed . We conclude that melatonin can improve sleep in COPD . Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients Nonalcoholic fatty liver disease is the most common chronic liver disease and nonalcocholic steatohepatitis ( NASH ) is its advanced form . Oxidative stress and hepatocyte apoptosis may be involved in pathogenesis of NASH and particularly in progress of NASH to liver fibrosis and cirrhosis , which are initiated by the inflammation and which promote the progress of the disease . The aim of this study was to evaluate the effects of melatonin and L-tryptophan on selected biochemical parameters of blood in patients with NASH . Forty five patients with NASH , confirmed by histopathological examination of liver biopsy sample s , were admitted to the study . They were divided into three groups ( I , II and III ) . The first group ( group I , n=15 ) received preparation Essentiale forte 3 times a day and tryptophan 500 mg twice daily for 4 weeks . In the second group ( group II , n=15 ) , Essentiale forte three times a day was administered with melatonin 5 mg applied twice a day for 4 weeks . The third group ( group III , n=15 ) received only Essentiale forte with placebo three times a day for 4 weeks . After four-week treatment we found statistically significant reduction in GGTP , triglycerides and proinflammatory cytokine levels in the melatonin-treated ( group I ) and the L-tryptophan-treated patients ( group II ) . Plasma level of melatonin was significantly elevated in groups treated with tryptophan ( group I ) and melatonin ( group II ) , but remained unchanged in placebo-treated group ( group III ) . Among patients from the third group ( treated with placebo ) no statistically significant differences in the measured biochemical parameters were observed . The present study suggests that melatonin and tryptophan have the significant impact on the reduction in plasma levels of proinflammatory cytokines and may be useful in the treatment of patients with NASH The effects of zinc supplementation on zinc status and on clinical and biological indicators of inflammation were investigated in 18 patients with chronic inflammatory rheumatic diseases and in 9 healthy control subjects . Patients with mild and recent onset disease were assigned to a 60-d trial to receive either 45 mg Zn ( as gluconate)/d or a placebo , while control subjects received the zinc supplement .  Baseline mean plasma zinc of the patients was low whereas mononuclear cell zinc content was elevated , suggesting a redistribution of the element related to the inflammatory process rather than to a zinc-deficient state . Zinc supplementation increased plasma zinc to a similar extent in patients and in control subjects , which suggested no impairment of zinc intestinal absorption as a result of the inflammatory process . On the contrary , erythrocyte and leukocyte zinc concentrations were not modified in the two groups examined . No beneficial effect of zinc treatment could be demonstrated on either clinical or inflammation indexes The balance between inflammatory and repair processes is important in maintaining lung homeostasis in chronic obstructive pulmonary disease ( COPD ) . The aim of the present study was to determine whether or not an integrated index of a biomarker involved in inflammation , C-reactive protein ( CRP ) , and another involved in wound repair , fibronectin , may be a good measure to predict clinical outcomes in COPD . Circulating blood levels of CRP and fibronectin were measured in 4,787 individuals with mild-to-moderate COPD who were prospect ively followed for > 7 yrs after blood collection as part of the Lung Health Study . To assess the balance between repair and inflammation , a simple ratio was calculated by dividing fibronectin levels by CRP levels and a Cox proportional hazards model was used to determine the relationship between this ratio and all-cause and disease-specific causes of mortality . The relationship between the fibronectin to CRP ratio and all-cause mortality was L-shaped . There was an exponential decay in the adjusted hazard function ( i.e. the risk of mortality ) as the ratio decreased until a value of 148 was reached , beyond which point the hazard function did not change significantly . Similar results were observed for the risk of coronary and cardiovascular mortality . Circulating fibronectin to CRP ratio is significantly associated with all-cause mortality of COPD patients . However , in contrast to other biomarkers , the relationship appears to be L-shaped ( and not linear ) , suggesting a threshold at ∼150 . While promising , future studies are needed to vali date this simple index as a biomarker in COPD We investigated the relationship between oxidative stress and poor oocyte quality  and whether the antioxidant melatonin improves oocyte quality . Follicular fluid was sample d at oocyte retrieval during in vitro fertilization and embryo transfer ( IVF-ET ) . Intrafollicular concentrations of 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) in women with high rates of degenerate oocytes were significantly higher than those with low rates of degenerate oocytes . As there was a negative correlation between intrafollicular concentrations of 8-OHdG and melatonin , 18 patients undergoing IVF-ET were given melatonin ( 3 mg/day ) , vitamin E ( 600 mg/day ) or both melatonin and vitamin E.  Intrafollicular concentrations of 8-OHdG and hexanoyl-lysine adduct were significantly reduced by these antioxidant treatments . One hundred and fifteen patients who failed to become pregnant with a low fertilization rate ( < or = 50 % ) in the previous IVF-ET cycle were divided into two groups during the next IVF-ET procedure ; 56 patients with  melatonin treatment  ( 3 mg/day ) and 59 patients without melatonin treatment . The fertilization rate was improved by melatonin treatment compared to the previous IVF-ET cycle . However , the fertilization rate was not significantly changed without melatonin treatment . Oocytes recovered from preovulatory follicles in mice were incubated with H2O2 for 12 hr . The percentage of mature oocytes with a first polar body was significantly reduced by addition of H2O2 ( 300 microm ) . The inhibitory effect of H2O2 was significantly blocked by simultaneous addition of melatonin . In conclusion , oxidative stress causes toxic effects on oocyte maturation and melatonin protects oocytes from oxidative stress . Melatonin is likely to improve oocyte quality and fertilization rates Abstract Background : Tuberculosis ( TB ) has reemerged to become the world ’s leading cause of death from a single infectious agent . Inflammatory cytokines play an important role during the course of the disease and may be responsible for tissue damage by lipid peroxidation . The study was aim ed to explore the anti-inflammatory and antioxidant effect of ginger in pulmonary TB patients . Methods : A total of 69 pulmonary TB patients participated in a r and omized and placebo-controlled study . The intervention group received 3 g of ginger extract daily for 1 month and placebo group was supplemented with starch capsule . Participants of both groups were taking st and ard antitubercular treatment during the study . The concentrations of tumor necrosis factor ( TNF ) alpha , ferritin and malondialdehyde ( MDA ) in blood sample s were analyzed before and after the intervention by using enzyme-linked immunosorbent assay for TNF alpha and ferritin and spectrophotometry for MDA . Results : Ginger supplementation significantly reduced the levels of TNF alpha , ferritin and MDA in ginger supplemented group in comparison to baseline . Ginger supplementation with antitubercular treatment significantly lowered TNF alpha , ferritin and MDA concentrations in comparison to control group . Conclusions : Ginger was found to be effective as an anti-inflammatory and antioxidant supplement along with anti-TB therapy as it possesses strong free radical scavenging property
The results of the present meta- analysis support that melatonin supplementation could be effective on ameliorating of inflammatory mediators
Inflammatory processes are involved in chronic diseases .
It has been suggested that melatonin reduces inflammation by its radical scavenging properties ; however , the results of the previous studies are inconclusive .
The objective of the present meta- analysis is to determine the direction and magnitude of melatonin supplementation effect on inflammatory biomarkers .