The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Imbalances in immune regulation are important features of migraine pathophysiology. In line with this, the current study investigated the efficacy of omega-3 fatty acids supplementation on inflammatory and anti-inflammatory markers in patients with migraines. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial consisted of 40 patients that were prone to experiencing episodic migraines. For two months, participants were randomized into one group that received omega-3 supplementation (n= 20), 600 mg of EPA and 300 mg of DHA, twice daily) or another group that received a placebo (n= 20). Transforming growth factor ß (TGF-ß), interleukin (IL)-4, interferon-gamma (IFN-γ), and interleukin (IL)-17 serum levels were assessed using enzyme-linked immunosorbent assay methods at baseline and following the intervention. The current study was registered on ClinicalTrials.gov with the registration number NCT02532023. RESULTS: After two months of intervention, the administration of omega-3 fatty acids resulted in a significant rise in the concentrations of anti-inflammatory cytokine IL-4 (p=0.010) as well as a significant reduction in concentrations of pro-inflammatory cytokine IFN-γ (p=0.001) compared with the placebo. However, no significant changes were observed in serum TGF-ß and IL-17 levels. DISCUSSION: Our findings indicated consumption of omega-3 fatty acids may have a potentially beneficial response on the inflammatory immune response in patients with migraines. Larger trials are needed to corroborate these findings.

The effects of nano-curcumin supplementation on Th2/tregulatory axis in migraine patients: a randomized, double-blind, placebo-controlled trial.

AIM: In the present study we aimed to investigate the effects of nano-curcumin supplementation on gene expression and serum levels of IL-4 and TGF-ß in migraine patients. METHODS: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. At the beginning and the end of the study, the interictal serum levels and gene expression of IL-4 and TGF-ß in peripheral blood mononuclear cells (PBMCs) isolated from migraine patients were measured, using ELISA and real-time PCR methods, respectively. RESULTS: Intra-group assays showed a significant rise in the gene expression of both IL-4 and TGF-ß (p < 0.05) in nano-curcumin group after two months of treatment, however the serum levels were only significantly changed for IL-4 (p < 0.05). On the contrast, inter-group assays revealed no statistical differences between nano-curcumin and placebo group in terms of IL-4 and TGF-ß gene expression, while the serum levels of IL-4 was observed to be increased significantly (p = 0.03) following two month nano-curcumin supplementation. CONCLUSION: The findings of the present trial suggest that the treatment with nano-curcumin could induce significant levels of IL-4, in favour of anti-inflammatory effects, while has a minimal effects on the both gene expression and serum levels of TGF-ß. Further studies are required to determine the exact mechanism of action of curcumin in patients with migraine.

Effect of Vitamin D on Paraxonase-1, Total Antioxidant Capacity, and 8-Isoprostan in Children with Attention Deficit Hyperactivity Disorder.

Method: In this double-blind, randomized, placebo-controlled trial, 75 children (aged 6-12) diagnosed with ADHD were randomly assigned into two groups. The supplementation group received vitamin D3 (2000 IU), and the control group received a placebo for 3 months. Blood samples were collected at baseline and after intervention to analyze the 25(OH)D, paraxonase-1 activity (PON-1), Total Antioxidant Capacity (TAC), and 8-isoprostan levels. Results: A significant rise in circulating 25(OH)D was observed in the vitamin D group versus the placebo group at the end of the study. There was no reduction in 8-isoprostan levels in the vitamin D group compared to the placebo group. Serum paraxonase-1 and TAC concentration decreased in both groups, but these alterations were not statistically significant in the treatment group versus the placebo group at the end of the intervention. Conclusion: Vitamin D supplementation for 3 months did not have beneficial effects on biomarkers of oxidative stress status. To confirm these findings, further studies on children are suggested.

Effect of Vitamin D Supplementation on Inflammatory Biomarkers in School-Aged Children with Attention Deficit Hyperactivity Disorder.

Method: This randomized double-blind, placebo-controlled trial was conducted on 75 school-aged children with a diagnosis of ADHD based on DSM-V criteria. Children were randomly allocated to receive either vitamin D3 (2000 IU/day) or a placebo for 3 months. Serum IL-6, TNF-α, and 25(OH) D were assessed before and after the intervention to determine the effects of vitamin D on the highlighted parameters. Results: Serum levels of 25(OH) D increased significantly in the vitamin D group (P=0.01). However, no significant differences in serum IL-6 and TNF-α were found between both groups at the baseline and at the end of the intervention. Conclusion: The findings revealed that vitamin D supplementation for 3 months is not efficacious in reducing inflammatory cytokines in children with ADHD. Further studies are required to confirm these results.

Omega-3 polyunsaturated fatty acids supplementation improve clinical symptoms in patients with Covid-19: A randomised clinical trial.

AIMS: We hypothesised that omega-3 fatty acids would be an appropriate adjunct therapy for alleviating the inflammatory response and clinical manifestation in hospitalised patients with Covid-19 disease. METHODS: This was a single-blind randomised controlled trial in Amir-Alam hospital in Tehran. Thirty adult men and women diagnosed with Covid-19 were allocated to either control group (receiving Hydroxychloroquine) or intervention group (receiving Hydroxychloroquine plus 2 grams of Docosahexaenoic acid [DHA] + Eicosapentaenoic acid [EPA]) for 2 weeks. Primary outcome of the intervention including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as clinical symptoms including body pain, fatigue, appetite and olfactory and secondary outcomes including liver enzymes were determined at the baseline and after omega-3 supplementation. Clinical signs were measured using self-reported questionnaires. There were commercial kits for determination of CRP and liver enzymes concentrations in the serum of patients. For determination of ESR automated haematology analyser was applied. The study of "Comparison of the effectiveness of omega-3 and Hydroxychloroquine on Inflammatory factors, liver enzymes and clinical symptoms in diabetic Covid-19 patients" was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20200511047399N1. RESULTS: In comparison to control group, patients receiving omega-3 indicated favourable changes in all clinical symptoms except for olfactory (P < .001 for body pain and fatigue, P = .03 for appetite and P = .21 for olfactory). Reducing effects of omega-3 supplementation compared with control group were also observed in the levels of ESR and CRP after treatment (P < .001 for CRP and P = .02 for ESR). However, no between group differences in the liver enzymes serum concentrations were observed after supplementation (P > .05). CONCLUSION: Current observations are very promising and indicate that supplementation with moderate dosages of omega-3 fatty acids may be beneficial in the management of inflammation-mediated clinical symptoms in Covid-19 patients.

The synergistic effects of ω-3 fatty acids and nano-curcumin supplementation on tumor necrosis factor (TNF)-α gene expression and serum level in migraine patients.

Migraine is a destabilizing neuroinflammatory disorder characterized by recurrent headache attacks. Evidences show tumor necrosis factor (TNF)-α play a role in neuroimmunity pathogenesis of migraine. TNF-α increase prostanoid production, hyperexcitability of neurons, and nociceptor activation resulted in neuroinflammation and neurogenic pain. ω-3 fatty acids and curcumin exert neuroprotective and anti-inflammatory effects via several mechanisms including suppression of TNF-α gene expression and its serum levels. The aim of this study is an evaluation of synergistic effects of ω-3 fatty acids and nano-curcumin on TNF-α gene expression and serum levels in migraine patients. The present study performed as a clinical trial over a 2 month period included 74 episodic migraine patients in 4 groups and received ω-3 fatty acids, nano-curcumin, and combination of them or placebo. At the start and the end of the study, the gene expression of TNF-α and TNF-α serum levels was measured by real-time PCR and ELISA method, respectively. Our results showed that the combination of ω-3 fatty acids and nano-curcumin downregulated TNF-α messenger RNA (mRNA) significantly in a synergistic manner (P < 0.05). As relative to gene expression, a significant greater reduction in serum levels of TNF-α were observed in the combination group, but no significant differences in other groups. Supplementation with ω-3 fatty acids or nano-curcumin alone did not show significant reduction either in mRNA or serum levels of TNF-α. In addition, a much greater reduction in attack frequency was found in the combination group (P < 0.001). These findings indicated that ω-3 fatty acids and curcumin supplementation can be considered as a new promising approach in migraine management.

The Effects of Nano-curcumin Supplementation on Leptin and Adiponectin in Migraine Patients: A Double-blind Clinical Trial Study from Gene Expression to Clinical Symptoms.

BACKGROUND: Migraine is a disabling neurogenic disorder characterized by recurrent headache attacks. Adipokines act as inflammatory and pain mediators that contribute to migraine pathogenesis. Leptin and adiponectin levels change in migraine patients and are associated with headache attacks. Curcumin can exert modulatory and analgesic effects on adipokines through several mechanisms, from gene expression to suppressing pain. The aim of the present study was to evaluate the effects of nano-curcumin supplementation on leptin and adiponectin gene expression, their serum levels and migraine symptoms in patients with migraine. METHODS: Forty-four episodic migraine patients enrolled in this trial were divided into two groups as nano-curcumin (80 mg/day) and placebo group, over a two-month period. At the beginning and the end of the study, the mRNA expression of leptin and adiponectin from isolated PBMCs and their serum levels were measured using real-time PCR and ELISA method, respectively. The headache frequencies, severity and duration of pain were also recorded. RESULTS: The results of the present research showed that nano-curcumin can up-regulate adiponectin mRNA and increase its serum level significantly (P < 0.05). In the case of leptin, a reduction in gene expression and concentration was found in the nano-curcumin group but it was not statistically significant (P > 0.05). Nano-curcumin also significantly reduced the frequency, severity and duration of headaches (P < 0.05). CONCLUSION: These findings indicate that nano-curcumin supplement can be considered as a promising approach to migraine management and clinical symptoms improvement.

Effect of vitamin B1 supplementation on blood creatinine and lactate levels and clinical outcomes in patients in intensive care units: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: The metabolic response to stress can deplete the remaining thiamine stores, leading to thiamine deficiency. OBJECTIVE: This study is the first meta-analysis of the effectiveness of thiamine supplementation on clinical and biochemical outcomes in adult patients admitted to the intensive care unit (ICU). DATA SOURCES: Scopus, PubMed, and Cochrane databases were searched to select studies up to 20 November 2022. STUDY SELECTION: Studies investigating the effect of thiamine supplementation on serum lactate and creatinine levels, the need for renal replacement therapy, length of ICU stay, and mortality rate in ICU patients were selected. DATA EXTRACTION: After excluding studies based on title and abstract screening, 2 independent investigators reviewed the full texts of the remaining articles. In the next step, a third investigator resolved any discrepancy in the article selection process. RESULTS: Of 1628 retrieved articles, 8 were selected for final analysis. This study showed that thiamine supplementation reduced the serum creatinine level (P = .03) compared with placebo. In addition, according to subgroup analysis, serum creatinine concentration was significantly lower in patients >60 years old (P < .00001). However, there was no statistically significant difference in the lactate level between the thiamine supplementation and placebo groups (P = .26). Thiamine supplementation did not decrease the risk of all-cause mortality (P = .71) or the need for renal replacement therapy (P = .14). The pooled results of eligible randomized controlled trials also showed that thiamine supplementation did not reduce the length of ICU stay in comparison to the placebo group (P = .39). CONCLUSION: This meta-analysis provides evidence that thiamine supplementation has a protective effect against blood creatinine increase in ICU patients. However, further high-quality trials are needed to discover the effect of thiamine supplementation on clinical and biochemical outcomes in ICU patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42023399710 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399710).

The effects of nano-curcumin supplementation on adipokines levels in obese and overweight patients with migraine: a double blind clinical trial study.

OBJECTIVE: The present study aimed to investigate the effects of nano-curcumin supplementation on adipokines levels and clinical signs in obese and overweight patients with migraine. RESULTS: Forty-four patients with episodic migraine participated in this clinical trial and were divided into two groups nano-curcumin (80 mg/day) and the control group over 2-month period. At the baseline and the end of the research, the serum levels of MCP-1, Resistin, and Visfatin were measured using the ELISA method. In addition, the headache attack frequencies, severity, and duration of pain were recorded. The results of the present study showed that nano-curcumin can significantly reduce MCP-1 serum levels in the nano-curcumin supplemented group (P = 0.015, size effect = 13.4%). In the case of resistin and visfatin, nano-curcumin supplementation exerted no statistically significant changes in serum levels (P > 0.05). Nano-curcumin also significantly reduced the attack frequencies, severity, and duration of headaches (P < 0.05). These findings indicate that targeting curcumin can be a promising approach to migraine management. However, further comprehensive human trials are needed to confirm these findings. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20160626028637N2 on the date 2020-07-10.

Are levels of adipokines and micronutrients different in male adult smokers and non-smokers? A case-control study.

OBJECTIVE: Smoking is a common public problem leading to increases in oxidative stress and decreases in the levels of some micronutrients, finally affecting adipokine levels. The aim of this study was to compare the serum levels of omentin (intelectin-1), chemerin, TNF-α, and some micronutrient intakes in male smokers and non-smokers. METHODS: 40 male smokers and 40 male non-smokers with a mean age of 38.6±14.1 years were included in this study. Serum levels of omentin, chemerin, and TNF-α were measured. To calculate the daily intake of energy, carbohydrate, protein, fat, and some of the micronutrients, the 24-h recall and semi-quantitative food frequency questionnaire (FFQ) was used. RESULTS: Omentin, chemerin, and TNF-α levels in male smokers were lower than non-smokers, but these differences were not statistically significant. However, after adjustment for total and saturated fat intakes and age, omentin (ß=138.4, p=0.027) and TNF-α (ß=144.5, p=0.015) revealed significant differences. CONCLUSION: The serum levels of omentin, chemerin, TNF-α, and some micronutrient intakes were not significantly different between smokers and non-smokers. Further population studies are needed to clarify this subject.

The Effect of L-Carnitine on Mortality Rate in Septic Patients: A Systematic Review and Meta-Analysis on Randomized Clinical Trials.

BACKGROUND: Recent clinical trial studies have reported that L-carnitine supplementation can reduce the mortality rate in patients with sepsis, but there are no definitive results in this context. The current systematic review and meta-analysis aimed to evaluate the effect of L-carnitine supplementation on 28-day and one-year mortality in septic patients. METHODS: A systematic search conducted on Pubmed, Scopus and Cochrane Library databases up to June 2019 without any language restriction. The publications were reviewed based on the Cochrane handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA). To compare the effects of L-carnitine with placebo, Risk Ratio (RR) with 95% confidence intervals (CI) were pooled according to the random effects model. RESULTS: Across five enrolled clinical trials, we found that L-carnitine supplementation reduce one-year mortality in septic patients with SOFA> 12 (RR: 0.68; 95% CI: 0.49 to 0.96; P= 0.03) but had no significant effect on reducing 28-day mortality ((RR: 0.93; 95% CI: 0.68 to 1.28; P= 0.65) compared to placebo. Finally, we observed that based on current trials, L-carnitine supplementation may not have clinically a significant effect on mortality rate. CONCLUSION: L-carnitine patients with higher SOFA score can reduce the mortality rate. However, the number of trials, study duration and using a dosage of L-carnitine are limited in this context and further large prospective trials are required to clarify the effect of L-carnitine on mortality rate in septic patients.

Anti-Neuroinflammatory Properties of n-3 Fatty Acids and Nano- Curcumin on Migraine Patients from Cellular to Clinical Insight: A Randomized, Double-Blind and Placebo-Controlled Trial.

BACKGROUND AND OBJECTIVES: Migraine is an exhausting neuro-inflammatory disorder recognized as recurrent headache attacks. Evidence has shown that Interleukin (IL)-1ß plays a substantial role in the neuro-immunity pathogenicity of migraine. n-3 fatty acids and curcumin revealed neuromodulatory and anti-inflammatory effects through several pathways, of which the suppression of IL-1ß gene expression is an important inflammatory pathway. The aim of this study was the investigation of synergistic relation of n -3 fatty acids and nano-curcumin on IL-1ß gene expression and serum levels in migraine patients. METHODS: This study was performed as a randomized, double-blind, placebo-controlled trial in a period of two months. A total of 80 episodic migraines were assigned into 4 groups of 1) n-3 fatty acids and curcumin combination; 2) n -3 fatty acids; 3) nano-curcumin; and 4) n-3 fatty acids and curcumin placebo. The gene expression and serum level of IL-1ß were measured by real-time PCR and ELISA methods respectively, at the beginning and the end of the interventions. RESULTS: Results showed the n-3 fatty acids and nano-curcumin combination significantly reduced the attack frequency in a synergistic status (P < 0.001). A significantly greater reduction in the serum level of IL-1ß was observed in the combination group, and the differences in the other groups were not statistically significant. The IL-1ß gene expression in the combination group showed a significant reduction for other treatment groups (P < 0.05), but these significant differences were absent after multiple testing Bonferroni corrections. CONCLUSION: Present findings revealed that n -3 fatty acids and curcumin co-supplementation can be suggested as a promising new approach in migraine headache management, but further studies are needed to confirm these findings.

The Biochemical Parameters and Vitamin D Levels in ICU Patients with Covid-19: A Cross-Sectional Study.

BACKGROUND: In Covid-19 infection, leukopenia, inflammation, and elevated liver enzymes are found in most patients. Also, vitamin D deficiency attenuates the immune system and predisposes a person to being more susceptible to infection. In this context, we aimed to evaluate vitamin D, electrolytes, complete blood count, liver enzymes, urea, creatinine, albumin, CRP and ESR levels in patients with Covid-19. METHODS: We conducted a cross-sectional study on 118 patients with Covid-19 who were hospitalized from 2020/2/19 to 2020/4/3 in ICU. Serum levels of electrolytes, liver enzymes, blood factors, urea, creatinine, CRP and ESR, as well as anthropometric parameters and serum vitamin D concentration, were measured. RESULTS: A total of 118 patients (80 male and 38 female) were enrolled in the study (65.05±15.75 years). Only 5.08% of patients had no risk factors and 55.9% had ≥ 2 risk factors. Diabetes (44.1%) and obesity (23.7%) were more common among patients. Laboratory findings showed that 80.50% of patients had hyponatremia, but other electrolytes including K, Mg, Ca and P were normal in the majority of participants as well as CBC, Cr, Urea, Alb, ALT and ALKP. The AST concentration increased in most patients (66.94%). All patients had high levels of inflammatory factors such as CRP and ESR. The mean of 25-hydroxy-vitamin D levels in participants (25.95 ± 14.56 ng/mL) was lower than its levels in the general population. However, it was not statistically significant (P= 0.88). A significant negative correlation was found between vitamin D and ALT (P= 0.02, -0.21) as well as vitamin D and CRP (P= 0.05, -0.17). CONCLUSION: Due to the regulatory role of vitamin D in the immune system and low levels of vitamin D in Covid-19 infected patients, the evaluation of vitamin D levels and prescribed supplements, if necessary, is suggested.

The omega-3 and Nano-curcumin effects on vascular cell adhesion molecule (VCAM) in episodic migraine patients: a randomized clinical trial.

OBJECTIVE: The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. RESULTS: In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. TRIAL REGISTRATION: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.

The Effect of Nano-Curcumin Supplementation on Pentraxin 3 Gene Expression and Serum Level in Migraine Patients.

BACKGROUND: This study was designed to investigate the effect of nano-curcumin supplementation on pentraxin 3 (PTX3) gene exp ression and serum level in migraine patients. METHODS: The present study, performed as a clinical trial, included 38 episodic migraine patients in two groups that received either nano-curcumin or placebo over a two-month period. At the start and the end of the study, PTX3 gene expression and serum levels were measured. RESULTS: After two months of treatment, PTX3 gene expression and serum levels were both significantly less in the nano-curcumin than in the placebo group (P= 0.01 and P< 0.001, respectively). No significant gene expression differences were found between the two groups. CONCLUSION: Curcumin may have a potential inhibitory effect on PTX3 gene expression and serum levels in migraine disease and can be considered as an efficient therapy in migraine management.

The effects of nano-curcumin supplementation on Th1/Th17 balance in migraine patients: A randomized controlled clinical trial.

BACKGROUND: The present study was aimed to evaluate the nano-curcumin supplementation on Th1/Th17 balance by assessment of gene expression and serum level of interferon gamma (IFN-γ) and interleukin-17 (IL-17) in migraine patients. METHODS: Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. The expression of IFN-γ and IL-17 from peripheral blood mononuclear cells and IFN-γ and IL-17 serum levels were measured, using a real-time PCR and ELISA methods, respectively. RESULTS: Compared to placebo group, two month nano-curcumin supplementation led to a significant reduction in serum levels and expression of IL-17 mRNA (P = 0.006 & 0.04, respectively), while there was no statistical difference regarding serum levels and expression of IFN-γ mRNA. CONCLUSION: Nano-curcumin supplementation in migraine patients led to a significant reduction in gene expression and plasma levels of IL-17 compared to control group.

The Effects of Resveratrol on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: Recent trial studies have found that resveratrol supplementation beneficially reduces oxidative stress marker, but, there is no definitive consensus on this context. The present systematic review and meta-analysis aimed to investigate the effect of resveratrol supplementation on oxidative stress parameters. METHODS: We searched databases of Pubmed, Scopus and Cochrane Library up to December 2018 with no language restriction. Studies were reviewed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane handbook. To compare the effects of resveratrol with placebo, weighted mean difference (WMD) with 95% confidence intervals (CI) were pooled based on the random-effects model. RESULTS: Among sixteen clinical trials, we found that resveratrol supplementation increased GPx serum levels significantly (WMD: 18.61; 95% CI: 8.70 to 28.52; P<0.001) but had no significant effect on SOD concentrations (WMD: 1.01; 95% CI: -0.72 to 2.74; P= 0.25), MDA serum levels (WMD: -1.43; 95% CI: -3.46 to 0.61; P = 0.17) and TAC (WMD: -0.09; 95% CI: -0.29 to 0.11; P = 0.36) compared to placebo. Finally, we observed that resveratrol supplementation may not have a clinically significant effect on oxidative stress. CONCLUSION: However, the number of human trials is limited in this context, and further large prospective clinical trials are needed to confirm the effect of resveratrol supplement on oxidative stress markers.

The Effects of Omega-3 Supplementation on the Expanded Disability Status Scale and Inflammatory Cytokines in Multiple Sclerosis Patients: A Systematic Review and Meta-Analysis.

Recent trial studies have shown that omega-3 supplementation can beneficially improve scores on the Expanded Disability Status Scale (EDSS), which is considered a gold standard for measuring disability and disease severity in Multiple Sclerosis (MS) patients, as well as reducing neuroinflammation. The present systematic review and meta-analysis aimed to evaluate the effect of omega-3 supplementation on EDSS and cytokines in MS. A systematic search was performed on Pubmed, Scopus and Cochrane Library up to October 2018. Studies were reviewed based on the Cochrane handbook, and the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Weighted Mean Difference (WMD) with 95% Confidence Intervals (CI) were pooled using a random effects model in order to compare the effects of omega-3 with placebos. Among 4 trials, omega-3 supplementation had no significant effect on EDSS scale (WMD: -0.07; 95% CI: -0.27 to 0.13; P=0.50), as well as serum levels of IL-1ß (WMD: -7.67; 95% CI: -23.31 to 7.97; P=0.34) and IL-6 (WMD: -153.57; 95% CI: -455.36 to 148.23; P=0.32). However, omega-3 significantly reduced TNF-α concentration (WMD: -16.76; 95% CI: -18.63 to -14.88; P < 0.00001) compared to placebo. Overall, omega-3 supplementation may not have a clinically considerable impact on EDSS or proinflammatory markers. However, the existing trials are limited in this context, and further clinical trials are required to confirm the potential effects of the omega-3 supplement on MS disease management.

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences.

OBJECTIVE: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer's, Parkinson's, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. METHODS: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. RESULTS: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1ß, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. CONCLUSION: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

The Neuromodulatory Effects of ω-3 Fatty Acids and Nano-Curcumin on the COX-2/ iNOS Network in Migraines: A Clinical Trial Study from Gene Expression to Clinical Symptoms.

BACKGROUND: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine's neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects of ω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients. METHODS: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who received ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded. RESULTS: The results of the present trial showed that ω-3 fatty acids and nano-curcumin can reinforce each other's effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05). CONCLUSION: These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.