Search

Background: Alcohol use is associated with a wide spectrum of neurological disorders, including cognitive dysfunction and dementia. Likewise, the high prevalence of cognitive dysfunction and dementia specifies the urgent need to identify modifiable risk factors. Because findings on alcohol and cognitive dysfunction and dementia have been inconsistent, the present dose-response meta-analysis of cohort and case control studies was conducted to evaluate the available evidence., Method and Materials: A systematic search was conducted on PubMed/MEDLINE, Scopus, Embase, and PsychInfo databases and Google Scholar up to April, 2023. In the dose-response meta-analysis, a restricted cubic spline regression model was conducted to evaluate a possible non-linear relation between alcohol intake and the outcomes. Random-effects model was used to perform the meta-analysis and evaluate heterogeneity. Egger's test and a funnel plot were used to assess small study effects. Subgroup analyses were carried out to explore possible sources of heterogeneity., Results: Seventeen eligible studies comprising 80,680 total persons with 4929 cases for dementia and 13,530 total persons with 1579 cases for cognitive dysfunction were included for dose-response analysis. When compared to the reference group of 0 g/day of alcohol intake, the dose-response meta-analysis revealed a significant non-linear (J-shaped) association between alcohol intake and the risk of each of cognitive dysfunction, (lower dose range: 1-30.5 g/day, RR: 0.97; 95 % CI 0.95-0.99; higher dose range: >30.5 g/day, RR: 1.07; 95 % CI 1.01-1.15) and dementia (lower dose range: 1-17.5 g/day, RR: 0.92; 95 % CI 0.88-0.96, higher dose range: >17.5 g/day, RR: 1.23; 95 % CI 1.09-1.35). The lowest risk was achieved at approximately 30 g/day of alcohol for cognitive dysfunction and 15 g/day for dementia. The J-shape association remained with subgroups defined by age (≤65; >65 years) or study duration (<10; ≥10 years) for dementia, and within age >65 and duration <10 years for cognitive dysfunction., Conclusion: We observed a J-shape association between alcohol consumption and both cognitive dysfunction and dementia, with light-to-moderate alcohol intake being associated with a reduced risk in adults. Further studies are needed to clarify more specifically the association between alcohol consumption and six domains of cognitive dysfunction based on diagnostic and statistical manual of mental disorders (DSM) criteria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Mahsa Samadi et al.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Niyaz Mohammadzadeh Honarvar et al.)

Background: Inositol is a sugar-alcohol and recognized as a key component of cell membrane phospholipids. It has crucial role in the cell signaling pathways and contribute to improving glycemic responses. Although some earlier studies have revealed the effect of inositol mediating glucose uptake by improving insulin sensitivity, the benefit of inositol supplementation in patients with overweight and obesity is not completely understood. This study aimed to assess the impact of inositol supplementation on body mass index (BMI) through a systematic review and meta-analysis of controlled clinical trials., Methods: A systematic search was performed to August 2021 in the following databases: PubMed-Medline, Embase, Web of Science and Scopus. Fifteen controlled clinical trials investigating the effect of inositol on adult's BMI were finally included in the study. A random-effects model was employed to estimate the effect size. Subgroup analysis was performed by dose, duration, age, type of inositol. Meta-regression was used to investigate presence of any linear relationship. Begg's and Egger's tests were carried out to detect small study effect., Results: The results of pooled analysis showed that inositol supplementation significantly decreased BMI scores (WMD = -0.41 kg/m 2 ; 95% CI: -0.78, -0.04; p  = 0.028). Subgroup analysis was performed to identify the source of heterogeneity among studies ( I 2  = 73.9%, p  < 0.001), demonstrating supplementation duration, baseline BMI, mean age of participants, type of inositol and dosage were potential sources of heterogeneity. The effect of intervention was more clinically significant in participants with polycystic ovary syndrome (PCOS) and overweight/obesity. Inositol in the form of myo-inositol (MI) had stronger effect on BMI reduction., Conclusion: The meta-analysis suggests that oral inositol supplementation has positive effect on BMI reduction. Inositol supplementation could be considered as an adjunct treatment to improve body mass index., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background: Aging affects the serum levels of various metabolites which may be involved in the pathogenesis of chronic diseases. The aim of this review article is to summarize the relationship between aging and alterations in the plasma phospholipids and sphingomyelins., Methods: PRISMA guidelines were employed during all steps. MEDLINE (PubMed), Scopus, Embase and Web of Sciences databases and Google Scholar were searched up to October 2020. Cohort studies investigating the relationship between aging and within-person changes in sphingomyelin (SM), phosphatidyl choline (PC), lyso PC (LPC) and phosphatidyl ethanolamine (PE) were included. Newcastle-Ottawa scale was used to assess the quality of included studies., Results: A total of 1425 studies were identified. After removing 610 duplicates and 723 irrelevant studies, full texts of 92 articles were evaluated. Of these 92, 6 studies (including data from 7 independent cohorts) met the inclusion criteria and are included in this review. All study populations were healthy and included both men and women. Results by sex were reported in 3 cohorts for PC, 5 cohorts for LPC, 3 cohorts for SM, and only 1 cohort for PE. In men, PC, SM, PE and LPC decreased with aging, although results for LPC were inconsistent. In women, LPC, SM, and PE increased age, whereas changes in PC were inconsistent., Conclusion: Within-person serum levels of phospholipids and sphingomyelins, decrease during aging in men and increase in women. Notably, however, there were some inconsistencies across studies of LPC in men and of PC in women., (Copyright © 2021. Published by Elsevier B.V.)

Obesity and overweight are associated with the burden of chronic diseases. The aim of the present meta-analysis is to determine the efficacy of spirulina in reducing of obesity indices. PubMed, Web of Science, Scopus, EMBASE and Cochrane library databases were searched up to November 2019. Randomized controlled trials comparing spirulina supplementation with a placebo or no treatment for anthropometric indices were included. Meta-analysis was performed using random-effects model. Subgroup analysis and meta-regression were carried out. Publication bias was evaluated using standard methods. Spirulina had ameliorative effects on weight (WMD = -1.85 Kg; 95% CI: -2.44, -1.26; p < .001; I 2 = 82.4%, p < .001), and waist circumference (WMD = -1.09 cm; 95% CI: -2.16, -0.01; p = .046; I 2 = 0.0%, p = .757) while no significant effect was shown on body mass index, even after sensitivity analysis (SMD = -0.53 Kg/m 2 ; 95% CI: -1.25, 0.19; p = .149; I 2 = 92.9%, p < .001); however, spirulina was effective in studies lasted for at least 12 weeks (SMD = -1.25 Kg/m 2 ; 95% CI: -2.21, -0.28; p = .011; I 2 = 90.8%, p < .001). Spirulina supplementation exerts beneficial effects on weight and waist circumference. The ameliorative effect of spirulina on body mass index was revealed in longer duration of supplementation., (© 2020 John Wiley & Sons Ltd.)

Introduction: The complications of diabetes are extensive which can be caused by excessive oxidative stress, inflammation and impaired insulin system. Plant-sourced bioactive compounds can reduce inflammation and oxidative stress. The aim of present study was to determine the effect of ginger supplementation on diabetic complications., Methods: The present study is a randomized double blind clinical trial which is conducted with 48 diabetic patients. The participants were randomly divided into two intervention and placebo groups which were received 2 g ginger powder and 2 g wheat flour respectively for 10 weeks. Nuclear factor kappa B (NF-κB) concentration and anthropometric measurements were evaluated at the baseline and at the end of study., Results: The effect of ginger supplementation on hip circumference was marginal and there was no significant effect on BMI and waist circumference. Mean NF-κB p65 concentrations were reduced in ginger supplementation group, however, the amount was not statistically significant., Conclusion: Ginger supplementation had significant effects on anthropometric evaluations. Ginger supplementation decreased mean NF-κB concentration in comparison with placebo, however the significance level was marginal. In order to achieve reliable information, more researches should be complemented with uptake of other diagnostic tools., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims Patients with type 2 diabetes mellitus (T2DM) are prone to cardiovascular disease (CVD) due to inflammation process and oxidative stress. ADMA (Asymmetric dimethylarginine) and ICAM-1 (inter-cellular adhesion molecule-1) play an important role in CVD pathogenesis. Ginger as an anti-oxidant and anti-inflammation can effect on these biomarkers. The aim of present study was to characterize the effect of ginger supplementation on ADMA and ICAM-1 serum levels in patients with T2DM. Methods The present study is a randomized double-blind clinical trial which is conducted among 45 diabetic patients (nginger=23, nplacebo=22). The participants were randomly divided into two intervention and placebo groups which were received 2 g ginger powder and 2 g wheat flour for 10 weeks, respectively. ADMA and ICAM-1 concentration were measured by ELISA method. Results Ginger supplementation decreased ADMA serum levels significantly (P=0.002) and sICAM-1 serum levels marginally (P=0.097) in supplementation group after intervention. No significant difference was observed between placebo and supplementation groups. Conclusions Present study was conducted among patients with type 2 diabetes mellitus to investigate the effect of ginger supplementation on ADMA and sICAM-1 levels. There was a significant decrement in ADMA serum concentration and slight reduction in sICAM-1 levels in intervention group. The amount of reduction in both biomarkers was not statistically significant in between-groups comparison.

Background: Several lines of evidence suggest that oxidized LDL (Ox-LDL) scavenger receptors play a crucial role in the genesis and progression of diabetic atherosclerosis. This study aimed to elucidate the effect of vitamin D3 on gene expression of lectin-like oxidized LDL receptor-1 (LOX-1), scavenger receptor-A (SR-A), Cluster of Differentiation 36 (CD36), and Cluster of Differentiation 68 (CD68) as the main Ox-LDL receptors in streptozotocin (STZ)-induced diabetic rat aortas., Methods: Eighteen Sprague-Dawley rats were randomly divided into three groups of six rats each. Two rats died during the study so five rats from each group were analyzed at the study's end. Diabetes was induced in overnight starved rats in two of the groups by intraperitoneal injections of 60 mg/kg of STZ. The vitamin D3/diabetic group then received weekly intraperitoneal injections of 5000 IU/kg of vitamin D3 dissolved in cottonseed oil for four weeks, diabetic controls received cottonseed oil, and healthy controls received sterile saline weekly for the same period. At the end of the four-week study period the animals were killed and the aortas were collected to examine the mRNA expression using real-time polymerase chain reaction (RT-PCR)., Results: SR-A and CD36 mRNA expression were significantly greater in the vitamin D3/diabetic rats than in both the diabetic control and healthy control rats. CD68 and LOX-1 expression were greater in the vitamin D3/diabetic rats than in the diabetic control and healthy control rats, respectively., Conclusion: Vitamin D3 may increase the risk of diabetic atherosclerosis by inducing scavenger receptors expression.

Migraine is a common chronic inflammatory neurological disease with the progressive and episodic course. Much evidence have shown a role of inflammation in the pathogenesis of migraine. Omega-3 fatty acids are an important components of cell membranes phospholipids. The intake of these fatty acids is related to decrease concentration of C-reactive protein (CRP), proinflammatory eicosanoids, cytokines, chemokines and other inflammation biomarkers. Many of clinical trials have shown the beneficial effect of dietary supplementation with omega-3 fatty acids in inflammatory and autoimmune diseases in human, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), multiple sclerosis (MS) and migraine headaches. Therefore, omega-3 fatty acids as an alternative therapy can be potentially important. This review focuses on the pathogenesis of a migraine, with an emphasis on the role of omega-3 fatty acid and its molecular mechanisms.

Background: Lipid and glycemic abnormalities are prevalent in diabetes leading to long term complications. Use of safe and natural foods instead of medications is now considered by many scientists., Objectives: This study aimed at determining the effect of ginger on lipid and glucose levels of patients with type 2 diabetes mellitus., Methods: In a double-blind placebo-controlled trial, 50 patients with type 2 diabetes were randomly allocated to 2 groups of intervention (n = 25) and placebo (n = 25). Each patient received 2000 mg per day of ginger supplements or placebo for 10 weeks. Serum levels of fasting blood sugar (FBS), total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and glycosylated hemoglobin (HbA1C) were analyzed. Daily dietary intakes and anthropometric parameters were also determined., Results: Data from 45 patients were analyzed (23 patients in the ginger group and 22 patients in the control group) at the end of the study. Ginger consumption significantly reduced serum levels of fasting blood glucose (-26.30 ± 35.27 vs. 11.91 ± 38.58 mg/dl; P = 0.001) and hemoglobin A1C (-0.38 ± 0.35 vs. 0.22 ± 0.29 %; P < 0.0001) compared to the placebo group. Ginger consumption also reduced the ratio of LDL-C/HDL-C (2.64 ± 0.85 vs. 2.35 ± 0.8; P = 0.009). However, there was no significant change in serum concentrations of triglycerides, total cholesterol, LDL-C, and HDL-C due to the ginger supplements., Conclusions: The current results showed that ginger could reduce serum levels of fasting blood glucose and hemoglobin A1C in patients with diabetes.

Paraoxonase 1 is known as one of the most important ant oxidative enzymes associated with HDL-c, and because of its antioxidant and antiinflammatory activities. EPA has the antioxidant, anti inflammatory, antithrombogenic, and antiarteriosclerotic properties. Therefore, we investigated the effect of EPA supplementation on the serum levels and activity of PON1 in type 2 diabetic patients. This study was designed as a randomized, double-blind, and placebo-controlled clinical trial. Thirty-six patients with type 2 diabetes were given written; informed consent randomly was classified into 2 groups. They were supplemented with 2 g/day of the capsules of EPA or placebo for eight weeks. Blood sample was given for measurement of the serum levels of lipids, the activity of PON1, FBS and HbA1c. The patients supplemented with EPA showed a significant increase in the serum levels and activity of PON1 and the serum ratio of PON1/HDL-c. There were no significant differences between the two groups regarding any demographic, clinical or biochemical data, total energy intake, and macronutrient intake at the baseline during the intervention, except for a significant increase of protein intake and the levels of HbA1c in the placebo group, and a significant increase of HDL-c, as well as a slight reduction of total cholesterol, LDL-c, TG and FBS in the supplement group. EPA is atheroprotective via increase in the serum levels and activity of PON1, as well as change in the serum levels of lipids, FBS and HbA1c.

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.

Alzheimer's disease (AD) is considered as one of the most prevalent neurodegenerative disorders characterized by progressive loss of mental function and ability to learn. AD is a multifactorial disorder. Various hypotheses are suggested for the pathophysiology of AD including "Aβ hypothesis," "tau hypothesis," and "cholinergic hypothesis." Recently, it has been demonstrated that neuroinflammation is involved in the pathogenesis of AD. Neuroinflammation causes synaptic dysfunction and neuronal death within the brain. Excessive production of pro-inflammatory mediators induces Aβ peptide production/accumulation and hyperphosphorylated tau generating inflammatory molecules and cytokines. These inflammatory molecules disrupt blood-brain barrier integrity and increase the production of Aβ42 oligomers. Retinoids and carotenoids are potent antioxidants and anti-inflammatory agents having neuroprotective properties. They are able to prevent disease progression through several mechanisms such as suppression of Aβ peptide production/accumulation, oxidative stress, and pro-inflammatory mediator's secretion as well as improvement of cognitive performance. These observations, therefore, confirm the neuroprotective role of retinoids and carotenoids through multiple pathways. Therefore, the administration of these nutrients is considered as a promising approach to the prevention and/or treatment of AD in the future. The aim of this review is to present existing evidences regarding the beneficial effects of retinoids and carotenoids on AD's risk and outcomes, seeking the mechanism of their action.

Background: Diabetes refers to a group of metabolic diseases with blood glucose of higher than normal ranges. Furthermore, n-3 polyunsaturated fatty acids are necessary for the regulation of the activity of human function. The effect of n-3 PUFA on diabetes has been investigated in animal studies, yet, the exact amount has not been set, to date. Irisin, as a new myokine, is released from skeletal muscle and Irisin levels decrease as a result of physical inactivity, overweightness, and obesity. Also, the reduction of serum irisin level is associated with development of insulin resistance and type 2 diabetes. This study was performed to assess the effects of n-3 PUFA supplementation on serum irisin level in patients with diabetes., Methods: This randomized clinical trial included 43 patients with type 2 diabetes (21 patients in the placebo group and 22 patients in the n-3 PUFA supplement group). They were randomized to groups, one receiving 10 weeks of either n-3 PUFA supplement and the other the placebo (1250 mg capsule, three times per day). Samples were also matched by age, gender, and body mass index (BMI) in the 2 groups. Anthropometric measurements, demographic information and dietary intakes were obtained both before and after the intervention. Serum irisin levels were measured before and after the intervention using human irisin enzyme linked immunosorbent assay (ELISA) kit. Independent t-test was used to compare the mean outcomes between groups., Results: At baseline, irisin serum levels were not significantly different between the placebo and n-3 PUFA supplementation groups (P > 0.05). However, a significant change was observed between the groups after intervention (P = 0.04). Also there was a significant difference in mean change (after versus before the intervention) (P = 0.05). Compared to the placebo, n-3 PUFA supplementation decreased serum FBS and HbA1C (P = 0.036 and 0.001; respectively). Also, there were significant differences between changes of diastolic blood pressure and HOMA-IR after the intervention between the groups. The duration of illness was not considered as a confounding factor because there was no significant association between irisin level (after versus before the intervention) and the illness duration., Conclusions: The current study indicated that n-3 PUFA supplementation with a dosage of 1250 mg three times per day, resulted in increased serum irisin level of diabetic patients., Competing Interests: Conflict of Interest:The authors declare that they had no conflict of interest.

Background: Omega-3 fatty acids have a protective role against cardiovascular disease and these protective properties are attributed to its anti-inflammatory effects. Myokines have anti-inflammatory properties and thereby reduce low-grade inflammation. Irisin, as a myokine, is considered to be therapeutic for human metabolic diseases. This study was conducted to determine the effects of Omega-3 fatty acids supplementation on serum irisin in men with coronary artery disease (CAD)., Methods: This study was an 8-week randomized, double-blind, placebo-controlled trial. Forty-eight CAD male patients (Omega-3, n = 24; control, n = 24) were randomly assigned to either Omega-3 or control groups by permuted block randomization method. Only the participants with more than 50% stenosis in at least one major coronary vessel were included.  A total of 3 participants in the control group were excluded from the study. Forty-five participants (Omega-3, n = 24; control, n = 21) completed the study. Participants took Omega-3 fatty acids supplement (720 mg eicosapentaenoic acid plus 480 mg docosahexaenoic acid) or placebo (edible paraffin) for 8 weeks. Serum irisin, high-sensitivity C-reactive protein (hs-CRP), lipid profile and anthropometric indices, body composition, and food intake were assessed before and after intervention. Statistical analyses were performed using SPSS software. Paired t-test was used for evaluating within-group effects from baseline. Variables with normal distribution were compared by independent t-test between 2 groups., Results: Compared to placebo, Omega-3 fatty acids increased serum irisin (P = 0.044) and decreased serum hs-CRP (P = 0.018) and LDL cholesterol (P = 0.031). Omega-3 fatty acids supplementation did not result in any significant changes in anthropometric measurements, blood pressure, serum lipids except for serum LDL, fasting blood glucose, body composition or serum insulin levels (all P > 0.05)., Conclusion: Omega-3 fatty acids supplementation could elevate serum irisin in male patients with CAD. Also, these fatty acids may able to decrease serum hs-CRP and LDL cholesterol.

Vitamin A, considered to be an essential nutrient, has important actions in immunological responses and the central nervous system (CNS). Neuroimmunological functions of vitamin A are mediated through its active metabolite, retinoic acid (RA). In the CNS, RA contributes to regeneration and plasticity, while also playing a key role in enhancing tolerance and reducing inflammatory responses by regulating T cell, B cell and dendritic cell populations. However, evidence has indicated lower plasma levels of vitamin A in patients with multiple sclerosis (MS). Vitamin A deficiency leads to dysregulation of immune tolerance and pathogenic immune cell production in this disease. Vitamin A may ameliorate MS pathogenesis through numerous mechanisms including a reduction in inflammatory processes by re-establishing the balance between pathogenic (Th1, Th17, Th9) and immunoprotective cells (Th2, Tregs), modulating B cell and dendritic cell function as well as increasing tolerance of autoimmunity and regeneration in the CNS. Thus, the results from the current review suggest that vitamin A can be considered as a potential treatment in MS disease management.

Vitamin A derivatives such as retinoic acid may improve the impaired balance of CD4+ T cells in autoimmune and inflammatory diseases. This study is a double-blind randomized trial to evaluate the effect of vitamin A (as form of retinyl palmitate) supplementation on multiple sclerosis (MS) patients. Thirty-nine patients were enrolled and randomly assigned to two groups. Both groups were followed for 6 months. The experimental group received 25,000 IU of retinyl palmitate daily, while the control group received a placebo. Before and after the study, the expression of interferon gamma (IFN-γ) and T-bet genes was evaluated in peripheral blood mononuclear cells of patients by RT-PCR. The results showed that after 6 months of supplementation, expression of IFN-γ and T-bet was significantly decreased. These data suggest that retinyl palmitate supplementation can modulate the impaired balance of Th1 and Th2 cells and vitamin A products that may be involved in the therapeutic mechanism of vitamin A in MS patients. This study provides information regarding the decreased gene expression of IFN-γ and T-bet in MS by retinyl palmitate supplementation.

Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis (MS) patients using vitamin A derivatives (retinoic acids) has been well documented. The present study determined the effect of vitamin A supplementation on psychiatric signs in MS patients. The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled randomized clinical trial. The treatment group was administered 25000 IU/d retinyl palmitate (RP) for 6 months followed by 10000 IU/d RP for another 6 months. The results for baseline characteristics, modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study. The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test. (ClinicalTrials.gov Identifiers: NCT01417273). The results showed significant improvement in the treatment group for fatigue (p=0.004) and depression (p=0.01). Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms.

Multiple sclerosis (MS) is an autoinflammatory condition of the central nervous system with impaired T helper (Th)17 and regulatory T cell (Treg) balance that is involved in disease immunopathogenesis. The vitamin A active metabolite, retinoic acid, can re-establish this imbalance through the modulation of gene expression of specific nuclear receptors including Forkhead box P3 (FoxP3). At present, few data exist on the impact of vitamin A supplementation on T cell balance. This study reports the results of a clinical trial, over a 6-month period, of 36 relapsing-remitting MS (RRMS) patients that received vitamin A (25,000 IU retinyl palmitate) or placebo (one capsule of placebo per day). Peripheral blood mononuclear cells were isolated from patients, and the expression of FoxP3 and transforming growth factor (TGF)-β gene expression was measured using real-time PCR at the beginning and end of the study. The results of this study showed that vitamin A upregulated TGF-β and FoxP3 gene expression. Therefore, vitamin A supplementation can be considered as a new approach in MS prevention and treatment.

Multiple Sclerosis (MS) is a chronic inflammatory disease that leads to degeneration of the brain and spinal tissue. Imbalances of CD4+ T cells including Thelper1 (Th1)/Thelper2 (Th2) and Thelper17 (Th17)/Tregulatory (Treg), their secreted cytokines and gene expressions, are important aspects of in immunopathogenesis of MS. Vitamin A and its metabolites can regulate the immune system and appears to be effective in preventing progression of the autoimmune disease such as MS. Disease progression was evaluated By Magnetic Resonance Imaging (MRI), Expanded Disability States Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) tests. Cytokine levels were measured using ELISA kits and gene expression was quantified by Real time PCR (RT-PCR) system. According to the difference between the epidemiological and clinical data on the relationship between vitamin A and immune system regulation, this study of the first time assesses Immune function as well as gene expression and progression of the disease following administration of vitamin A supplement.

The aim of this study was to investigate the role of vitamin A on RORγt and IL-17 gene expression in multiple sclerotic patients. Patients in the vitamin A group received 25,000 IU retinyl palmitate per day, while patients in the placebo group took one capsule of placebo per day for 6 months. Gene expression was measured by real-time PCR at the first and end of the study. The results of this study show that vitamin A downregulates IL-17 and RORγt gene expression. No changes in gene expression occurred in the placebo group.

Vitamin A and its derivatives have been shown to modulate the immune system via retinoic acid receptor (RAR). This study explored the impact of retinyl palmitate supplementation on RAR subtype gene expression in peripheral blood mononuclear cells (PBMCs) in multiple sclerosis (MS) patients. The study designed as a double-blind randomized clinical trial in which relapsing remitting multiple sclerosis patients were evaluated. Both groups received one capsule 50,000 IU vitamin D3 per 2 weeks and one intramuscular injection interferon beta-1a per week. The intervention group received one 25,000 IU retinyl palmitate capsule daily for 6 months and the placebo group received one placebo capsule daily. The PBMCs were isolated from participants and the expression level changes of RAR-α and RAR-γ genes were determined by real-time PCR. After supplementation, in the intervention group, the RAR-α gene expression level was significantly decreased compared to the placebo group (p = 0.03); however, the expression of RAR-γ gene did not significantly change (p = 0.10). These results show that vitamin A supplementation can significantly downregulate the expression of RAR-α gene in PBMCs of MS patients that suggest the presence of in vivo regulatory mechanisms for the action of vitamin A on the immune system.