Effects of crocin on inflammatory biomarkers and mental health status in patients with multiple sclerosis: A randomized, double-blinded clinical trial.

BACKGROUND: Multiple sclerosis (MS), as a demyelinating disease correlated with inflammation and oxidative stress, affects the central nervous system and causes a wide range of complications, including psychiatric disorders. Considering the anti-inflammatory and antioxidant properties associated with the bioactive components of saffron, such as crocin (trans-crocetin bis(ß-d-gentiobiosyl) ester), and their potential impact on ameliorating psychiatric symptoms, our study aimed to investigate the effect of crocin on biomarkers of inflammation, oxidative stress, and mental health, e.g., depression and anxiety in individuals with MS. METHOD: Patients with MS were randomized into two groups, taking either 15 mg crocin tablets twice a day (n = 25; 30 mg/day) or placebo tablets (n = 25) for 8 weeks. The valid and reliable Beck depression and anxiety scale questionnaire was recorded, and fasting blood samples were collected to measure biomarkers, including high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and nitric oxide (NO) at baseline and week 8 following the intervention. RESULTS: The data analysis using ANCOVA showed that supplementation with crocin for 8 weeks significantly lowered hs-CRP levels (p-value= 0.01). In addition, within-group comparisons showed crocin significantly decreased anxiety (p-value= 0.01). However, crocin did not affect serum MDA and NO after 8 weeks of intervention. CONCLUSION: Our findings suggest that crocin may keep promise in attenuating inflammation, evidenced by reducing hs-CRP in patients with MS. However, supplementation for 8 weeks may not be sufficient to improve mental health, and future clinical studies with higher sample sizes and various doses and durations are recommended.

The influence of propolis plus Hyoscyamus niger L. against COVID-19: A phase II, multicenter, placebo-controlled, randomized trial.

The incubation period of COVID-19 symptoms, along with the proliferation and high transmission rate of the SARS-CoV-2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID-19 with acute disease conditions in a double-blinded approach. The study was performed on 140 patients with COVID-19 in a double-blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID-19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID-19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID-19. So, this syrup promises to be an effective treatment in the great challenge of COVID-19.

The effect of vitamin D supplementation on tobacco-related disorders in individuals with a tobacco use disorder: a randomized clinical trial.

Vitamin D deficiency in cigarette smokers (CS) might associate with several complications, including metabolic deficits, depression and anxiety. This study evaluated the effects of vitamin D on mental health symptoms, nicotine misuse, and biomarkers of metabolic diseases in individuals with a tobacco use disorder. A randomized, double-blind, placebo-controlled trial was conducted with 60 CS subjects receiving either 50,000 IU vitamin D supplements (n = 30) or placebo (n = 30) every 2 weeks for 24-weeks. Nicotine misuse, mental health scale, and metabolic parameters were measured before and after the intervention in the CS subjects. Compared with the placebo-group, after the 24-weeks intervention, serum 25 (OH) vitamin D levels increased in the intervention group (ß 2.96; 95% CI, 0.91, 5.01; P = 0.006). In addition, vitamin D supplementation significantly improved Beck Depression Inventory (BDI) (ß -2.06; 95% CI, -3.84, -0.28; P = 0.02). In addition, vitamin D administration significantly decreased fasting plasma glucose (FPG) (ß -4.56; 95% CI, -8.94, -0.19; P = 0.04), insulin (ß -0.50; 95% CI, -0.88, -0.13; P = 0.009), and homeostasis model of assessment-estimated insulin resistance (HOMA-IR) levels (ß -0.21; 95% CI, -0.33, -0.08; P = 0.001). Furthermore, vitamin D resulted in a significant elevation in total antioxidant capacity (TAC) (ß 81.20; 95% CI, 18.30, 144.11; P = 0.01), and plasma glutathione (GSH) levels (ß 73.05; 95% CI, 18.56, 127.54; P = 0.01), compared with the placebo-group. Administration of vitamin D for 24-weeks to CS subjects had beneficial effects on symptoms of depression and several metabolic biomarkers. While this preliminary study suggests that vitamin D might have beneficial effects, its clinical efficacy in individuals with a tobacco use disorder should be further validated in future clinical trials.

Efficacy of Persian medicine herbal formulations (capsules and decoction) compared to standard care in patients with COVID-19, a multicenter open-labeled, randomized, controlled clinical trial.

Persian medicine has recommended clinical experiences and proper herbal remedies for prevention and treatment of microbial infections and respiratory diseases. An open-label, randomized, controlled, multicenter trial was conducted at five hospitals in Tehran and Isfahan provinces of Iran on 358 hospitalized adult patients. A total of 174 patients received standard care and 184 received herbal remedies (polyherbal decoction every 8 hr and two herbal capsules every 12 hr) plus standard care for 7 days. The primary clinical endpoint was the duration of hospital stay, and secondary outcomes were clinical improvement of symptoms based on self-assessment questionnaire. Results demonstrated that these natural decoction and capsules treatment plus routine care significantly decreased duration of hospital dyspnea (3.291 day vs. 6.468 days), accelerated clinical improvement, and decreased symptoms such as dry cough, dyspnea, muscle pain, headache, fatigue, anorexia, chills, runny nose, sputum cough, and vertigo in the treatment group compared with standard-care group. Significant effects of these polyherbal formulations on improving the symptoms of COVID-19 could be incredibly promising for managing this pandemic with acceptable tolerability.

Effect of biotin supplementation on neuropathic pain induced by chronic constriction of the sciatic nerve in the rat.

BACKGROUND AND PURPOSE: Neuropathic pain is one of the most common types of chronic pain that is very difficult to treat. Numerous studies have shown the potential role of vitamins in relieving both hyperalgesia and allodynia. Based on the convincing evidence, this study was designed to evaluate the possible antinociceptive effect of biotin on neuropathic pain in rats. EXPERIMENTAL APPROACH: This study was performed on male Sprague Dawley rats weighing 200-300 g. Neuropathic pain was induced by tying the sciatic nerve. Chronic constriction injury (CCI) of the sciatic nerve resulted in hyperalgesia and allodynia. To measure the thermal hyperalgesia, the plantar test was used. Also to evaluate the cold and mechanical allodynia, acetone test and von Frey test were applied. Biotin (4, 8, and 16 mg/kg) was administered orally as two different treatment regimens, acute and chronic. FINDINGS/RESULTS: Acute oral administration of biotin (4, 8, and 16 mg/kg p.o.) on the 7th, 14th, and 21st postoperative days couldn't reduce pain sensitivity compared to the CCI group. However, following the oral administration of biotin (8 and 16 mg/kg p.o.) from the first day after the surgery until day 21, mechanical allodynia (P < 0.001) and heat hyperalgesia (P < 0.05) significantly relieved. CONCLUSION AND IMPLICATIONS: Our results suggest that biotin can be considered as a potential therapeutic for the treatment of neuropathic pain, and supplementation with this vitamin could reduce the required doses of analgesic drugs. However, further studies are needed to confirm this hypothesis.

The effect of propolis plus Hyoscyamus niger L. methanolic extract on clinical symptoms in patients with acute respiratory syndrome suspected to COVID-19: A clinical trial.

The outbreak of Coronavirus disease 2019 (COVID-19) has caused a global health crisis. Nevertheless, no antiviral treatment has yet been proven effective for treating COVID-19 and symptomatic supportive cares have been the most common treatment. Therefore, the present study was designed to evaluate the effects of propolis and Hyoscyamus niger L. extract in patients with COVID-19. This randomized clinical trial was conducted on 50 cases referred to Akhavan and Sepehri Clinics, Kashan university of medical sciences, Iran. Subjects were divided into two groups (intervention and placebo). This syrup (containing 1.6 mg of methanolic extract along with 450 mg of propolis per 10 mL) was administered three times a day to each patient for 6 days. The clinical symptoms of COVID-19 such as: dry cough, shortness of breath, sore throat, chest pain, fever, dizziness, headache, abdominal pain, and diarrhea were reduced with propolis plus Hyoscyamus niger L. extract than the placebo group. However, the administration of syrup was not effective in the control of nausea and vomiting. In conclusion, syrup containing propolis and Hyoscyamus niger L. extract had beneficial effects in ameliorating the signs and symptoms of COVID-19 disease, in comparison with placebo groups.

The effect of vitamin C on procalcitonin biomarker in community-acquired pneumonia.

INTRODUCTION: Community acquired pneumonia (CAP) is a prevalent low respiratory infection. Diagnosis is based on clinical symptoms, radiologic evidence and culture. Biomarkers such as IL6, CRP and procalcitonin are helpful in diagnosis. Procalcitonin is a soluble biomarker in serum that increase in systemic inflammation and bacterial infections. People with normal procalcitonin have low risk to infect pneumonia. Patient with CAP have more oxidative stress than normal people. Studies show that receiving vitamin C can reduce incidence of pneumonia. The present study was designed to evaluate the effect of vitamin C supplement on procalcitonin biomarker in patient with CAP. METHODS: Patients with CAP who passed inclusion and exclusion criteria after obtaining informed consent, were assigned randomly in two groups of drug and placebo. The drug group received vitamin C (1000 mg/d) daily and medications that physician prescribed for treating CAP for 10 days and placebo group received placebo and medications that physician prescribed. The serum level of procalcitonin was measured at the beginning of the study and after 10 days of intervention. RESULTS: 35 patients finished the study. Serum level of procalcitonin on the first and tenth day did not show any significant difference between drug and placebo groups. CONCLUSIONS: To clarify the relationship between the effects of vitamin C on procalcitonin in CAP, a larger sample size is required.

The effect of crocin (the main active saffron constituent) on the cognitive functions, craving, and withdrawal syndrome in opioid patients under methadone maintenance treatment.

Individuals under methadone maintenance treatment (MMT) programs are susceptible to several complications, including withdrawal syndrome, craving, and cognitive deficits. This study was designed to elevate the effect of crocin administration on withdrawal syndrome, craving, and cognitive function in subjects under MMT programs. It was a clinical trial that was conducted among 60 patients referred to Soltan Mirahmad Clinic for addict patients in Kashan, Iran. The patients were allocated to two groups including placebo and intervention groups. The intervention group received 30 mg/day crocin (n = 30) and placebo (n = 30) once a day, in 12 weeks. Withdrawal syndrome, craving, and cognitive function parameters were measured before and after the intervention in subjects under MMT programs. Compared with the placebo group, crocin resulted in a significant improvement in craving score (p = .03), and withdrawal symptoms score (p = .01) in the intervention group. In addition, crocin supplementation did not affect cognitive function parameters (e.g., TMT, FAS test, and DGSP score). Overall, crocin supplementation for 12 weeks to patients under MMT programs had beneficial effects on craving and withdrawal symptoms score, but did not affect the cognitive function parameters.

Nanomicellar-curcumin exerts its therapeutic effects via affecting angiogenesis, apoptosis, and T cells in a mouse model of melanoma lung metastasis.

BACKGROUND: Curcumin is a natural phytochemical polyphenol with significant anti-cancer effects and negligible side effects. In this study, the therapeutic capacity of nanomicellar-curcumin for treating lung metastasis was evaluated in an immunocompetent mouse model of metastatic melanoma. MARTIALS AND METHODS: Two doses of nanomicellar-curcumin (i.e. 10 and 20 µM) were used to induce cytotoxicity in 3 melanoma cell lines. A total of 60 mice were allocated to 20 mice in each of three groups (10 for survival and 10 for assays). Groups were no treatment control, PBS control, nanomicellar-curcumin 20 mg/kg IP 4 times a week, for three weeks). Immunohistochemistry, TUNEL assay, and Western blots were used on lung samples. RESULTS: Nanomicellar-curcumin inhibited the in vitro growth of B16 F10 melanoma cells at 20 µM over 72 h. In vivo, 20 mg/kg nanomicellar-curcumin injected IP, delayed tumor cell growth and significantly extended mouse survival rate. Tumor infiltration of regulatory T cells and angiogenesis were reduced, while IFN-γ and CXCL10 were increased. CONCLUSION: Nanomicellar-curcumin can inhibit lung metastasis and growing melanoma via activation of apoptosis, activated T cells and inhibition of angiogenesis, tumor growth and regulatory T cells.

The Effect of Transcranial Direct Current Stimulation on Relapse, Anxiety, and Depression in Patients With Opioid Dependence Under Methadone Maintenance Treatment: A Pilot Study.

BACKGROUND AND OBJECTIVE: Patients under methadone maintenance therapy (MMT) are susceptible to several complications including mental disturbances and risk of relapse. The present study was designed to evaluate the effects of tDCS on relapse, depression, and anxiety of opioid-dependent patients under methadone maintenance treatment (MMT). METHODS: It was a randomized-clinical trial that conducted among 27 male patients referred to the outpatient addiction clinic of Ibn-e-Sina psychiatric hospital in Mashhad from July 2018 to May 2019. Participants were allocated to two treatment groups including intervention and sham groups. The intervention group received seven sessions of tDCS, in the F3 (cathode) and F4 (anode) areas of the brain, each one lasts 20 min, in two consecutive weeks. Depression, anxiety, and stress scale-21 (DASS-21) were measured before, during, and after the intervention in patients under MMT. Relapse on the morphine, cannabis, and methamphetamine was screened by urine dipstick tests of morphine, cannabis, and methamphetamine. RESULTS: Depression, anxiety, and stress of participants were significantly reduced in the intervention group compared with the control after the seventh session of tDCS (P < 0.001, P=0.01, and P=0.01, respectively). In addition, the relapse rate showed no significant changes between the two groups (P=0.33). CONCLUSION: Overall, our study demonstrated that depression, anxiety, and stress of participants were significantly reduced after the seventh session of tDCS, but did not affect on the relapse rate. Therefore, it can be applied as a safe and effective technique to relieve mental disorder among receiving MMT. CLINICAL TRIAL REGISTRATION: http://www.irct.ir, identifier IRCT20180604039979N1.

The effects of saffron (Crocus sativus L.) on mental health parameters and C-reactive protein: A meta-analysis of randomized clinical trials.

BACKGROUND: The findings of trials investigating the effects of saffron (Crocus sativus L.) supplementation on depression, anxiety, and C-reactive protein (CRP) are inconsistent. The current meta-analysis of randomized controlled trials (RCTs) was carried out to assess the effects of saffron (Crocus sativus L.) administration on mental health parameters and CRP levels. METHODS: Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until 30th July 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. RESULTS: Twenty one trials were included in this meta-analysis. Consumption of saffron resulted in a significant reduction in Beck Depression Inventory (BDI) (11 studies with 12 effect size) (WMD: -4.86; 95 % CI: -6.58, -3.14), Beck Anxiety Inventory (BAI) (5 studies) (WMD: -5.29; 95 % CI: -8.27, -2.31) and Pittsburgh Sleep Quality Index (PSQI) scores (3 studies with 4 effect size) (WMD: -2.22; 95 % CI: -2.73, -1.72). Saffron intake did not affect Hamilton Depression Rating Scale (HDRS-D), Hamilton Anxiety Rating Scale (HARS-A) scores and C-reactive protein (CRP) levels. CONCLUSIONS: This meta-analysis demonstrated that saffron intake significantly reduced BDI, BAI and PSQI scores, but did not affect HDRS-D, HARS-A scores and CRP levels.

Clinical and metabolic responses to crocin in patients under methadone maintenance treatment: A randomized clinical trial.

Patients under methadone maintenance treatment (MMT) programs are susceptible to several complications including metabolic and clinical disorders. This study was designed to determine the effect of crocin supplementation on mental health parameters and metabolic profiles in subjects under MMT. The current randomized, double-blind, placebo-controlled, clinical trial was conducted among 53 patients under MMT to receive either 15 mg/day of crocin (n = 26) or placebo (n = 27) twice a day for 8 weeks. Crocin administration significantly decreased Beck Depression Inventory score (P = 0.01) and Beck Anxiety Inventory score (P = 0.008) compared with the placebo. In addition, crocin administration resulted in a significant reduction in fasting glucose (P = 0.003), insulin levels (P = 0.01), insulin resistance (P = 0.008), triglycerides (P = 0.001), very low-density lipoprotein (P = 0.001), total cholesterol levels (P = 0.03), and a significant increase in insulin sensitivity (.003) compared with the placebo. Additionally, crocin intake was associated with a significant reduction in high-sensitivity C-reactive protein (p < .001) and malondialdehyde (P = 0.001) and a significant rise in total antioxidant capacity levels (P = 0.01) compared with the placebo. The findings of this clinical trial indicate that taking crocin for 8 weeks by patients under MMT had beneficial effects on their mental health and improved their metabolic profiles.

Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients.

BACKGROUND: This study determined the effects of a novel combination of vitamin D and probiotic on metabolic and clinical symptoms in chronic schizophrenia. METHODS: This trial was conducted among 60 patients with chronic schizophrenia to receive either 50,000 IU vitamin D3 every 2 weeks plus 8 × 109 CFU/day probiotic (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: Vitamin D and probiotic co-supplementation was associated with a significant improvement in the general (- 3.1 ± 4.7 vs. + 0.3 ± 3.9, P = 0.004) and total PANSS scores (- 7.4 ± 8.7 vs. -1.9 ± 7.5, P = 0.01). Vitamin D and probiotic co-supplementation also significantly increased total antioxidant capacity (+ 51.1 ± 129.7 vs. -20.7 ± 53.3 mmol/L, P = 0.007), and significantly decreased malondialdehyde (- 0.3 ± 0.9 vs. + 0.2 ± 0.4 µmol/L, P = 0.01) and high sensitivity C-reactive protein levels (- 2.3 ± 3.0 vs. -0.3 ± 0.8 mg/L, P = 0.001) compared with the placebo. Moreover, taking vitamin D plus probiotic significantly reduced fasting plasma glucose (- 7.0 ± 9.9 vs. -0.2 ± 9.9 mg/dL, P = 0.01), insulin concentrations (- 2.7 ± 2.3 vs. + 0.4 ± 2.0 µIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (- 0.8 ± 0.7 vs. + 0.1 ± 0.7, P < 0.001), triglycerides (- 7.8 ± 25.2 vs. + 10.1 ± 30.8 mg/dL, P = 0.01) and total cholesterol levels (- 4.9 ± 15.0 vs. + 5.9 ± 19.5 mg/dL, P = 0.04) and total-/HDL-cholesterol ratio (- 0.1 ± 0.6 vs. + 0.3 ± 0.8, P = 0.04). CONCLUSION: Probiotic and vitamin D for 12 weeks to chronic schizophrenia had beneficial effects on the general and total PANSS score, and metabolic profiles. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT2017072333551N2). 07-31-2017 2.

Inhibitory effects of chronic administration of vitamin D3 on pentylenetetrazole-induced seizures in mice.

Vitamin D3 as a neuroactive steroid hormone plays an important role in the nervous system. Recent clinical and experimental studies have shown an association between vitamin D-related disorders and epilepsy. Therefore, this study was designed to examine the effects of chronic administration of vitamin D3 on pentylenetetrazole (PTZ)-induced seizure in mice. This interventional study was conducted on 120 mice in 12 groups. Two control groups acutely and chronically received a mixture of almond oil and paraffin; three groups were acutely given vitamin D3 at doses of 2000, 4000 and 6000 IU/kg; three groups chronically received vitamin D3 with similar doses for two weeks and two groups chronically and acutely received a sub-effective dose of vitamin D3 and diazepam. Slow intravenous infusion of PTZ (5 mg/mL) was performed at a constant rate (0.3 mL/min) via an infusion pump to induce clonic and tonic seizures. Acute injection of different concentrations of vitamin D3 (2000, 4000 and 6000 IU/kg i.p.) did not significantly increase a seizure threshold. However, a seizure threshold in the groups chronically treated with 4000, and 6000 IU/kg of vitamin D3 was significantly higher than that in the control group (P < 0.001). Moreover, a combination of the sub-effective dose of vitamin D3 (2000 IU/kg) and diazepam (0.1 mg/kg) significantly increased seizure threshold. Our findings suggest that administration of vitamin D supplement can be considered as a potential add-on treatment in seizure and due to the vitamin D deficiency results from the long-term use of most anti-seizure drugs, this supplementation becomes more important.

Vitamin D supplementation attenuates the behavioral scores of neuropathic pain in rats.

Objective(s): Neuropathic pain due to lesion or dysfunction of the peripheral or central nervous system is often refractory to the conventional analgesics. Currently, there is no proven treatment to prevent or cure neuropathic pain. A recent surge of new data suggests the potential effects of vitamin D in the medical community. This study was designed to determine whether acute or chronic vitamin D administration was effective in alleviating symptoms of neuropathic pain in a rat model of neuropathic pain. Materials and Methods: Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted in thermal hyperalgesia, mechanical, and cold allodynia. Results: Acute vitamin D injections (250, 500, and 1000 unit/kg i.p.) on the 7th, 14th, and 21st postoperative days could not attenuate mechanical and cold allodynia as well as heat hyperalgesia compared to CCI group. But when vitamin D (1000 unit/kg i.p.) administration was started on the first day after surgery and given daily until the 21st day, cold allodynia and heat hyperalgesia considerably were attenuated. However, no differences in paw withdrawal thresholds were observed. Conclusion: These results indicate that chronic vitamin D administrations can attenuate the behavioral scores of neuropathic pain in rats.

The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment.

This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (ß -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (ß -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (ß -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (ß 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (ß -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (ß -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (ß 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (ß 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (ß -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (ß -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (ß -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.

Prophylactic effect of riboflavin on pediatric migraine: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIM: Riboflavin may have an acceptable effect on migraine among children. This study was carried out to determine the prophylactic effect of riboflavin on migraine in children. METHODS: This randomized clinical trial study was performed at Shahid Beheshti Hospital in Kashan, Iran from December 2012 to February 2015. Ninety children with migraine were allocated randomly into 3 groups (placebo, low-dose and high-dose riboflavin). The outcomes (frequency, intensity and duration of headaches) were measured at baseline and 12 weeks of medication in each group, and the decrease of them were compared. SPSS software version 16 was used for analysis of the data. Descriptive statistics, Chi-square, Fisher's exact and t-test were used for statistical analyses. RESULTS: There was a significant decrease of migraine frequency (p=0.000) and mean duration (p=0.000) in the high-dose group compared with the placebo group. No significant reduction of frequency and mean duration of attacks were reported in the low-dose group compared to the placebo group (p=0.49 and p=0.69 respectively). There was no significant reduction of migraine intensity in the low-dose and high-dose groups compared to the placebo group (p=0.71 and p=0.74 respectively). CONCLUSION: High-dose riboflavin is a safe, well tolerated, cost-effective method of prophylaxis for children with migraine. TRIAL REGISTRATION: The trial was registered at the Iranian Clinical Trial Registry with number IRCT2013020412361N1. FUNDING: The study was supported by the Deputy of Research, Kashan University of Medical Sciences (grant number 91073).

Clinical trial of the effects of vitamin D supplementation on psychological symptoms and metabolic profiles in maintenance methadone treatment patients.

BACKGROUND: Vitamin D deficiency may be associated with some complications including nonspecific musculoskeletal pain and periodontal disease in maintenance methadone treatment (MMT) patients. This study was designed to determine the effect of vitamin D supplementation on psychological symptoms and metabolic profiles in MMT patients. METHODS: This randomized, double-blind, placebo-controlled, clinical trial was carried out among 68 MMT patients. Participants were randomly allocated to receive either 50,000IU vitamin D supplements (n=34) or placebo (n=34) every 2weeks for 12weeks. Fasting blood samples were taken at baseline and post-intervention to evaluate relevant variables. RESULTS: After the 12-week intervention, serum 25(OH) vitamin D levels significantly increased in the intervention group compared with the placebo group (+8.1±4.9 vs. -0.4±3.0, P<0.001). In addition, vitamin D supplementation significantly improved Pittsburgh Sleep Quality Index (-1.5±2.2 vs. -0.2±2.3, P=0.02) and Beck Depression Inventory (-4.8±7.3 vs. -1.5±6.1, P=0.04) compared with the placebo. Patients who received vitamin D supplements had significantly decreased fasting plasma glucose (-7.5±10.6 vs. +0.3±10.7mg/dL, P=0.004), serum insulin levels (-3.6±5.3 vs. -0.9±3.5 µIU/mL, P=0.01), homeostasis model of assessment-insulin resistance (-1.0±1.3 vs. -0.2±0.7, P=0.003), serum triglycerides (-9.6±30.8 vs. +15.6±30.2mg/dL, P=0.001), total- (-8.7±20.9 vs. +11.0±27.4mg/dL, P=0.001) and LDL-cholesterol (-11.1±17.9 vs. +5.9±27.5mg/dL, P=0.004) compared with the placebo. Additionally, vitamin D intake resulted in a significant decrease in serum high sensitivity C-reactive protein (-2.2±4.2 vs. +2.0±3.7mg/L, P<0.001), and significant increases plasma total antioxidant capacity (+26.2±99.8 vs. -86.3±127.5mmol/L, P<0.001) and glutathione levels (+292.3±172.4 vs. +48.9±208.9µmol/L, P<0.001) compared with the placebo. There was no significant effect of vitamin D supplementation on serum HDL-cholesterol, and other markers of insulin metabolism, inflammation and oxidative stress. CONCLUSIONS: Totally, taking 50,000IU vitamin D supplement every 2weeks for 12weeks in MMT patients had beneficial effects on psychological symptoms and few metabolic profiles.