Effect of probiotic supplementation on migraine prophylaxis: a systematic review and meta-analysis of randomized controlled trials.

Objective: The prevalence of migraine is higher in patients with gastrointestinal disorders. Possible underlying mechanisms could be increased intestinal permeability and systemic inflammation. Probiotics may reduce gut permeability as well as inflammation, and therefore may improve the clinical features of migraine. This systematic review and meta-analysis aimed to evaluate the impact of probiotic supplementation on the frequency and severity of migraine attacks.Methods: A systematic review of the literature was conducted using ISI Web of Science, PubMed/Medline, Scopus, Cochrane Library, EMBASE, Google Scholar, Magiran.com and Sid.ir to identify eligible studies published up to October 2019. A meta-analysis of eligible trials was performed using the random-effects model to estimate pooled effect size.Results: Three randomized controlled trials with 179 patients (probiotic group = 94, placebo group = 85) were included. Probiotic supplementation had no significant effect on frequency (weighted mean difference (WMD) = -2.54 attacks/month, 95%CI: -5.31-0.22, p = 0.071) and severity of migraine attacks (WMD = -1.23 visual analog scale (VAS) score, 95%CI = -3.37-0.92, p = 0.262) with significant heterogeneity among the studies (I2 = 98%, p < 0.001).Conclusions: A pooled analysis of available randomized controlled clinical trials showed that probiotic supplementation had no significant effect on the frequency and severity of episodic migraine attacks.

The synergistic effects of nano-curcumin and coenzyme Q10 supplementation in migraine prophylaxis: a randomized, placebo-controlled, double-blind trial.

Introduction: Migraine is a disabling neurovascular disorder characterized by increasing levels of pro-inflammatory cytokines and oxidative stress biomarkers. Curcumin and coenzyme Q10 (CoQ10) can exert neuroprotective effects through modulation of inflammation and oxidative stress. The aim of the present study was to evaluate the combined effects of nano-curcumin and CoQ10 supplementation on migraine symptoms and quality of life in migraine patients.Methods: One-hundred men and women (mean age 32 years) with episodic migraine based on the International Headache Society (IHS) criteria participated in this study. The subjects were randomly divided into four groups as (1) combination of nano-curcumin (80 mg) plus CoQ10 (300 mg), (2) nano-curcumin (80 mg), (3) CoQ10 (300 mg) and (4) the control (nano-curcumin and CoQ10 placebo included oral paraffin oil) beside usual prophylactic drugs for 8 weeks. Frequency, severity, duration of headache attacks, the headache diary results (HDR) and headache disability based on migraine-specific questionnaires were assessed at the baseline and end of the study.Results: Ninety-one of 100 patients completed the study. The results showed a significant effect of nano-curcumin and CoQ10 supplementation on frequency, severity, duration of migraine attacks and HDR compared to other groups (All P < 0.001). Nano-curcumin and CoQ10 group also had better scores in migraine-specific questionnaires at the end of the study compared to other groups (All P < 0.001). There were no side effects reported by the participants.Conclusions: These findings suggest a possible synergistic effect of nano-curcumin and CoQ10 on clinical features of migraine.Trial registration number: IRCT2017080135444N1.

Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies.

PURPOSE: Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection. METHODS: Online databases including Web of Science, PubMed, Scopus, Cochrane Library and Google scholar were searched to detect relevant publications up to 1 May 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done. RESULTS: In total, 14 studies with 29,909 COVID-19 infected patients and 1445 cases of death were included in the current meta-analysis. Significant associations were found between older age (≥65 vs <65 years old) (pooled ORs = 4.59, 95%CIs = 2.61-8.04, p < .001), gender (male vs female) (pooled ORs = 1.50, 95%CIs = 1.06-2.12, p = .021) and risk of death from COVID-19 infection. In addition, hypertension (pooled ORs = 2.70, 95%CIs = 1.40-5.24, p = .003), cardiovascular diseases (CVDs) (pooled ORs = 3.72, 95%CIs = 1.77-7.83, p = .001), diabetes (pooled ORs = 2.41, 95%CIs = 1.05-5.51, p = .037), chronic obstructive pulmonary disease (COPD) (pooled ORs = 3.53, 95%CIs = 1.79-6.96, p < .001) and cancer (pooled ORs = 3.04, 95%CIs = 1.80-5.14, p < .001), were associated with higher risk of mortality. CONCLUSIONS: Older age (≥65 years old), male gender, hypertension, CVDs, diabetes, COPD and malignancies were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.

Liver injury is associated with severe coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of retrospective studies.

The coronavirus disease 2019 (COVID-19) outbreak is a major threat to human beings. Lung injury has been reported as the major outcome of COVID-19 infection. However, liver damage has also been considered to occur in severe cases. The current meta-analysis of retrospective studies was carried out to summarize available findings on the association between liver injury and severity of COVID-19 infection. Online databases including PubMed, Scopus, Web of Science, and Cochrane Library were searched to detect relevant publications up to 1 April 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. Furthermore, publication bias test and sensitivity analysis were also applied. In total, 20 retrospective studies with 3428 COVID-19 infected patients (severe cases, n = 1455; mild cases, n = 1973), were included in this meta-analysis. Higher serum levels of aspartate aminotransferase (weighted mean difference, 8.84 U/L; 95% confidence interval [CI] 5.97 to 11.71; P < 0.001), alanine aminotransferase (weighted mean difference, 7.35 U/L; 95% CI, 4.77 to 9.93; P < 0.001), total bilirubin (weighted mean difference, 2.30 mmol/L; 95% CI, 1.24 to 3.36; P < 0.001), and lower serum levels of albumin (weighted mean difference, -4.24 g/L; 95% CI, -6.20 to -2.28; P < 0.001) were associated with a significant increase in the severity of COVID-19 infection. The incidence of liver injury, as assessed by serum analysis (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels), seems to be higher in patients with severe COVID-19 infection.

The effect of probiotics on inflammatory biomarkers: a meta-analysis of randomized clinical trials.

PURPOSE: No study has summarized earlier findings on the effect of probiotic supplementation on inflammatory biomarkers. This systematic review and meta-analysis was conducted to systematically review the available placebo-controlled clinical trials about the effect of probiotic supplementation on several inflammatory biomarkers in adults. METHODS: Relevant papers published up to March 2018 were searched up through PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar, using following suitable keywords. Clinical trials that examined the effect of probiotic supplementation on inflammation in adults were included. RESULTS: Overall, 42 randomized clinical trials (1138 participants in intervention and 1120 participants in control groups) were included. Combining findings from included studies, we found a significant reduction in serum hs-CRP [standardized mean difference (SMD) - 0.46; 95% CI - 0.73, - 0.19], TNF-a (- 0.21; - 0.34, - 0.08), IL-6 (- 0.37; - 0.51, - 0.24), IL-12 (- 0.47; - 0.67, - 0.27), and IL-4 concentrations (- 0.48; - 0.76, - 0.20) after probiotic supplementation. Pooling effect sizes from 11 studies with 12 effect sizes, a significant increase in IL-10 concentrations was seen (0.21; 0.04, 0.38). We failed to find a significant effect of probiotic supplementation on serum IL-1B (- 0.17; - 0.37, 0.02), IL-8 (- 0.01; - 0.30, 0.28), and IFN-g (- 0.08; - 0.31, 0.15) and IL-17 concentrations (0.06; - 0.34, 0.46). CONCLUSIONS: Probiotic supplementation significantly reduced serum concentrations of pro-inflammatory cytokines including, hs-CRP, TNF-a, IL-6, IL-12, and IL-4, but it did not influence IL-1B, IL-8, IFN-g, and IL-17 concentrations. A significant increase in serum concentrations of IL-10, as a anti-inflammatory cytokine was also documented after probiotic supplementation.

Effect of coenzyme Q10 supplementation on clinical features of migraine: a systematic review and dose-response meta-analysis of randomized controlled trials.

Objective: Coenzyme Q10 is an antioxidant and an essential mitochondrial cofactor which has been suggested to improve the clinical features of migraine. Several randomized clinical trials have examined the effects of Coenzyme Q10 on migraine with inconclusive results. The aim of this systematic review and meta-analysis was to evaluate the impact of Coenzyme Q10 supplementation on the frequency, severity, and duration of migraine attacks. Methods: A systematic review of the literature was conducted using ISI Web of Science, PubMed, Cochrane library and Scopus to identify eligible studies up to April 2018. Studies included were randomized clinical trials of Coenzyme Q10 supplementation that reported the frequency, severity, or duration of migraine attacks as a primary outcome. A meta-analysis of eligible studies was performed using the fixed effects model or the random effects model to estimate pooled effect size. Results: Four randomized clinical trials with 221 participants were included. Coenzyme Q10 supplementation significantly reduced the frequency of migraine attacks (weighted mean difference: -1.87 attacks/month, 95% CI: -2.69 to -1.05, p < 0.001) without significant heterogeneity among the studies (I 2 = 36.6%, p = 0.192). Coenzyme Q10 supplementation had no significant effect on severity (weighted mean difference: -2.35 visual analog scale score, 95% CI: -5.19 to 0.49, p = 0.105) and duration of migraine attacks (weighted mean difference: -6.14 h, 95% CI: -13.14 to 0.87, p = 0.086) with high heterogeneity. Conclusion: Pooled analyses of available randomized clinical trials suggest that Coenzyme Q10 supplementation may reduce the frequency of migraine attacks per month without affecting the severity or duration of migraine attacks.

The effects of curcumin supplementation on body mass index, body weight, and waist circumference in patients with nonalcoholic fatty liver disease: A systematic review and dose-response meta-analysis of randomized controlled trials.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity; its prevalence is elevating due to the rising epidemic of obesity. Several clinical trials have examined the effects of curcumin supplementation on anthropometric variables in NAFLD patients with inconclusive results. This dose-response meta-analysis aimed to evaluate the impact of curcumin supplementation on body mass index (BMI), body weight, and waist circumference (WC) in patients with NAFLD. A systematic review of the literature was conducted using PubMed/Medline, ISI Web of Science, Scopus, Cochrane Library, EMBASE, Google Scholar, Sid.ir, and Magiran.com to identify eligible studies up to March 2019. A meta-analysis of eligible studies was performed using the random-effects model to estimate the pooled effect size. Eight randomized controlled trials with 520 participants (curcumin group = 265 and placebo group = 255) were included. Supplementation dose and duration ranged from 70 to 3,000 mg/day and 8 to 12 weeks, respectively. Curcumin supplementation significantly reduced BMI (weighted mean difference [WMD] = -0.34 kg/m2 , 95% CI [-0.64, -0.04], p < .05) and WC (WMD = -2.12 cm, 95% CI [-3.26, -0.98], p < .001). However, no significant effects of curcumin supplementation on body weight were found. These results suggest that curcumin supplementation might have a positive effect on visceral fat and abdominal obesity that have been associated with NAFLD.

Effects of Coffee, Black Tea and Green Tea Consumption on the Risk of Non-Hodgkin's Lymphoma: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

Aim: Several studies have evaluated the association between coffee, black and green tea consumption and non-Hodgkin's lymphoma (NHL) risk, while the results were inconsistent. We conducted a dose-response meta-analysis of available observational studies to assess the association among coffee, black and green tea intake and the risk of NHL in the general population. Methods: Studies published up to August 2018 were identified on the basis of a literature search in PubMed, ISI Web of Science, Scopus and Cochrane databases using Mesh and non-Mesh relevant keywords. Relative risks (RRs) with 95% confidence intervals (CIs) and the dose-response relationships were calculated using random-effects models. Results: In the meta-analysis of 19 effect sizes (315,972 participants with 4,914 cases of NHL), we found that higher green tea intake was associated with a 39% reduced risk of NHL (pooled RR = 0.61; 95% CIs = 0.38-0.99, I2=60.4%, pheterogeneity=0.080) in high- versus low-intake meta-analysis. No association was observed between coffee intake (pooled RR = 1.21; 95% CIs = 0.97-1.50, I2=52.6%, pheterogeneity < 0.05), black tea intake (pooled RR = 1.01; 95% CI = 0.82-1.24, I2=0%, pheterogeneity=0.875) and risk of NHL in high- versus low-intake meta-analysis. Conclusions: Findings from this dose-response meta-analysis suggest that green tea intake may be associated with reduced risk of NHL.

Dietary Fat Intake and Risk of Ovarian Cancer: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

Observational studies have reported controversial evidence of the association between dietary fat intake and ovarian cancer. This dose-response meta-analysis aimed to clarify quantitatively the association between dietary fat intake and ovarian cancer. The linear and non-linear relationships between fat intake and risk of ovarian cancer were investigated. Heterogeneity, sensitivity analysis, and publication bias were also assessed. Overall, 21 studies involved approximately 900,000 subjects were included. A significant nonlinear association was found between total fat intake with the risk of ovarian cancer, with a relatively steep slope at total fat intake higher than 30 g/day (p non-linearity <.01). Moreover, the risk of ovarian cancer was increased in non-linear form for both saturated and monounsaturated fat from 25 g/day (p non-linearity <.05). According to the findings from the linear meta-analysis, we observed a 2, 2, 1, and 1% greater risk of ovarian cancer per 10, 0.5, 2.5 g/day and 50 mg/day increase in total, trans and monounsaturated fat intake as well as cholesterol, respectively. However, this association for monounsaturated fat was marginally significant (p=.052). The findings of this meta-analysis suggest that dietary total, trans, saturated and partially monounsaturated fat as well as cholesterol intake are positively associated with increased risk of ovarian cancer.

Dietary total antioxidant capacity and mortality from all causes, cardiovascular disease and cancer: a systematic review and dose-response meta-analysis of prospective cohort studies.

PURPOSE: No conclusive information is available about the association between dietary total antioxidant capacity (DTAC) and risk of mortality. Current meta-analysis of prospective cohort studies was done to summarize available findings on the association between DTAC and risk of death from all-cause, cancer and cardiovascular diseases (CVDs). METHODS: Online databases were searched to detect relevant publications up to January 2018, using relevant keywords. To pool data, either fixed-effects or random-effects model was used. Furthermore, linear and non-linear dose-response analyses were also done. RESULTS: In total, five prospective studies were included in the current systematic review and meta-analysis. In a follow-up period of 4.3-16.5 years, there were 38,449 deaths from all-cause, 4470 from cancer and 2841 from CVDs among 226,297 individuals. A significant inverse association was found between DTAC and all-cause mortality (combined effect size: 0.62, 95% CI 0.60-0.64). Such finding was also seen for cancer (combined effect size: 0.81, 95% CI 0.75-0.88) and CVD (combined effect size: 0.71, 95% CI 0.63-0.82) mortality. Findings from linear dose-response meta-analysis revealed that a 5 mmol/day increment in DTAC based on ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) was associated with 7% and 15% lower risk of all-cause mortality, respectively. Based on findings from non-linear dose-response meta-analysis, a significant reduction in risk of all-cause mortality was seen when increasing FRAP from 2 to 12 mmol/day (P-nonlinearity = 0.002) and ORAC from 5 to 11 mmol/day (P-nonlinearity < 0.001). CONCLUSIONS: Adherence to diet with high total antioxidant capacity was associated with decreased risk of death from all-cause, cancer and CVDs.

Dietary acid load and risk of hypertension: A systematic review and dose-response meta-analysis of observational studies.

BACKGROUND AND AIM: Previous studies have assessed diet-induced mild metabolic acidosis in relation to blood pressure, however, data are conflicting. Current systematic review and dose-response meta-analysis aimed to summarize earlier findings from observational studies on the association between dietary acid load and hypertension. METHODS AND RESULTS: We searched the online databases for relevant publications up to Feb 2019, using relevant keywords. Overall, 14 studies (3 prospective and 11 cross-sectional studies) that included 306,183 individuals and 62,264 cases of hypertension were included in the current meta-analysis. Combining effect sizes from both prospective and cross-sectional studies revealed no significant non-linear association between dietary acid load (based on net endogenous acid production (NEAP) method) and hypertension. However, stratified analysis based on study design showed a significant non-linear association between dietary acid load and hypertension in prospective studies (P = 0.006), but not cross-sectional ones. According to linear dose-response analysis, no significant association was found between dietary acid load (based on NEAP) and hypertension (combined effect size: 1.01, 95% CI: 0.97-1.06, P = 0.51). In terms of dietary acid load based on potential renal acid load (PRAL) method, no significant non-linear association was seen with hypertension (P = 0.52). However, in linear dose-response analysis, a-20 unit increase in PRAL values was associated with 3% increased risk of hypertension (combined effect size: 1.03, 95% CI: 1.00-1.06, P = 0.03). CONCLUSION: We found a significant positive association between dietary acid load and hypertension. Further studies, particularly those with prospective nature, are needed to confirm our findings.

Dietary and circulating vitamin C, vitamin E, ß-carotene and risk of total cardiovascular mortality: a systematic review and dose-response meta-analysis of prospective observational studies.

OBJECTIVE: The present review aimed to quantify the association of dietary intake and circulating concentration of major dietary antioxidants with risk of total CVD mortality. DESIGN: Systematic review and meta-analysis. SETTING: Systematic search in PubMed and Scopus, up to October 2017.ParticipantsProspective observational studies reporting risk estimates of CVD mortality across three or more categories of dietary intakes and/or circulating concentrations of vitamin C, vitamin E and ß-carotene were included. A random-effects meta-analysis was conducted. RESULTS: A total of fifteen prospective cohort studies and three prospective evaluations within interventional studies (320 548 participants and 16 974 cases) were analysed. The relative risks of CVD mortality for the highest v. the lowest category of antioxidant intakes were as follows: vitamin C, 0·79 (95 % CI 0·68, 0·89; I 2=46 %, n 10); vitamin E, 0·91 (95 % CI 0·79, 1·03; I 2=51 %, n 8); ß-carotene, 0·89 (95 % CI 0·73, 1·05; I 2=34 %, n 4). The relative risks for circulating concentrations were: vitamin C, 0·60 (95 % CI 0·42, 0·78; I 2=65 %, n 6); α-tocopherol, 0·82 (95 % CI 0·76, 0·88; I 2=0 %, n 5); ß-carotene, 0·68 (95 % CI 0·52, 0·83; I 2=50 %, n 6). Dose-response meta-analyses demonstrated that the circulating biomarkers of antioxidants were more strongly associated with risk of CVD mortality than dietary intakes. CONCLUSIONS: The present meta-analysis demonstrates that higher vitamin C intake and higher circulating concentrations of vitamin C, vitamin E and ß-carotene are associated with a lower risk of CVD mortality.

Dietary and Biochemical Characteristics Associated with Normal-Weight Obesity.

Background: Inflammation and oxidative stress have been reported to be higher in subjects with normal weight obesity (NWO) syndrome [normal body mass index (BMI) (<25 kg/m2) but excessive body fat (for women ≥ 30% and for men ≥ 20%) according to World Health Organization (WHO) definitions]; however, it is unclear whether this is due to inadequate dietary antioxidant intake or the pathophysiology of NWO. The aim of present study was to assess the association between dietary factors and body antioxidant status with NWO syndrome in male university students. Methods: This study was a case-control study carried out on ninety age-matched male university students [30 normal weights (NW), 30 NWO and 30 overweight-obese (OB)]. A validated food frequency questionnaire (98 items) and 3-day 24-h recalls were used for dietary assessment. Total antioxidant capacity (TAC) of diet and serum and high-sensitive C-reactive protein (hs-CRP) concentrations were also measured. Results: Dietary intake of fruits (frequency factor (FF) = 2.3 vs 2.9, p < 0.05), legumes (FF = 0.7 vs 1.3, p < 0.01), nuts and seeds (FF = 0.4 vs 0.8, p < 0.05), beta-cryptoxanthin (p < 0.05), lycopene (p < 0.05) and serum TAC levels (p < 0.01) were significantly lower in NWO compared to the NW group. No significant differences in these parameters were observed between NWO and OB group. A significant negative correlation was observed between serum TAC levels and BMI (r = -0.57, p < 0.001) and body fat percent (r = -0.52, p < 0.001). Conclusions: This study shows that NWO male subjects consume lower amounts of dietary antioxidants and share the same low body antioxidant status as obese individuals, although they appear lean.

Cardiac injury is associated with severe outcome and death in patients with Coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of observational studies.

Coronavirus disease 2019 (COVID-19) is a global pandemic impacting 213 countries/territories and more than 5,934,936 patients worldwide. Cardiac injury has been reported to occur in severe and death cases. This meta-analysis was done to summarize available findings on the association between cardiac injury and severity of COVID-19 infection. Online databases including Scopus, PubMed, Web of Science, Cochrane Library and Google Scholar were searched to detect relevant publications up to 20 May 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. In total, 22 studies with 3684 COVID-19 infected patients (severe cases=1095 and death cases=365) were included in this study. Higher serum levels of lactate dehydrogenase (weighted mean difference (WMD) =108.86 U/L, 95% confidence interval (CI)=75.93-141.79, p<0.001) and creatine kinase-MB (WMD=2.60 U/L, 95% CI=1.32-3.88, p<0.001) were associated with a significant increase in the severity of COVID-19 infection. Furthermore, higher serum levels of lactate dehydrogenase (WMD=213.44 U/L, 95% CI=129.97-296.92, p<0.001), cardiac troponin I (WMD=26.35 pg/mL, 95% CI=14.54-38.15, p<0.001), creatine kinase (WMD=48.10 U/L, 95% CI=0.27-95.94, p = 0.049) and myoglobin (WMD=159.77 ng/mL, 95% CI=99.54-220.01, p<0.001) were associated with a significant increase in the mortality of COVID-19 infection. Cardiac injury, as assessed by serum analysis (lactate dehydrogenase, cardiac troponin I, creatine kinase (-MB) and myoglobin), was associated with severe outcome and death from COVID-19 infection.

Metformin Therapy Reduces Obesity Indices in Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Purpose: Few studies have summarized findings for the effect of metformin on obesity indices. Therefore, we aimed to conduct a systematic review and meta-analysis on the effect of metformin on obesity indices among children and adolescents. Methods: Relevant articles published up to September 2018 were searched in SCOPUS, Medline, and Google Scholar using appropriate keywords. All clinical trials that examined the effect of metformin on obesity indices in children and adolescents were included. Results: Overall, 38 studies, including 2199 participants (39.75% male and 60.25% female), were included. The pooled results indicated that metformin significantly reduced BMI [weighted mean difference (WMD): -1.07 kg/m2; 95% confidence interval (CI): -1.43 to -0.72]. Same findings were found for waist circumference (WC) (WMD: -1.93 cm; 95% CI: -2.69 to -1.16). Metformin also reduced body weight in all participants (WMD: -2.51 kg; 95% CI: -3.14 to -1.89). Moreover, it reduced body fat mass in patients with overweight or obesity (WMD: -1.90%; 95% CI: -3.25 to -0.56) and chronic diseases (WMD: -1.41%; 95% CI: -2.23 to -0.58), but not among those with growth problems. Metformin therapy did not affect lean body mass (LBM) in patients with overweight or obesity and growth problems; however, it reduced LBM in patients with chronic diseases (WMD: -1.49 kg; 95% CI: -2.69 to -0.30). Conclusions: We found a significant reduction in BMI, body weight, WC, and fat mass following administration with metformin. However, the effect of metformin on LBM was not significant. Further studies are required to confirm these findings.

Short-term curcumin supplementation enhances serum brain-derived neurotrophic factor in adult men and women: a systematic review and dose-response meta-analysis of randomized controlled trials.

The reduction of brain-derived neurotrophic factor (BDNF) affects cognitive function, learning, and memory and also causes behavioral disorders. Several randomized controlled trials have examined the neuroprotective effects of curcumin and its ability to increase BDNF levels, with inconclusive results. The aim of this systematic review was to evaluate the impact of curcumin supplementation on serum BDNF levels. A systematic review of the literature was conducted using PubMed, Scopus, ISI Web of Science, Cochrane library, and Google scholar to identify eligible studies up to January 2019. The studies included were randomized control trials of curcumin supplementation that reported the serum BDNF level as a primary outcome. A dose-response meta-analysis of eligible studies was performed using the random-effects model to estimate pooled effect size. Four randomized control trials with 139 participants were included. Curcumin supplementation dose and duration ranged from 200 to 1820 mg/d and 8 to 12 weeks, respectively. Curcumin supplementation significantly increased serum BDNF levels (weighted mean difference: 1789.38 pg/mL, 95% confidence interval: 722.04-2856.71, P < .01) with significant heterogeneity among the studies (I2 = 83.5%, P < .001). Subgroup analysis showed that sex, mean age of participants, curcumin dosage, and trial duration were potential sources of heterogeneity. The significant positive impact of curcumin supplementation on BDNF levels indicates its potential use for neurological disorders that are associated with low BDNF levels.

Dietary total antioxidant capacity and risk of cancer: a systematic review and meta-analysis on observational studies.

BACKGROUND: Recent studies have shown that dietary total antioxidant capacity (D-TAC) may affect risk of cancer; however, findings are conflicting. Hence, we aimed to summarize the current evidence on the association between D-TAC and risk of cancer. METHODS: We searched the online databases of PubMed, ISI Web of Science, Scopus, ProQuest, Science Direct and Embase until October 2018 using relevant keywords. To pool data, fixed- or random-effects models were used where appropriate. RESULTS: In total, 19 studies including 8 prospective and 11 case-control studies with 721429 individuals and 16159 cases of cancer were included in the current systematic review and meta-analysis. Combining 15 effect sizes from 6 prospective and 8 case-control studies revealed a significant inverse association between D-TAC (obtained from ferric reducing antioxidant power (FRAP)) and risk of cancer (combined effect size: 0.86, 95% CI: 0.81-0.92, P < 0.001). Such inverse association was also seen for D-TAC obtained from other methods including trolox equivalence antioxidant capacity (TEAC) (combined effect size: 0.80, 95% CI: 0.70-0.90, P < 0.001), total radical trapping antioxidant parameter (TRAP) (combined effect size: 0.69, 95% CI: 0.62-0.78, P < 0.001) and oxygen radical absorbance capacity (ORAC) (combined effect size: 0.72, 95% CI: 0.52-1.00, P = 0.04). In addition, a significant non-linear association was found between D-TAC (based on FRAP and TRAP) and cancer risk (P-nonlinearity<0.001). Based on linear dose-response meta-analysis, a-10 mmol/day increase in FRAP and a-5 mmol/day increase in TRAP and TEAC were associated with 9%, 17% and 14% reduction in risk of cancer, respectively. Furthermore, D-TAC was inversely associated with risk of colorectal (combined effect size: 0.82, 95% CI: 0.75-0.89, P < 0.001), gastric (combined effect size: 0.63, 95% CI: 0.53-0.73, P < 0.001), and endometrial cancer (combined effect size: 0.78, 95% CI: 0.69-0.89, P < 0.001). CONCLUSIONS: Diet with high antioxidant capacity might have protective effects against cancer.

Dietary Antioxidants, Circulating Antioxidant Concentrations, Total Antioxidant Capacity, and Risk of All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Observational Studies.

The associations of various dietary or circulating antioxidants with the risk of all-cause mortality in the general population have not been established yet. A systematic search was performed in PubMed and Scopus, from their inception up to October 2017. Prospective observational studies reporting risk estimates of all-cause mortality in relation to dietary intake and/or circulating concentrations of antioxidants were included. Random-effects meta-analyses were conducted. Forty-one prospective observational studies (total n = 507,251) involving 73,965 cases of all-cause mortality were included. The RRs of all-cause mortality for the highest compared with the lowest category of circulating antioxidant concentrations were as follows: total carotenes, 0.60 (95% CI: 0.46, 0.74); vitamin C, 0.61 (95% CI: 0.53, 0.69); selenium, 0.62 (95% CI: 0.45, 0.79); ß-carotene, 0.63 (95% CI: 0.57, 0.70); α-carotene, 0.68 (95% CI: 0.58, 0.78); total carotenoids, 0.68 (95% CI: 0.56, 0.80); lycopene, 0.75 (95% CI: 0.54, 0.97); and α-tocopherol, 0.84 (95% CI: 0.77, 0.91). The RRs for dietary intakes were: total carotenoids, 0.76 (95% CI: 0.66, 0.85); total antioxidant capacity, 0.77 (95% CI: 0.73, 0.81); selenium, 0.79 (95% CI: 0.73, 0.85); α-carotene, 0.79 (95% CI: 0.63, 0.94); ß-carotene, 0.82 (95% CI: 0.77, 0.86); vitamin C, 0.88 (95% CI: 0.83, 0.94); and total carotenes, 0.89 (95% CI: 0.81, 0.97). A nonsignificant inverse association was found for dietary zinc, zeaxanthin, lutein, and vitamin E. The nonlinear dose-response meta-analyses demonstrated a linear inverse association in the analyses of dietary ß-carotene and total antioxidant capacity, as well as in the analyses of circulating α-carotene, ß-carotene, selenium, vitamin C, and total carotenoids. The association appeared to be U-shaped in the analyses of serum lycopene and dietary vitamin C. The present study indicates that adherence to a diet with high antioxidant properties may reduce the risk of all-cause mortality. Our results confirm current recommendations that promote higher intake of antioxidant-rich foods such as fruit and vegetables.

Maternal dietary nitrate intake and risk of neural tube defects: A systematic review and dose-response meta-analysis.

Despite growing evidence for the potential teratogenicity of nitrate, knowledge about the dose-response relationship of dietary nitrate intake and risk of specific birth defects such as neural tube defects (NTDs) is limited. Therefore, the aim of this meta-analysis was to synthesize the knowledge about the dose-response relation between maternal dietary nitrate intake and the risk of NTDs. We conducted a systematic search in PubMed, ISI Web of Science and Scopus up to February 2018 for observational studies. Risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated using a random-effects model for highest versus lowest intake categories. The linear and non-linear relationships between nitrate intake and risk of NTDs were also investigated. Overall, 5 studies were included in the meta-analyses. No association was observed between nitrate intake and NTDs risk in high versus low intake (RR: 1.33; 95% CI: 0.89-1.99, p = 0.158) and linear dose-response (RR: 1.03; 95% CI: 0.99-1.07, p = 0.141) meta-analysis. However, there were positive relationships between nitrate intake and risk of NTDs in non-linear (pnon-linearity<0.05) model. Findings from this dose-response meta-analysis indicate that maternal nitrate intake higher than ∼3 mg/day is positively associated with NTDs risk.