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Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.
Zheng, SH, Chen, XX, Chen, Y, Wu, ZC, Chen, XQ, Li, XL
Reproductive biology and endocrinology : RB&E. 2023;21(1):79
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Endometriosis is a common gynaecological disorder in reproductive-age women which leads to infertility and pain symptoms. Current pain management approaches involve medications and surgical treatments, but their side effects and risk of recurrence have led to the exploration of alternative options. The aim of this study was to clarify the potential effects of antioxidant vitamins supplementation on endometriosis. This study was a systematic review and meta-analysis of eleven studies, comprising a total of 589 patients. Results showed that antioxidant vitamins supplementation can effectively alleviate endometriosis-related pain and reduce inflammatory markers. Authors conclude that antioxidant vitamins supplementation can be considered as an alternative treatment either on its own or in combination with other methods for managing endometriosis-related pain. However, further research would help to provide a clearer understanding of the role of antioxidant vitamins supplementation in women with endometriosis.
Abstract
OBJECTIVE This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION PROSPERO registration number: CRD42023415198.
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Polyphenol supplementation and executive functioning in overweight and obese adults at risk of cognitive impairment: A systematic review and meta-analysis.
Farag, S, Tsang, C, Murphy, PN
PloS one. 2023;18(5):e0286143
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It is recognised that overweight and obesity pose an increased risk for the development of cardiometabolic disease, and increasing evidence indicates a link to cognitive impairment associated with early onset dementia in such populations. This study's aim was to elaborate on existing knowledge of the effectiveness or otherwise of polyphenols in general to improve executive function (EFs) in an obese/ overweight population at risk of cognitive impairment. This study was a systematic review and meta-analysis of twenty-three randomised controlled trials. Results showed a nonsignificant effect of polyphenols on EFs. Authors concluded that further research should consider investigating polyphenols supplementation in a younger population at risk of cognitive impairment.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Overweight and obesity have increasing evidence that indicates a link to compromised executive functions such as memory and decision-making processes and cognitive impairment
- This meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions among overweight and/or obese populations with a susceptibility to cognitive impairment.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
A systematic review and meta-analysis were undertaken to investigate the impact of polyphenol supplementation on executive functions (cognitive functions which constitute part of the working memory and decision-making processes) among overweight and/or obese populations.
Method:
A comprehensive literature search was conducted using four electronic databases: PubMed/Medline, PsycInfo, Scopus and the Cochrane Trials Library. Inclusion criteria encompassed primary research studies which investigated the impact of polyphenols versus placebo on executive function in overweight or obese adults.
The review comprised a total of 23 randomised controlled trials (RCTs), incorporating a participant pool of N = 1,976 individuals. The mean ages of participants in all 23 studies receiving polyphenol supplementation were 62.92 years (SD = 8.06 years) and the mean BMIs ranged from 25.5 kg/m2 to 33.7 kg/m2. Various dietary polyphenols were investigated in the studies, with the main groups being isoflavones, flavonoids, resveratrol, phenolic acid, curcumin, walnuts and blueberry powder.
- The JADAD scale was employed to assess the methodological quality of the incorporated studies
- Hedges g, accompanied by 95% confidence intervals (CI) for endpoints, was computed utilising a random effects model whenever applicable
- Various statistical methods were considered for potential application in evaluating publication bias
- Sensitivity analysis was conducted to assess the robustness of the obtained results.
Results
- Meta analysis of the 23 primary studies produced a non-significant effect of polyphenol supplementation on executive function (g = 0.076, CI = -0.018 to 0.170)
- A double-blind, randomised, placebo-controlled parallel study reported significant benefits in 60 participants (mean age 67 years) taking 80mg of curcumin over placebo for digital vigilance and serial subtraction tasks (p=0.041)
- A double-blind, randomised, placebo-controlled parallel intervention trial showed significant benefits in 79 patients (mean age of 61 years) taking 150mg of resveratrol for visuospatial working memory double span and trail making test (p= 0.012).
Conclusion:
This meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions among overweight and/or obese populations.
Clinical practice applications:
- Research has documented the association between compromised executive functions and obesity/overweight, emphasising neuroinflammation and oxidative stress as potential mechanisms
- A plausible intervention involves the utilisation of polyphenols, known for their antioxidant and anti-inflammatory properties
- This systematic review and meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions
- A potential beneficial impact for 80mg of curcumin and 150mg of resveratrol was revealed in younger populations (mean ages of 67 and 61 years).
Considerations for future research:
- A potential beneficial impact of 80mg of curcumin and 150mg of resveratrol supplementation was revealed in a younger population (mean ages of 67 and 61 years), highlighting the necessity for in-depth exploration in subsequent studies
- The diversity in tasks employed for assessing executive functions and the comprehensive reporting of the phenolic composition of supplements had limitations that warrant consideration in future research
- The exact constituent and dose of supplementation needs to be described as this is necessary for the identification of the potential beneficial compounds for cognitive health and to support clinical practice.
Abstract
BACKGROUND AND OBJECTIVES Increasing evidence indicates a link between obesity and cognitive impairment. Furthermore, there is limited literature regarding the effect of polyphenols, a plant derived compounds, on executive functioning in an overweight/obese population at-risk of cognitive impairment. The aim of the present systematic review and meta-analysis of randomized controlled trials is to examine the effect of polyphenol supplementation on executive functions in overweight and/or obese populations at risk of cognitive impairment. METHODS A comprehensive literature search was conducted from inception to March 2023 using four electronic databases: PubMed/Medline, PsycInfo, Scopus and Cochrane trials library. Published primary research studies in English that compared the effect of polyphenols with placebo on executive function in overweight/obese adults were considered eligible for the meta-analysis. Jadad scale was used for the methodological quality rating of the included studies. Hedges g with 95% confidence intervals (CI) for endpoints were calculated using random effect model where applicable. Rosenthal's Fail-safe N, funnel plots, the Begg and Mazumdar's rank correlation test (Kendall's S statistic P-Q), Egger's linear regression test, and Duval and Tweedie's trim-and-fill test were identified for potential use as appropriate, to examine publication bias. Sensitivity analysis was conducted to examine the robustness of the results. RESULTS AND CONCLUSION A total of 23 RCT studies involving N = 1,976 participants were included in the review. The results of the meta-analysis revealed a non-significant effect for polyphenol supplementation on executive function (g = 0.076, CI = -0.018 to 0.170). Observations from primary studies within the meta-analysis showed a potential positive effect of polyphenol supplementation in a younger population at-risk of cognitive impairment and it is recommended to investigate this further in future studies. Moreover, the variability of the tasks used to examine executive functions as well as the adequate reporting of supplement's phenolic composition is a limitation that future work should also consider.
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Effects of probiotic administration on overweight or obese children: a meta-analysis and systematic review.
Li, Y, Liu, T, Qin, L, Wu, L
Journal of translational medicine. 2023;21(1):525
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The prevalence of overweight or obesity in children is increasing due to changes in dietary structure and exercise habits, as determined by the body mass index (BMI) calculated from height and weight. Childhood obesity can cause some clinical complications such as hypertension, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease. The aim of this study was to examine the effects of probiotics on eight factors in children with overweight or obesity. This study was a systematic review and meta-analysis of four studies with a total of 206 overweight or obesity children. Among them, 105 were in the probiotic group, and 101 were in the placebo group. Results showed that probiotics can improve high- and low-density lipoprotein cholesterol, adiponectin, leptin, and TNF-α in overweight or obese children. The systematic review showed that probiotics work mainly by reshaping disturbed intestinal microbiota, regulating lipid metabolism, reducing inflammation and immune response, playing a positive effect of short-chain fatty acids produced, alleviating oxidative stress and endoplasmic reticulum stress, and inhibiting the growth and reproduction of pathogens in the gut. Authors concluded that probiotics could regulate lipid metabolism and immune response to some degree in children with overweight or obesity.
Abstract
BACKGROUND This paper aimed to examine the effects of probiotics on eight factors in overweight or obese children by meta-analysis, namely, body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), adiponectin, leptin and tumor necrosis factor-α (TNF-α) and summarize the mechanisms of action of probiotics based on the existing researches. METHODS Six databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed and CNKI) were searched until March 2023. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model or random effect model to observe the effects of probiotic administration on the included indicators. RESULTS Four publications with a total of 206 overweight or obesity children were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HDL-C (MD, 0.06; 95% CI 0.03, 0.09; P = 0.0001), LDL-C (MD, - 0.06; 95% CI - 0.12, - 0.00; P = 0.04), adiponectin (MD, 1.39; 95% CI 1.19, 1.59; P < 0.00001), leptin (MD, - 2.72; 95% CI - 2.9, - 2.54; P < 0.00001) and TNF-α (MD, - 4.91; 95% CI - 7.15, - 2.67; P < 0.0001) compared to those in the placebo group. Still, for BMI, the palcebo group seemed to be better than the probiotic group (MD, 0.85; 95% CI 0.04, 1.66; P = 0.04). TC (MD, - 0.05; 95% CI - 0.12, 0.02; P = 0.14) and TG (MD, - 0.16; 95% CI - 0.36, 0.05; P = 0.14) were not different between two groups. CONCLUSIONS This review drew that probiotics might act as a role in regulating HDL-C, LDL-C, adiponectin, leptin and TNF-α in overweight or obesity children. Additionally, our systematic review yielded that probiotics might regulate lipid metabolism and improve obese associated symptoms by some paths. This meta-analysis has been registered at PROSPERO with ID: CRD42023408359.
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Absence of Effects of L-Arginine and L-Citrulline on Inflammatory Biomarkers and Oxidative Stress in Response to Physical Exercise: A Systematic Review with Meta-Analysis.
Porto, AA, Gonzaga, LA, Benjamim, CJR, Valenti, VE
Nutrients. 2023;15(8)
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L-citrulline is a non-essential amino acid that acts as a precursor to L-arginine. L-arginine is a semi-essential amino acid used for nitric oxide production which is crucial for maintaining physiological function and immune regulation. Previous research has shown that L-citrulline and L-arginine supplementation may offer antioxidant and anti-inflammatory benefits in reducing exercise-related oxidative stress and inflammation. This systematic review and meta-analysis included seven randomised controlled trials to investigate the effect of L-citrulline and L-arginine on antioxidants, oxidative stress, and inflammatory and anti-inflammatory markers. This systematic review and meta-analysis showed no significant improvements in oxidative stress and inflammation followed by the supplementation of L-citrulline and L-arginine before exercise. However, further robust studies that include different dosages and exercise intensities are required to assess the beneficial effects of L-citrulline and L-arginine supplements to support physical exercise-induced oxidative stress and inflammation due to the heterogeneity of the included studies. Healthcare professionals can use the results of this study to understand the potential benefits of L-citrulline and L-arginine supplementation in people prone to producing proinflammatory cytokines.
Abstract
The repercussions on oxidative and inflammatory stress markers under the effects of arginine and citrulline in response to exercise are not fully reached. We completed a systematic review to investigate the effects of L-Citrulline or L-Arginine on oxidative stress and inflammatory biomarkers following exercise. EMBASE, MEDLINE (PubMed), Cochrane Library, CINAHL, LILACS, and Web of Science databases were used to record the trials. This study includes randomized controlled trials (RCTs) and non-RCTs with subjects over 18 years old. Those under the intervention protocol consumed L-Citrulline or L-Arginine, and the controls ingested placebo. We recognized 1080 studies, but only 7 were included (7 studies in meta-analysis). We observed no difference between pre- vs. post-exercise for oxidative stress (subtotal = -0.21 [CI: -0.56, 0.14], p = 0.24, and heterogeneity = 0%. In the sub-group "L-Arginine" we found a subtotal = -0.29 [-0.71, 0.12], p = 0.16, and heterogeneity = 0%. For the "L-Citrulline" subgroup we observed a subtotal = 0.00 [-0.67, 0.67], p = 1.00, and heterogeneity was not applicable. No differences were observed between groups (p = 0.47), and I² = 0%) or in antioxidant activity (subtotal = -0.28 [-1.65, 1.08], p = 0.68, and heterogeneity = 0%). In the "L-Arginine" sub-group, we found a subtotal = -3.90 [-14.18, 6.38], p = 0.46, and heterogeneity was not applicable. For the "L-Citrulline" subgroup, we reported a subtotal = -0.22 [-1.60, 1.16], p = 0.75, and heterogeneity was not applicable. No differences were observed between groups (p = 0.49), and I² = 0%), inflammatory markers (subtotal = 8.38 [-0.02, 16.78], p = 0.05, and heterogeneity = 93%. Tests for subgroup differences were not applicable, and anti-inflammatory markers (subtotal = -0.38 [-1.15, 0.39], p = 0.34 and heterogeneity = 15%; testing for subgroup differences was not applicable). In conclusion, our systematic review and meta-analysis found that L-Citrulline and L-Arginine did not influence inflammatory biomarkers and oxidative stress after exercise.
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Polyphenol Intake in Pregnant Women on Gestational Diabetes Risk and Neurodevelopmental Disorders in Offspring: A Systematic Review.
Salinas-Roca, B, Rubió-Piqué, L, Montull-López, A
Nutrients. 2022;14(18)
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In Europe, gestational diabetes affects approximately 10.9% of pregnant women. According to previous research, the cardiometabolic health of the mother and the mother's dietary habits during pregnancy may affect the foetus' neurodevelopment. Taking polyphenol supplements and eating foods rich in polyphenols is beneficial for promoting health across generations. In this systematic review, fourteen studies were included in order to evaluate the effects of polyphenols on gestational diabetes and mental health in the offspring. A higher prevalence of neurodevelopmental diseases in offspring is associated with gestational diabetes. The results of this systematic review revealed that polyphenol intake during pregnancy might have a beneficial effect on improving cardiometabolic health, reducing inflammation, DNA methylation and oxidative stress, thus reducing the risk of developing fetal neurodevelopmental disorders, such as attention deficit hyperactivity disorder, autism spectrum disorder and learning disorders. There is a need for further robust research, as the existing evidence regarding the safety of long-term polyphenol supplementation and its effects on gestational diabetes and fetal neurodevelopment is very limited. In spite of this, healthcare professionals can use the findings of this systematic review to learn more about the positive health benefits of polyphenols in pregnant women.
Abstract
The intake of foods containing polyphenols can have a protective role to avoid comorbidities during pregnancy and, at the same time, promote transgenerational health. This review aims to describe the effect of polyphenol intake through supplements or polyphenol-rich foods during pregnancy on the incidence and evolution of gestational diabetes mellitus (GDM), as well as the link with the neurodevelopment of the fetus. Using PRISMA procedures, a systematic review was conducted by searching in biomedical databases (PubMed, Cinahl and Scopus) from January to June 2022. Full articles were screened (n = 419) and critically appraised. Fourteen studies were selected and were divided into two different thematic blocks considering (i) the effect of polyphenols in GDM and (ii) the effect of GDM to mental disorders in the offspring. A positive relationship was observed between the intake of polyphenols and the prevention and control of cardiometabolic complications during pregnancy, such as GDM, which could be related to thwarted inflammatory and oxidative processes, as well as neuronal factors. GDM is related to a greater risk of suffering from diseases related to neurodevelopment, such as attention deficit hyperactivity disorder, autism spectrum disorder and learning disorder. Further clinical research on the molecule protective mechanism of polyphenols on pregnant women is required to understand the transgenerational impact on fetal neurodevelopment.
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Effect of vitamin E on Semen Quality Parameters: A Meta-Analysis of a Randomized Controlled Trial.
Wang, R, Wang, S, Song, Y, Zhou, H, Pan, Y, Liu, L, Niu, S, Liu, X
Urology journal. 2022;19(5):343-351
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The incidence of male infertility is increasing year by year. The mechanism of male infertility is complex. One of the important causes of male infertility is the decline in semen quality. The aim of this study was to evaluate the effectiveness of oral vitamin E in improving semen quality. This study is a meta-analysis of eight articles with a total of 459 patients, including 238 cases in the experimental group and 221 cases in the control group. Results show that oral vitamin E treatment could significantly increase the total sperm count and reduce the volume of semen. It was further found that oral vitamin E treatment for up to 6 months could improve the forward motility of sperm but not for 3 months. Authors conclude that vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients.
Abstract
PURPOSE To explore the effectiveness of vitamin E in male infertility, a systematic review and meta-analysis was conducted. MATERIALS AND METHODS The retrieval time was from January 1947 to May 2021, without language restriction. Stata 12.0 was used for the meta-analysis. RESULTS A total of 8 randomized controlled trials involving 459 patients were included. The results showed that after vitamin E treatment, semen volume was reduced (95% CI: - 0.55 to - 0.06, SMD = - 0.30, p = 0.015), total sperm count was increased (95% CI: 0.02-0.45, SMD = 0.23, p = 0.035), and the differences were statistically significant. There were no statistically significant differences in increasing sperm concentration (95% CI: -0.21-0.29, SMD = 0.04, p = 0.769), total sperm motility (95% CI: -0.01-0.42, SMD = 0.20, p = 0.061) or sperm forward motility rate (95% CI: -0.06-0.65, SMD = 0.29, p = 0.106). Subgroup analysis showed that vitamin E treatment for six months could improve sperm forward motility (95% CI: 0.46-1.14, SMD = 0.80, p <0.001). CONCLUSION Vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients, and long-term treatment could improve the forward motility rate of sperm. The decrease of semen volume may be the result of different abstinence time before and after the test.
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Efficacy of cinnamon supplementation on glycolipid metabolism in T2DM diabetes: A meta-analysis and systematic review.
Zhou, Q, Lei, X, Fu, S, Li, Z, Chen, Y, Long, C, Li, S, Chen, Q
Frontiers in physiology. 2022;13:960580
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Diabetes mellitus (DM) is categorised into three main types: type 1 diabetes mellitus, type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus. T2DM accounts for approximately 90% of diabetes mellitus cases. The aim of this study was to assess the effects of cinnamon on glucose and lipid levels in patients with T2DM. This study is a systematic review and meta-analysis of fifteen randomised controlled trials with a total of 1020 patients. Results show that blood glycolipid [a carbohydrate that is covalently linked to a lipid] levels were improved dramatically in diabetes patients who received cinnamon instead of a placebo. Cinnamon supplementation also exerted a favourable impact on metabolic (especially glucose, body mass index and lipids) abnormalities. Authors conclude that their findings show a beneficial impact on hypoglycaemia and lipids with cinnamon and cinnamon extract, implicating the extracts as therapeutic agents that might ameliorate hyperglycaemia in diabetes.
Abstract
Background: Cinnamon is a spice used in cooking and in large quantities as a medical complement with hypoglycemic and lipid-lowering properties. The potential pharmacological mechanisms underlying cinnamon's anti-diabetic properties and its active ingredients have not been adequately determined. The current meta-analysis aims to systematically review the potential pharmacological mechanisms underlying the hypoglycemic and hypolipidemic efficacy of cinnamon administration and summarize clinical recommendations of cinnamon and its active ingredients. Method: Relevant randomized clinical trials (RCTs) were identified through a literature search that spanned the years January 2005 to April 2022. Retrieve electronic databases including Web of Science, PubMed, Embase, Medline, and the Cochrane Library. To obtain standardized mean differences (SMDs), continuous outcomes were pooled and 95 percent confidence intervals (CIs) were provided. Categorical outcomes were aggregated to calculate relative risks (RRs) and were accompanied by 95% CIs. Heterogeneity was measured using the Cochrane Q-test and I2 statistics, with a p < 0.05 considered as substantial heterogeneity. If I2 was less than 50%, a fixed effect model was employed; otherwise, a random effect model was used. Subgroup analyses and sensitivity analyses were performed to identify the origins of heterogeneity. Publication bias was retrieved by means of a funnel-plot analysis and Egger's test. The data were analyzed using revman (V.5.3) and stata (V.15) software packages. Results: These 16 RCTs included a total of 1,020 patients who were followed for a duration ranging from 40 days to 4 months. According to the current meta-analysis results, glycolipid levels in diabetic individuals who received cinnamon were significantly improved as compared to those who got placebo (All p < 0.05). An adverse effect was only detected in one patient. Conclusion: These findings imply that cinnamon has a significant influence on lipid and glucose metabolism regulation. An even more pronounced effect was observed in patients with HbA1c of 8%. The results of this study suggested that cinnamon may be utilized as hypoglycemic and lipid-lowering supplement in clinical settings with a guaranteed safety profile.Systematic Review Registration: [PROSPERO], identifier [CRD42022322735].
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Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.
Yang, K, Chen, J, Zhang, T, Yuan, X, Ge, A, Wang, S, Xu, H, Zeng, L, Ge, J
Frontiers in immunology. 2022;13:949746
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Non-alcoholic fatty liver disease (NAFLD) is characterised by fat accumulation in the liver that can result in liver damage. NAFLD affects approximately 25% of the global population. There is evidence that dietary polyphenols can improve metabolism and insulin resistance and reduce inflammation and oxidative stress, which are the mechanisms that lead to liver damage in NAFLD. This systematic review and meta-analysis aimed to assess the effectiveness of dietary polyphenols in the treatment of non-alcoholic fatty liver disease (NAFLD). Eight dietary polyphenols, such as curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein, were evaluated for their efficacy and safety. The administration of 80-3,000 mg of Curcumin for an 8-12 week duration is effective and safe for reducing body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), and insulin resistance (HOMA-IR). Compared with the placebo, Naringenin reduced the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Hesperidin may potentially decrease body mass index (BMI), AST, ALT, TG, TC, and HOMA-IR. Catechin is safe, and 500-1000 mg supplementation for 12 weeks may reduce BMI, HOMA-IR, and TG. NAFLD patients who received silymarin showed improvements in ALT and AST, as well as reductions in hepatic fat accumulation and liver stiffness. 94–2100 mg of Silymarin supplementation for 8–48 weeks may reduce liver enzyme levels. Researchers can use the results of this study to understand the clinical utility of different polyphenol supplements in the treatment of NAFLD. Because the current evidence is highly heterogeneous in nature and limited in scope, further robust research is required on various classes of polyphenols and their effectiveness in reducing the severity of NAFLD.
Abstract
Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.
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Association between dietary inflammatory index and oral cancer risk: A systematic review and dose-response meta-analysis.
Luo, Z, Zhu, X, Hu, Y, Yan, S, Chen, L
Frontiers in oncology. 2022;12:920452
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Oral cancer is the most prevalent subtype of head and neck cancers. Inflammation and oxidative stress triggered by certain dietary components may be a potential mechanism for oral cancer. The aim of this study was to comprehensively assess the dose–response relationship between dietary inflammatory index (DII) and oral cancer risk. This study is a systematic review and meta-analysis of five studies. The studies were all case–control studies with a total of 1,278 cases and 5,137 controls. Results show that a more pro-inflammatory diet, represented by the higher DII score, was associated with an elevated risk of oral cancer. Authors conclude that reducing pro-inflammatory food components and promoting anti-inflammatory food components would be beneficial in the prevention and control of oral cancer.
Abstract
Background: Dietary inflammatory index (DII) has been suggested to be associated with oral cancer risk. However, a quantitative comprehensive assessment of the dose-response relationship has not been reported. We performed a meta-analysis to clarify the risk of oral cancer with DII. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to 1 March 2022. Fixed- or random-effects models were utilized to estimate the pooled odds ratio (OR) of oral cancer with DII, as appropriate. Restricted cubic splines were used to model the dose-response relationship. Results: We included five case-control studies involving 1,278 cases and 5,137 controls in the meta-analysis. Risk of oral cancer was increased by 135% with the highest versus lowest DII level [OR: 2.35, 95% confidence interval (CI): 1.88-2.94], and 79% with higher versus lower DII level (OR: 1.79, 95% CI: 1.49-2.15). We found no evidence of a nonlinear dose-response association of DII with oral cancer (pnon-linearity = 0.752), and the risk was increased by 17% (OR: 1.17, 95% CI: 1.05-1.30) with 1 unit increment in DII score. Conclusion: This meta-analysis suggested that a higher DII score was associated with increased risk of oral cancer. Therefore, reducing pro-inflammatory components and promoting anti-inflammatory components of diet may be effective in the prevention of oral cancer.
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Effect of mitochondrial-targeted antioxidants on glycaemic control, cardiovascular health, and oxidative stress in humans: A systematic review and meta-analysis of randomized controlled trials.
Mason, SA, Wadley, GD, Keske, MA, Parker, L
Diabetes, obesity & metabolism. 2022;24(6):1047-1060
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Plain language summary
Reactive oxygen species (ROS) are free radical oxygen molecules produced by mitochondria, which cause molecular damage known as oxidative stress. Chronic diseases such as diabetes, heart disease, cancer, and Parkinson's disease are more likely to develop when ROS levels are elevated. Mitochondrial‐targeted antioxidants (mitoAOX) may be effective in treating chronic diseases by targeting mitochondrial ROS. In this systematic review and meta-analysis, 19 randomised controlled trials were included to evaluate the effects of mitoAOXs on glycaemic control, cardiovascular health, and oxidative stress in humans. The evidence is limited, but there were improvements in endothelial function, blood pressure, oxidative stress, and functional capacity. The mitoAOX agents, dosage, and participant characteristics varied between the studies, making it difficult to draw conclusions. Due to the heterogeneity of studies included in this study, there is a need for larger, longer-term robust studies to investigate mitoAOXs' effects on mitochondrial ROS and markers of oxidative stress in different clinical populations. As a result of this study, healthcare professionals can gain a better understanding of mitoAOX's potential in tackling oxidative stress. However, caution must be exercised before implementing it as a therapeutic strategy due to concerns over possible adverse effects and a low evidence certainty.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Mitochondria are a major producer of reactive oxygen species (ROS) in cells. Excess mitochondrial ROS has been implicated in the pathophysiology of various chronic diseases including Parkinson’s disease, cardiovascular disease (CVD), Type 2 diabetes and cancer.
- This review reported that there is limited evidence to support the use of mitoAOXs in the management of glycaemic control and cardiovascular health. However, there are promising findings on the effect of mitoAOXs on endothelial function that warrant consideration and further investigation in target clinical population groups.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
A systematic review and meta-analysis was conducted to evaluate the current evidence from randomised control trials (RCTs) in humans on the effects of mitochondrial-targeted antioxidant (mitoAOXs) on glycaemic control, cardiovascular health, and oxidative stress.
Methodology
19 Randomised control trials (n= 884 participants) using mitoAOXs (including Elamipretide, MitoQ and MitoTEMPO) were included from MEDLINE-PubMed, Scopus, EMBASE and Cochrane Library databases. A Cochrane Collaboration’s tool was used to assess risk bias and to grade the quality of the trials and their certainty of the evidence.
Results
Primary clinical outcomes were:
- A quantitative analysis on glycaemic control found no significant effect for fasting glucose in response to MitoQ supplementation.
- A quantitative analysis on cardiovascular health related outcomes found a significant lowering effect of mitoAOXs brachial flow-mediated dilation (FMD) (standardized mean difference: 1.19, 95% CI: 0.28, 2.16; I2: 67%) and an improved blood pressure (standardized mean difference: -0.32, 95% CI:-0.95, 0.30; I2: 0%) in patients with atherosclerosis-related impairment of renal blood flow.
- A quantitative analysis on oxidative stress-related outcomes found no significant effect of mitoAOX on malondialdehyde or F2-Isoprostanes.
Clinical practice applications:
- The findings from this review suggest limited evidence to support the use of mitoAOX in the management of glycaemic control or cardiovascular health.
- However, there are some potential promising findings which included improved endothelial function (particularly brachial FMD) and improved blood pressure in patients with atherosclerosis-related impairment of renal blood flow.
- Based on this review, practitioners may consider recommending the use of mitoAOXs only in quite specific circumstances, namely to improve endothelial function in patients with a risk of brachial FMD or high blood pressure associated with atherosclerosis-related impairment of renal blood flow.
Considerations for future research:
- The studies included in this review were mostly one to three months in duration therefore, there is a need for long-term, follow-up studies to be conducted to better investigate these outcomes.
- Given the pathogenic factors of elevated mitochondrial ROS and oxidative stress in chronic diseases such as CVD and Type2 diabetes, further investigation is needed into the effects of mitoAOXs on mitochondrial ROS and oxidative stress markers in target clinical population groups.
- It appears that mitoAOXs may improve endothelial function, therefore further research is needed to focus on the effect of mitoAOXs on endothelial function in target clinical populations.
- Additionally, further reviews are required to provide a more comprehensive review of the safety and adverse effects of mitoAOXs.
- Furthermore, only antioxidants specific to microconidia were included in this review. It is possible that other more general acting antioxidants may have redox-related effects in mitochondria. Therefore, a more comprehensive review is needed to include all possible antioxidant compounds that have mitochondrial effect.
Abstract
AIM: To investigate the effects of mitochondrial-targeted antioxidants (mitoAOXs) on glycaemic control, cardiovascular health, and oxidative stress outcomes in humans. MATERIALS AND METHODS Randomized controlled trials investigating mitoAOX interventions in humans were searched for in databases (MEDLINE-PubMed, Scopus, EMBASE and Cochrane Library) and clinical trial registries up to 10 June 2021. The Cochrane Collaboration's tool for assessing risk of bias and Grading of Recommendations, Assessment, Development and Evaluations were used to assess trial quality and evidence certainty, respectively. RESULTS Nineteen studies (n = 884 participants) using mitoAOXs (including Elamipretide, MitoQ and MitoTEMPO) were included in the systematic review. There were limited studies investigating the effects of mitoAOXs on glycaemic control; and outcomes and population groups in studies focusing on cardiovascular health were diverse. MitoAOXs significantly improved brachial flow-mediated dilation (n = 3 trials; standardized mean difference: 1.19, 95% CI: 0.28, 2.16; I2 : 67%) with very low evidence certainty. No significant effects were found for any other glycaemic, cardiovascular or oxidative stress-related outcomes with mitoAOXs in quantitative analyses, with evidence certainty rated mostly as low. There was a lack of serious treatment-emergent adverse events with mitoAOXs, although subcutaneous injection of Elamipretide increased mild-moderate injection site-related events. CONCLUSION While short-term studies indicate that mitoAOXs are generally well tolerated, there is currently limited evidence to support the use of mitoAOXs in the management of glycaemic control and cardiovascular health. Review findings suggest that future research should focus on the effects of mitoAOXs on glycaemic control and endothelial function in target clinical population groups.