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Clinical Efficacy of Creatine Phosphate Sodium and/or Vitamin C in the Treatment of Children with Viral Myocarditis: A Meta-Analysis.
Li, Q, Liu, S, Ma, X, Yu, J
Computational and mathematical methods in medicine. 2022;2022:3840891
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Viral myocarditis (VMC) is a kind of infectious myocardial disease in which viral infection triggers myocardial interstitial inflammatory cell infiltration and adjacent myocardial cell necrosis, further leading to cardiac dysfunction and other systemic damage. The current main treatment of VMC includes antiviral, myocardial nutritional support, and immunomodulatory measures, but conventional treatment (CT) often fails to effectively control the disease, and thus, the recurrence rate is high. The aim of this study was to investigate the clinical utility of creatine phosphate sodium (CPS) and/or vitamin C in the treatment of VMC in children. This study is a systematic review and meta-analysis of 19 studies. A total of 1,957 VMC patients were included, with 968 patients in the control group and 989 patients in the observation group. Results show that compared with the control group who underwent CT therapy alone, the observation group receiving CT therapy together with CPS and/or vitamin C, had better performance in effective rate and better myocardial markers. Authors conclude that their findings may help to guide and standardize the treatment of VMC in children.
Abstract
Background: This study performed a meta-analysis to explore the clinical efficacy of creatine phosphate sodium (CPS) and/or vitamin C for viral myocarditis (VMC) in children, to provide guidance for its clinical treatment. Methods: A literature search was performed on PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang databases to obtain published clinical randomized controlled trials (RCTs) on CPS and/or vitamin C for VMC in children, with a time span from 2013 to 2022. Relevant data was extracted and meta-analysis was performed using the statistical software Stata 16.0. Results: A total of 723 studies were retrieved and 19 studies were finally included for meta-analysis, with a total of 1,957 patients. The meta-analysis results showed that the observation group (conventional treatment + CPS and/or vitamin C) was superior to the control group (conventional treatment alone) in treatment effective rate (OR = 3.60, 95% CI (2.55, 5.07), and P < 0.001). Additionally, the observation group had lower levels of cardiac troponin-I (SMD = - 2.63, 95% CI (- 3.51, - 1.76), and P < 0.001), creatine kinase isoenzyme (SMD = -2.78, 95% CI (- 3.53, - 2.03), and P < 0.001), lactate dehydrogenase (SMD = -1.95, 95% CI (- 2.49, - 1.42), and P < 0.001), aspartate aminotransferase (SMD = -0.87, 95% CI (- 1.84, 0.09), and P = 0.076), tumor necrosis factor-α (SMD = -3.90, 95% CI (- 4.47, - 3.06), and P < 0.001), and higher superoxide dismutase levels (SMD = 2.48, 95% CI (1.64, 3.33), and P < 0.001). Except aspartate aminotransferase, there were significant differences between the two groups in the other parameters. Conclusion: CPS and/or vitamin C treatment could greatly improve the treatment, protect myocardial function, and relieve inflammatory response in children with VMC.
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Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.
Liu, S, D'Amico, D, Shankland, E, Bhayana, S, Garcia, JM, Aebischer, P, Rinsch, C, Singh, A, Marcinek, DJ
JAMA network open. 2022;5(1):e2144279
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Older adults are the fastest growing age group in the world. As we age, we tend to lose muscle mass and strength which has consequences. Studies have shown that mitochondrial dysfunction plays an important part in age-related diseases. A reduction in the cells ability to dispose of its dysfunctional mitochondria (mitophagy) contributes to poor mitochondrial quality. Urolithin A is a natural food metabolite of the gut microbiome and has been shown to boost mitochondrial health by triggering mitophagy in both preclinical models of aging and in older adults. In this double-blind, placebo-controlled randomized clinical trial, 66 older adults were given either 1000mg of urolithin A or a placebo for 4 months. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 months, and 4 months. Six-minute walk distance and maximal ATP production were assessed using magnetic resonance spectroscopy at baseline and at the end of study at 4 months. This study found that the improvements in the 6-minute walk distance and maximal ATP production in hand muscles were not significant for urolithin A. However, long-term supplementation with urolithin A significantly enhanced skeletal muscle endurance and improved the metabolic markers of mitochondrial function in older adults. This trial suggests that urolithin A may be a promising approach to counteract age-associated muscle decline. Future study is needed to confirm the role of urolithin A supplementation in healthy aging.
Abstract
Importance: Aging is associated with a decline in mitochondrial function and reduced exercise capacity. Urolithin A is a natural gut microbiome-derived food metabolite that has been shown to stimulate mitophagy and improve muscle function in older animals and to induce mitochondrial gene expression in older humans. Objective: To investigate whether oral administration of urolithin A improved the 6-minute walk distance, muscle endurance in hand and leg muscles, and biomarkers associated with mitochondrial and cellular health. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial in adults aged 65 to 90 years was conducted at a medical center and a cancer research center in Seattle, Washington, from March 1, 2018, to July 30, 2020. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 months, and 4 months. Six-minute walk distance and maximal ATP production were assessed using magnetic resonance spectroscopy at baseline and at the end of study at 4 months. The analysis used an intention-to-treat approach. Interventions: Participants were randomized to receive daily oral supplementation with either 1000 mg urolithin A or placebo for 4 months. Main Outcomes and Measures: The primary end point was change from baseline in the 6-minute walk distance and change from baseline to 4 months in maximal ATP production in the hand skeletal muscle. The secondary end points were change in muscle endurance of 2 skeletal muscles (tibialis anterior [TA] in the leg and first dorsal interosseus [FDI] in the hand). Cellular health biomarkers were investigated via plasma metabolomics. Adverse events were recorded and compared between the 2 groups during the intervention period. Results: A total of 66 participants were randomized to either the urolithin A (n = 33) or the placebo (n = 33) intervention group. These participants had a mean (SD) age of 71.7 (4.94) years, were predominantly women (50 [75.8%]), and were all White individuals. Urolithin A, compared with placebo, significantly improved muscle endurance (ie, increase in the number of muscle contractions until fatigue from baseline) in the FDI and TA at 2 months (urolithin A: FDI, 95.3 [115.5] and TA, 41.4 [65.5]; placebo: FDI, 11.6 [147.4] and TA, 5.7 [127.1]). Plasma levels of several acylcarnitines, ceramides, and C-reactive protein were decreased by urolithin A, compared with placebo, at 4 months (baseline vs 4 mo: urolithin A, 2.14 [2.15] vs 2.07 [1.46]; placebo, 2.17 [2.52] vs 2.65 [1.86]). The mean (SD) increase from baseline in the 6-minute walk distance was 60.8 (67.2) m in the urolithin A group and 42.5 (73.3) m in the placebo group. The mean (SD) change from baseline to 4 months in maximal ATP production in the FDI was 0.07 (0.23) mM/s in the urolithin A group and 0.06 (0.20) mM/s in the placebo group; for the TA, it was -0.03 (0.10) mM/s in the urolithin A group and 0.03 (0.10) mM/s in the placebo group. These results showed no significant improvement with urolithin A supplementation compared with placebo. No statistical differences in adverse events were observed between the 2 groups. Conclusions and Relevance: This randomized clinical trial found that urolithin A supplementation was safe and well tolerated in the assessed population. Although the improvements in the 6-minute walk distance and maximal ATP production in the hand muscle were not significant in the urolithin A group vs the placebo group, long-term urolithin A supplementation was beneficial for muscle endurance and plasma biomarkers, suggesting that urolithin A may counteract age-associated muscle decline; however, future work is needed to confirm this finding. Trial Registration: ClinicalTrials.gov Identifier: NCT03283462.
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Pasta meal intake in relation to risks of type 2 diabetes and atherosclerotic cardiovascular disease in postmenopausal women : findings from the Women's Health Initiative.
Huang, M, Lo, K, Li, J, Allison, M, Wu, WC, Liu, S
BMJ nutrition, prevention & health. 2021;4(1):195-205
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Among major sources of dietary carbohydrates, pasta has long been a staple food in diverse human cultures around the world. Interest in the health effects of pasta on the human body has steadily increased since the 1980s. The aim of this study was to evaluate the association between pasta meal intake and long-term risk of developing diabetes or atherosclerotic cardiovascular disease (ASCVD, including coronary heart disease (CHD) and stroke) in postmenopausal women. This study is a large prospective cohort study of 84, 555 post-menopausal women aged between 50 and 79 years. Results show a significant association between higher intakes of pasta meal and long-term risk of developing stroke and ASCVD, and a suggestive association between higher intakes of pasta meal and long-term risk of developing CHD, while no significant relation was observed between pasta meal intake and risk of developing diabetes. Authors conclude that substituting pasta meal for other commonly consumed starchy foods such as fried potato or white bread may possibly represent a feasible and easy-to-implement method of dietary modification to improve cardiometabolic outcomes.
Abstract
OBJECTIVE To evaluate the association between pasta meal intake and long-term risk of developing diabetes or atherosclerotic cardiovascular disease (ASCVD, including coronary heart disease (CHD) and stroke) in postmenopausal women. DESIGN Prospective cohort study. SETTING Women's Health Initiative (WHI) in the USA. PARTICIPANTS 84 555 postmenopausal women aged 50-79 in 1994, who were free of diabetes, ASCVD and cancer at baseline who were not in the dietary modification trial of the WHI, completed a validated food frequency questionnaire, and were evaluated for incident diabetes and ASCVD outcomes during the follow-up until 2010. MAIN OUTCOME MEASURE Diabetes and ASCVD. RESULTS Cox proportional hazards models were used to estimate the association (HR) between quartiles of pasta meal consumption (residuals after adjusting for total energy) and the risk of incidence diabetes, CHD, stroke or ASCVD, accounting for potential confounding factors, with testing for linear trend. We then statistically evaluated the effect of substituting white bread or fried potato for pasta meal on disease risk. When comparing the highest to the lowest quartiles of residual pasta meal intake, we observed significantly reduced risk of ASCVD (HR=0.89, 95% CI 0.83 to 0.96, p trend=0.002), stroke (HR=0.84, 95% CI 0.75 to 0.93, p trend=0.001), CHD (HR=0.91, 95% CI 0.83 to 1.00, p trend=0.058) and no significant alteration in diabetes risk (HR=1.02, 95% CI 0.96 to 1.07, p trend=0.328). Replacing white bread or fried potato with pasta meal was statistically associated with decreased risk of stroke and ASCVD. CONCLUSIONS Pasta meal intake did not have adverse effects on long-term diabetes risk and may be associated with significant reduced risk of stroke and ASCVD. The potential benefit of substituting pasta meal for other commonly consumed starchy foods on cardiometabolic outcomes warrants further investigation in additional high-quality and large prospective studies of diverse populations.
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Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study.
Li, ZH, Zhong, WF, Liu, S, Kraus, VB, Zhang, YJ, Gao, X, Lv, YB, Shen, D, Zhang, XR, Zhang, PD, et al
BMJ (Clinical research ed.). 2020;368:m456
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Fish oil is a rich source of long chain omega 3 fatty acids, a group of polyunsaturated fats that primarily include eicosapentaenoic acid and docosahexaenoic acid. The aim of this study was to investigate the associations of habitual use of fish oils with the risk of certain outcomes (the incidence of, and mortality from, cardiovascular disease (CVD) as well as all-cause mortality) and to explore modifying factors that might affect these associations. This study is a large-scale cohort study of 427 678 participants aged between 40 to 69 years. Results showed that a considerable proportion (31.2%) of all participants reported habitual use of fish oil supplements. Findings also indicate that habitual fish oil supplementation was associated with a significantly lower all-cause mortality and incidence of, and mortality from, CVD and myocardial infarction. Authors conclude that habitual use of fish oils is beneficial for CVD events in the general population, supporting their use for the prevention of mortality from all causes and CVD.
Abstract
OBJECTIVES To evaluate the associations of habitual fish oil supplementation with cardiovascular disease (CVD) and mortality in a large prospective cohort. DESIGN Population based, prospective cohort study. SETTING UK Biobank. PARTICIPANTS A total of 427 678 men and women aged between 40 and 69 who had no CVD or cancer at baseline were enrolled between 2006 and 2010 and followed up to the end of 2018. MAIN EXPOSURE All participants answered questions on the habitual use of supplements, including fish oil. MAIN OUTCOME MEASURES All cause mortality, CVD mortality, and CVD events. RESULTS At baseline, 133 438 (31.2%) of the 427 678 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.87 (95% confidence interval 0.83 to 0.90) for all cause mortality, 0.84 (0.78 to 0.91) for CVD mortality, and 0.93 (0.90 to 0.96) for incident CVD events. For CVD events, the association seemed to be stronger among those with prevalent hypertension (P for interaction=0.005). CONCLUSIONS Habitual use of fish oil seems to be associated with a lower risk of all cause and CVD mortality and to provide a marginal benefit against CVD events among the general population.
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Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: Assessment of Causal Relations.
Livesey, G, Taylor, R, Livesey, HF, Buyken, AE, Jenkins, DJA, Augustin, LSA, Sievenpiper, JL, Barclay, AW, Liu, S, Wolever, TMS, et al
Nutrients. 2019;11(6)
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It is generally accepted that certain diet and lifestyle choices contribute to a person’s risk of developing type 2 diabetes (T2D). In this meta-analysis, researchers set out to review previous studies and assess whether there is any evidence that the amount and type of carbohydrate (measured by Glycaemic Index (GI) and Glycaemic Load (GL)) in a person’s diet has a direct influence on their risk of developing T2D. The authors concluded with a high level of confidence that eating high GI and GL foods can lead to a higher risk of developing T2D. They suggest that nutrition advice that favours low GI and GL foods could produce significant cost savings for public healthcare.
Abstract
While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.
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High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial.
Han, JE, Jones, JL, Tangpricha, V, Brown, MA, Brown, LAS, Hao, L, Hebbar, G, Lee, MJ, Liu, S, Ziegler, TR, et al
Journal of clinical & translational endocrinology. 2016;4:59-65
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Patients in intensive care (ICU) have a high prevalence of Vitamin D deficiency. (Measured by plasma concentration of 25 hydroxy Vitamin D (25(OH)D)). Several studies have shown associations between Vitamin D deficiency and increased hospital length of stay (LOS), readmission rates, sepsis, mortality and other respiratory complications. There are studies to show improvements in clinical outcomes with high dose vitamin D therapy in critically ill patients but the literature is limited. The aim of this small pilot study was to test the safety and efficacy of high levels of Vitamin D supplementation, in divided doses over several days, on mechanically ventilated adult ICU patients. The levels of 25(OH)D increased in both supplemented groups (group 1: 250,000 IU over 5 days and group 2: 500,000 IU over 5 days), and not in the placebo. These groups both had reduced LOS compared with the placebo. The other measured outcomes were not statistically affected. High dose Vitamin D was well tolerated in these critically ill patients but further testing is required to clarify the benefits.
Abstract
BACKGROUND There is a high prevalence of vitamin D deficiency in the critically ill patient population. Several intensive care unit studies have demonstrated an association between vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) < 20 ng/mL] and increased hospital length of stay (LOS), readmission rate, sepsis and mortality. MATERIAL AND METHODS Pilot, double blind randomized control trial conducted on mechanically ventilated adult ICU patients. Subjects were administered either placebo, 50,000 IU vitamin D3 or 100,000 IU vitamin D3 daily for 5 consecutive days enterally (total vitamin D3 dose = 250,000 IU or 500,000 IU, respectively). The primary outcome was plasma 25(OH)D concentration 7 days after oral administration of study drug. Secondary outcomes were plasma levels of the antimicrobial peptide cathelicidin (LL37), hospital LOS, SOFA score, duration of mechanical ventilation, hospital mortality, mortality at 12 weeks, and hospital acquired infection. RESULTS A total of 31 subjects were enrolled with 13 (43%) being vitamin D deficient at entry (25(OH)D levels < 20 ng/mL). The 250,000 IU and 500,000 IU vitamin D3 regimens each resulted in a significant increase in mean plasma 25(OH)D concentrations from baseline to day 7; values rose to 45.7±19.6 ng/mL and 55.2 ± 14.4 ng/mL, respectively, compared to essentially no change in the placebo group (21±11.2 ng/mL), p<0.001. There was a significant decrease in hospital length of stay over time in the 250,000 IU and the 500,000 IU vitamin D3 group, compared to the placebo group (25 ± 14 and 18 ± 11 days compared to 36 ± 19 days, respectively; p=0.03). There was no statically significant change in plasma LL-37 concentrations or other clinical outcomes by group over time. CONCLUSIONS In this pilot study, high-dose vitamin D3 safely increased plasma 25(OH)D concentrations into the sufficient range and was associated with decreased hospital length of stay without altering other clinical outcomes. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov (NCT01372995).
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Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry.
Wu, W, Li, R, Li, X, He, J, Jiang, S, Liu, S, Yang, J
Viruses. 2015;8(1)
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This mechanism study examines the role of quercetin at inhibiting influenza infection. Influenza A viruses (IAVs) are responsible for seasonal global pandemics and mortality, and genetic variations make it almost impossible to develop timely vaccines. Novel therapeutic strategies are anti-influenza agents are therefore of great interest. Two classes of anti-influenza drugs are widely used to inhibit viral entry and development, with varying side effects reported. Targeting viral entry and suppression of the infection at its early stage is an attractive therapeutic strategy. Quercetin is known to have anti-viral effects, alongside antioxidant, antibacterial and antiproliferation properties. Cells were infected with different influenza strains and exposed to quercetin, and the cytopathic effect and inhibition rates were measured at intervals. The results showed quercetin reduced transcription in influenza-virus-infected cells in a dose-dependent manner. This implies that quercetin’s mechanism of action may inhibit influenza in the early stage of viral attachment. Additional experiments found that quercetin directly targets the viral hemagglutinin protein particles rather than the host cells. The study concludes that quercetin possesses interesting anti-influenza activities which could be developed as a future therapeutic option for the therapy and prophylaxis of IAV infection.
Abstract
Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.