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Biomedicine & Pharmacotherapy =... Jul 2020This study provides a critical overview of experimental studies in vitro, in humans, and in animals that evaluated the efficacy of Berberine and its effect on management...
This study provides a critical overview of experimental studies in vitro, in humans, and in animals that evaluated the efficacy of Berberine and its effect on management of obesity and the related metabolic consequences. As a result of this review, we summarized the effects of Berberine in different models and the related mechanism of actions. In preclinical models, Berberine demonstrates that it affects gut microbiota by reducing diversity of microbes starting at a dosage of 100 mg/kg/day. Moreover, in animal models, Berberine explicates an action on glucose through the inhibition of α-glycosidase at a dose of 200 mh/kg/day. Berberine is also known to be effective against differentiation of adipocytes through a decrease in LXRs, PPARs, and SREBPs expression at 150 mg/kg/day. Other mechanism ascribed to Berberine are related to its inhibition of hepatic gluconeogenesis through the Phospheoenolpyruvate carboxykinase (PEPCK), Glucose-6-phosphate (G6Pase) and AMP-activated protein kinase (AMPK). Furthermore, Berberine (associated to Red Yeast Rice) is effective in decreasing lipid levels in rats, which consequently lowers the change of weight gain at dosage of 40 mg/kg to 380 mg/kg/day. All the above preclinical data are confirmed in human studies where Berberine can modulate the diversity of gut microbes at the dose of 500 mg/day. In addition, Berberine is found to have a beneficial impact on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans, an amelioration on glucose accumulation at 1.0 g daily dose was also observed. For all these reasons, this review gives an important good account of the impact of Berberine in obesity treatment and prevention.
Topics: Adipocytes; Berberine; Blood Glucose; Cholesterol; Gastrointestinal Microbiome; Gluconeogenesis; Humans; Insulin Resistance; Obesity; Weight Loss
PubMed: 32353823
DOI: 10.1016/j.biopha.2020.110137 -
Molecules (Basel, Switzerland) Dec 2022In recent years, research has demonstrated the efficacy propolis as a potential raw material for pharmaceuticals and nutraceuticals. There is limited report detailing... (Review)
Review
In recent years, research has demonstrated the efficacy propolis as a potential raw material for pharmaceuticals and nutraceuticals. There is limited report detailing the mechanisms of action of propolis and its bioactive compounds in relation to their anti-inflammatory properties. Thus, the aim of the present review is to examine the latest experimental evidence (2017-2022) regarding the anti-inflammatory properties of propolis. A systematic scoping review methodology was implemented. After applying the exclusion criteria, a total of 166 research publications were identified and retrieved from Scopus, Web of Science, and Pubmed. Several key themes related to the anti-inflammatory properties of propolis were subsequently identified, namely in relation to cancers, oral health, metabolic syndrome, organ toxicity and inflammation, immune system, wound healing, and pathogenic infections. Based on the latest experimental evidence, propolis is demonstrated to possess various mechanisms of action in modulating inflammation towards the regulatory balance and anti-inflammatory environment. In general, we summarize that propolis acts as an anti-inflammatory substance by inhibiting and downregulating TLR4, MyD88, IRAK4, TRIF, NLRP inflammasomes, NF-κB, and their associated pro-inflammatory cytokines such as IL-1β, IL-6, IFN-γ, and TNF-α. Propolis also reduces the migration of immune cells such as macrophages and neutrophils, possibly by downregulating the chemokines CXCL9 and CXCL10.
Topics: Humans; Propolis; Anti-Inflammatory Agents; Cytokines; Inflammation; Macrophages
PubMed: 36500579
DOI: 10.3390/molecules27238473 -
Clinical Therapeutics Dec 2022Voriconazole, an antifungal drug, is metabolized by a cytochrome P450 isozyme. Increased adverse effects are observed in Asians because of the high rate of poor... (Meta-Analysis)
Meta-Analysis Review
Clinical Practice Guideline for the Therapeutic Drug Monitoring of Voriconazole in Non-Asian and Asian Adult Patients: Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring.
PURPOSE
Voriconazole, an antifungal drug, is metabolized by a cytochrome P450 isozyme. Increased adverse effects are observed in Asians because of the high rate of poor metabolizers. In this therapeutic drug monitoring (TDM) guideline, recommendations were made according to ethnic group.
METHODS
Five clinical questions were used. For the preparation of the guideline, the performance of TDM in multicenter studies was surveyed (study 1). We also conducted a systematic review and meta-analysis (study 2) to establish recommendations for non-Asians and Asians.
FINDINGS
In study 1, 401 patients were surveyed. A risk of supratherapeutic concentrations was found in Japanese patients who adhered to the recommended dose. Target trough levels were achieved in 87% of patients with dose reductions. Although the trough level measured at the onset of adverse effects (AEs) was significantly associated with hepatotoxicity, no significant correlation was found between the initial trough level and hepatotoxicity, which indicated that hepatotoxicity was successfully prevented by the trough-guided dosing. In study 2, 22 studies (11 Asian locations and 11 non-Asian locations) were included in meta-analysis for the relationship between trough cutoff level (3, 4, 5, 5.5, and 6 µg/mL) and AEs. Significant differences were found for all cutoff levels, with the highest odds ratio for 4.0 µg/mL in Asian locations. In contrast, in non-Asian locations, no more than 1 study was available for any trough cutoff level, except for 5.5 µg/mL, at which level a significant increase in AEs was found. These findings indicate that TDM is strongly recommended to prevent AEs in Asians, and TDM is generally recommended for non-Asians to address subtherapeutic concentrations. TDM on day 3 is recommended to assess pharmacokinetic properties, including loading and maintenance doses. If the patient condition permits, delaying until day 5 is suggested for Asians because of the prolonged t in poor metabolizers. A trough level ≥1.0 µg/mL is strongly recommended to improve efficacy. Trough levels ≥2.0 µg/mL are suggested for invasive aspergillosis. To decrease adverse effects, trough levels <4.0 µg/mL are strongly recommended in Asians, whereas trough levels <5.5 µg/mL are generally recommended in non-Asians. Maintenance doses of 4 and 3 mg/kg twice daily are recommended in non-Asians and Asians, respectively.
IMPLICATIONS
Different indications, timings, and target trough levels for TDM and different regimens are suggested for Asians and non-Asians.
Topics: Humans; Adult; Voriconazole; Drug Monitoring; Consensus; East Asian People; Antifungal Agents; Drug-Related Side Effects and Adverse Reactions; Chemical and Drug Induced Liver Injury
PubMed: 36424314
DOI: 10.1016/j.clinthera.2022.10.005 -
European Journal of Investigation in... Aug 2023This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact... (Review)
Review
This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact patients' physical health and overall quality of life. The study utilized the PRISMA methodology and included cross-sectional, retrospective studies, and randomized clinical trials from reputable databases like SCOPUS, CLARIVATE, SCIENCE DIRECT, and PUBMED. Out of the 64 selected studies, various psychotropic drug classes were analyzed, including antidepressants, anticonvulsants, and antipsychotics. Among the antidepressants, such as amitriptyline, Imipramine, and clomipramine, weight gain, constipation, and cardiovascular effects were the most commonly reported metabolic adverse effects. SSRI antidepressants like Fluoxetine, Sertraline, Citalopram, Escitalopram, and Paroxetine exhibited a high prevalence of gastrointestinal and cardiac alterations. Regarding anticonvulsants, valproic acid and Fosphenytoin were associated with adverse reactions such as weight gain and disturbances in appetite and sleep patterns. As for antipsychotics, drugs like Clozapine, Olanzapine, and Risperidone were linked to weight gain, diabetes, and deterioration of the lipid profile. The findings of this review emphasize the importance of continuous monitoring for adverse effects, particularly considering that the metabolic changes caused by psychopharmacological medications may vary depending on the age of the patients. Future research should focus on conducting field studies to further expand knowledge on the metabolic effects of other commonly prescribed psychotropic drugs. Overall, the study highlights the significance of understanding and managing metabolic alterations induced by psychopharmacological treatment to enhance patient care and well-being.
PubMed: 37623307
DOI: 10.3390/ejihpe13080110 -
Nutrients Feb 2021Sleep is an essential component of physical and emotional well-being, and lack, or disruption, of sleep due to insomnia is a highly prevalent problem. The interest in...
Sleep is an essential component of physical and emotional well-being, and lack, or disruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control. Currently available evidence suggests that herbal extracts may exert some of their hypnotic and anxiolytic activity through interacting with GABA receptors and modulating GABAergic signaling in the brain, but their mechanism of action in the treatment of insomnia is not completely understood.
Topics: Brain; Humans; Phytotherapy; Receptors, GABA; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 33561990
DOI: 10.3390/nu13020530 -
Biomedicine & Pharmacotherapy =... Jan 2021Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines...
Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines (TCMs) have shown considerable effects in the treatment of metabolic disorders by regulating the gut microbiota. However, the underlying mechanisms are unclear. Studies have shown that TCMs significantly affect glucose and lipid metabolism by modulating the gut microbiota, particularly mucin-degrading bacteria, bacteria with anti-inflammatory properties, lipopolysaccharide- and short-chain fatty acid (SCFA)-producing bacteria, and bacteria with bile-salt hydrolase activity. In this review, we explored potential mechanisms by which TCM improved metabolic disorders via regulating gut microbiota composition and functional structure. In particular, we focused on the protection of the intestinal barrier function, modulation of metabolic endotoxemia and inflammatory responses, regulation of the effects of SCFAs, modulation of the gut-brain axis, and regulation of bile acid metabolism and tryptophan metabolism as therapeutic mechanisms of TCMs in metabolic diseases.
Topics: Animals; Bacteria; Blood Glucose; Drugs, Chinese Herbal; Dysbiosis; Energy Metabolism; Gastrointestinal Microbiome; Humans; Intestines; Lipid Metabolism; Medicine, Chinese Traditional; Metabolic Diseases; Treatment Outcome
PubMed: 33197760
DOI: 10.1016/j.biopha.2020.110857 -
Nutrients Oct 2020The Mediterranean diet (MD) may provide metabolic benefits but no systematic review to date has examined its effect on a multitude of outcomes related to metabolic... (Meta-Analysis)
Meta-Analysis
The Mediterranean diet (MD) may provide metabolic benefits but no systematic review to date has examined its effect on a multitude of outcomes related to metabolic health. This systematic review with meta-analysis (International Prospective Register of Systematic Reviews, PROSPERO; number CRD42019141459) aimed to examine the MD's effect on metabolic syndrome (MetSyn) incidence, components and risk factors (primary outcomes), and incidence and/or mortality from MetSyn-related comorbidities and receipt of pharmacologic treatment for MetSyn components and comorbidities (secondary outcomes). We searched Pubmed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science for controlled trials published until June 2019, comparing the MD with no treatment, usual care, or different diets in adults. Studies not published in English and not promoting the whole MD were excluded. Two authors independently extracted data and assessed risk of bias using the Cochrane Collaboration's and Risk of Bias in non-randomised studies (ROBINS-I) tools. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects meta-analyses, subgroup analyses and meta-regressions were performed, and heterogeneity was quantified using the I statistic. We identified 2654 reports and included 84 articles reporting 57 trials ( = 36,983). In random effects meta-analyses, the MD resulted in greater beneficial changes in 18 of 28 MetSyn components and risk factors (body weight, body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) index, total-, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, triglycerides, alanine transaminase, hepatic fat mass, C-reactive protein, interleukin-6, tumour necrosis factor-a, and flow-mediated dilatation) and lower risk of cardiovascular disease incidence (risk ratio (RR) = 0.61, 95% confidence intervals (CI) 0.42-0.80; I = 0%), and stroke (RR = 0.67, 95% CI 0.35-0.98; I = 0%). Only six studies reported effects on pharmacotherapy use, and pooled analysis indicated no differences between diet groups. Lack of consistency in comparator groups and other study characteristics across studies resulted in high heterogeneity for some outcomes, which could not be considerably explained by meta-regressions. However, a consistent direction of beneficial effect of the MD was observed for the vast majority of outcomes examined. Findings support MD's beneficial effect on all components and most risk factors of the MetSyn, in addition to cardiovascular disease and stroke incidence. More studies are needed to establish effects on other clinical outcomes and use of pharmacotherapy for MetSyn components and comorbidities. Despite the high levels of heterogeneity for some outcomes, this meta-analysis enabled the comparison of findings across studies and the examination of consistency of effects. The consistent direction of effect, suggesting the MD's benefits on metabolic health, supports the need to promote this dietary pattern to adult populations.
Topics: Adult; Biomarkers; Blood Pressure; Comorbidity; Controlled Clinical Trials as Topic; Diet, Mediterranean; Health; Humans; Incidence; Insulin Resistance; Metabolic Syndrome; Metabolism; Oxidative Stress; Risk Factors
PubMed: 33143083
DOI: 10.3390/nu12113342 -
The Cochrane Database of Systematic... Aug 2020A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility.
OBJECTIVES
To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women.
SEARCH METHODS
We searched the following databases (from their inception to September 2019), with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of relevant studies and searched the trial registers.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events.
MAIN RESULTS
We included 63 trials involving 7760 women. Investigators compared oral antioxidants, including: combinations of antioxidants, N-acetylcysteine, melatonin, L-arginine, myo-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Only 27 of the 63 included trials reported funding sources. Due to the very low-quality of the evidence we are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment (odds ratio (OR) 1.81, 95% confidence interval (CI) 1.36 to 2.43; P < 0.001, I = 29%; 13 RCTs, 1227 women). This suggests that among subfertile women with an expected live birth rate of 19%, the rate among women using antioxidants would be between 24% and 36%. Low-quality evidence suggests that antioxidants may improve clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.65, 95% CI 1.43 to 1.89; P < 0.001, I = 63%; 35 RCTs, 5165 women). This suggests that among subfertile women with an expected clinical pregnancy rate of 19%, the rate among women using antioxidants would be between 25% and 30%. Heterogeneity was moderately high. Overall 28 trials reported on various adverse events in the meta-analysis. The evidence suggests that the use of antioxidants makes no difference between the groups in rates of miscarriage (OR 1.13, 95% CI 0.82 to 1.55; P = 0.46, I = 0%; 24 RCTs, 3229 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.63 to 1.56; P = 0.99, I = 0%; 9 RCTs, 1886 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10; P = 0.47, I = 0%; 3 RCTs, 343 women; low-quality evidence). Low-quality evidence showed that there was also no difference between the groups in rates of ectopic pregnancy (OR 1.40, 95% CI 0.27 to 7.20; P = 0.69, I = 0%; 4 RCTs, 404 women). In the antioxidant versus antioxidant comparison, low-quality evidence shows no difference in a lower dose of melatonin being associated with an increased live-birth rate compared with higher-dose melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I = 0%; 2 RCTs, 140 women). This suggests that among subfertile women with an expected live-birth rate of 24%, the rate among women using a lower dose of melatonin compared to a higher dose would be between 12% and 40%. Similarly with clinical pregnancy, there was no evidence of a difference between the groups in rates between a lower and a higher dose of melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I = 0%; 2 RCTs, 140 women). Three trials reported on miscarriage in the antioxidant versus antioxidant comparison (two used doses of melatonin and one compared N-acetylcysteine versus L-carnitine). There were no miscarriages in either melatonin trial. Multiple pregnancy and gastrointestinal disturbances were not reported, and ectopic pregnancy was reported by only one trial, with no events. The study comparing N-acetylcysteine with L-carnitine did not report live birth rate. Very low-quality evidence shows no evidence of a difference in clinical pregnancy (OR 0.81, 95% CI 0.33 to 2.00; 1 RCT, 164 women; low-quality evidence). Low quality evidence shows no difference in miscarriage (OR 1.54, 95% CI 0.42 to 5.67; 1 RCT, 164 women; low-quality evidence). The study did not report multiple pregnancy, gastrointestinal disturbances or ectopic pregnancy. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency.
AUTHORS' CONCLUSIONS
In this review, there was low- to very low-quality evidence to show that taking an antioxidant may benefit subfertile women. Overall, there is no evidence of increased risk of miscarriage, multiple births, gastrointestinal effects or ectopic pregnancies, but evidence was of very low quality. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.
Topics: Abortion, Spontaneous; Administration, Oral; Antioxidants; Female; Humans; Infertility, Female; Live Birth; Minerals; Oxidative Stress; Pentoxifylline; Placebos; Pregnancy; Pregnancy Rate; Pregnancy, Multiple; Randomized Controlled Trials as Topic; Vitamins
PubMed: 32851663
DOI: 10.1002/14651858.CD007807.pub4 -
Pharmacological Research Jun 2023Due to the lipophilic nature of vitamin D, overweight and obese patients have an increased risk of inadequate circulating 25-hydroxy-vitamin D (25(OH)D) concentrations.... (Meta-Analysis)
Meta-Analysis Review
Due to the lipophilic nature of vitamin D, overweight and obese patients have an increased risk of inadequate circulating 25-hydroxy-vitamin D (25(OH)D) concentrations. Vitamin D deficiency has in turn several consequences especially among children and adolescents. Therefore, a few supplementation strategies of vitamin D for pediatric subjects with an excessive body weight have been proposed, but their efficacy remains controversial. The aim of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation in overweight and obese children and adolescents. Three databases (PubMed, Embase and Web of Science) were searched to collect trials on the effect of vitamin D supplementation in the pediatric overweight or obese population. Twenty-three studies were included in the systematic review. Results on modification of metabolic or cardiovascular outcomes were controversial. On the other hand, the meta-analysis showed a mean difference by 1.6 ng/ml in subjects supplemented with vitamin D as compared to placebo. In conclusion, vitamin D supplementation slightly increases 25(OH)D levels in pediatric subjects with overweight and obesity. However, the effects on metabolic and cardiovascular outcomes remain controversial. New efforts should be devoted to promoting effective interventions to improve the health of children and adolescents with overweight and obesity.
Topics: Humans; Child; Adolescent; Overweight; Pediatric Obesity; Vitamin D; Vitamin D Deficiency; Dietary Supplements; Vitamins; Weight Gain
PubMed: 37178775
DOI: 10.1016/j.phrs.2023.106793 -
Nutrients May 2020Nitric oxide related ergogenic aids such as arginine (Arg) have shown to impact positively on sport performance through several physiological and metabolic mechanisms.... (Meta-Analysis)
Meta-Analysis
Nitric oxide related ergogenic aids such as arginine (Arg) have shown to impact positively on sport performance through several physiological and metabolic mechanisms. However, research results have shown to be controversial. The great differences regarding required metabolic pathways and physiological demands between aerobic and anaerobic sport disciplines could be the reasons. The aim of this systematic review and meta-analysis was to evaluate the effects of Arg supplementation on aerobic (≤VOmax) and anaerobic (>VOmax) performance. Likewise, to show the effective dose and timing of this supplementation. A structured search was carried out in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and PICOS guidelines in PubMed/MEDLINE, Web of Science (WOS), and Scopus databases from inception to January 2020. Eighteen studies were included which compare Arg supplementation with placebo in an identical situation and testing its effects on aerobic and anaerobic performance tests. Trials analyzing supplementation with other supplements were removed and there was not athlete's level, gender, ethnicity, or age filters. The performed meta-analysis included 15 studies and random effects model and pooled standardized mean differences (SMD) were used according to Hedges' g. Results revealed that Arg supplementation could improve aerobic (SMD, 0.84; 95% CI, 0.12 to 1.56; magnitude of SMD (MSMD), large; I2, 89%; = 0.02) and anaerobic (SMD, 0.24; 95% CI, 0.05 to 0.43; MSMD, small; I2, 0%; = 0.01) performance tests. In conclusion, acute Arg supplementation protocols to improve aerobic and anaerobic performance should be adjusted to 0.15 g/kg of body weight ingested between 60-90 min before. Moreover, chronic Arg supplementation should include 1.5-2 g/day for 4-7 weeks in order to improve aerobic performance, and 10-12 g/day for 8 weeks to enhance anaerobic performance.
Topics: Aerobiosis; Anaerobiosis; Arginine; Athletic Performance; Body Weight; Dietary Supplements; Energy Metabolism; Female; Humans; Male; Nitric Oxide; Performance-Enhancing Substances
PubMed: 32370176
DOI: 10.3390/nu12051300