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New meta-analyses, RCTs and systematic reviews that we monitor daily in PubMed. Independently indexed, not editorially curated.
Comprehensive Physiology · 2025
This study aimed to identify metabolites and metabolic pathways associated with blood-brain barrier (BBB) dysfunction in human and animal metabolomic research. PubMed, Scopus, Web of Science, and Embase were searched (last search: 24 November 2025) without date limits. Original studies applying metabolomic techniques (1H-NMR, LC-MS, GC-MS) to CSF, serum, or plasma and reporting metabolites linked to BBB damage were included. Study selection, full-text assessment, and data extraction were performed independently by two reviewers, with disagreements resolved by a third. Risk of bias was evaluated using SYRCLE and ROBINS-I tools. Metabolites reported in ≥ 2 studies were mapped to metabolic pathways using MetaboAnalyst with hypergeometric testing and Holm-Bonferroni and FDR corrections. Of 12,182 records identified, eight studies (four human, four animal) met the inclusion criteria. Across these, 157 metabolites were identified, 25 of which were reported in more than one study. Frequently observed metabolites included glutamate, glutamine, alanine, choline, creatine, and branched-chain amino acids (valine, leucine, isoleucine). Pathway analysis revealed significant enrichment of alanine, aspartate and glutamate metabolism, nitrogen metabolism, and BCAA biosynthesis (FDR = 0.01). Glutamate and glutamine most consistently correlated with BBB dysfunction and neuroinflammatory processes. Substantial heterogeneity was observed, partly due to differences in analytical platforms, sample types, and reporting standards. Metabolites and pathways related to glutamate, nitrogen metabolism, and BCAA may play key roles in BBB impairment. Metabolomics shows promise for identifying BBB biomarkers, but larger, methodologically standardized studies are required. OSF identifier: dapu9.
Annals of medicine · 2026
Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC. A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening. Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies. Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC. Systematic integration of gut microbiota, obesity, and breast cancer interactions.Gut dysbiosis resulting from obesity exacerbates breast cancer via immune pathways.Probiotics inhibit breast cancer, mitigate high-fat diet-induced obesity, and dietary modulation of gut microbiota metabolites improves breast cancer prognosis.
Langenbeck's archives of surgery · 2026
Hemorrhagic shock (HS) is a major risk factor for mortality and complications after severe trauma. Yet, complex mechanisms on a cellular and physiological level are still not fully understood, Metabolomics offers a powerful tool to unravel these complex biochemical alterations following HS and trauma (T). However, no systematic synthesis of metabolomic findings in in standardized translational animal models of HS and HS + T exists to date. To systematically review and compare metabolomic alterations in animal models of isolated hemorrhagic shock and hemorrhagic shock with trauma, highlighting key metabolic pathways and their modulation by resuscitation strategies. We performed a systematic review on Pubmed and EMBASE to identify relevant metabolomic changes measured in with mass spectrometry in translational animal models following HS and HS + T. Studies were categorized into two groups in regard to our main objective: Isolated HS and HS + T. Key metabolite changes were extracted and analyzed qualitatively across seven major metabolic domains: energy, amino acids, purines, arginine/urea cycle, lipids, sulfur/creatine, and redox balance. Overall, 25 studies were included in our analysis. HS and HS + T both exhibited consistent changes in lactate (↑), succinate (↑), glutamine (↑), and acylcarnitines (↑), indicating hypoxia-driven glycolysis, mitochondrial dysfunction, and enhanced proteolysis. HS + T models displayed more pronounced alterations in branched-chain amino acids, purine catabolites (urate, inosine), and markers of oxidative stress. ATP depletion and glutathione imbalance were common, particularly in the trauma group. Plasma resuscitation partially corrected several abnormalities, especially in redox, purine, and glutamine pathways, compared to saline. Metabolic responses to hemorrhagic shock are reproducible across animal models and are amplified by the presence of trauma. Trauma accentuates proteolysis, oxidative stress, and nucleotide turnover. Plasma-based resuscitation appears superior to crystalloid in correcting these derangements. These findings support the exploration of targeted metabolic therapies and advocate for metabolomics-informed resuscitation strategies in trauma care. The online version contains supplementary material available at 10.1007/s00423-025-03917-z.
BMC musculoskeletal disorders · 2026
Resistance training is the cornerstone of sarcopenia management. However, whether combining it with amino acid-based supplementation, including essential amino acids, branched-chain amino acids, leucine, and derivatives such as HMB, provides additional benefits remains unclear. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials until February 2025. Meta- and subgroup analyses were performed using a random-effects model. The Cochrane ROB2 tool and GRADE framework were used to assess the risk of bias and evidence certainty. We included nine randomized controlled trials involving 496 participants with sarcopenia. Evidence rated as low to very low certainty indicated that, compared with resistance training alone, combined amino acid supplementation and resistance training significantly improved handgrip strength (SMD = 0.69, 95% CI: 0.04 to 1.35), gait speed (SMD = 0.64, 95% CI: 0.02 to 1.25), Short Physical Performance Battery scores (SMD = 1.69, 95% CI: 0.81 to 2.57), and Five Times Sit-to-Stand Test performance (SMD = -1.42, 95% CI: -2.68 to -0.16). No significant effects were observed for skeletal muscle mass index or appendicular skeletal muscle mass. Subgroup analyses showed that baseline protein intake, intervention setting, amino acid supplement type, resistance-training frequency, and whether the supplement contained co-nutrients were significant effect modifiers. Resistance training combined with amino acid supplementation may improve muscle strength and physical function in older adults with sarcopenia, although effects on muscle mass remain limited. Responsiveness to the intervention may vary by baseline protein intake, training frequency, setting, type of amino acid supplementation, and whether the supplement includes co-nutrients, all of which should be considered when designing sarcopenia management strategies.
The Cochrane database of systematic reviews · 2026
Hepatic encephalopathy is a brain dysfunction characterised by neurological and psychiatric changes due to liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. The previous version of this updated review meta-analysed data from 16 randomised clinical trials on branched-chain amino acids (BCAAs) versus control interventions, and found that BCAAs did not affect mortality but had a beneficial effect on hepatic encephalopathy. As data on critical outcomes were insufficient and new trials were published, we updated the review again. To assess the beneficial and harmful effects of BCAAs versus any control intervention for people with cirrhosis and hepatic encephalopathy. We identified trials through manual and electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database (LILACS), Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched other resources and contacted experts for additional published and unpublished trials. The latest search date was 12 December 2024. We included randomised clinical trials, irrespective of bias control, language, outcomes reported, or publication status, that compared any form of branched-chain amino acid with no intervention, placebo, diets, non-absorbable disaccharides, antibiotics, or any other intervention with a potential effect on hepatic encephalopathy, in children and adults with overt or minimal hepatic encephalopathy associated with acute or chronic liver disease. The critical outcomes were all-cause mortality, hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and serious adverse events (including nausea and diarrhoea). The important outcomes were quality of life and markers of nutritional status, including serum albumin and nitrogen balance. We evaluated outcomes at the longest available follow-up duration. The longest follow-up was also our primary time point for analysis. We assessed the risk of bias (RoB) of the critical and important outcomes using the Cochrane RoB 2 tool. We used standard Cochrane methodology. We performed meta-analyses, based on intention-to-treat, with risk ratios (RRs) for dichotomous outcomes, standardised mean differences (SMDs) for continuous outcomes in trials using different scales, and mean differences (MDs) for continuous outcomes when trials used the same scales, all with 95% confidence intervals (CI). We conducted the main analysis using a random-effects model. We assessed the overall certainty of the evidence per outcome with the GRADE approach, with five components (risk of bias, indirectness, heterogeneity, imprecision using the minimally contextualised approach, and dissemination bias). We added two new randomised clinical trials to this review update. Thus, the 18 trials, published between 1984 and 2023, included 934 adults (mean age 47 to 64 years). We found no trials in children. Participants had overt hepatic encephalopathy (13 trials) and covert hepatic encephalopathy (five trials). Ten trials assessed oral BCAA supplements and eight trials assessed intravenous BCAAs. The control groups received no intervention or placebo (two trials), diets (11 trials), lactulose (three trials), or neomycin (two trials). Most participants had cirrhosis (minimum 97%). One trial included participants with acute hepatitis. The follow-up periods were from four days to two years (104 weeks). Ten trials were conducted in Europe, four in Asia, two in the USA, and one each in Brazil and Australia. Three trials received support from for-profit organisations in the form of interventions. BCAAs may have little to no effect on all-cause mortality compared with the control interventions, but the evidence is very uncertain (RR 0.89, 95% CI 0.71 to 1.12; 17 studies, 867 participants; very low-certainty evidence). We found no evidence of small-study effects. All trials reported the effect of BCAAs on hepatic encephalopathy. The evidence suggests that BCAAs reduce hepatic encephalopathy (RR 0.79, 95% CI 0.64 to 0.96; 18 studies, 934 participants; low-certainty evidence). The follow-up ranges for the two outcomes were four days to two years. Nausea and diarrhoea, considered as serious adverse events, occurred in 58 of 477 (12%) participants in the BCAAs group and 16 of 538 (3%) participants in the control intervention group (diets). The evidence is very uncertain about the effect of BCAAs on nausea and diarrhoea (RR 2.05, 95% CI 0.40 to 10.58; 6 studies, 1015 participants; very low-certainty evidence). Three trials provided data on quality of life, but we were unable to meta-analyse the data because of the methods used to register the scores. All participants in the three trials had cirrhosis, but some did not have hepatic encephalopathy at baseline. When the analyses were limited to people with hepatic encephalopathy, none of the trials found beneficial or harmful effects of BCAAs on the global 36-item Short Form Health Survey (SF-36) score or any of the subscales. BCAAs may have little to no effect on albumin concentration (range 12 to 56 weeks) (MD 0.60, 95% CI -0.90 to 2.09; I² = 0%; 3 studies, 176 participants; very low-certainty evidence), but the evidence is uncertain. The evidence is very uncertain about the effect of BCAAs on nitrogen balance (range four days to two years) (SMD 0.82, 95% CI -1.01 to 2.64; 3 studies, 108 participants; very low-certainty evidence). We downgraded the certainty of evidence for risk of bias, indirectness, and imprecision. Three trials are ongoing. We added two new trials to the analyses. The evidence suggests BCAAs reduce hepatic encephalopathy, but the certainty of evidence is low. We do not know if BCAAs, compared with controls, have any effect on all-cause mortality, nausea and diarrhoea, albumin, and nitrogen balance because of very low-certainty evidence. We could not meta-analyse the data on quality of life. Trials in children are lacking. We lack randomised clinical trials comparing BCAAs with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics. No funding REGISTRATION: Protocol (1997): Gluud C, Koretz RL. Branched-chain amino acids for hepatic encephalopathy (Protocol for a Cochrane Review). The Cochrane Library 1997, Issue 1. Original review (2003): doi.org/10.1002/14651858.CD001939 Review update (2015 Feb): doi.org/10.1002/14651858.CD001939.pub2 Review update (2015 Sep) doi.org/10.1002/14651858.CD001939.pub3 Review update (2017): doi.org/10.1002/14651858.CD001939.pub4.
Clinical nutrition ESPEN · 2026
The effectiveness of beta-hydroxy-beta-methylbutyrate (HMB) for sarcopenia in decompensated cirrhosis patients remains unclear. This pilot trial investigated the effect of HMB-containing oral nutritional supplement (ONS) on muscle mass as the primary outcome. Secondary outcomes included changes in muscle strength, quality, and physical performance. This randomized controlled trial included 21 patients with stable decompensated cirrhosis and sarcopenia (April 2022-January 2024). Participants received either an HMB-containing ONS (daily total of 1.48 g Calcium HMB, 21 g protein, 524 kcal) (HMB group, n = 12) or maltodextrin (control group, n = 9) for 12 weeks. The primary outcome was the 12-week change in muscle mass measured by bioelectrical impedance analysis. Secondary outcomes included handgrip strength, anthropometry, and physical performance. At 12 weeks, there were no significant between-group differences in muscle mass parameters (e.g., appendicular skeletal muscle mass index [ASMI], fat-free mass index [FFMI]) or handgrip strength. However, the HMB group demonstrated significant within-group improvements from baseline in phase angle (4.6°-5.0°, p = 0.015), mid-arm muscle circumference [MAMC] (23.3-24.4 cm, p = 0.008), and 5-time chair stand test performance (18.6-16.5 s, p = 0.047). The supplement was well-tolerated with no significant adverse events. In patients with stable decompensated cirrhosis and sarcopenia, 12-week HMB-containing ONS was well-tolerated. While it did not significantly increase muscle mass or handgrip strength compared to the control group, HMB-containing ONS showed promise for improving key sarcopenia-related parameters-phase angle, mid-arm muscle circumference, and chair stand test performance when compared to baseline. Larger adequately powered randomized controlled trials are needed to confirm these findings. (Trial Registration: Thai Clinical Trials Registry on April 22, 2024, No. TCTR20240422012. The registration can be accessed at: https://thaiclinicaltrials.org/).
Nutrients · 2026
Background/Objectives: Circulating amino acid concentrations and their excretion can provide insights into dietary protein intake and metabolism. Alterations in amino acid homeostasis occur in various disorders due to nutritional imbalances or metabolic changes, including obesity. A ketogenic diet (KD) has gained popularity for weight management; however, its metabolic effects are not fully known. Therefore, the aim of this study was to evaluate the effect of an eight-week, energy-restricted Mediterranean-type KD on the amino acid metabolism in women with overweight and class I obesity. Methods: A randomized, single-center, controlled trial was conducted with 80 women with a BMI of 25.5-35 in age between 18 and 45 years, without any chronic diseases. Randomly divided women received food catering with approximately 1750 kcal daily for eight weeks, containing KD or standard diet (STD), respectively. The concentration of amino acids was assessed by gas chromatography-mass spectrometry after the derivatization with chloroformate in serum and urine collected at the baseline, after 4 weeks, and at the end of the intervention. Results: The results collected from 66 participants were included in the final analyses. Independent of diet type, weight reduction was associated with increased circulating α-aminobutyric acid and decreased proline, glutamate, and tyrosine. The KD led to lower concentrations of alanine, methionine, threonine, and tryptophan, alongside higher levels of branched-chain amino acids (BCAA) and α-aminobutyric acid compared to the STD. Urinary amino acid excretion decreased after weight reduction. KD was associated with higher urinary excretion of BCAA and β-aminoisobutyric acid. Conclusions: In summary, both weight reduction and KD significantly affect the amino acid metabolism, which might have implications for inflammation, oxidative stress, and cardiometabolic risk.
The Cochrane database of systematic reviews · 2026
Hepatic encephalopathy is a common complication of cirrhosis. Its development is associated with increased morbidity and mortality. Its exact pathogenesis is unknown, but ammonia, produced by bacterial action in the intestine, plays a key role. Antibiotics modulate the gut flora and may reduce intestinal ammonia production. Aminoglycosides such as neomycin, paromomycin, and ribostamycin have been used to treat hepatic encephalopathy, as have other antibiotics such as vancomycin and metronidazole. To assess the beneficial and harmful effects of aminoglycosides, vancomycin, and metronidazole versus placebo, no intervention, other antibiotics, or other active pharmacological interventions, for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and three other databases to 15 April 2025. We also searched online trials registries for ongoing and unpublished trials, undertook manual searches of meeting and conference proceedings, checked bibliographies of relevant articles, and corresponded with investigators and pharmaceutical companies. We included randomised clinical trials (RCTs) involving participants with cirrhosis and hepatic encephalopathy, or who were at risk of developing hepatic encephalopathy, comparing aminoglycosides, vancomycin, or metronidazole to (1) placebo or no intervention; or (2) other pharmacological agents, including non-absorbable disaccharides, other antibiotics, or other potentially beneficial agents (e.g. branched-chain amino acids, L-ornithine L-aspartate, nitazoxanide (a broad-spectrum antiparasitic/antiviral agent), and nicotinohydroxamic acid (a potent urease inhibitor). We included trials irrespective of publication status, outcomes reported, language, or blinding. We excluded trials involving people with hepatic encephalopathy associated with acute liver failure or with non-cirrhotic portal hypertension. The critical outcomes were all-cause mortality, hepatic encephalopathy, and serious adverse events. The important outcomes were non-serious adverse events and health-related quality of life (HRQoL). Our primary time point was the maximum length of follow-up. We used Cochrane's original risk of bias tool (RoB 1) to assess the risk of bias. We used standard Cochrane methods. We undertook random-effects meta-analyses to calculate risk ratios (RRs) or standardised mean differences (SMDs), with 95% confidence intervals (CIs). We assessed heterogeneity with the I2 statistic, and the certainty of evidence with the GRADE framework. We included 24 RCTs, involving 1405 participants experiencing 1418 hepatic encephalopathy events. Twenty-three trials evaluated the treatment of hepatic encephalopathy and one, the secondary prevention of hepatic encephalopathy; we analysed these trials jointly. The trials assessed three aminoglycosides: neomycin (15 trials), paromomycin (three trials), and ribostamycin (one trial), as well as vancomycin (two trials), and metronidazole (three trials). Overall, 670 participants received these pharmacotherapies while 735 participants received a placebo or other potentially beneficial agents. We classified 22 of the 24 trials to be at an overall high risk of bias based on domain-level assessments. The certainty of evidence for all comparisons was low to very low, mainly due to risk of bias, imprecision, and heterogeneity. Twenty-three of the 24 trials, involving 1383 participants, reported all-cause mortality data. Aminoglycosides may increase mortality slightly compared to other potentially active agents (RR 1.64, 95% CI 1.03 to 2.62; I² = 0%; 3 studies, 166 participants). The evidence was very uncertain about whether aminoglycosides versus a placebo (RR 1.02, 95% CI 0.62 to 1.69; I² = 0%; 3 studies, 137 participants), non-absorbable disaccharides (RR 1.21, 95% CI 0.57 to 2.59; I² not applicable; 4 studies, 266 participants), or other antibiotics (RR 1.00, 95% CI 0.24 to 4.23; I² = 83%; 8 studies, 496 participants) result in a difference in mortality risk. The evidence was also very uncertain when comparing vancomycin to non-absorbable disaccharides (RR 0.94, 95% CI 0.26 to 3.40; I² not applicable; 2 studies, 72 participants), and metronidazole to other active agents (RR 0.97, 95% CI 0.14 to 6.66; I² = 0%; 3 studies, 242 participants). Nineteen trials involving 1281 participants reported data on hepatic encephalopathy. There may be little to no difference in the effects of aminoglycosides versus non-absorbable disaccharides (RR 0.84, 95% CI 0.67 to 1.05; I² = 0%; 3 studies, 251 participants), aminoglycosides versus other potentially active agents (RR 1.21, 95% CI 0.79 to 1.85; I² = 0%; 3 studies, 166 participants), and metronidazole versus other active agents (RR 1.50, 95% CI 0.89 to 2.54; I² = 48%; 2 studies, 208 participants). The evidence is very uncertain about the effect of aminoglycosides versus placebo, other antibiotics, and vancomycin versus non-absorbable disaccharides. Twenty trials, involving 1186 participants, reported a total of 328 serious adverse events. Aminoglycosides may slightly increase the risk of serious adverse events compared with other potentially active agents (RR 1.60, 95% CI 1.03 to 2.47; I² = 0%; 3 studies, 166 participants). The evidence is very uncertain when comparing aminoglycosides to placebo and other antibiotics, or when comparing vancomycin to non-absorbable disaccharides. Eighteen trials, involving 922 participants, reported a total of 96 non-serious adverse events. There may be a slight increase in the risk of adverse events when comparing aminoglycosides to placebo (RR 2.80, 95% CI 1.11 to 7.04; I² not applicable; 2 studies, 98 participants), and to other antibiotics (RR 3.24, 95% CI 1.08 to 9.70; I² = 0%; 8 studies, 251 participants). The evidence is very uncertain about the effects of aminoglycosides versus non-absorbable disaccharides or other active agents, and metronidazole versus other active agents. Only one trial assessed HRQoL, but reported the data in a form that precluded meta-analysis. Eight trials received support from pharmaceutical companies while six did not. Ten trials did not provide this information. Due to low- or very low-certainty evidence, we do not know if aminoglycosides benefit hepatic encephalopathy compared to placebo or other potentially active agents. There may be a slight increase in the risks of mortality and serious adverse events with aminoglycosides compared to other agents, and of non-serious adverse events when compared to placebo and other antibiotics. We do not know if vancomycin or metronidazole improve clinically relevant outcomes. Only one trial assessed health-related quality of life. This Cochrane review received no specific funding. https://doi.org/10.1002/14651858.CD012734.
The American journal of clinical nutrition · 2026
Protein intake among children in resource-rich countries often exceeds current recommendations. Higher protein consumption during infancy has been associated with an increased risk of obesity later in life. We conducted a secondary analysis of a randomized controlled trial where 250 infants were randomly assigned to receive either a protein-reduced Nordic diet or a conventional Swedish complementary diet. Our aims were to examine the metabolic responses to the intervention using plasma metabolomics and to test the pathways proposed by the Early Protein Hypothesis by linking cumulative protein intake to circulating branched-chain amino acids (BCAAs), insulin-like growth factor-1 (IGF-1), and growth outcomes using structural equation modeling (SEM). Targeted proton nuclear magnetic resonance (1H-NMR) metabolomics was performed on plasma samples collected at 12 and 18 mo. Two SEM models were constructed: one modeled body weight and the other modeled BMI as growth outcomes using data collected up to age 18 mo. Model fit indices were assessed, and path diagrams were used to visualize relationships. The Nordic diet led to reduced-protein intake and a distinct infant plasma metabolomic profile. Circulating BCAAs and their catabolites were significantly lower in the reduced-protein Nordic diet compared with the conventional diet. Cumulative protein intake positively correlated with plasma IGF-1 concentrations {weight-based SEM: β = 0.40 [95% confidence interval (CI): 0.03, 0.48]; BMI-based SEM: β = 0.43 [95% CI: 0.05, 0.50]}. Plasma total BCAAs were positively associated with plasma IGF-1 levels [weight-based SEM: β = 0.16 (95% CI: 0.00, 0.76); BMI-based SEM: β = 0.17 (95% CI: 0.02, 0.78)]. After accounting for metabolite-mediated effects on IGF-1 and insulin, cumulative protein intake remained significantly associated with infant body weight [β=0.36 (95% CI: 0.02, 0.99)], but not BMI. Complementary feeding during infancy substantially shapes the plasma metabolome. Reducing protein intake from complementary feeding helps attenuate rapid infant weight gain, a well-established early-life predictor of later obesity.
Diabetes, obesity & metabolism · 2026
Elevated branched-chain amino acids (BCAAs; leucine, valine, isoleucine) are linked to type 2 diabetes (T2D) risk, characterised by defective insulin secretion in pancreatic β-cell and peripheral insulin resistance. Causative interaction between BCAA metabolism and these two diabetic pathogenesis remains unclear. Using publicly available datasets from the European population, we conducted a meta-analysis of genome-wide association studies (GWAS), followed by multi-trait analysis of GWAS (MTAG), to identify genetic loci associated with BCAAs and their catabolites. Two-sample bidirectional Mendelian Randomisation (MR) examined putative causal associations of genetically determined BCAAs and their catabolites with 10 traits related to insulin and glucose metabolism. Sensitivity analyses evaluated robustness and specificity of observed associations. MTAG identified 57.14%, 59.09%, and 63.41% novel genetic loci for circulating leucine, valine and isoleucine, respectively. Genetically elevated valine had a significant association with increased insulin fold change during oral glucose challenge test (OGTT) (β [95% CI] = 0.135 [0.045, 0.225]), False discovery rate adjusted p-value (p FDR = 0.022), and suggestive association with fasting glucose level (β [95% CI] = 0.031 [0.004, 0.058], inverse-variance weighted p-value [p IVW] = 0.025). In the reverse direction, genetically determined homeostasis model assessment of β-cell (HOMA-B) exhibited significant inverse associations with BCAAs (Leucine: β [95% CI] = -0.140 [-0.244, -0.036], p FDR = 0.034; Valine: β [95% CI] = -0.147 [-0.255, -0.040], p FDR = 0.030; Isoleucine: β [95% CI] = -0.149 [-0.248, -0.049], p FDR = 0.020). Moreover, β-hydroxyisovalerate, a leucine-derived catabolite, was inversely related to 2-h glucose level after OGTT (β [95% CI] = -0.149 [-0.227, -0.071], p FDR = 0.045). In the reverse direction, genetically predicted peak insulin response was suggestively associated with elevated isoleucine catabolite, 2-hydroxy-3-methylvalerate (β [95% CI] = 0.074 [0.018, 0.130], p IVW = 9.20 × 10-3). Our genetic analysis indicates BCAA catabolism and insulin secretion/action interact with each other; their aberrance might form a vicious cycle promoting T2D progression.
Scientific reports · 2020
We examined the acute effects of L-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). L-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8-15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signal task ~ 1 h post-dose. NIH Cognition Toolbox was administered ~ 2 h post-dose. Treatment vs. placebo effects were examined in multi-level mixed-effects models. L-Theanine improved total cognition composite in NIH Cognition Toolbox (p = 0.040) vs. placebo. Caffeine worsened and L-theanine had a trend of worsening inhibitory control (i.e. increased Stop-signal reaction time; p = 0.031 and p = 0.053 respectively). L-Theanine-caffeine combination improved total cognition composite (p = 0.041), d-prime in the Go/NoGo task (p = 0.033) and showed a trend of improvement of inhibitory control (p = 0.080). L-Theanine-caffeine combination was associated with decreased task-related reactivity of a brain network associated with mind wandering (i.e. default mode network). L-Theanine-caffeine combination may be a potential therapeutic option for ADHD-associated impairments in sustained attention, inhibitory control and overall cognitive performance.
Prostaglandins & other lipid mediators · 2025
Several meta-analyses have examined the effect of Nigella sativa (N. Sativa) supplementation on inflammatory and oxidative markers, with conflicting results. So, the current study evaluated the effect of N. Sativa on some oxidative and inflammatory parameters. The Embase, Web of Science, Scopus, PubMed databases, and Google Scholar were systemically searched to identify papers indexed before February 2023. The pooled results were calculated with the use of a random-effects model to evaluate the effects of N. Sativa on inflammatory and oxidative markers. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. Overall, seven meta-analyses were included in the study. N. Sativa supplementation significantly decreased serum C-reactive protein (CRP) (ES = -0.42; 95 % CI: -0.58, -0.25, p < 0.001), tumor necrosis factor-alpha (TNF-α) (ES= -1.27; 95 % CI: -2.29, -0.25; p = 0.015), and malondialdehyde (MDA) (ES = -0.67; 95 % CI: -0.97, -0.36, p < 0.001) levels, and significantly improved total antioxidant capacity (TAC) (ES = 0.34; 95 % CI: 0.20, 0.47, p < 0.001) and superoxide dismutase (SOD) (ES = 50.66; 95 % CI: 34.15, 67.18, p < 0.001) levels. N. Sativa supplementation had beneficial effects on CRP, TNF-α, MDA, SOD, and TAC. Thus, N. Sativa can be recommended as an adjuvant anti-inflammatory and anti-oxidant agent.
Narra J · 2024
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, requiring long-term treatment that can have side effects, particularly in pediatric patients. Nigella sativa has shown potential for improving SLE symptoms due to its anti-inflammatory and immunomodulatory effects. The aim of this study was to investigate the immunomodulatory effect of N. sativa oil (NSO) on disease activity, T lymphocyte activity and inflammatory cytokine profiles in pediatric SLE patients. A randomized, double-blinded, placebo-controlled clinical trial was conducted at Saiful Anwar Hospital in Malang, Indonesia. Pediatric patients with SLE were randomly assigned to receive either one gram of NSO or a placebo containing starch in capsule form as adjunct therapy alongside their SLE primary treatment. Blood samples were collected before treatment and after eight weeks of daily capsules. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2 K); flow cytometry was used to identify T helper lymphocytes, and serum cytokine levels were measured using ELISA. The statistical analysis tests were performed to compare the outcomes between groups at baseline or after the treatment, and within-group comparisons before and after the study period, as appropriate. A total of 32 patients were included in the study. A significant decrease in the SLEDAI-2 K score was observed at post-treatment in both the NSO and placebo groups (p < 0.001 and p = 0.025, respectively). The percentage of T helper 17 (Th17) cells was significantly reduced in both the NSO and placebo groups post-treatment compared to pre-treatment (p = 0.026 and p = 0.034, respectively). Conversely, the post- treatment percentage of regulatory T (Treg) cells increased significantly in both groups. A significant reduction in interleukin (IL)-2 levels was observed in the NSO and placebo groups at post-treatment compared to pre-treatment (p = 0.006 and p = 0.046, respectively). Additionally, there were increases in IL-4 and IL-6 serum levels in both groups at post-treatment compared to pre-treatment (p < 0.05). This study highlights that although disease activity was not significantly different between NSO and placebo groups, NSO could affect the inflammatory cytokine profiles in pediatric SLE patients.
Paediatric drugs · 2025
Nigella sativa is a widely used medicinal plant with several potential therapeutic uses. This study aimed to investigate the possible beneficial cardioprotective effect of Nigella sativa in pediatric patients with type 1 diabetes mellitus. Sixty children and adolescents with type 1 diabetes were randomized into two groups: group I (n = 30) who received Nigella sativa seed oil 450 mg twice daily after meals for 3 months in addition to insulin, and group II (n = 30) who received insulin alone. Echocardiographic examinations were performed before and after the treatment. The lipid profile, malondialdehyde, nitric oxide, tumor necrosis factor-α, transforming growth factor-β, and troponin I were also measured before and after Nigella sativa treatment. After 3 months of Nigella sativa administration, group I had significantly lower cholesterol and low-density lipoprotein-cholesterol, malondialdehyde, nitric oxide, tumor necrosis factor-α, transforming growth factor-β, and troponin I levels compared with their pretreatment levels and compared with group II. In addition, group I had a significantly higher left ventricular E'/A' ratio and two-dimensional left ventricular global longitudinal strain (2D-LV GLS) compared with baseline values and compared with group II after treatment. Nigella sativa can improve subclinical left ventricular dysfunction in pediatric patients with type 1 diabetes mellitus. this clinical trial was registered at www.pactr.org with ID: PACTR202302478939306.
Journal of ovarian research · 2025
Adolescence is a critical period for health, as conditions like polycystic ovarian syndrome (PCOS) can affect long-term outcomes, including diabetes and other non-communicable diseases in adulthood. This study evaluated the effects of Nigella sativa L. extract on glycemia among adolescents with PCOS. This secondary analysis used data from a randomized controlled trial conducted between March 2022 and March 2023. One hundred sixteen adolescent girls aged 12-18 years with PCOS were randomized into two groups. The intervention group received 1000 mg/day of Nigella sativa extract for 16 weeks, while the control group received 10 mg/day of medroxyprogesterone for 10 days per menstrual cycle over the same period. Fasting plasma glucose (FPG) and one- and two-hour post-prandial glucose levels were measured at baseline and after the intervention. 103 completed the study (50 in the Nigella sativa group and 53 in the control group). At baseline, there were no significant differences in FPG (p = 0.294), though the control group had higher one-hour (p = 0.002) and two-hour (p = 0.006) post-prandial glucose levels. Post-intervention, significant interaction effects were observed for FPG (p = 0.004) and two-hour post-prandial glucose (p = 0.023), indicating more significant reductions in the Nigella sativa group compared to the control group. Considering the observed effect of Nigella sativa supplementation on FPG and two-hour post-prandial glucose, it may offer a complementary approach to managing glycemia in adolescent PCOS. However, further research is warranted.
Complementary therapies in medicine · 2025
Black seed is known for its health benefits in traditional medicine. While recent studies suggest it may improve cardiometabolic health, its impact on type 2 diabetes mellitus (T2DM) remains unclear. This study aims to meta-analysis randomized controlled trials (RCTs) to assess the effects of black seed supplementation on cardiometabolic indices in T2DM patients. Following PRISMA guidelines, a comprehensive database search was conducted up to January 2025, and data were extracted from relevant RCTs. Mean differences (MD) and standard deviations (SD) were analyzed using a random-effects model, heterogeneity was assessed, and publication bias was evaluated. The pooled meta-analysis of 16 RCTs showed that black seed supplementation significantly reduced fasting blood glucose (FBG) (MD: -21.43 mg/dL; p = 0.005), hemoglobin A1c (HbA1c) (MD: -0.44; p = 0.01), total cholesterol (TC) (MD: -18.80 mg/dL; p = 0.04) and low-density lipoprotein (LDL) (MD: -19.53 mg/dL; p = 0.003). No significant effects were observed for 2-hour postprandial glucose (2-hpp), fasting insulin, homeostatic model assessment (HOMA), triglycerides (TG), high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and body weight, or body mass index (BMI). Subgroup analyses revealed that black seed supplementation effectively reduced FBG for longer than 8 weeks; additionally, HbA1c, HOMA, and LDL in higher doses (>1 g/day), shorter durations (≤8 weeks), and use of the oil form. Black seed supplementation appears to significantly improve FBG, HbA1c, TC, and LDL levels in patients with T2DM. However, no significant effects were observed on other metabolic parameters, including insulin, TG, liver enzymes, kidney function, or body weight. These findings suggest that black seed may be a beneficial adjunct therapy for glycemic and lipid control in T2DM patients but require further research to confirm its broader metabolic effects.
Narra J · 2025
Nigella sativa seed extract has been shown to have a significant effect on endometrial thickness and vaginal cytology in ovariectomized animal models, suggesting potential benefits for managing menopausal symptoms. However, to the best of the author's knowledge, no human studies have been done to support these conclusions. The aim of this study was to investigate the effects of N. sativa seed extract on estradiol, follicle- stimulating hormone (FSH), and the vaginal maturity index (VMI) in postmenopausal women. A single-blinded, randomized placebo-controlled experiment was carried out at Haji Adam Malik Hospital, Medan, Indonesia, with 50 eligible postmenopausal women patients randomized into three groups. Group 1 received a placebo, while groups 2 and 3 were given N. sativa seed extract at 910 mg/day and 1,365 mg/day, respectively. All participants were blinded to the treatment they received. The study used Shad Nigella Plus, an Indonesian herbal medicine containing 455 mg of N. sativa seed extract per capsule. Before the treatments, estradiol levels, FSH levels, and VMI were measured at baseline and remeasured after eight weeks of treatment. Two participants in the intervention group withdrew due to nausea, a reported side effect of N. sativa seed extract consumption. Both treatment groups showed significant increases in estradiol levels (p = 0.01 and p = 0.001) and VMI (p = 0.004 and p = 0.001) after eight weeks of daily N. sativa seed extract administration compared to the placebo group. However, no significant differences were found between the two doses in estradiol levels and VMI (p = 0.12 and p = 0.673, respectively). Moreover, FSH levels showed no significant difference throughout both interventions (p = 0.53 and p = 0.96, respectively). In conclusion, twice-daily N. sativa seed extract at 910 mg/day or 1,365 mg/day for eight weeks significantly increased estradiol levels and VMI in menopausal women but had no significant effect on FSH levels. These findings support the potential role of N. sativa seed extract as a natural treatment for menopausal symptoms.
Current drug targets · 2025
Kidney stones have always been a significant matter in the healthcare sector worldwide, with a high prevalence rate, especially in women. Urolithiasis is the solid mineral deposits in the renal calyces and kidney pelvis. Expounding upon the pathophysiology, various mechanisms such as supersaturation, crystallization, and aggregation are explored. Some new targets can potentially stop the disease's underlying cause that has been found. To compile the Recent Progression and treatment approaches for kidney stone management. A systematic review was conducted using a comprehensive literature search on the roles of osteopontin, vitamin D, nephrocalcin, and other factors in kidney stone formation in Google Scholar, PubMed, Elsevier, etc. OPN is a multifunctional protein that limits the formation of stones by participating in resorption. The other is the concentration of vitamin D, which raises calcium absorption and causes kidney stones to form. Further, the review encapsulates the spectrum of treatment approaches encompassing phytoconstituents, pharmacotherapy, and minimally invasive procedures, including surgical interventions. From the Phytochemical-based literature survey, Rubicodifolin, L-ascorbic acid, Thymoquinone, etc., show promising activity in managing kidney stone. Apart from that, we have found such data that has been published in reputed journals. This synthetic drug-based approach shows traditional drug-based targeting. Where Nifedipine, Chlorthalidone, Allopurinol, etc., were used for symptomatic relief. Peptide-based approach reveals that several peptides for the treatment of kidney stone, where Lumasiran, a phase III clinical trial peptide molecule, targets glycolate oxidase and reduces calcium oxalate crystal levels. To implement more effective treatments, it is necessary to identify and develop a targeted therapy for the druggable targets. Various such druggable targets have been reported such as osteopontin which has come out as a protein with various functions including involvement in the inhibition of crystal adherence to the renal epithelium. Another such target is vitamin D and nephrocalcin.
PloS one · 2025
Episiotomy, a common surgical procedure during childbirth, often leads to complications such as pain, infection, and delayed healing. Nigella sativa has demonstrated anti-inflammatory and wound-healing properties in prior studies and have received United States Food and Drug Administration (FDA) approval for food use, indicating their safety. This study aimed to evaluate the efficacy of Nigella sativa emulgel on episiotomy wound healing and pain intensity in primiparous women. A triple-blind, randomized controlled trial was conducted at Taleghani Hospital, Tabriz, Iran (May 2023-April 2024). Seventy-four primiparous women with mediolateral episiotomy were randomized to receive either Nigella sativa emulgel or placebo, applied topically three times daily for 7 days post-discharge. Wound healing was assessed using the REEDA scale (Redness, Edema, Ecchymosis, Discharge, Approximation; primary outcome), and pain intensity was measured via visual analog scale (VAS; secondary outcome). Outcomes were evaluated at discharge (baseline) and 10 ± 1 days postpartum. Data were analyzed using independent t-tests, ANCOVA (adjusted for baseline scores), and Mann-Whitney U tests for non-normal distributions (SPSS v26). At 10 ± 1 days postpartum, the Nigella sativa group showed significantly better wound healing (REEDA score: MD -0.79, 95% CI -1.20 to -0.39; p = 0.001) and lower pain scores (VAS: MD -0.74, 95% CI -1.3 to -0.11; p = 0.021) compared to placebo. Subscale analysis revealed improvements in redness (p = 0.037), edema (p = 0.041), and ecchymosis (p = 0.043). No adverse effects were reported, and satisfaction was higher in the Nigella sativa group (86.5% vs. 56.7%; p = 0.046). Topical Nigella sativa emulgel significantly improved episiotomy wound healing and reduced pain intensity, with high patient satisfaction. These findings support its potential as a natural therapeutic option, though larger multi-center trials are needed for broader validation. Iranian Registry of Clinical Trials IRCT20120718010324N68.
Respiratory medicine · 2025
Bronchial asthma is a highly prevalent health condition associated with low quality of life and high economic costs. Treatments from traditional, complementary and integrative medicine (TCIM) are commonly used by individuals with bronchial asthma. However, a synthesis of the evidence on plant-derived medications is lacking. This review aims to systematically summarize the evidence on the efficacy, effectiveness and safety of European/Western phytotherapy (PT) and medications from anthroposophic medicine (AM) in individuals with bronchial asthma. Four electronic databases and additional references were screened for clinical trials published between 1990 and 2023. The findings of the included studies were qualitatively synthesized and study quality was assessed. Of 23 included studies, 19 examined European/Western PT and four investigated AM medications. Nine studies of sufficient quality reported beneficial effects of various plants (e.g., Nigella sativa) on asthma symptoms, pulmonary function and immunological parameters. The medications were considered safe in studies that reported on safety. This systematic review suggests several medications from European/Western PT and AM that may be beneficial and appear to be safe in the treatment of bronchial asthma. However, further rigorous studies are needed to provide evidence-based guidance on add-on treatment options for individuals with bronchial asthma.