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Nutrients · 2025
Objectives: This study aimed to evaluate the efficacy of various nutritional supplements in enhancing endurance performance and subjective thermal perception in athletes exposed to high-temperature environments through a systematic review and network meta-analysis. Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, Cochrane Library, and EBSCOhost from inception to January 2025. Studies were included if they evaluated the effects of nutritional supplements on either endurance performance or subjective thermal perception in athletes under heat stress. Two independent reviewers screened the literature, extracted data, and assessed the risk of bias. A network meta-analysis was performed using R software (version 4.3.1). The search was limited to English-language publications and employed both MeSH and free-text terms related to "athletes," "nutritional supplements," and "exercise performance," using Boolean operators (AND/OR) to construct the strategy. Results: Twenty-five randomized controlled trials (RCTs) involving 552 participants were included, yielding 22 comparisons: 18 assessed endurance performance, and 11 assessed subjective perception. Standardized mean differences (SMDs) and posterior probabilities (P-scores based on Bayesian ranking) were calculated using random-effects and Bayesian models. Menthol (SMD = -1.83, 95% CI [-3.15, -0.51]; P-score = 71.04%) and taurine (SMD = 0.91, 95% CI [0.08, 1.73]; P-score = 12.75%) demonstrated significant positive effects on endurance. Menthol energy gel showed the greatest improvement in thermal comfort (SMD = 2.14, 95% CI [1.01, 3.26]; P-score = 99.54%). Conclusions: Menthol and taurine appear effective in enhancing endurance in hot environments, while menthol energy gel substantially improves perceived thermal comfort. Future research should apply stricter controls regarding environmental conditions, supplement dosage, and participant characteristics. While individual supplements may offer limited benefits, synergistic combinations may yield greater improvements in performance and comfort.
European journal of nutrition · 2025
The study investigates whether postprandial amino acid responses differ between normalweight (NW) and overweight/obese (OW) individuals following consumption of plant protein-enriched wheat biscuits with the same protein content but different protein composition. It highlights the importance of developing functional snack products with specific amino acid profile that could benefit individuals with overweight/obesity. Thirty volunteers (15 NW and 15 OW) participated in an acute, randomized crossover trial, in which they consumed two plant protein-enriched wheat biscuits differing in amino acid profile-one enriched in L-arginine (arginine biscuit, ArgB) and the other in branched-chain amino acids (branched-chain amino acids biscuit, BCAAsB)-as well as a conventional wheat biscuit (CB) in separate sessions with one week intervals. Postprandial amino acids (AAs) responses were measured for 180 min following ingestion. Fasting and postprandial AAs concentrations were determined by Ultra-High Performance Liquid Chromatography coupled with Time-of-Flight Mass Spectrometry (UHPLC-ToF-MS). OW subjects exhibited higher fasting concentrations of methionine, tryptophan and tyrosine (p < 0.05) while NW subjects, higher levels of glutamine (p < 0.05). Postprandial responses of all the determined AAs to enriched biscuits were higher in the NW compared to the OW group with incremental areas under the curve (iAUCs) of alanine, glutamine and threonine reaching statistical significance (p < 0.05). In the OW group, ingestion of BCAAsB resulted also in lower iAUC values of asparagine and serine, while consumption of ArgB led to a lower iAUC of glycine and a higher iAUC of taurine compared to the NW group (p < 0.05). Ingestion of plant protein-enriched wheat biscuits by OW subjects resulted in lower postprandial responses of alanine, glutamine and threonine compared to NW. AAs composition of BCAAs-enriched biscuit resulted also in lower responses of asparagine and serine while that of the L-arg-enriched biscuit, in lower glycine but higher taurine responses in OW compared to NW subjects. Depletion of all the above-mentioned AAs has been recorded in obesity. Higher taurine concentrations can lead in beneficial effects since taurine improves glycemic control and insulin sensitivity and it has shown potential anti-obesity properties. These findings underscore the challenge of designing protein-rich foods that could elicit beneficial metabolic responses for overweight/obese individuals.
Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie · 2026
Genetic and phenotypic parameters of traits related to growth, production and reproduction are crucial in the formulation of successful breeding programmes. Given the diversity in the cattle population of India, meta-analysis offers a comprehensive insight into the overall performance of the crossbred population for the efficient implementation of animal improvement programmes. The present study aimed to undertake meta-analysis and estimate the genetic and phenotypic parameters of performance traits in Indian crossbred cattle. A total of 130 articles were included in this study after data editing and quality control. The heterogeneity index reached 91.2% for phenotypic parameters, 99.4% for heritability estimates, and 99.4% for phenotypic correlations. Pooled least squares mean ranged from 20.54 to 25.84 kg for body weight at birth, 1542.05 to 2691.44 kg for first lactation milk yield, 996.05 to 1259.38 days for age at first calving in crossbred cattle. Pooled heritability estimates ranged from 0.13 to 0.69 for growth traits, 0.09 to 0.76 for production traits, and 0.05 to 0.25 for reproduction traits. The pooled repeatability estimates were moderate and ranged from 0.22 to 0.42. Pooled genetic correlations were positive and ranged from 0.09 to 0.97. This is the first attempt to estimate the genetic and phenotypic parameters of performance traits in Indian crossbred cattle using a meta-analytical approach. Meta-analysis revealed that the heritability estimate of production and reproduction performance was low to moderate in all the crossbred populations. This suggested the influence of environment and other non-additive genetic effects, wherein improvement is possible through the integration of effective selection and optimum management strategies. Pooled estimates of genetic and phenotypic parameters from this investigation may be used for the effective implementation of breeding programmes in the herds/populations, where these parameters are not estimated/available for any reason.
Scandinavian journal of medicine & science in sports · 2025
This systematic review and meta-analysis evaluated the acute effects of a single dose of taurine supplementation on exercise performance and examined potential moderators related to participant characteristics, exercise modality, dosing, and administration protocols. Six electronic databases were searched up to July 2025, identifying 23 eligible randomized trials (k = 69, N = 308). A three-level random-effects meta-analysis indicated that acute taurine ingestion may be associated with small-to-moderate improvements in overall performance (g = 0.25, 95% CI [0.10, 0.39], I2 = 61%). Moderator analyses suggested that benefits were more apparent in males and across aerobic endurance, strength/power, and agility/coordination tasks, whereas evidence for anaerobic capacity and muscular endurance remained inconsistent. No significant dose-response relationship was detected within the commonly used 1-6 g range, suggesting potential threshold effects rather than linear trends. Both capsule and beverage formulations appeared effective, and nonlinear meta-regression indicated that ingestion about 1 h before exercise might yield the most favorable outcomes, although this timing effect was not robust in sensitivity analyses. Further analyses showed that several subgroup effects were attenuated after excluding influential studies, and prediction intervals frequently included the null, reflecting uncertainty in replicability. The overall certainty of evidence, assessed using GRADE, was rated low to very low due to heterogeneity, imprecision, and risk of bias. Collectively, these findings suggest that acute single-dose taurine supplementation holds promise as an ergogenic aid, but its effectiveness likely varies depending on dosage, blinding procedures, and exercise context. Additional high-quality trials are needed to establish more definitive recommendations.
European journal of sport science · 2025
Caffeine and taurine are commonly co-ingested pre-exercise but elicit different thermoregulatory responses; however, their combined effect on thermoregulation is unknown. Therefore, we evaluated the effects of oral caffeine and taurine co-ingestion on time to exhaustion (TTE) and thermoregulatory responses to cycling in the heat at the gas exchange threshold (GET). Ten healthy nonheat acclimated participants took part in a double-blind crossover study, completing a TTE in the heat (35°C; 40% relative humidity), cycling at a power output associated with the GET and 1 h after ingesting: caffeine (5 mg/kg) and taurine (50 mg/kg) combined or placebo. Pulmonary gas exchange, core and mean skin temperatures and whole-body sweat rate (WBSR) were recorded throughout. Heat production was determined using partitional calorimetry. There were no differences in TTE between conditions (p = 0.608); however, the rate of oxygen consumption (p = 0.017), minute ventilation (p = 0.029) and heat production (p = 0.019) were higher following the supplement. There were no differences between conditions for skin (p = 0.539) and core temperature (p = 0.699), mean skin blood flow (p = 0.119), respiratory exchange ratio (p = 0.546) and WBSR (p = 0.897). Pre-exercise co-ingestion of caffeine and taurine in the heat had no ergogenic effect despite increasing the ventilatory and metabolic demand. Collectively, these data indicate minimal effects on whole-body thermoregulation.
Journal of the International Society of Sports Nutrition · 2025
Caffeine (CAF) and taurine (TAU) have each demonstrated ergogenic effects across physical and cognitive domains. Often co-formulated in commercial energy drinks, they are widely regarded as the two principal bioactive compounds. However, findings regarding their combined efficacy remain inconclusive. This systematic review and Bayesian network meta-analysis aimed to quantify the individual and combined effects of CAF and TAU on physical capacity, cognitive function, and physiological responses, with a focus on identifying potential synergistic or antagonistic interactions. Cochrane Library, PubMed, SciELO, SportsDiscus-EBSCO and Web of Science were searched through 25 July 2025. The pooled effect of each outcome was summarized using SMD (Hedge's g) by Bayesian arm-based multilevel network meta-analysis, and SUCRA ranking was applied to estimate the relative treatment effect. Twelve studies were included (8 on physical capacity, 7 on blood lactate (B[la]), and 6 each on cognitive function, heart rate (HR), and rating of perceived exertion (RPE)). Posterior estimates indicated that CAF+TAU was associated with a credible positive effect on anaerobic capacity (g = 0.46, 95% CrI [0.19, 0.71]) and reaction time (g = 0.75, 95% CrI [0.29, 1.18]) compared to CAF or TAU alone. CAF showed the greatest posterior reduction in RPE (g = -0.64, 95% CrI [-1.20, -0.10]), while its posterior mean estimate suggested a potential increase in B[la] (g = 0.24, 95% CrI [-0.48, 0.96]). In contrast, TAU showed a possible tendency toward reducing B[la] (g = -0.30, 95% CrI [-1.01, 0.42]). No credible differences in HR were observed across conditions. Effects on aerobic performance and physiological measures were variable and appeared to be context-dependent. SUCRA rankings consistently favored CAF+TAU across most outcome domains. CAF+TAU co-supplementation provides a balanced ergogenic effect, combining the central stimulation of CAF with the neuromodulatory and metabolic support of TAU, particularly beneficial for high-intensity, reaction-based tasks. Its effects on endurance and physiological indices vary by condition, highlighting the need for personalized application.
Brain, behavior, and immunity · 2026
Obesity is associated with depressive symptoms due to biological and psychological factors. Dietary interventions, including the Ketogenic (Keto) and Mediterranean (Med) diets, impact weight loss and mental health differently. While the Keto diet promotes rapid weight loss by increasing ketone body levels, its effects on mental health, particularly in individuals with obesity, remain unclear. This exploratory pilot study explores the impact of both diets on depression and impulsiveness, focusing on the gut-brain axis. Sixty-four participants (Body Mass Index 30-45 kg/m2, ages 18-65) were randomly assigned to follow one of the two diets for three months. Due to attrition, 37 participants (Med n = 23; Keto n = 14) completed the study. Depression and impulsivity scores were evaluated before and after the intervention. Stool samples were collected for microbiota analysis, and faecal transplants were performed in healthy mice. Brain and serum metabolites in recipient mice were analysed using High-Resolution Magic Angle Spinning (HR-MAS) and Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy. The Med diet showed greater improvement in depression scores compared to the Keto diet, while the latter was associated with reductions in impulsivity (urgency subscale). However, faecal transplants from the Keto group induced anxiety-like behaviours in recipient mice, which correlated with significant microbiota and metabolite changes. The Keto group exhibited increased levels of taurine, alanine, and betaine in the brain, and threonine levels were correlated with behavioural changes. These findings suggest that the Med diet offers more consistent short-term benefits related to depressive symptoms, while the Keto diet modulated impulsivity. The animal model findings highlighted the role of diet-induced microbiota changes and metabolite alterations in the gut-brain axis. Long-term studies in a larger population are needed to tailor dietary interventions, essential for optimizing mental and physical health in obesity.
Cardiovascular toxicology · 2025
Energy drinks (EDs), widely consumed for their stimulant effects, typically contain caffeine alongside taurine, guarana, and other bioactive compounds. While generally regarded as safe, growing evidence links chronic EDs consumption to significant cardiovascular risks. Caffeine, the primary active ingredient, acts through adenosine receptor antagonism and increased calcium release, potentially provoking arrhythmias and myocardial stress. Taurine and other additives further influence cardiac excitability and contractility. This systematic review, conducted under PRISMA 2020 guidelines, investigated the cardiac histopathological consequences of chronic EDs use. A literature search spanning 2021 to March 2025 across PubMed, Google Scholar, and Scopus identified studies reporting EDs-related cardiac effects. Data extraction and analysis revealed consistent associations with QTc prolongation, atrial and ventricular arrhythmias, myocardial infarction, Takotsubo cardiomyopathy, and hypertensive episodes-even in young, healthy individuals. Animal studies support these findings, showing myocardial necrosis, myofiber disarray, mitochondrial damage, and inflammation, particularly when EDs are combined with alcohol. Notably, similarities between EDs and cocaine emerged, including shared mechanisms involving ion channel blockade, sympathetic overactivation, vasoconstriction, and prothrombotic states. Chronic use of either substance can result in structural heart damage and remodelling. Although EDs and cocaine differ in legal status and potency, their overlapping cardiovascular effects warrant greater clinical awareness and public education. Excessive EDs consumption poses a real cardiotoxic risk, especially in vulnerable populations, underscoring the need for further human research and potential regulatory consideration.
Biomeditsinskaia khimiia · 2025
Sepsis-associated encephalopathy (SAE) is a condition characterized by acute brain dysfunction developed in the absence of a primary infection in the central nervous system. The aim of this study was to perform a pilot, untargeted metabolomic profiling of the blood plasma of SAE patients to identify metabolic changes potentially associated with the pathological condition and to generate hypotheses for further studies of its pathogenesis, as well as to the search for promising biomarkers, and the assessment of the severity of the patient's condition. Metabolomic profiling was performed using HPLC-HR-MS, followed by statistical analysis of the obtained data. This blinded, randomized, controlled clinical trial revealed significant differences in the metabolic profiles of the study and control groups. Functional analysis showed the metabolic pathways most affected by pathological processes in SAE patients. These included metabolism of acylcarnitines, lysophosphatidylcholines, and taurine, folate biosynthesis, and the drug metabolism involving the cytochrome P450 pathway. In SAE patients with impaired consciousness, including delirium and coma, decreased levels of long-chain acylcarnitines and lysophosphatidylcholines were observed. The metabolomic profiles of SAE patients differed significantly between the groups of deceased and surviving patients: concentrations of sulfur-containing amino acids were significantly lower in the group of deceased than in the group of survivors. Our study identified 64 candidate biomarkers that could potentially be used to predict sepsis outcomes. However, further study is needed using an expanded and independent cohort of patients.
Clinical nutrition ESPEN · 2026
Graft dysfunction after liver transplantation is marked by elevated liver enzymes. Taurine, an antioxidant amino acid, may support graft function. This study evaluated taurine's effect on post-transplant liver biomarkers. In this randomized, double-blind trial, adults undergoing liver transplantation (Sept 2020-June 2021) were enrolled. Exclusions were death within 72 h or multi-organ transplant. Patients received oral taurine or placebo (2 g/day) from transplant day to day 30. The primary outcomes were changes in liver enzymes and bilirubin. Secondary outcomes included mortality, intensive transplantation unit (ITU)/hospital stay, and ventilation duration. Of 225 patients, 56 were excluded (29 refusals, 27 early deaths). The 169 analyzed patients were evenly randomized. The taurine group had significantly greater reductions in aspartate aminotransferase (AST), total bilirubin, and international normalized ratio (INR). Taurine was also associated with significantly lower mortality (p < 0.05), shorter ITU stay (mean difference: -4.09 days), shorter hospital stay (mean difference: -3.49 days), and reduced mechanical ventilation duration (mean difference: -20.06 h) compared to placebo. All patients showed expected post-operative declines in alanine aminotransferase (ALT), AST, and bilirubin. Supplementation with 2 g/day taurine for 30 days after transplantation was associated with improved graft function markers (AST, total bilirubin, INR) and better clinical recovery outcomes. These results suggest taurine may be a beneficial adjunct therapy to support early post-transplant recovery.
Nutrients · 2026
Background: Evidence is accumulating that gut bacterial communities modulate the outcome of dietary interventions. Objective: To assess how gut microbial enterotypes correlate with obesity-related outcomes during one month of whole milk consumption. Methods: This post hoc analysis used data from a previously published trial, which included a lead-in phase during which men with abdominal adiposity replaced habitual dairy product consumption with 400 g/day of whole milk for one month. We compared body weight, urinary metabolites, fecal metabolites, and gut microbiome composition and function based on shotgun metagenomic sequencing at the beginning and at the end of the lead-in phase between individuals with the two most prevalent enterotypes, the Bacteroides1 (B1) enterotype (n = 24) and the Ruminococcaceae (R) enterotype (n = 38). Results: Individuals with the B1 enterotype, but not those with the R enterotype, exhibited decreases in body weight and the relative abundance of Streptococcus thermophilus. Multiple linear regression analysis identified enterotype as a strong predictor of body weight change (p = 0.0034). In addition, urinary taurine level change was positively associated with body weight change in B1 individuals, not in R individuals. Conclusions: Our findings reveal an enterotype-specific response to an identical dietary modification, underscoring the value of integrating enterotype information into nutrition-intervention design and personalized nutrition strategies.
Amino acids · 2026
Taurine (Tau) is a sulfur-containing amino acid that has therapeutic roles in several diseases, including inflammatory conditions. The involvement of Tau in modulating systemic lupus erythematosus (SLE) autoimmunity has been indicated in preclinical models, but reports are contradictory. This systematic review aimed to summarize current research regarding the potential role of Tau in SLE, to notice knowledge gaps, and to offer suggestions for the way ahead. The literature search was carried out using PubMed, Scopus, Web of Science, and Google Scholar databases until October 2025. Search alert services were also applied to notice related papers published after the primary search. All studies investigating the effects of Tau in SLE that met the inclusion criteria were eligible. Out of 77 articles initially found, only six preclinical studies (animal and in-vitro) were eligible, and no qualified clinical study was identified. Five studies indicated that Tau was helpful in improving clinical parameters, decreasing T helper 1 (Th1) and Th17 cells and inflammatory mediators (e.g., tumor necrosis factor-α, C-reactive protein, and inducible nitric oxide synthase), removing reactive oxygen species and decreasing oxidative markers like malondialdehyde, increasing regulatory T (Treg) and Th2 cells and anti-inflammatory interleukin-4 and interleukin-10 cytokines, increasing antioxidant enzymes superoxide dismutase and glutathione peroxidase, and inhibiting both FAS- and mitochondrial-dependent apoptotic signaling components. However, only one preclinical study reported that Tau aggravated SLE progression characterized by increased generation of type I interferons, enhanced autoantibodies and proteinuria, further lymphocyte activation, and critical nephritis. The current review provides evidence about the role of Tau in SLE and highlights the importance of further well-designed clinical trials to confirm these results, establish optimal dose and assess safety and long-term efficacy.
Hepatology communications · 2026
Fatigue affects 60%-80% of patients with cirrhosis, yet no universally effective pharmacologic therapy exists. Taurine, an amino sulfonic acid with antioxidant and membrane-stabilizing properties, may address metabolic mechanisms underlying fatigue. We hypothesized that L-taurine supplementation would significantly reduce fatigue severity compared to standard care in patients with decompensated cirrhosis. This single-center, parallel-arm, open-label randomized controlled trial enrolled adults with decompensated cirrhosis (Child-Turcotte-Pugh score 7-13) and clinically significant fatigue (Fatigue Assessment Scale score >22) at a tertiary care center in South India. Participants were randomized via block randomization to L-taurine (1000 mg/d) plus standard care or standard care alone for 12 weeks. The primary outcome was the change in the Fatigue Assessment Scale score. Analysis of covariance examined treatment-by-anaemia interactions. Effect sizes were calculated using Cohen's d. Of 220 randomized patients, 202 completed the study (standard care: n=100; taurine: n=102). The mean FAS change was -6.83±8.70 (standard care) versus -8.08±7.95 (taurine), with no significant difference (mean difference -1.25; 95% CI: -3.55 to 1.05; p=0.288; Cohen's d=-0.15). However, a significant treatment-by-anemia interaction was observed (p=0.009). In patients without anemia (n=41), taurine produced a large treatment effect (-11.90±4.04 vs. -4.57±9.23; p=0.002; Cohen's d=-1.02), whereas patients with anemia (n=161) showed no benefit (p=0.832). Adverse events occurred in 11.8% of patients treated with taurine, all of which were mild. L-taurine did not improve fatigue in unselected patients with decompensated cirrhosis. A post hoc subgroup analysis suggested potential benefit in patients without anemia; however, given the open-label design, small subgroup size, post hoc nature of the analysis, and the inherent limitations of unblinded patient-reported outcomes, this finding should be considered hypothesis-generating. A confirmatory, placebo-controlled trial enrolling patients without anemia is warranted (Clinical Trials Registry India number CTRI/2023/06/054455).
Liver international : official journal of the International Association for the Study of the Liver · 2025
The relationship between frailty and gut microbiota has not been previously addressed in patients with cirrhosis. We studied by metagenomic shotgun sequencing the faecal microbiota composition associated with frailty in 29 patients with cirrhosis from a previous study (Román, Hepatol Commun 2024). Frail and prefrail patients were randomised to a multifactorial intervention (home exercise, branched-chain amino acids and a multistrain probiotic) or control for 12 months. We observed a positive correlation between the abundance of Rothia dentocariosa and the Liver frailty index (LFI), and between Bacteroides faecis and gait speed. After the multifactorial intervention, LFI improved and the main changes in the microbiota composition were a decrease in the abundance of Akkermansia muciniphila, and an increase in Streptococcus thermophilus, Lactobacillus acidophilus and several species of Bifidobacterium. We conclude that frailty in patients with cirrhosis was associated with a distinct microbiome signature. After a long-term multifactorial intervention, frailty improved in parallel with changes in microbiome composition. Trial Registration: ClinicalTrials.gov identifier: NCT04243148.
Archives of gerontology and geriatrics · 2026
Sarcopenia impairs self-care ability in older adults. While branched-chain amino acids (BCAAs)/leucine enhance muscle protein synthesis and resistance training promotes muscle growth, the combined effect on sarcopenia remains unclear. This meta-analysis evaluates whether combining resistance training with BCAA-rich supplements synergistically improves body composition and function in sarcopenic elders. We systematically searched four databases and analyzed outcomes using Stata 18.0. Standardized mean differences (SMDs) were calculated via random-effects models. Twelve randomized trials (n = 459) were included. Only skeletal muscle index significantly improved with combined intervention vs. control (SMD = 0.337, 95 % CI [0.035,0.639], p = 0.029). No significant differences were found in: hand grip strength (SMD = 0.289, p = 0.080), 30-s chair stand (SMD = -0.794, p = 0.169), SPPB (SMD = -0.321, p = 0.124), walking speed (SMD = 0.344, p = 0.283), knee extension strength (SMD = 0.332,p = 0.328), total lean mass (SMD = 0.024, p = 0.908), or fat mass (SMD = -0.036, p = 0.866; all p > 0.05). BCAA supplementation post-resistance training only increased skeletal muscle index in older adults, without improving other functional or body composition outcomes.
Nutrients · 2025
β-lactoglobulin (BLG) is a protein found within whey protein (WP) that is rich in essential amino acids, most notably, leucine (LEU). LEU is considered the most potent EAA in the postprandial stimulation of muscle protein synthesis (MPS), such that suboptimal protein/essential amino acid (EAA) doses containing higher LEU content elicit muscle anabolism comparable to larger protein doses. Our objective was to test the effects of naturally LEU-rich BLG (~10 g protein) versus isonitrogenous whey protein isolate (WPI, ~10 g) on MPS. Ten healthy young men (26 ± 2 y; 179 ± 2 cm; 81 ± 3 kg) received BLG (1.57 g LEU) or WPI (1.02 g LEU) in a randomised double-blind cross-over fashion. A primed constant intravenous infusion of [1,2 13C2] LEU was used to determine MPS (isotope ratio mass spectrometry) at baseline and in response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 × 8 unilateral leg extensions; 75% 1-RM). Plasma insulin and EAA's were quantified. Plasma EAA, branched-chain amino acid (BCAA), and LEU concentrations increased rapidly following both protein supplements but exhibited a significantly greater EAA/BCAA/leucinemia following BLG (p < 0.05 for all). MPS increased significantly in both FED (~52%) and FED-EX (~58%) states, with no significant differences between supplements. Both BLG and WPI effectively stimulated MPS doses in young healthy males, with BLG offering an advantage in EAA/BCAA/LEU bioavailability. It follows that future research should explore the potential of BLG in populations exhibiting anabolic resistance and exercise anabolism deficiency, such as older adults as well as frail and clinical populations, to assess its utility in preserving muscle mass under conditions of suboptimal protein intake.
Clinical nutrition ESPEN · 2026
Liver cirrhosis is a chronic, and progressive condition often complicated by malnutrition, sarcopenia, hepatic encephalopathy (HE), and frailty. Malnutrition is highly prevalent in patients with cirrhosis and is associated with an increased risk of decompensation and mortality. Consequently, leading liver societies (ESPEN, EASL, AASLD) recommend personalized nutritional interventions in patients with cirrhosis. While several studies have examined the effects of BCAAs on clinical and functional outcomes in cirrhosis, few have synthesized these outcomes in a single meta-analysis. Despite a growing number of RCTs on HPHC diets and HMB, existing reviews remain largely limited to sarcopenia-related outcomes. To date, no meta-analysis has evaluated the impact of nutritional interventions on frailty-related outcomes in cirrhosis. To assess the impact of oral nutritional interventions, including branched-chain amino acids (BCAAs), high-protein, high-calorie (HPHC) diets, β-hydroxy β-methylbutyrate (HMB), and high-protein diets on clinical and functional outcomes in adults with cirrhosis. We conducted a systematic review and meta-analysis of 21 randomized controlled trials (RCTs), of which 18 involving 3128 adults with cirrhosis were included in the meta-analysis, following PRISMA 2020 guidelines. RCTs published between January 1, 2000, and June 1, 2025, involving ≥4 weeks of oral nutritional therapy in patients with cirrhosis were included. Data were pooled using random effects model. Sensitivity, subgroup, and meta-regression analyses explored robustness and potential effect modifiers. The certainty of evidence was assessed using GRADE criteria. Nutritional intervention significantly reduced the risk of overt HE (RR 0.70; 95 % CI 0.52-0.95; NNT 11; I2 0 %), liver-related decompensation events (RR 0.69; 95 % CI 0.53-0.90; NNT 16; I2 0 %), hospitalization (RR 0.65; 95 % CI 0.49-0.86; NNT 8; I2 21.8 %), and mortality (RR 0.64; 95 % CI 0.49-0.84; NNT 23; I2 0 %). Handgrip strength improved significantly (MD 2.41 kg; 95 % CI 0.58-4.24; I2 87 %), and LFI showed borderline improvement (MD -0.35; 95 % CI -0.70 to -0.0005; I2 84.4 %). HPHC diets appeared more effective than BCAAs for mortality and HGS, though comparator bias limits definitive conclusions. Meta-regression indicated greater mortality benefit with higher MELD scores. While studies ≤6 months showed significant mortality reduction, longer-duration studies did not; however, duration was not a significant moderator in subgroup analysis or meta-regression. Oral nutritional therapy is associated with reduced risk of decompensation, overt hepatic encephalopathy, hospitalization, and short-term mortality in cirrhosis. While improvements in sarcopenia and frailty were observed, high heterogeneity limits firm conclusions. These findings support current guidelines and highlight the need for longer-duration and head-to-head trials to identify optimal nutritional strategies. CRD420251073182.
Journal of the International Society of Sports Nutrition · 2025
Sarcopenia may disrupt the hypothalamic‒pituitary‒adrenal axis, affecting neurotransmitter and hormone levels. However, the impact of sarcopenia on these markers, particularly in comparison to non-sarcopenic controls, is understudied. Additionally, the effects of resistance exercise and nutritional support on neurotransmitter levels in sarcopenic patients are largely unknown. This study explores these neurochemical changes and their response to therapeutic interventions. This post hoc analysis of a randomized controlled trial included 57 sarcopenic and 57 non-sarcopenic participants from the same cohort. Grip strength and body composition were measured. Sarcopenic patients received a 12-week intervention involving resistance exercise and supplementation with branched-chain amino acids, calcium, and vitamin D3. Plasma adrenaline, noradrenaline, dopamine, serotonin, and cortisol were assessed using enzyme-linked immunosorbent assay (ELISA). Sarcopenic individuals had significantly lower levels of serotonin (13.28 vs 19.21  ng/mL, p = 0.002), adrenaline (97.6 vs 110.9  pg/mL, p < 0.001), and noradrenaline (169.2 vs 302.5  pg/mL, p < 0.001), with a trend toward reduced dopamine (246.9 vs 270.6  pg/mL, p = 0.053). Cortisol levels were similar between the groups (48.2 vs 49.5  ng/mL, p = 0.436). Generalized estimating equations adjusted for age and gender, showed sarcopenia was linked to reduced serotonin (β = -5.92, p = 0.002), adrenaline (β = -13.32, p < 0.001), and noradrenaline (β = -132.9, p < 0.001), while the intervention raised noradrenaline levels (β = 27.75, p = 0.001). Sarcopenic patients exhibit lower serotonin, adrenaline, and noradrenaline compared to non-sarcopenic controls, with no significant difference in cortisol levels. Resistance exercise and nutritional interventions increased noradrenaline in sarcopenic individuals. Further studies are needed to evaluate the long-term effects on neurotransmitter and hormone levels.
Journal of the International Society of Sports Nutrition · 2025
Essential (EAA) and branched chain (BCAA) amino acid ingestion support whole-body anabolism after resistance exercise and can attenuate markers of postexercise myofibrillar protein breakdown (i.e. urinary 3-methylhistidine; 3MH). Leucine is often considered a primary anabolic EAA through its ability to activate the mechanistic target of rapamycin complex 1 (mTORC1) and stimulate muscle protein synthesis. The dipeptide leucine (dileucine) has been shown to more effectively stimulate myofibrillar protein synthesis than leucine in young males at rest. Therefore, we aimed to determine the effect of a dileucine-containing essential amino acid formula (DIEAA; 2 g dileucine, 1 g leucine, 9.15 g total EAA) on the anabolic and catabolic responses following resistance exercise in young recreationally active adults when compared with ingesting branched chain amino acids (BCAA; 3 g leucine, 1.5 g isoleucine, 1.5 g valine) or isonitrogenous (to DIEAA) collagen hydrolysate (COL). In a randomized, double-blind, crossover design, 12 healthy adults (8 M, 4F, aged 24 ± 3 y) performed a 60 min bout of whole-body resistance exercise, after which they ingested DIEAA, BCAA, or COL protein beverages containing 100 mg L-[1-13C]leucine (#NCT05754125). Total exogenous leucine retention (as an estimate of whole-body anabolism) was assessed over the 6 h postprandial period by determining total leucine oxidation from 13CO2 enrichment (isotope ratio mass spectrometry) in repeated breath samples. A urinary 3MH:creatinine ratio (3MH:Cr) over 6 h was used as an estimate of skeletal muscle myofibrillar protein breakdown. To further assess the anabolic potential of nutrients, C2C12 myotubes were treated with a subset (n = 7) of human serum-conditioned media for 4 h to measure downstream mTORC1 substrate phosphorylation, protein synthesis (puromycin and L-ring-[D5]phenylalanine incorporation) and breakdown (ubiquitinated protein), and myotube hypertrophy. Total exogenous leucine retention were similar (p = 0.68) between DIEAA (215.72 ± 42.45 μmol·kg-1) and BCAA conditions (219.15 ± 45.26 μmol·kg-1), with both DIEAA and BCAA being greater (p < 0.0001) than COL (37.25 ± 8.16 μmol·kg-1). There were no differences (p = 0.58) in 3MH:Cr between supplement conditions. There was no effect of condition ex vivo on puromycin incorporation into nascent peptides (p = 0.31), total protein ubiquitination as an estimate of protein breakdown (p = 0.59), phosphorylation of downstream mTORC1 substrates p-RPS6S240/244 (p = 0.39) or p-4E-BP1T37/46 (p = 0.50), and myotube diameter (p = 0.55). Stable isotope-derived rates of mixed muscle protein synthesis (MPS) demonstrated a trend toward a main effect (p = 0.086) with pairwise comparisons revealing a large effect of DIEAA compared to COL (dz = 1.47), a medium effect of DIEAA compared to BCAA (dz = 0.81), and a trivial effect of BCAA comapred to COL (dz = 0.002). Dileucine-supplemented EAA and BCAA support greater whole-body anabolism compared with COL after resistance exercise independent of attenuation in urinary estimates of myofibrillar protein breakdown. Exploratory ex vivo experiments reveal a potential anabolic effect of DIEAA in stimulating MPS. Collectively, these findings suggest that consuming dileucine with sufficient EAA and BCAA increases exogenous leucine retention to support whole-body anabolism during postexercise recovery in individuals performing resistance training.
Clinical nutrition ESPEN · 2026
Muscle wasting is frequently observed in critically ill patients, leading to increased rates of complications and mortality, and could be determined by measuring the quadriceps femoris muscle thickness (QFMT). One significant contributing factor is inflammation, with interleukin-6 (IL-6) as one of the important markers. Branched-chain amino acids (BCAAs), especially leucine, enhance muscle protein synthesis, and reduce inflammation. This study examined the effects of high leucine BCAA supplementation on QFMT and IL-6 levels in critically ill patients. This multicentre, double-blind, randomised controlled trial was conducted in two hospitals in Indonesia from December 2023 to May 2024. Recently admitted critically ill patients were randomly assigned to receive 40 g/day of BCAA (19 g/day of leucine, with a ratio of leucine : isoleucine : valine = 2:1:1.2) supplementation, either enterally or partial parenterally, for 10 days, or to a control group. QFMT was measured using an ultrasound (US), and IL-6 serum levels were measured at baseline and day 10. We performed a linear mixed model to analyse the effects of other factors on outcomes. Forty participants were included in this study; most (78 %) were male, median age 49 (21), and had a surgical diagnosis (55 %). Patients in both groups had similar initial QFMT and IL-6 levels. On day 10 of the study, loss of muscle thickness was found to be less prominent in the BCAA than the control group (0 vs. -13 %, p = 0.001), and the BCAA group showed a significant reduction in IL-6 levels than control (-59.1 vs. 126.5 pg/mL, p = 0.012). Supplementing critically ill patients with high leucine BCAA potentially attenuates muscle mass loss and reduces IL-6 levels. NCT06167772.