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The prevalence of obesity in developing and developed countries has been well recognized, and the worldwide obesity rates have nearly tripled since 1975, according to the World Health Organization. CitruSlim, a standardized product containing a blend of Citrus bergamia and Eurycoma longifolia, can reduce cortisol, cholesterol, triglycerides, and hyperglycemia. These properties can contribute to reduction in body weight or body mass index (BMI) in obese patients. A randomized, double-blind, placebo-controlled clinical study was designed to evaluate the efficacy and tolerability of CitruSlim in body weight management in obese individuals, and the results were compared with that of placebo. A total of 97 participants were allocated, randomized, and treated with CitruSlim high-dose (HD, 400 mg), CitruSlim low-dose (LD, 200 mg), and placebo for 112 days. At the end of the study, CitruSlim HD and CitruSlim LD significantly reduced BMI compared to the placebo group and were well tolerated; however, it did not improve parameters associated with dyslipidemia and metabolic disturbances. The study findings suggested that CitruSlim was effective in reducing body weight in obese patients. © 2021 John Wiley & Sons Ltd.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. Thus, identification of new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to reduce the side effects of anti-TB drugs, such as liver toxicity and other detrimental changes, is urgently needed. In this study, to develop a novel candidate drug for effective TB treatment with few side effects in the host, we selected pasakbumin A isolated from Eurycoma longifolia (E. longifolia) Jack, which protected host cells against Mtb infection-induced death. Pasakbumin A significantly inhibited intracellular Mtb growth by inducing the autophagy via the ERK1/2-mediated signaling pathway in Mtb-infected macrophages. We further investigated whether pasakbumin A could be used as a potential adjuvant for TB treatment. Treatment with pasakbumin A and anti-TB drug rifampicin (RMP) potently suppressed intracellular Mtb killing by promoting autophagy as well as TNF-α production via the ERK1/2- and NF-κB-mediated signaling pathways in Mtb-infected cells. Our results suggest that pasakbumin A could be developed as a novel anti-TB drug or host-directed therapeutic (HDT) strategy to protect against host cell death and improve host defense mechanisms against Mtb infection in macrophages.

WHAT IS KNOWN AND BACKGROUND: Eurycoma longifolia (E. longifolia), a herb commonly consumed for its aphrodisiac properties, is widely used by Asian males. This may include hypertensive patients receiving propranolol which may cause sexual dysfunction as one of its side-effects. There is no published study of the potential pharmacokinetic interaction between propranolol and the herb. OBJECTIVE: To study propranolol's pharmacokinetics when E. longifolia is consumed, comparing volunteers given either propranolol or a placebo. METHODS: This is a placebo-controlled randomized single-blinded crossover study of the effect of a water-based extract of E. longifolia on the pharmacokinetics of a single dose of proporanolol (Inderal(®)) in 14 healthy non-smoker young males. Eighty milligram of propranonol was orally administered with (i) placebo (Lactose) or (ii) 200 mg of water-based extract of E. longifolia (0·0272 ± 0·0026%eurycomanone) following an overnight fasting. Blood samples were collected at 0, 0·5, 1, 1·5, 2, 3, 4, 6, 8 and 10 h for propranolol's plasma concentration determinations using a validated high-performance liquid chromatography (HPLC) method. RESULTS AND DISCUSSION: When propranolol was administered with E. longifolia, its bioavailability (AUC0-∞) decreased by 29% while C(max) was reduced by 42% and T(max) was significantly prolonged by almost 86%. The terminal elimination half-life, however, was not significantly affected. CONCLUSION: The bioavailability of propranolol is significantly decreased when consumed together with E. longifolia. The interaction is due to a reduction in absorption, rather than an increase in propranolol's metabolism. Although the pharmacodynamics of propranolol was not affected in healthy volunteers, caution is still advisable with co-administration of the drug and the herb. © 2010 Blackwell Publishing Ltd.

Testosterone boosters are heavily marketed on social media and marketplaces to men with claims to significantly increase testosterone. Lax industry regulation has allowed sales of supplements to thrive in the absence of verification of their purported benefits. Our primary objective was to systematically review all data published in the last two decades on testosterone boosters and determine their efficacy. Our outcome of interest was total testosterone increase versus placebo in four different populations: male athletes, men with late-onset hypogonadism infertile men and healthy men. Following search and screening, 52 studies were included in our review, relating to 27 proposed testosterone boosters: 10 studies of cholecalciferol; 5 zinc/magnesium; 4 Tribulus terrestris and creatine; 3 Eurycoma longifolia and Withania somnifera; 2 betaine, D-aspartic acid, Lepidium meyenii and isoflavones; while the remainder were single reports. Our findings indicate that most fail to increase total testosterone. The exceptions were β-hydroxy β-methylbutyrate and betaine, which can be considered effective for male athletes. Eurycoma longifolia, a blend of Punica granatum fruit rind and Theobroma cacao seed extracts (Tesnor™) and purified Shilajit extract (PrimaVie™) can be considered possibly effective for men with late-onset hypogonadism; Eurycoma longifolia and Withania somnifera possibly effective for healthy men; and a non-hormonal aromatase inhibitor (Novadex XT™) possibly effective for male athletes. © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Background and Objectives: Male hypogonadism is a clinical disorder characterized by reduced serum testosterone in men. Although treatment using herbal medicines, including Eurycoma longifolia, has been investigated, the benefits remain unclear. This study aims to investigate the efficacy of E. longifolia as a sole intervention to increase testosterone levels in males. Materials and Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) according to the PRISMA guidelines. Relevant articles were retrieved from the databases PubMed, Scopus, Web of Science, Cochrane, Ovid/Embase, and Google Scholar. Results: After literature screening, a total of nine studies was included in the systematic review. Five RCTs were included in the meta-analysis. A significant improvement in total testosterone levels after E. longifolia treatment was mostly reported in both healthy volunteers and hypogonadal men. The random model effect revealed a significant increase (SMD = 1.352, 95% CI 0.565 to 2.138, p = 0.001) in the total testosterone levels in men receiving E. longifolia supplementation, which was confirmed in the hypogonadism subgroup. Conclusions: This systematic review and meta-analysis of the literature supports the possible use of E. longifolia supplementation for enhancing testosterone production. Although more research is required before its use in clinical practice, this may represent a safe and promising therapeutic option, particularly in hypogonadal men.

The objective was to study available evidence for ingredients of popular over-the-counter testosterone and erectile dysfunction (ED) supplements. The top 16 male testosterone and 16 ED supplements in the USA were identified from the most popular online retailers: A1 Supplements, Amazon, Vitamin Shoppe, and Walmart. In total, 37 ingredients were identified and PUBMED online database was reviewed for randomized-controlled trials (RCT) studying their efficacy. Ingredients were categorized based on evidence quantity using an adapted version of the American Heart Association scoring system. In total, 16 ingredients from testosterone supplements and 21 from ED supplements were identified. Tribulus, Eurycoma longifolia, Zinc, L-arginine, Aspartate, Horny goat weed, and Yohimbine were most common. In all, 105 RCTs studying the identified ingredients were found. No whole supplement products have published RCT evidence. 19% of ingredients received an A grade for strong positive evidence with net positive evidence in two or more RCTs. In total, 68% received C or D grades for contradicting, negative, or lacking evidence. Overall, 69% of ingredients in testosterone supplements and 52% of ingredients in ED supplements have published RCT evidence. Many male supplements claim to improve testosterone or ED parameters; however, there is limited evidence, which should be considered when counseling patients.

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders.

OBJECTIVE: To determine the efficacy of Tongkat Ali (Eurycoma longifolia) herbal extract on erectile function improvement. METHODS: Comprehensive electronic databases were searched from inception through October 2014. Randomized controlled trials investigating Tongkat Ali compared to placebo were included. Outcome of interest was the improvement of erectile dysfunction. The difference of changes from baseline of the outcome between Tongkat Ali and placebo was pooled using weighted mean difference (WMD). Methodological quality of included studies was assessed using Jadad's quality scale and Cochrane's risk of bias. RESULTS: Of the 342 articles identified, 2 studies involving a total of 139 participants were analyzed. No significance between group difference was found in the mean WMD of the change in the 5- item version of the international index of erectile function (IIEF-5) at week-12 (0.91; 95% CI: -1.50 to 3.33 with I(2)=89.5%, P-value=0.002) with statistical heterogeneity. Based on the subgroup analysis, significant improved IIEF-5 score of 2.15 (95% CI 1.03-3.27) was found in subjects with lower baseline IIEF-5 score, but this was not seen among those with higher baseline IIEF-5 score. CONCLUSION: Based on current evidence, the herbal extract of Tongkat Ali may have clinical effect on erectile function. However, more efficacy trials are warranted to further support current evidence.

An evidence-based systematic review of tongkat ali (Eurycoma longifolia) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Objective: Seaweed and microalgae provide antioxidants, polyunsaturated fatty acids, and bioactive compounds that may enhance exercise performance and accelerate recovery. However, evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of algae-derived supplementation on exercise performance and physiological recovery outcomes in healthy and athletic adults. Methods: This review was registered in PROSPERO (CRD420251166723) and conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, Embase, Cochrane Library, EBSCO, and CNKI were systematically searched for randomized controlled trials (RCTs) evaluating algae supplementation in exercise contexts. Inclusion and exclusion criteria were defined based on the PICOS framework. Primary outcomes included VO2max, Time to exhaustion (TTE), maximal power output (WRmax), Time-Trial (TT) performance, and creatine kinase (CK). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were performed. Results: Twenty-two RCTs (n = 822) investigating Spirulina, Chlorella, brown-algal polysaccharides, or astaxanthin met inclusion criteria. Algae supplementation showed a suggestive improvement in VO2max (SMD = 0.88, 95% CI: 0.00-1.75) and significantly improved in TTE (SMD = 1.06, 95% CI: 0.16-1.96), with smaller effects on WRmax (SMD = 0.29, 95% CI: 0.03-0.55), and no significant benefit for TT performance (SMD = -0.27, 95% CI: -0.74 to 0.21). Regarding recovery, CK concentrations were significantly reduced (SMD = -0.78, 95% CI: -1.28 to -0.28). Subgroup analysis suggested greater effects for Chlorella supplementation, higher dosages, and aerobic training contexts; reductions in muscle-damage markers were more evident following resistance exercise. Sensitivity analyses supported the robustness of the main findings with minimal evidence of publication bias. Conclusions: Algae-derived supplements-particularly Spirulina and Chlorella-may modestly enhance aerobic exercise performance and attenuate exercise-induced muscle damage under certain conditions. Eff

Objectives: The aim of this study was to explore the combined effects of resistance exercise and whey protein supplementation on plasma irisin levels in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) under a 30% calorie-restricted weight loss diet. Methods: Thirty adult patients with MASLD were randomized into the following three groups for a 4-week intervention: calorie restriction group (CR) (n = 8), CR with resistance exercise group (EX) (n = 11), and CR with resistance exercise and whey protein group (EX + P) (n = 11; 0.7 g/kg per day). All participants received boxed meals providing 70% of their total energy expenditure. The participants in the resistance exercise groups performed full-body resistance exercises 5 days/week (50-75% one-repetition maximum). Plasma irisin level, controlled attenuation parameter (CAP), and body composition were assessed before and after the intervention. Results: Plasma irisin levels significantly increased in the EX (+2.24 ng/mL, p = 0.016) and EX + P (+4.86 ng/mL, p = 0.004) groups but not in the CR group. Muscle mass increased significantly only in the EX + P group. The CAP decreased in all groups. The change in irisin level was negatively correlated with the change in CAP (r = -0.459, p = 0.032). Conclusions: Resistance exercise under calorie-restricted conditions effectively increased plasma irisin levels in patients with MASLD, whereas caloric restriction alone did not. Furthermore, a stronger increasing trend in the plasma irisin levels was observed with whey protein supplementation. An increase in irisin levels was significantly associated with hepatic fat reduction, suggesting that irisin may serve as a biomarker reflecting improvements in hepatic steatosis following lifestyle intervention.

Background: There is a growing number of studies suggesting the effectiveness of dietary supplements in preventing and treating endometriosis. It has been suggested that deficiencies in vitamins D and E as well as zinc are associated with the increased risk of endometriosis development. Beneficial effects of magnesium, curcumin, resveratrol and epigallocatechin-3-gallate were found in experimental animal studies. A reduction in pain related to endometriosis was shown in women using omega-3 and alpha-lipoic acid. Meanwhile, decreasing endometriotic lesion size after the supplementation of omega-3, N-acetylcysteine, vitamin C and epigallocatechin-3-gallate was observed in animal and human studies. Thus, the aim of this critical review was to summarize the available data describing the effects of dietary supplements used in the treatment of endometriosis. Material and Methods: The PubMed, Embase, Cochrane, and Web of Science databases were searched for related studies until 15 December 2025. Finally, 34 studies were included in the synthesis. Results: Of these 34 studies, only 23 were randomized, placebo-controlled trials. There have been no RCTs evaluating the effectiveness of vitamin E, zinc, alpha-LA, EGCG and DIM in the treatment of endometriosis. Single studies evaluating the effectiveness of vitamin C, magnesium, resveratrol, NAC and PEA with PLD have not confirmed it. Meanwhile single studies evaluating the effectiveness of selenium, propolis and quercetin have confirmed it. Of the four studies assessing the effectiveness of vitamin D, two confirmed it and two did not; of the two studies assessing probiotics, one confirmed its effectiveness and one did not; of the two studies assessing curcumin, one confirmed its effectiveness and one did not; and of the three studies assessing omega-3, two confirmed its effectiveness and one did not. All four RCTs assessing the combination of vitamins C and E confirmed their effectiveness. Conclusions: Despite encouraging observations from experimental studies, the results of RCTs are less encouraging and do not allow for the formulation of recommendations concerning the use of supplements in the treatment of endometriosis

Background/Objectives: Nitric oxide (NO) is a key mediator of vascular, metabolic, and redox pathways, influencing exercise performance. Beetroot, a natural source of inorganic nitrate, increases NO bioavailability and may modulate oxidative stress and inflammation, though data in endurance athletes remain limited. The aim of this study was to assess the effects of a novel beetroot-based nitrate supplement (B-bNs) on NO metabolism, oxidative stress, and inflammation in non-professional triathletes. Methods: This was a randomized 2 × 2 cross-over pilot study with two 7-day periods (B-bNs vs. No treatment), separated by a 15-day washout (4 visits: Day 1, 7, 22 and 28). Samples were collected at baseline (T0), 2 h post-first dose (T1), and after 7 days (T2) for the supplementation period (B-bNs) and at T0 and T2 for the "no treatment" period. The following biomarkers from plasma and urine were evaluated: NO pathway (NO metabolites (NOx), nitrite (NO2), inducible nitric oxide synthase (iNOS), peroxynitrite, 3-nitrotyrosine (3-NT)), oxidative stress (reactive oxygen species (ROS) production, 8-isoprostane, superoxide dismutase (SOD) activity), and cytokines (IL-6, IL-10). A total of 10 male triathletes (mean age 48.1 ± 9.8 years and BMI 23.9 ± 2.2 kg/m2) participated in this study. Results: No adverse events were reported. After 7 days of supplementation (T2 vs. T0), significant increases in NOx in plasma and urine (about +155%), iNOS (+56%), peroxynitrite (+60%), 3-NT (+8.6%), ROS (+413%) and IL-6 (+73%) were recorded. These values resulted significantly higher compared to "no treatment" (all p = 0.002), with no significant differences for 3-NT, SOD, 8-isoprostane, IL-6, and IL-10. Conclusions: Beetroot-based nitrate supplementation may enhance the NO-related pathway in non-professional endurance athletes with nitric-peroxydation activation, occurring without evidence of lipid oxidative damage. Larger placebo-controlled trials with standardized diet/training and performance outcomes are needed to determine the functional significance of these preliminary findings. This study was registered in the ISRCTN registry (ISRCTN10885376).

BACKGROUND AND OBJECTIVES: This study examined the effects of a novel phytochemical supplement blend on markers of exercise-induced muscle damage. METHODS: In a randomised, parallel group design, 24 healthy participants (14 males) consumed 300 mg of a phytochemical blend (calcium fructoborate, turmeric and pomegranate; PB) or inert placebo for 9 days (n = 12 per condition). On day 7, participants performed 150 drop jumps to induce muscle damage. Markers of neuromuscular function, muscle soreness/pain, perceived exhaustion and sleep quality, were measured pre-exercise and 24, 48, and 72 h post-exercise; systemic markers of inflammation, muscle damage, and oxidative stress were measured on these days as well post-exercise and 2.5 h post-exercise. RESULTS: There was an interaction effect for pressure pain threshold in the vastus lateralis (p = 0.041), which was ~21% higher in PB 72 h post-exercise (p = 0.074; ds = 0.767). Perceived sleep quality was greater 72 h post-exercise in PB (p = 0.049; rrb = 0.423) and those in the PB condition reported feeling more recovered and less mentally drained post-exercise (p ≤ 0.043). There were no statistically significant between-condition differences for any markers of neuromuscular function, inflammation, oxidative stress or muscle damage (p > 0.05). CONCLUSION: In conclusion, a novel PB showed promise for attenuating muscle pain and perceived exhaustion, and improving sleep quality, in the days after muscle damaging exercise. The study protocol was pre-registered on the Open Science Framework Registry (registration number: qgw3a).

Background/Objectives: Creatine is a supplement that, beyond its physiological effects, has been shown to have positive effects on cognitive abilities. In our previous study, we showed that a single dose of 0.35 g/kg creatine induces changes in brain metabolism during sleep deprivation and reduces deterioration in cognitive performance. The present study investigates whether supplementation of a lower dose is associated with cognitive effects during sleep deprivation, focusing exclusively on cognitive performance outcomes. Methods: Twenty-nine healthy subjects performed cognitive tests at the evening baseline and 3, 5.5, and 7.5 h after receiving a single dose of creatine monohydrate (0.2 g/kg) or a placebo during a total of 21 h of sleep deprivation (SD). Results: The results show a mitigating effect of creatine on sleep deprivation-induced deterioration in logical and numerical tasks, language-related processing speed, and the Psychomotor Vigilance Test (PVT). Compared to males, females benefit more in logic, PVT and processing speed in language and logic tasks. Conclusions: Our results show that a dose of 0.2 g/kg creatine is associated with a reduced deterioration in cognitive performance during sleep deprivation. Although the effect is less pronounced than with a high dose of 0.35 g/kg, there is still an improvement of up to 12%.

Background/Objectives: Oxidative stress plays an important role in the pathophysiology of endometriosis, contributing to inflammation, immune dysregulation, and lesion progression. This has led to growing interest in antioxidant-based strategies as potential supportive interventions. Methods: A literature search was conducted using PubMed, Scopus, and Web of Science databases, covering studies published from database inception until the end of January 2026. The review focused on clinically relevant endpoints, including pain intensity, markers of inflammation and oxidative stress, reproductive parameters, and quality of life. Results: Among the analyzed interventions, the most consistent clinical effects were observed with melatonin, with randomized controlled trials indicating a moderate reduction in pain. N-acetylcysteine shows potentially beneficial effects; however, the available clinical data remain limited and heterogeneous. For other supplements, the evidence is inconsistent or insufficient to support clear clinical conclusions, and in many cases relies on indirect or mechanistic findings rather than well-established clinical outcomes. Conclusions: Current evidence does not support the use of non-mineral antioxidant supplements as standalone therapy for endometriosis. They may be considered as adjunctive strategies, although their clinical effectiveness remains uncertain and requires confirmation in well-designed randomized clinical trials.

BACKGROUND: The first 1000 days of life, from conception to 2 years of age, represent a critical window during which nutrition can exert long-lasting effects on neurodevelopment, immune maturation, and susceptibility to prematurity-related morbidity. Docosahexaenoic acid (DHA) is a key structural n-3 long-chain polyunsaturated fatty acid of the brain and retina, characterized by rapid fetal accretion during the third trimester. METHODS: We conducted a narrative review of studies published from March 2015 up to December 2025, including randomized controlled trials, follow-up studies, and systematic reviews/meta-analyses about DHA supplementation during pregnancy, lactation, infancy and early childhood, and its role on development. RESULTS: Across the first 1000 days, DHA supplementation improves biochemical DHA status, particularly in populations with low baseline levels (moderate to high level of evidence), while clinical outcomes remain heterogeneous. During pregnancy, some benefits in specific cognitive and behavioral domains have been demonstrated, whereas effects on global cognition and long-term behavior are frequently null (moderate evidence). Visual outcomes appear favorable, with improvements in visual acuity (moderate evidence). In preterm infants, enteral DHA-often combined with arachidonic acid (ARA)-is feasible and well tolerated. DHA may reduce inflammatory markers and necrotizing enterocolitis risk when in equilibrium with ARA (low to moderate evidence), while no evidence supports the link between DHA and reduced risk of bronchopulmonary dysplasia and retinopathy of prematurity (moderate evidence). Neurodevelopmental outcomes are mixed: neuroimaging studies suggest enhanced white matter maturation with DHA + ARA, whereas most trials show no clear benefit regarding standardized developmental scores (moderate evidence). CONCLUSIONS: DHA is biologically essential during the first 1000 days, but its clinical impact depends on timing, dose, baseline status, and prematurity-related context. The balance between DHA and ARA, rather than DHA supplementation alone, emerges as a key determinant of clinical efficacy, supporting a shift toward precision-based n

Chronic kidney disease (CKD) is a progressive condition associated with metabolic disturbances, systemic inflammation, and the accumulation of gut-derived uremic toxins. Increasing evidence highlights the role of gut microbiota dysbiosis in the progression of CKD through the gut-kidney axis. Consequently, microbiome-targeted nutritional strategies, including probiotics, prebiotics, and synbiotics, have emerged as promising complementary approaches to modulate intestinal microbial composition and metabolic functions. This review summarizes and critically evaluates the current clinical evidence regarding the use of these interventions in CKD patients. Clinical studies indicate that supplementation with probiotics, prebiotics, and synbiotic formulations may promote beneficial shifts in the composition of the gut microbiota, enhance saccharolytic fermentation, and increase the production of short-chain fatty acids (SCFAs). These changes have been associated with reduced circulating levels of gut-derived uremic toxins such as indoxyl sulfate and p-cresyl sulfate, as well as with the attenuation of systemic inflammation and oxidative stress. However, available trials remain heterogeneous in terms of study design, probiotic strains, prebiotic substrates, dosing regimens, and patient populations, and are frequently limited by small sample sizes and short intervention durations. As a result, evidence for improvements in renal function and long-term clinical outcomes remains inconclusive. While synbiotics may offer theoretical advantages by combining microbial supplementation with targeted substrates that support microbial growth and metabolic activity, current evidence does not consistently demonstrate superior clinical efficacy. Overall, these interventions often improve surrogate biomarkers, but their effects on renal function and hard clinical outcomes remain uncertain. Larger, longer-duration multicenter randomized controlled trials with standardized formulations are needed to establish their clinical utility and to better elucidate microbiota-host interactions in CKD. Advancing this field may support the development of personalized microbiome-based therapeutic strat

BACKGROUND: Recent research has highlighted the potential of postbiotics for addressing obesity and associated metabolic disorders. In this randomized, double-blind clinical trial, the efficacy of a postbiotic product in managing overweight and associated parameters was assessed. METHODS: Sixty individuals were randomized into two groups: one group (n = 30) received the Postbiotic (heat-killed L. fermentum strain K8-Lb1) and the other (n = 30) a Placebo control. Body weight, waist circumference, body composition, vital signs, blood biomarkers and questionnaires for quality of life, eating behavior, eating control and gastrointestinal symptoms were assessed. RESULTS: After a 12-week intervention, body fat mass (primary parameter) was significantly (p = 0.016) reduced in the Postbiotic group (98.15 ± 3.32% of baseline) compared to the Placebo group (100.41 ± 3.39%). In line with this, body weight (p = 0.047) and waist circumference (p = 0.034) were significantly reduced and visceral fat tended to be reduced (p = 0.053). Accordingly, the Postbiotic group tended (p = 0.066) to feel more in control of their body weight. Despite weight loss, muscle mass tended (p = 0.062) to increase. ALT, AST and GGT tended to be reduced, which may indicate an improvement in liver steatosis. Estimated average glucose (eAG) differed significantly between the groups in individuals with normal fasting glucose levels. The ability to concentrate significantly (p = 0.014) improved. CONCLUSIONS: Under an ad libitum diet, the postbiotic L. fermentum strain K8-Lb1 reduced body fat mass, body weight, and waist circumference, improved the ability to concentrate, and showed a trend towards an increase in muscle mass. The results of this pilot trial need confirmation by a pivotal trial.

Saskatoon berry (SB), a traditional food of Indigenous people, has been associated with cardiometabolic benefits in animal models; however, its effects on humans remain unclear. This study investigated the effects of dried SB consumption on cardiometabolic outcomes, gut microbiota, and short-chain fatty acids (SCFAs) profiles in healthy adults. In a 10-week, single-arm, and open-label trial, 20 healthy adults consumed 40 g/day of freeze-dried whole SB. Biochemical measures, physical exams, dietary records, participant feedback, and fecal samples were collected before and after the intervention. Gut microbiota composition and fecal SCFAs were profiled using 16S-rRNA sequencing and gas chromatography-mass spectrometry, respectively. SB intake significantly reduced fasting plasma glucose, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), non-high-density lipoprotein-cholesterol (non-HDL-c), systolic blood pressure, and high-sensitivity C-reactive protein, while increasing dietary fiber intake. Fiber intake was negatively correlated with TC, LDL-c and non-HDL-c (p < 0.05). The relative abundance of fecal Prevotellaceae increased after SB consumption and was positively correlated with multiple fecal SCFAs (p < 0.05-0.0001), while being negatively associated with lipid profiles and blood pressure. No adverse cardiovascular, hepatic, or renal dysfunction were observed; however, the significant increase in sugar intake may pose a risk for elevated blood glucose. Therefore, limiting other high-sugar foods during SB supplementation may be advisable for individuals with glucose intolerance. Overall, SB intake improved glucose and lipid metabolism and lowered blood pressure and inflammatory markers in healthy adults. These cardiometabolic benefits may be mediated by fiber and anthocyanins in SB and through modulation of gut microbiota and SCFA production; however, further confirmation is needed in subsequent randomized controlled trials.

INTRODUCTION: Trivalent chromium is an essential trace element involved in carbohydrate and lipid metabolism. The widespread global prevalence of metabolic syndrome and its close association with cardiovascular diseases and type 2 diabetes mellitus have increased scientific interest in the potential metabolic effects of chromium. However, currently available evidence regarding its clinical significance remains inconsistent. METHODS: This narrative review describes the role of trivalent chromium in the context of metabolic syndrome. A systematic literature search was conducted in the Scopus and Web of Science databases for studies published between 2015 and 2025. The review included randomized controlled trials, observational studies, experimental studies, systematic reviews, and meta-analyses that investigated chromium intake, supplementation, or the association between chromium levels and components of metabolic syndrome. RESULTS: The reviewed studies reported heterogeneous findings regarding the effects of trivalent chromium on components of metabolic syndrome. While some studies demonstrated improvements in glucose metabolism, insulin sensitivity, and lipid profiles, other studies reported no clear or statistically significant effects. The inconsistency of results has been attributed to differences in study design, studied populations, types and dosages of chromium supplementation, and duration of interventions. DISCUSSION: The lack of uniform research methodologies, limited sample sizes, and the absence of standardized protocols for chromium supplementation hinder the comparability of results. In addition, the heterogeneity of the studied populations limits the reliability of the available data. CONCLUSION: Available evidence does not support the widespread clinical use of trivalent chromium. Therefore, further large-scale studies are required to determine its efficacy and safety.

OBJECTIVE: To evaluate the efficacy and safety of Lactiplantibacillus plantarum Z6 (L. plantarum Z6) supplementation in infants with functional constipation (FC) and to explore its effects on gut microbiota composition. STUDY DESIGN: In this randomized, placebo-controlled trial, 100 infants diagnosed with FC were enrolled and allocated to receive either L. plantarum Z6 or placebo. Clinical outcomes, including weekly bowel movement frequency, Bristol stool scale scores, and Wexner constipation scores, were assessed. Serum 5-hydroxytryptamine (5-HT) levels and fecal microbiota profiles were analyzed to evaluate neurogastrointestinal and microbial responses. RESULTS: L. plantarum Z6 supplementation significantly increased weekly bowel movements and Bristol stool scores while reducing Wexner scores (p < 0.05). Serum 5-HT concentrations were elevated, indicating improved gastrointestinal motility. Gut microbiota analysis revealed enhanced α-diversity, higher abundances of Bifidobacterium, Gemmiger, and Lactobacillus, and reduced Streptococcus. Correlation analysis demonstrated a positive association between L. plantarum Z6 intake and Bifidobacterium enrichment, suggesting targeted modulation of beneficial taxa. CONCLUSIONS: L. plantarum Z6 is a safe and effective probiotic intervention for infantile functional constipation. The results highlight its potential to improve bowel function and beneficially reshape the gut microbiota, offering a microbiota-targeted therapeutic strategy for pediatric gastrointestinal disorders. Chinese Clinical Trial Registry ID: ChiCTR2300073079. © 2026 Wiley‐VCH GmbH.

BACKGROUND: Traumeel (Tr14) and diclofenac gels are commonly prescribed topical treatments for Grade I-II acute lateral ankle sprain (LAS). A meta-analysis of two multi-center trials was performed to compare their clinical efficacy and supplement the evidence in support of topical treatments. METHODS: Data from two Phase III prospective, randomised, double-blind, reference-controlled clinical trials, TAASS (2013) and TRAUMED (2024) were examined. An Individual Patient Data (IPD) meta-analysis was performed on those with an initial pain VAS (Visual Analogue Scale) score ≥ 50 mm, using the statistical analysis plan from the latter to ensure methodological consistency. RESULTS: A total of 628 patients underwent meta-analysis (mean baseline pain VAS = 72.3, mean age = 32.5). The primary endpoint of the IPD meta-analysis, Area Under the Curve (AUC) of pain VAS scores, indicated beneficial effects of Tr14 gel compared with diclofenac gel, statistically significant on Days 4, 7, and 14 (Day 4 mean difference MDAUC-META = -6.9 [95%CI -13.7 to -0.1], PAUC-META = 0.05; Day 7 MDAUC-META = -26.3 [95%CI -40.4 to -12.2], PAUC-META = 0.0003; Day 14 MDAUC-META = -63.6 [95%CI -92.3 to -34.8]), PAUC-META < 0.0001). A robust Wilcoxon-Mann-Whitney (WMW) analysis revealed percent changes from baseline in pain and function that were significantly superior for Tr14 gel in the pre-planned method of synthesis, compared to diclofenac gel, on all days (all PMETA < 0.05). Finally, translational effect sizes indicated less than "small" superiority on Day 4 (SMD 0.15, OR 0.78, NNT 23), and "small-medium-sized" superiority on Days 7 and 14 (Day 7: SMD 0.31, OR 0.59, NNT 12; Day 14: SMD 0.37, OR 0.53, NNT 10) for pain measured by VAS, as compared to diclofenac gel. CONCLUSION: The IPD meta-analysis of the TAASS and TRAUMED trials confirms the efficacy of Tr14 gel. In-depth analysis reveals it is a statistically favourable treatment with respect to pain, and function, compared to the gold-standard diclofenac gel. Taking this together, Tr14 gel represents a statistically favourable treatment option for Grade I-II ankle sprain within the context of the analysed endpoints. © 2026. The Author(s).

INTRODUCTION: While recent trials have shown daily prenatal low-dose 500 mg calcium supplementation to be noninferior to the recommended high-dose 1500 mg regimen for prevention of preeclampsia, its effects on maternal anemia and iron status remain unclear. METHODS: We conducted two individually randomized, non-inferiority trials in India and Tanzania (N=11,000 each) comparing daily 500 mg to 1500 mg calcium supplementation during pregnancy. All participants received standard IFA (60 mg iron) and were counseled to take calcium supplements several hours apart from the IFA. All participants had hemoglobin measured at baseline and at 32 weeks of gestation, while a random subset of participants had ferritin quantified at the same time points. Using an intention-to-treat approach, we assessed effects of 500 mg compared to 1500 mg calcium supplementation on mean hemoglobin and inflammation-adjusted serum ferritin (log-scale) using generalized linear models, and on anemia and iron deficiency anemia using log-binomial models. RESULTS: Third-trimester hemoglobin and serum ferritin were measured in 8,953 and 1,336 participants in India, respectively. In Tanzania, 8,496 participants had hemoglobin, and 882 had ferritin assessed. In both trials, there was no difference between 500 and 1500 mg calcium supplementation on third-trimester hemoglobin [India: mean difference (MD) 0.01 (95% confidence interval (CI): -0.03, 0.04); Tanzania: MD -0.02 (95% CI: -0.07, 0.03)], anemia [India: relative risk (RR) 1.01 (95% CI: 0.95, 1.07); Tanzania: RR 1.00 (95% CI: 0.96, 1.05)], or iron deficiency anemia [India: RR 1.20 (95% CI: 0.93, 1.57); Tanzania: RR 0.94 (95% CI: 0.77, 1.15)]. CONCLUSION: Low and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes. Future studies should assess the effects of co-administering or combining calcium and IFA into a single tablet on adherence and bioavailability of iron. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identifier, NCT03350516; Clinical Trials Registry India number, CTRI/018/2/12119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/TR/010/.