Veterinary medicine and scienceShahab Bahadoran, Shadi Vaeznia, Hossein Hassanpour
OBJECTIVES: The combination of high-altitude and heat stress promotes oxidative damage and immune dysfunction in broiler chickens. This study investigated the potential of dietary Echinacea purpurea to mitigate these detrimental effects. METHODS: In a 42-day trial, 108 one-day-old male Ross 308 broilers were randomly assigned to one of three dietary regimens: an unsupplemented basal diet (Control), or the basal diet supplemented with 0.25% (E0.25) or 0.75% (E0.75) hydroalcoholic E. purpurea extract. Birds were reared at 2100 m altitude and exposed to chronic heat stress. On Day 42, serum was analysed for nitric oxide (NO) and malondialdehyde (MDA). Hepatic relative telomere length was quantified via qPCR, and the expression of cytokine genes (IL10, IL1β, TNFα and IFNγ) was assessed by RT-qPCR. RESULTS: Dietary E. purpurea at both levels significantly lowered serum NO and MDA concentrations compared to the control group (p < 0.05). Relative telomere length was unaffected by treatment. Gene expression analysis revealed that the E0.75 group had significantly elevated transcripts of IL-10 (900% increase) and IFN-γ (351% increase), while IL-1β and TNF-α remained unchanged. Consequently, the composite pro-/anti-inflammatory cytokine ratio [(IFNγ + IL-1β + TNFα)/IL-10] was reduced in both supplemented groups (P < 0.05). CONCLUSION: Supplementation with E. purpurea alleviated systemic oxidative stress and induced a distinct immunomodulatory response, upregulating key cytokines IL-10 and IFN-γ in broilers under dual environmental stress. Telomere length in liver tissue was not preserved under these conditions. These results indicate that E. purpurea is a promising phytogenic feed additive for enhancing broiler resilience in challenging environments.
Journal of inherited metabolic diseaseNina N Stolwijk, Bart M F Penninx, Annet M Bosch, Mirjam Langeveld, Gajja S Salomons, Carla E M Hollak, Essential Nutritional Therapy Products for IMDs Consens…
Nutritional therapy is critical in managing inherited metabolic diseases (IMDs), and includes specialized diets and single nutritional therapy products (sNTPs) such as vitamins, cofactors, and amino acids. Many sNTPs function as medicines, but are regulated as food (e.g., food supplements), which can limit access, reimbursement, and consistent supply. Essential medicines, as defined by World Health Organization (WHO), meet key healthcare needs and must be available, affordable, and quality-assured. Some sNTPs might meet this threshold, supporting their potential inclusion in the WHO essential medicines list. A modified Delphi process was conducted with a panel of 36 experts from 18 European countries to identify which sNTPs are essential for IMD treatment. Ninety-six sNTPs and their target IMDs were assessed using a literature-informed five-criteria framework, that included evaluation of the level of scientific evidence for usefulness and effectiveness. Overall, 31 sNTPs were deemed essential in the management of 55 IMDs, consisting of vitamins (n = 12), minerals (n = 4), amino acids (n = 6), sugars (n = 2), and other nutrients (n = 7). Evidence supporting their use ranged from levels 3 to 4 of the Oxford Centre for Evidence-Based Medicine (OCEBM), reflecting the limited clinical trial data inherent to rare diseases. Seven of these are already included in the WHO essential medicines list. Recognition of the remaining 24 essential sNTPs could improve their availability and reimbursement, and in some cases, may warrant formal authorization as medicines. Subsequent research should focus on access inequities, cost barriers, and incorporate patient perspectives to optimize the use and impact of sNTPs in IMD management.
Veterinary medicine and scienceRohban Hameed, Muhammad Tahir, Rifat Ullah Khan, Sohail Ahmad, Luciana Rossi, Rasha K Al-Akeel
BACKGROUND: Soybean meal (SBM) is a major protein source in broiler diets, but its cost and dependence on a limited number of protein sources have increased interest in alternative feed ingredients. Rapeseed meal has considerable potential as an alternative protein source; however, its utilisation is constrained by antinutritional factors that can limit nutrient availability and broiler performance. Extrusion processing and exogenous enzyme supplementation may improve the nutritional value of rapeseed meal. We hypothesised that replacing part of dietary SBM with extruded rapeseed meal (ERSM), in combination with protease and non-starch polysaccharide (NSP)-degrading enzymes, would improve or maintain broiler performance and nutrient utilisation while supporting intestinal health. METHODS: A total of 320 day-old Ross 308 male broiler chickens were randomly assigned to four dietary treatments in a completely randomised design. During the finisher period (22-35 days), birds received a corn-SBM control diet or diets in which 5%, 7.5%, or 10% of SBM protein was replaced with ERSM. All diets contained identical levels of protease and NSP-degrading enzymes. Growth performance, nutrient digestibility, carcass characteristics, intestinal morphology and caecal microbial populations were evaluated to determine the effects of increasing ERSM inclusion. RESULTS: Dietary ERSM affected feed intake (p = 0.029), final body weight (p = 0.017), feed conversion ratio (p = 0.009) and mortality (p = 0.041), with the 5% and 7.5% ERSM treatments generally producing the most favourable performance. Apparent digestibility of dry matter, crude protein, crude fibre, fat and ash was improved in ERSM-fed birds (p < 0.05). Carcass yield, breast weight and thigh weight increased with ERSM inclusion (p ≤ 0.025), whereas liver weight decreased at the highest inclusion level (p = 0.034). ERSM also improved intestinal morphology by increasing villus height and the villus height-to-crypt depth ratio and reducing crypt depth (p ≤ 0.016). In addition, ERSM increased beneficial caecal bacterial populations and reduced Escherichia coli and Clostridium counts (p ≤ 0.050). CONCLUSIONS: Replacing SBM protein with 5%-7.5% ERSM in diets supplemented with protease and NSP-degrading enzymes improved growth performance, nutrient digestibility, carcass characteristics, intestinal morphology and caecal microbial balance in broilers. The findings indicate that appropriately processed rapeseed meal can partially substitute for SBM while maintaining or improving important productive and intestinal health outcomes.
Comprehensive reviews in food science and food safetyRuijun Wang, Zhiqi Li, Lina Zhang, Yuanming Pan, Zhanbiao He
The interplay between diet, gut microbiota, and host immunity is central to food science. The Lachnospiraceae family ferments dietary fibers to produce short-chain fatty acids (SCFAs), notably butyrate and propionate, with immunomodulatory potential. This critical review distinguishes established findings from hypotheses. Strain-level functional heterogeneity is substantial; findings from one genus cannot be generalized. Specific substrates (inulin, pectin, resistant starch, and arabinoxylan) and food processing methods shape SCFA profiles. Mechanistically, SCFAs regulate immunity via histone deacetylase inhibition, G-protein-coupled receptor activation, and Treg/Th17 modulation. However, most mechanistic data derive from rodent models; human evidence remains largely correlational and cross-sectional. Three major knowledge gaps exist: the lack of strain-level functional characterization, the absence of causal human intervention trials for the vast majority of Lachnospiraceae strains (with Anaerobutyricum soehngenii being the sole exception, tested only in metabolic disease), and limited translation into food systems. Regulatory barriers (generally recognized as safe [GRAS] status exists only for A. soehngenii CH106 and strictly for food use; no other strain has GRAS or qualified presumption of safety [QPS]), safety concerns (rare opportunistic pathogenicity), and technological challenges (oxygen sensitivity and viability in food matrices) further hinder development. Postbiotics (preparations of inactivated microbial cells or their components) and metabolite-based preparations (e.g., purified SCFAs or fermentation supernatants), alongside synbiotic formulations, offer practical near-term alternatives. Importantly, under the International Scientific Association for Probiotics and Prebiotics (ISAPP) definition, purified metabolites without cellular biomass do not qualify as postbiotics. We conclude that although Lachnospiraceae hold promise for immunomodulatory functional foods, current evidence does not support clinical or commercial claims. Priority research directions include longitudinal human cohorts, strain-level culturomics, and multi-omics integration. This review provides a realistic, food science-centered framework for future investigations.
Veterinary medicine and scienceFatemeh Shayesteh, Milad Shahini Shams Abadi, Leila Rouhi, Abbas Doosti, Nader Bagheri
Inflammatory bowel disease is a significant health concern not only in humans but also in companion animals and livestock, where it manifests as chronic diarrhoea, abdominal pain, and mucosal injury. Probiotics have gained increasing attention as potential therapeutic agents due to their immunomodulatory effects and ability to restore intestinal homeostasis. This study investigated the therapeutic efficacy of Bacillus coagulans and Lactobacillus acidophilus in an acetic acid-induced ulcerative colitis model in Wistar rats. Forty male rats were randomly assigned to control, colitis, mesalazine, B. coagulans, and L. acidophilus treatment groups. Disease severity was evaluated by macroscopic and histopathological scoring, colon length and weight, pro-inflammatory cytokine levels (IL-1β, IL-17), and inflammasome-associated gene expression (NLRP3, Caspase-1, IL-18, TNF-α). The results showed that colitis induction significantly increased pro-inflammatory cytokine expression and histological damage compared with controls. Both probiotics markedly reduced inflammatory markers, improved colon morphology, and attenuated inflammasome activation. Their protective effects were comparable to mesalazine, the standard treatment. These findings suggest that B. coagulans and L. acidophilus can serve as effective adjunct therapies for ulcerative colitis in veterinary practice, with potential translational applications for companion animals and livestock.
Veterinary medicine and scienceRamazan Sheikh-Nazari, Kaveh Jafari-Khorshidi, Mohammad Ali Jafari
BACKGROUND: While canola seed is a valuable protein and energy source in poultry nutrition, its use is often limited by antinutritional factors that impair nutrient utilisation and bird performance. OBJECTIVES: This study investigated the effects of phytase and protease enzymes in diets containing canola seed on performance, nutrient digestibility, digestive enzyme activity, intestinal morphology, ileal microbial populations, intestinal viscosity and tibia bone mineralisation in broiler chickens. METHODS: A total of 300 male Ross 308 one-day-old chicks were used in a completely randomised design with 5 treatments, 5 replicates and 12 chicks per replicate. The experimental treatments included: control: a corn-soybean meal-based control diet without canola seed; CS-10: a diet containing 10% canola seed; CS-PRO: a diet containing 10% canola seed supplemented with protease; CS-PHY: a diet containing 10% canola seed supplemented with phytase and CS-PRO-PHY: a diet containing 10% canola seed supplemented with a combination of protease and phytase. RESULTS: Feed intake and body weight gain were significantly higher in the control and CS-PRO-PHY treatments at different experimental periods compared to the CS-10 diet (P < 0.05). Apparent metabolisable energy and the digestibility of crude fibre and ash were higher in the control group and in broilers fed CS-PHY and CS-PRO-PHY compared with birds fed the CS-10 and CS-PRO diets (P < 0.05). At Day 10, amylase and lipase activity were highest in broilers fed the CS-PRO-PHY (P = 0.001). The villus height and villus height-to-crypt depth ratio on Days 10 and 42 were significantly higher in broilers fed the control diet, the CS-PRO-PHY and CS-PHY compared to the CS-10 (P < 0.01). At Day 10, Lactobacillus populations were highest in broilers fed the CS-PRO-PHY and the control diet, and lowest in the CS-10 (P = 0.03). Duodenal and jejunal digesta viscosity was significantly higher in broilers fed the CS-10 diet compared with all other treatments (P < 0.01). Tibia weight, length and weight-to-length index of the bone in the CS-PRO-PHY treatment were significantly greater than those in the CS-10 and CS-PRO treatments (P < 0.05). Moreover, bone strength in the control, CS-PRO-PHY and CS-PHY treatments was higher than in the CS-10 treatment (P = 0.034). CONCLUSIONS: Supplementation of broiler diets containing 10% canola seed with protease and phytase, particularly in combination, effectively mitigated the negative effects of canola on nutrient digestibility, intestinal morphology, microbial balance, digesta viscosity and bone quality, leading to restoration of performance.
Veterinary medicine and scienceSaeid Sedghi, Zahra Keshtmand, Saba Hosseini
BACKGROUND: Escherichia coli infections of the genitourinary tract are a major cause of renal and reproductive dysfunction in males, often impairing spermatogenesis and fertility. Probiotics and postbiotics have emerged as microbiota‑based interventions with strain‑specific immunomodulatory and antioxidant properties. OBJECTIVES: This experimental study evaluated the effects of a probiotic or postbiotic supplementation containing Lactobacillus helveticus, Lactobacillus rhamnosus, and Lactobacillus casei on renal and testicular tissues, as well as sperm parameters, in male Wistar rats infected with E. coli. METHODS: Twenty-eight male Wistar rats (200-220 g) were randomly assigned to four groups: control, E. coli-infected, E. coli + probiotic (109 CFU/mL), and E. coli + postbiotic (109 CFU/mL). Probiotic or postbiotic supplementation was administered orally (gavage) once daily for 35 consecutive days, starting immediately after the final day of bacterial challenge. Biochemical markers (urea, creatinine, sodium, potassium), histological changes, total antioxidant capacity (TAC), gene expression (IL‑6, TNF‑α, Bax, Bcl‑2), and sperm quality were assessed. Statistical analysis was performed using one‑way ANOVA with Tukey's post hoc test (p < 0.05). RESULTS: E. coli infection significantly impaired renal and testicular histology, elevated pro‑inflammatory and pro‑apoptotic gene expression, reduced TAC, and deteriorated sperm parameters. Probiotic and postbiotic supplementation mitigated these effects, restoring antioxidant capacity, enhancing Bcl‑2 expression, reducing IL‑6 and TNF‑α levels, and improving sperm viability and morphology. Histological evaluation confirmed partial recovery of kidney and testicular structures in treated groups. CONCLUSION: Multi‑strain probiotic-postbiotic mixtures confer protective effects against infection‑induced oxidative stress, apoptosis, and inflammation in renal and testicular tissues, while improving sperm quality. These findings highlight their translational potential as adjunctive therapies for infection‑associated male infertility and renal impairment.
Fundamental & clinical pharmacologyNatalia Kostakis, Jean-Christophe Lega, Remy Boussageon
BACKGROUND: The results of randomized controlled trials (RCTs) regarding the effect of vitamin D supplementation on mortality reduction are conflicting. OBJECTIVE: The aim of this study was to assess the level of evidence through a sensitivity analysis of the meta-analysis by Shah et al. (2024) using the Rebuilt the Evidence Base (REB) method. METHODS: The main inclusion criterion was a double-blind, placebo-controlled RCT design. The exclusion criteria were trials combining vitamin D with other nutrients and unpublished RCTs. The main outcome was all-cause mortality. A bias analysis was performed, followed by a hypothetico-deductive analysis to determine the confirmatory or exploratory nature of each RCT. The REB method was used to interpret the results and assess the level of evidence. RESULTS: Among the 25 RCTs included in the meta-analysis by Shah et al., the analysis was performed on 8 RCTs at low risk of bias including 30 320 participants. Seven RCTs raised some concerns, and two RCTs were at high risk of bias according to ROB2. Bias arose from the randomization process, deviations from intended interventions, missing outcome data, and selection of the reported results. The results were statistically significant, in favor of vitamin D supplementation: RR = 0.96 (95% CI [0.92, 1.00]), p = 0.04. No RCT was conclusive. CONCLUSION: According to the REB method, there is an evidence signal regarding the benefit of vitamin D supplementation in the population aged 75 and older, which remains to be confirmed.
European journal of nutritionEmilia Zawieja, Monika Młodzik-Czyżewska, Agata Chmurzynska
BACKGROUND & AIMS: The aim of this study was to investigate the effects of betaine supplementation on mitochondrial and redox-associated parameters in premenopausal women with overweight or obesity. We hypothesized that betaine enhances selected mitochondrial enzyme content and improves antioxidant defense. METHODS: In this randomized controlled trial, premenopausal women with overweight or obesity were assigned to receive anhydrous betaine supplementation (3 g/d) or a placebo condition for eight weeks. Mitochondrial enzyme content was assessed in peripheral blood mononuclear cells (PBMCs), including citrate synthase (CS) and cytochrome c oxidase (COX). Redox-related parameters were evaluated in plasma; these included the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as oxidized glutathione (GSSG) concentration. Preintervention and postintervention measurements were compared between groups. RESULTS: A significant treatment × time interaction was observed for CS concentration in PBMCs (p = 0.043). The pre-to-post change differed significantly between the betaine and placebo groups (between-group difference in change: 102.3 μg/mg protein, 95% CI 3.19 to 201.4), although the within-group pre-post changes were not statistically significant. No significant treatment × time interaction was observed for COX (p = 0.326). Plasma CAT activity showed a significant treatment × time interaction (p = 0.003, ηp2 = 0.213) and increased significantly only in the betaine group. No significant effects were observed for SOD (p = 0.825), GPx (p = 0.359), or GSSG (p = 0.693). CONCLUSIONS: Betaine supplementation may selectively influence PBMC mitochondrial-associated parameters and circulating antioxidant enzyme activities in premenopausal women with overweight or obesity. The differential change in CS between the betaine and placebo groups and the increase in plasma CAT activity warrant further investigation, particularly to determine their physiological significance and underlying mechanisms. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT06344377.
European journal of nutritionMahsa Rezazadegan, Parvane Saneei, Maryam Soheilipour, Niloufar Rezazadegan, Reza Amani
BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder that is related to impaired gut microbiota (GM) composition and sleep disorders. Zinc and probiotics play key roles in gut barrier integrity maintenance and microbiota modulation. Therefore, the current study investigated the effect of zinc and probiotic co-supplementation on oxidative stress biomarkers and sleep quality in IBS patients. METHODS: In this parallel, randomized clinical trial, 84 participants with IBS were randomly allocated to three groups and received: 1- a zinc gluconate tablet (20 mg elemental zinc) and a probiotic placebo; 2- a zinc gluconate tablet and a probiotic capsule; 3- two placebos for a period of 90 days. After 10-12 h overnight fasting, serum zinc, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity as well as sleep quality were assessed by validated methods. Oxidative stress index (OSI) was also calculated. RESULTS: Supplementation with zinc, without or with probiotic, enhanced serum zinc (mean change: 6.36 ± 0.80 and 13.03 ± 3.82, vs. -1.76 ± 1.82 µg/dL; p = 0.008) compared to placebo. Zinc supplement alone and in combination with probiotics significantly decreased serum TOS level (mean change: - 1.47 ± 0.38 and - 1.67 ± 0.60, respectively, p = 0.001) and OSI (mean change: -1.70 ± 0.28 and - 2.05 ± 0.63, respectively, p = 0.004) in comparison to the placebo group. However, no significant between-group effects were observed for serum MDA, TAC, SOD activity, and sleep quality. CONCLUSION: Zinc supplementation, alone or with probiotics, may improve serum zinc and TOS levels, and OSI in IBS patients. Future studies are warranted to confirm these findings and their clinical relevance. TRIAL REGISTRATION: This study was registered on January 29, 2024, at the Iranian Registry of Clinical Trials ( https://www.irct.ir ) (registration number: IRCT20180818040827N5).
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune PharmacologyVamsi K Singu, Nghi M Nguyen, Alexander Ky, Victoria L Schaal, Pranavi Athota, Austin Gowen, Matthew VanOrmer, Olivia Loh, Ashley J Blount, Corrine Hanson, Sow…
In recent years, opioid abuse has become a major public health crisis affecting millions of individuals throughout the world. This widespread abuse of prescription opioids and dramatic increase in their availability have created the opioid epidemic. Further, oxycodone (oxy), which is prescribed for multiple types of pain, is gaining momentum as a pain reliever in pregnant women. Whilst successful in inducing analgesia, oxy freely passes through the placenta and can impact the overall development of the fetus in major ways. Currently, mechanisms that lead to impairment in the exposed offspring, including identification of biomarkers, are not well described. To fill this gap, our study utilizes a preclinical rodent model to test the therapeutic efficacy of omega-3 fatty acids (O3FA) in attenuating neurodevelopmental deficits in offspring exposed to chronic stress (CS) and oxy in utero which mirrors real-world cases of opioid use during pregnancy co-occurring with chronic psychosocial stress. Our results show that O3FA supplementation partially rescues phenotypic, biochemical, molecular, and behavioral endpoints. Notably, our proteomic study identified distinct key synaptic signatures, including functional pathways impacted in different treatment groups. Furthermore, RT-qPCR results identified key inflammatory markers whose expression was ameliorated by O3FA supplementation. Together, this study bridges an important knowledge gap pertinent to maternal-fetal health that reflects a combined exposure of oxy and CS that is clinically relevant and enumerates the therapeutic efficacy of O3FA in mitigating neurodevelopmental deficits in offspring exposed to in utero oxy and CS.
BMJ openLuna Khanal, Karina Cernioglo, Jennifer T Smilowitz, J Bruce German, Mark A Underwood, Kara Kuhn-Riordon, Nicole T Cacho
INTRODUCTION: An adequate supply of a mother's own milk plays a critical role in optimising health outcomes for at-risk hospitalised infants. Insufficient milk production disproportionately affects the mothers of these infants. In the USA, metoclopramide is the only approved drug available for off-label use as a galactagogue. Nicotinamide riboside (NR), a direct precursor to nicotinamide adenine dinucleotide (NAD+), has been shown in a murine model to augment high-quality milk production and enhance cognitive and physical development of pups. Human testing with NR has been limited, and studies in lactating individuals have not been performed. The aim of this study is to assess the feasibility of NR supplementation in mothers whose infants are admitted to the neonatal intensive care unit (NICU) for at least 4 weeks. METHOD AND ANALYSIS: This double-blind, randomised, placebo-controlled pilot feasibility trial aims to investigate NR supplementation in mothers of infants who are anticipated to be hospitalised in the NICU for at least 4 weeks. We plan to enroll 40 mother-infant pairs with the expectation that 30 will complete the study (n=15 in each group). The intervention period with maternal NR supplementation or placebo supplementation and maternal milk, urine and blood sampling will be 19 days, including an enrollment day.The primary endpoint of the study includes feasibility of enrolling ≥50% of eligible mothers. Secondary endpoints include compliance, adherence or withdrawal from the protocol. Similarly, the study will assess the difference in mean milk volume, macronutrient and micronutrient content, human milk glycans, milk and urine metabolites and infant feeding practice between the two groups. Optional secondary endpoints include differences in serum prolactin, liver function, plasma lipidome, serum metabolites, serum cellular communication network factor 3 concentrations, serum NAD+-related precursors and intermediates between mothers of the two groups. Exploratory outcomes include changes in mothers' weight and infants' developmental and NICU outcomes. Safety endpoints include the frequency of adverse events. ETHICS AND DISSEMINATION: The Institutional Review Board (IRB) protocol version date is 1 June 2026, approved by the IRB at the University of California Davis Medical Center (approval number: 1557473). Study investigators will communicate trial results to participants, healthcare professionals and the public through peer-reviewed publications and presentations at scientific conferences. Trial results will also be reported on ClinicalTrials.gov and made available through PubMed Central, in accordance with regulatory requirements. Deidentified participant data will be available to qualified researchers upon request after publication. Approved requests will be granted access within 12 months and are subject to study team and IRB approval and a data use agreement. TRIAL REGISTRATION NUMBER: NCT04614714.
Journal of the International Society of Sports NutritionCui Xingchen, Liu Meng, Cao Yinhang, Zhao Can
BACKGROUND: Weight reduction before competition has long been a major challenge for combat-sports athletes. Unscientific weight-loss practices not only increase the risk of hormonal imbalance, electrolyte disturbance, and impaired immune function but also compromise athletic capacities such as aerobic and anaerobic performance and explosive power. This study investigated the potential benefits of tangeretin, a natural citrus extract, on athletic performance. These benefits include the regulation of hormone secretion, the optimization of carbohydrate and lipid metabolism, and the promotion of muscle synthesis and lipid utilization, which may help athletes reach their target weight. OBJECTIVE: To examine the effects of tangeretin supplementation on body-composition and sports-performance indicators in female combat-sports athletes, and to evaluate its efficacy for simulated precompetition weight loss. METHODS: Thirty female combat-sports athletes (4 wrestlers, 3 boxers, 9 sanda athletes, 3 judokas, and 11 taekwondo athletes) were recruited. A paired, randomized, double-blind design was used. All 30 participants were first paired according to sport and competitive level, then randomly allocated to either a tangeretin group or a placebo group (15 per group). The 30-day intervention comprised a double-blind nutritional supplement, a dietary questionnaire, blood sampling and analysis, body-composition assessment, isokinetic muscle-strength testing, and aerobic-capacity testing, to evaluate the effects of tangeretin (400 mg/day) on performance and health-related outcomes. These outcomes included body-composition indicators (e.g. body-fat percentage, fat mass, lean-body mass), fat-distribution indicators (e.g. limb and regional fat mass, gynoid fat mass), glucose and lipid-metabolism indicators (e.g. LDL-C, total cholesterol, free fatty acids), hormone indicators (e.g. cortisol, testosterone), muscle-strength indicators (e.g. peak torque of hip, knee, and ankle flexors and extensors), and maximal-oxygen-uptake-derived indicators (e.g. VO2max heart rate, time to exhaustion). Statistical significance was assessed using two-way repeated-measures analysis of variance (ANOVA). RESULTS: (1) Body weight: 80.0% of athletes in the tangeretin group lost weight to varying degrees, and 33.3% (5 athletes) reached their competition weight class. (2) Body fat: body-fat percentage in the tangeretin group decreased from 23.92 ± 0.87% to 22.92 ± 0.89%; trunk, upper-limb, lower-limb, and android-region fat mass decreased by 6.77%, 8.77%, 4.43%, and 8.09%, respectively. (3) Glucose and lipid metabolism: HDL-C increased by 8.86% (P = 0.002), whereas triglycerides decreased by 25.00% (P = 0.048). (4) Sports performance: peak torque during hip, knee, and ankle flexion and extension increased significantly in the tangeretin group. VO2max also improved from 42.80 ± 1.13 to 43.46 ± 1.32 ml/kg/min. CONCLUSION: Tangeretin supplementation effectively reduced body weight and fat mass (both overall and regionally) in female combat-sports athletes. Among the participants, 80.0% lost weight to varying degrees, and 33.3% reached their competition weight class, indicating a strong effect on precompetition weight loss. Moreover, tangeretin improved aerobic capacity and lower-limb joint muscle strength, thereby enhancing competitive performance.
Journal of the International Society of Sports NutritionReza Sabzevari Rad, Marefat Siahkouhian
AIM: The study aimed to assess the effect of Tabata-style functional training with or without cinnamon supplementation on the performance of the Army Combat Fitness Test (ACFT), serum irisin levels, and body composition in cadets at military academies. METHODS: In a randomized controlled design, 48 male cadets (22.8 ± 1.3 years) were allocated to 4 groups: Tabata group (n = 14), cinnamon group (n = 10), Tabata+cinnamon (n = 14), and control group (n = 10). This was a 6-week intervention. Tabata training was performed three times per week (8 × 20s work/10s rest; 87%-95% HRmax), and cinnamon (Cinnamomum zeylanicum) supplementation was administered three times per day (1.5g per day). The ACFT components, serum irisin, body fat percentage (BFP), visceral fat index (VFI), lean body mass (LBM), and body mass index (BMI) were evaluated before and after treatment. RESULTS: The group × time interaction was significant for ACFT score, irisin, and body composition markers (p < 0.001). Bonferroni post hoc showed that ACFT test scores in both groups, COMB and TAB, improved significantly compared to the CON group (p < 0.05). Significant improvement was observed for groups COMB and TAB in 3 repetition maximum Deadlift, Standing Power Throw, Release Pushups, Sprint-Drag-Carry, Leg Tuck, and 2-Mile Run compared to CON group (p < 0.05). The most significant increase in serum irisin levels was observed in COMB group compared to the other groups (p < 0.001). All groups showed significant reductions in body weight, BMI, and VFI when compared to the control group (p < 0.05). Among the groups, TAB group had a remarkably lower BFP than the others (p < 0.001). Additionally, LBM increased significantly in all groups compared to the control group (p < 0.001). CONCLUSION: Tabata-style training combined with cinnamon supplementation markedly enhanced performance, body composition, and circulating irisin in young male military cadets, yielding significant improvements in functional capacity and demonstrating the advantage of pairing high-intensity exercise with targeted nutritional intervention.
Gut microbesAnna Voulgari-Kokota, Els Janson, Ineke Heikamp de Jong, Jan Knol, Ruurd van Elburg, Niek E van der Aa, Lisa M Hortensius, Jeroen Dudink, Caroline G M de Theij…
Preterm birth, a major cause of brain injury, is often linked to dysregulated gut microbiome development. This association underscores microbial metabolic function as a modifiable target to support neurodevelopment. In this secondary analysis of data derived from a randomized controlled trial (Trial Registration: ISRCTN96620855), we tested whether daily nutritional supplementation with Bifidobacterium breve M-16V, short- and long-chain oligosaccharides, and L-glutamine could steer the gut microbiome of very and extremely preterm infants toward communities that support brain maturation. The gut microbiome was profiled with longitudinal shotgun metagenomics at nine time points during the intervention, which started at 48-72 h after birth and continued until 36 weeks postmenstrual age. Additionally, MRI scans were conducted when infants reached term-equivalent age to evaluate brain maturation. Supplementation promoted the early establishment of Bifidobacterium-rich communities in the test group, with enhanced capacity for amino acid biosynthesis and pyruvate fermentation towards acetate and lactate production. Integration of microbiome data with brain developmental markers post hoc showed that the same functions were markedly reduced in infants with delayed white-matter myelination. By integrating microbiome functional capacity profiling and evaluation of brain maturation via MRI, this study demonstrated that early microbial modulation could influence brain development, positioning the preterm gut microbiome as a clinically actionable target.
Letters in applied microbiologyDo-Won Park, Ji Hyung Kim, Do-Young Park
Limosilactobacillus fermentum is a promising probiotic species with reported benefits for gastrointestinal health and host metabolism. In this study, a novel L. fermentum strain, DX2034, isolated from the feces of a healthy Korean infant, was characterized through phenotypic and genomic analyses, and its anti-adipogenic activity was evaluated in differentiated 3T3-L1 adipocytes. DX2034 exhibited high tolerance to simulated gastric and bile conditions and showed stronger adhesion to Caco-2 cells than the reference strain L. fermentum CECT5716. The strain showed no hemolytic activity and was susceptible to most tested antibiotics. Whole-genome sequencing revealed a single circular chromosome of 2 160 171 bp with no acquired antibiotic resistance genes, virulence-associated factors, or concerning secondary metabolite biosynthetic gene clusters. Comparative genomic analysis identified genomic regions showing low similarity to reference strains, including a putative glycosyltransferase-associated locus, and genes associated with stress adaptation, gastrointestinal persistence, surface modification, and quorum sensing. Heat-killed DX2034 significantly reduced lipid accumulation, intracellular triglyceride content, and expression of adipogenesis-related genes, including C/EBPα, PPARγ, FABP4, LPL, and FASN. These effects were attenuated by the TLR2 inhibitor C29, suggesting involvement of TLR2-associated signaling. Collectively, DX2034 exhibits favorable probiotic-associated characteristics, genomic safety, and TLR2-associated anti-adipogenic activity, supporting its potential as a functional probiotic or postbiotic candidate.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical SciencesSeyed Yaser Ghelmani, Seyede Hamide Rajaie, Roghayeh Zare, Narjes Hazar, Ali Khiveh, Morteza Zaboli Mahdiabadi, Seyed Hamdollah Mosavat, Morvarid Salamati, Maj…
BACKGROUND: Orthostatic hypotension (OH) and related symptoms are common complications in individuals with type 2 diabetes mellitus (T2DM). Antioxidant compounds, such as those found in rosehip fruit, may have the potential to alleviate orthostatic symptom burden. This study evaluated the effects of rosehip fruit extract on orthostatic symptoms in adults with T2DM. METHODS: This randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted over four weeks among 60 adults with T2DM and OH referred to the Yazd Center for Diabetes. Participants were randomly assigned to receive either rosehip fruit extract (two capsules daily, each containing 500 mg) or placebo. Orthostatic symptoms were assessed using the Orthostatic Intolerance Questionnaire (OIQ). Clinical relevance was evaluated using predefined minimal clinically important difference thresholds. RESULTS: Of the 60 randomized participants, 57 completed the 4-week intervention. At the end of the study, a greater proportion of participants in the rosehip group no longer met diagnostic criteria for orthostatic hypotension compared with the placebo group (prevalence ratio = 2.57, 95% CI: 1.18-5.62). The rosehip group experienced significantly greater reductions in OIQ scores compared with placebo, and these differences remained statistically significant after adjustment for baseline values and age (P = 0.001). The magnitude of symptom improvement in the rosehip group exceeded the predefined thresholds for clinical relevance. CONCLUSION: Rosehip extract significantly reduced orthostatic symptom burden and the prevalence of OH in patients with T2DM. Benefits were primarily reflected in symptomatic scores and systolic blood pressure. While promising and well-tolerated, these preliminary results require confirmation in larger, multicenter trials incorporating long-term objective hemodynamic monitoring.
A man in his 40s presented with rapid weight gain, fatigue and clinical signs of Cushing's syndrome, including abdominal striae and centripetal obesity. Laboratory testing revealed suppressed serum cortisol and adrenocorticotropic hormone levels. He denied prescribed glucocorticoid use but disclosed consumption of the supplement Artri King Reforzado Con Ortiga Y Omega 3 for joint pain. The U.S. Food and Drug Administration (FDA) had recalled this product for undeclared dexamethasone. The patient's symptoms started a few weeks after he discontinued the supplement and gradually improved with initiation of hydrocortisone for treatment of secondary adrenal insufficiency due to exogenous glucocorticoid use. This case illustrates the potential harm of adulterated supplements and the importance of obtaining a thorough medication and supplement history in cases of suspected iatrogenic Cushing's syndrome.
The concurrent manifestation of muscle wasting and excessive adiposity, termed Sarcopenic Obesity (SO), represents a growing public health challenge. Inulin, a widely used prebiotic, has been shown to improve metabolic disorders, but its specific effects on SO and the mechanisms governing the gut-liver-muscle axis remain underexplored. This study evaluated the therapeutic potential of inulin in db/db mice exhibiting SO features. Our data indicate that inulin supplementation effectively curbed weight gain and fat deposition while preserving lean mass. Crucially, it ameliorated systemic hyperglycemia and dyslipidemia. In the liver, inulin attenuated steatosis by potentiating the AMPK/PPARα oxidative pathway; in skeletal muscle, it reversed atrophy by enhancing myogenic factors (MyoD and MyHC I) and suppressing atrophic ligases (Atrogin-1 and MuRF1). Mechanistically, inulin restored intestinal barrier integrity, thereby reducing serum lipopolysaccharide (LPS) and proinflammatory cytokine levels. Metagenomic sequencing and targeted metabolomics revealed that inulin restructured the gut microbiota composition, characterized by an enrichment of Ligilactobacillus, Prevotella and Bifidobacterium, and modulated the bile acid (BA) profile. Crucially, protein quantification confirmed that inulin significantly upregulated the expression of core bile acid receptors (FXR and TGR5) in both colonic and hepatic tissues. These findings demonstrate that inulin ameliorates SO through an integrated mechanism involving gut microbiota remodeling, BA-FXR/TGR5 receptor activation, and intestinal barrier reinforcement to harmonize the gut-liver-muscle axis, highlighting its potential as a functional food ingredient for managing SO.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical SciencesAnurag Biswas, Bijoy Ghosh, Pallvi Kumari, Ankita Rangra, Kaunava Roy Chowdhury, Akshay Kumar
BACKGROUND: The human microbiome can actively influence how drugs are handled and processed in our body. More knowledge of host-microbiome-drug interactions has shifted drug delivery from current approaches to precision therapeutics. OBJECTIVES: The review is to evaluate various targeted strategies and mechanisms of drug delivery systems (DDS) driven by pharmacomicrobiomics. Moreover, the pharmacomicrobiomics-based DDS will also be discussed in terms of their therapeutic applications, translation, and new technologies for microbiome precision. METHODS: Assessment on the latest development on microbiome-drug interactions and microbiome-based drug delivery strategies, including microbial enzyme activated prodrugs, nano- and micro-particle systems, probiotics, prebiotics, postbiotics, bacteriophages, genetically modified microorganisms, smart materials, and niche-selective delivery systems. The researchers also investigated clinical evidence, security, regulatory issues, Pharmacoeconomics and new emerging multi-omics and AI based strategies. RESULTS: Microbiome-targeted DDS enable localized drug activation, site-specific delivery, and reduced systemic exposure. Enzyme-responsive systems achieved up to a 3-fold increase in local drug concentration, while SER-109 (VOWST) reduced CDI recurrence to 12% versus 40% with placebo at 8 weeks. FMT combined with pembrolizumab achieved objective responses in 40% (6/15) of previously non-responsive melanoma patients. Engineered microbial therapeutics, including SYNB1618 and AG013, further demonstrate the growing translational potential of programmable microbiome-based therapies. CONCLUSION: Pharmacymicrobiomics-driven drug delivery systems (DDS) represent an innovative approach to precision therapeutics utilizing microbes. However, challenges such as individual microbiome variability, unvalidated biomarkers, safety concerns, intricate regulatory hurdles, and inconsistent translational outcomes from preclinical studies persist. A comprehensive integration of omics data and interdisciplinary collaboration is essential to enhance the predictability of microbiome therapies. Future efforts should focus on microbiome profiling, validating mechanism-based biomarkers, scalable manufacturing, and conducting clinical studies to define patient selection, ensure therapeutic consistency, and confirm long-term benefits.
Tropical animal health and productionJosé E Miranda-Yuquilema, Davinia Sánchez-Macías, Joselin Vizuete-Cajo, Erika Muñoz-Alvear
The growing demand for animal protein is driving the search for natural alternatives, such as probiotics, following the ban on growth-promoting antibiotics due to bacterial resistance. The objective of this study was to evaluate the effect of including probiotics made from agro-industrial waste fermented with Lactobacillus acidophilus and Kluyveromyces fragilis and their combination on carcass traits, non-carcass components and colour and pH evolution during muscle-to-meat conversion of 90-day-old male guinea pigs. A total of 40 male guinea pigs were randomly assigned to one of four groups: (a) Ct, control group; (b) LA, supplemented with Lactobacillus acidophilus; (c) Kf, supplemented with Kluyveromyces fragilis; (d) LAKf, supplemented with a combination of L. acidophilus and K. fragilis. The combination of L. acidophilus and K. fragilis significantly increased live weight at slaughter compared to the control group, demonstrating synergistic effects between bacterial and yeast probiotics. Carcass yields (HCY and CCY) were not significantly influenced by probiotic supplementation, remaining within the standard ranges for the breed. Tissue composition showed proportional scaling with body weight, and non-carcass components development remained proportional to body size across treatments, indicating that growth benefits were achieved without imposing metabolic stress or requiring compensatory organ hypertrophy. Probiotic supplementation influenced meat colour parameters, particularly reducing yellowness (b*) and improving colour stability during chilling in yeast-containing treatments. The pH evolution during the post-mortem period was not affected by probiotic supplementation, indicating normal glycolytic processes and favourable conditions for meat quality development. These findings support the use of fermented agro-industrial substrates as effective probiotic delivery systems in guinea pig production, offering a sustainable approach that addresses both waste valorisation and animal nutrition challenges.
Journal of the International Society of Sports NutritionGianna F Mastrofini, Riccardo F Romersi, Maria G Lombardi, Katelynn T Persaud, Monica M Ryan, Katie R Hirsch, Amy L Fraley, J Jay Dawes, Sten O Stray-Gundersen…
BACKGROUND: Stress and poor sleep are prevalent public health concerns that negatively impact well-being and daily functioning. Although adaptogens and sleep-focused supplements have separately demonstrated potential benefits, few studies have examined combined effects, particularly in healthy populations. Therefore, this study evaluated the impact of morning adaptogens, evening sleep-focused supplements, and their combination on stress, mood, and subjective and objective sleep quality. METHODS: Using a double-blind, placebo-controlled design, 103 healthy physically active adults (F = 53; age = 34.8 ± 9.6 yrs; BMI = 24.0 ± 2.7 kg/m2) were randomized to one of four treatment groups: 1) AMPM (n = 25): active morning (AM) and active evening (PM); 2) AM (n = 26): active AM and placebo PM; 3) PM (n = 25): placebo AM and active PM; and 4) PL (n = 27): placebo AM and placebo PM). The AM group contained 600 mg ashwagandha and 300 mg Rhodiola rosea (R. rosea). The PM group contained 2 g Magnesium L-threonate (MgT) (delivering 145 mg of magnesium), 200 mg L-theanine, and 50 mg apigenin. The total study duration was four weeks, consisting of one baseline week, two weeks of supplementation, and one washout week. Participants completed daily stress questionnaires and weekly questionnaires on perceived stress, affect, and subjective sleep (Patient-Reported Outcome Measurement Information System (PROMIS), and monthly subjective sleep (Pittsburgh Sleep Quality Index (PSQI) at baseline and post-washout. Objective sleep data were collected nightly using a wearable sleep monitoring device. Data were analyzed using baseline-adjusted linear mixed-effects models with alpha set at 0.05. Tukey-adjusted post hoc comparisons were performed, and effect sizes are reported as partial eta squared (η2) and Cohen's d (d). RESULTS: The AM group showed a decrease in weekly perceived stress (p = 0.034; η2 = 0.020), whereas there were no differences in daily stress (p < 0.05). For positive affect, there was a significant effect in the AM group at the end of the cessation period (p = 0.003; d = 1.68), which continued to increase, whereas the AMPM group showed a decrease (p = 0.009; d = 0.16). The AM group showed a decrease in subjective sleep-related impairments (p = 0.032, d = 2.74) and in objective wake after sleep onset (p = 0.047, η2 = 0.020). PSQI subjective sleep quality was significantly improved in the AM group compared with the AMPM group (mean difference = 0.66 AU, p < 0.001, d = 1.45). CONCLUSIONS: Morning supplementation with adaptogens (ashwagandha and R. rosea) was associated with improvements in subjective stress, sleep quality, and positive affect following 14 days in healthy physically active adults as compared to the placebo product. Minimal effects on other outcomes may reflect limited benefits in healthy individuals over a short supplementation period. Future research should investigate longer interventions and populations with greater baseline stress and sleep disturbance.
Journal of the International Society of Sports NutritionJesús García-Durán, Antonio J Sánchez-Oliver, Noelia M Rodríguez-Martín, María-Soledad Fernández-Pachón, Justo Pedroche, Francisco Millán, José Antonio Gonzále…
BACKGROUND: This randomized, double-blind, placebo-controlled trial examined the effects of a chickpea protein hydrolysate (CPH) on biomarkers associated with exercise-induced muscle damage and inflammation in federated male road cyclists. METHODS: Twenty-four participants completed a 14-day intervention receiving either 12 g/day of chickpea protein hydrolysate (EXP) or a placebo (PLA) following training sessions. The selected dose was based on previous studies demonstrating antioxidant and immunomodulatory bioactive properties of the hydrolysate. Nutritional intake and training were registered. Body composition and biochemical markers of muscle damage and inflammation were assessed before and after the study. RESULTS: No significant differences were observed in body composition, training load, or dietary intake between groups, indicating controlled experimental conditions. However, between-group analyses of change scores revealed significant differences for lactate dehydrogenase (LDH; p = 0.04) and C-reactive protein (CRP; p = 0.02), favoring the experimental group. LDH decreased in the EXP group while increasing slightly in the placebo group, whereas CRP decreased in EXP and increased in PLA. Although creatine kinase (CK) showed a favorable pattern in the EXP group, the between-group comparison did not reach statistical significance (p = 0.062). Myoglobin followed a similar downward trend. The high baseline protein intake (>2 g/kg/day) and short intervention duration may have limited changes in body composition, nevertheless, the observed biomarker responses suggest that CPH supplementation may influence selected physiological processes associated with exercise-induced inflammation and cellular stress. CONCLUSIONS: In trained cyclists with high habitual protein intakes, 14 days of CPH supplementation did not alter body composition but was associated with favorable changes in selected biomarkers related to exercise-induced inflammation and cellular stress compared with placebo. Given the short intervention period and the absence of direct assessments of recovery or performance, these findings should be interpreted as short-term biochemical responses. Further studies are required to determine their physiological relevance and whether these biomarker changes translate into meaningful improvements in recovery, training adaptation, or athletic performance.
World journal of microbiology & biotechnologyMansheen Kaur, Alok Kumar Mishra
The gut microbiota is pivotal in regulating host metabolism, immune signaling, and the integrity of the mucosal barrier, thus serving as a critical factor in various metabolic, inflammatory, and gastrointestinal disorders. Traditional probiotics, primarily comprising Lacticaseibacillus and Bifidobacterium species, have been utilized to enhance gut health; however, the strain-dependent effects and variable clinical outcomes associated with these probiotics have prompted increased interest in next-generation probiotics (NGPs). Akkermansia muciniphila, a commensal organism that degrades mucin and resides at the mucosal interface, has emerged as a prominent NGP owing to its ability to reinforce epithelial integrity, modulate immune responses, and foster metabolic homeostasis. Of particular significance is its surface protein, Amuc_1100, which acts as a parabiotic molecule. This protein engages host pattern-recognition pathways, bolsters tight-junction proteins, and alleviates low-grade inflammation. In contrast to live bacterial formulations, purified Amuc_1100 presents advantages concerning stability, safety, and regulatory compliance. This review aims to synthesize contemporary insights into gut microbiome functionality while comparing traditional probiotics with next-generation alternatives. Additionally, it delineates the therapeutic potential of A. muciniphila and Amuc_1100. The discussion further encompasses clinical advancements, regulatory frameworks, and formulation considerations that are propelling the shift towards mechanism-based microbiome therapeutics.
World journal of microbiology & biotechnologyDivya Limbu, Manab Deb Adhikari
Probiotics offer significant health benefits when consumed in adequate amounts; however, their viability is often compromised during processing, storage, and transit through the gastrointestinal tract, which limits their effectiveness in functional food applications. In the present study, seventeen indigenous LAB strains were isolated from fermented radish, among which six strains showed potential probiotic characteristics. The strain revealed to have the most desirable probiotic attributes was identified as Lactiplantibacillus plantarum, as confirmed by 16 S rRNA gene sequencing. Further, we assessed the viability and stability of L. plantarum RAD1 under simulated gastrointestinal conditions and in pasteurized mosambi juice after encapsulation with alginate and Citrus limetta peel powder (CLPP). The alginate beads (Alg) and CLPP-coated Alg beads (Alg@CLPP) were characterized by SEM and FTIR to evaluate the size, morphology, and interaction between the bacteria and wall materials. The Alg@CLPP beads showed a satisfactory encapsulation efficiency of around 96.07% and significantly improved cell viability in simulated gastric fluids compared to free cells. The viability of free and encapsulated L. plantarum RAD1 was also studied in pasteurized mosambi juice, and physicochemical characterization of the juice was performed in terms of pH and titratable acidity over 28 days of storage at 4℃. The CLPP-coated beads revealed a protective effect on RAD1, enhancing its survival in fruit juice under storage conditions. In conclusion, this study presents a formulation for encapsulating probiotics as dietary supplements, aiming to promote human health benefits while also proposing an innovative approach to valorizing agricultural by-products, thereby addressing food waste while contributing to the development of sustainable, health-oriented dietary supplements.
Journal of the International Society of Sports NutritionDamoon Ashtary-Larky, Darren G Candow, Jose Antonio, Christian Quiceno, Fabrizio Angelini, Scott C Forbes, Sajjad Moradi, Fatemeh Kazeminasab, Reza Bagheri
AIM: Soccer places repeated demands on short-duration, high-intensity performance, including sprints, accelerations, jumps, and technical actions performed over the course of a match. Because these efforts depend heavily on rapid adenosine triphosphate (ATP) resynthesis, creatine is a plausible ergogenic aid for soccer players. However, findings in soccer-specific studies have been inconsistent, and previous reviews have addressed narrower questions using smaller evidence sets. This systematic review therefore examined the effects of creatine supplementation on performance, body composition, and recovery/fatigue-related outcomes in soccer players. METHODS: PubMed, Scopus, and Web of Science were searched from inception to 15 May 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. We included controlled clinical trials of creatine supplementation in male or female soccer players of any age or competitive level when an eligible placebo, control, or comparison condition was available. Outcomes were grouped into performance, body composition, and recovery/fatigue domains. Domains from the revised Cochrane risk-of-bias tool for randomised trials (RoB 2) and the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool were used to produce study-level methodological summaries rather than formal result-specific risk-of-bias assessments. Because the studies differed substantially in design, supplementation protocols, populations, and outcomes, findings were synthesised qualitatively rather than pooled in a meta-analysis. RESULTS: Source-level verification left 45 eligible reports representing 41 unique studies: 28 randomised parallel-group studies, 2 randomised crossover/repeated-condition studies, and 11 non-randomised or allocation-unverifiable controlled studies. Some trials reported favourable findings for repeated-sprint performance, anaerobic power, and muscular strength, but the comparative evidence was inconsistent and the certainty of evidence was very low. Findings for vertical jump performance and technical skills were mixed, while change-of-direction and endurance outcomes showed no consistent benefit. Recovery- and fatigue-related findings were also largely null or inconsistent. Body mass often increased, particularly after loading protocols, whereas evidence for gains in lean mass was limited and inconsistent. CONCLUSION: The soccer-specific evidence for creatine supplementation remains suggestive rather than conclusive. Favourable findings have been reported for some repeated-sprint, anaerobic-power, and strength outcomes, but the comparative evidence is heterogeneous, often limited by unclear or nonsignificant between-group effects, and of very low certainty. Firm conclusions about efficacy are therefore not possible. Body mass commonly increased, especially after loading protocols, while effects on lean mass, endurance, change-of-direction ability, and recovery/fatigue-related outcomes remain uncertain.
This study evaluated the effects of dietary Bixa orellana leaf meal on the growth performance and haemato-biochemical responses of Amur carp (Cyprinus carpio haematopterus) against Edwardsiella tarda infection. A total of 180 fish (9.23 ± 0.82 g) were equally distributed into four groups: control (0%), T1 (1%), T2 (3%), and T3 (5%) B. orellana supplementation for 90 days. Edwardsiella tarda was injected intraperitoneally into fish for 14 days after the feeding trial; RPS and histopathological changes was recorded. The result revealed a considerable improvement (P < 0.05) in growth performance (Weight gain, SGR, PER and survival rate) and a decreased feed conversion ratio with increasing BoLM supplementation. However, hematological indices differed significantly among treatments, with T3 showing higher TEC, TLC, hemoglobin, and hematocrit values. Fish Serum biochemical response showed a significant increase, as indicated by total protein, globulin, and albumin in T3 and T2, whereas glucose and cortisol levels were highest in the control group. Histopathological examination revealed distinct tissue alterations in the gills, liver, and intestine among the experimental groups following E. tarda challenge. Furthermore, the treatment group significantly reduced mortality rate following challenges with E. tarda challenge. In conclusion, 5% B. orellana supplementation enhanced growth performance, haemato-biochemical (health) status, and disease resistance in Amur carp.
Current microbiologyNazanin Sadat Seddighi, Ahad Ali Harati Asl, Mohammad Reza Asadi Karam, Seyed Reza Khatibi, Omid Azizi
Helicobacter pylori infects nearly half of the global population and causes gastritis through virulence factors such as CagA and VacA. Increasing antibiotic resistance has reduced the effectiveness of conventional eradication therapies, highlighting the need for alternative strategies, including probiotics. This study evaluated the effects of post-infection supplementation with Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, or their combination on cagA and vacA mRNA expression in a rat model of H. pylori infection. Male Wistar rats (n = 40) were randomly assigned to five groups (n = 8 each), including uninfected controls, H. pylori-infected untreated rats, and infected groups receiving L. plantarum CRD7, L. rhamnosus CRD11, or their combination. Infection was established by oral gavage and confirmed by rapid urease testing, bacterial isolation, and quantitative colony counting. Probiotics were administered orally after infection, and gastric tissues were collected for RNA extraction. Expression levels of cagA and vacA were quantified by qRT-PCR using the 2^(-ΔΔCt) method. H. pylori infection significantly increased cagA (2.7 ± 0.6-fold) and vacA (7.2 ± 0.7-fold) expression compared with controls. Probiotic supplementation reduced cagA expression to 1.86 ± 0.43-fold with L. rhamnosus, 1.2 ± 0.45-fold with L. plantarum, and 0.7 ± 0.8-fold with the combined treatment. Similarly, vacA expression decreased to 3.6 ± 0.44-fold, 1.2 ± 0.6-fold, and 1.7 ± 0.8-fold, respectively. One-way ANOVA showed a trend toward reduced cagA expression (p = 0.08) and significant differences in vacA expression among groups (p < 0.001). Post-infection supplementation with L. plantarum CRD7 and L. rhamnosus CRD11, particularly in combination, attenuated the expression of key H. pylori virulence-associated genes and may represent potential adjunctive strategies for modulating H. pylori virulence-associated gene expression.
Allergen immunotherapy (AIT) represents a cornerstone in managing IgE-mediated allergic diseases, such as allergic rhinitis and asthma. By administering controlled doses of allergens over time, AIT aims to readjust immune tolerance, thereby modifying allergic responses. However, clinical responses to AIT remain heterogeneous, with a subset of patients achieving only partial benefit. This heterogeneity underlines the need for novel adjunctive approaches to potentiate the immunomodulatory effects of AIT. In this context, vitamin D has gained considerable interest, given its well-established role in immune homeostasis and regulation, as well as its emerging relevance in modulating allergic disease. This structured narrative review aims to assess the potential role of vitamin D supplementation during AIT on clinical outcomes as well as the significance of endogenous vitamin D levels on AIT clinical efficacy. A total of 18 studies were reviewed, 13 evaluating the impact of vitamin D supplementation during AIT and 5 assessing the influence of endogenous vitamin D levels on AIT outcomes. Most supplementation studies reported clinical outcomes favoring the addition of vitamin D to AIT, but three found no additional benefit, and two reported a benefit only at an earlier time point, respectively in vitamin D-deficient patients. Of the five studies examining endogenous status, three reported that higher 25-hydroxyvitamin D (25(OH)D) levels were associated with better AIT outcomes. Other findings that were reported as secondary outcomes included favorable immunologic changes, such as IL-10 production, decreased allergen-specific IgE levels, and enhanced regulatory Treg-cell activity, without formal assessment of their contribution to clinical benefit. Nevertheless, findings remain inconsistent across studies due to heterogeneity in study design, supplementation regimens, and outcome measures. While the available evidence suggests that adequate vitamin D status or supplementation may be associated with better clinical responses to AIT, the current findings remain limited by heterogeneity in study design, supplementation regimens, outcome measures, and generally small sample sizes. Therefore, the evidence should be considered suggestive rather than conclusive. Although correction of vitamin D deficiency is appropriate on general clinical grounds, its specific use as an adjunct to improve AIT outcomes cannot yet be routinely recommended. Further adequately powered, standardized, placebo-controlled studies are needed to clarify its role and inform clinical recommendations.
Gout is a common inflammatory disease closely associated with hyperuricemia, and its global prevalence is increasing, highlighting the need for safer and more effective therapeutic strategies. Recently, microbiome-based therapeutics have emerged as promising alternatives, and the development of functionally validated NGP and their advanced forms, post-NGP strains, is gaining increasing attention. In this study, microbiome-derived bacterial strains were screened based on their in vitro uric acid (UA)-reducing capacity and hypoxanthine utilization. Among the tested strains, Mitsuokella jalaludinii exhibited the most pronounced uric acid reduction and growth enhancement in response to purine substrates compared to conventional lactic acid bacteria. This strain reduced uric acid levels by approximately 30% after 48 h (p < 0.001) and showed significantly increased growth in purine-enriched minimal medium (p < 0.01). WGS further confirmed its strain-level novelty, leading to its designation as PMC73, and revealed the presence of genetic features associated with purine metabolism and UA regulation. In a MSU-induced RAW 264.7 macrophage model, PMC73 significantly reduced UA levels (p < 0.001) and modulated immune responses by increasing anti-inflammatory cytokines while decreasing pro-inflammatory cytokines. These effects were associated with suppression of the NLRP3-caspase-1, along with downregulation of URAT1 and XOD, indicating coordinated regulation of uric acid production, reabsorption, and inflammatory pathways. Based on safety evaluation, including d-lactate production, cytotoxicity assays and oral toxicity assessment in a mouse model, demonstrated that PMC73 exhibited no pathogenic or toxic properties. Therefore, PMC73 represents a promising microbiome-based candidate with relevance to gout-associated hyperuricemia, warranting further in vivo and clinical investigations.
Molecular nutrition & food researchDiene France de de Souza, Gabriel Cipriano Rocha, Dairon Pérez Fuentes, Lucas Eduardo Oliveira Porto, Pedro Vitoriano Oliveira, Marliane de Cássia Soares da Si…
Selenium plays an important role in antioxidant defense and metabolic regulation. This study evaluated the effects of dietary supplementation with non-enriched and selenium-enriched Pleurotus ostreatus mushrooms, as well as selenized yeast, on selenium deposition and antioxidant responses in piglets, a relevant model for human nutrition. Sixty-four weaned piglets were fed control or supplemented diets for 21 days. Growth performance was not affected, indicating that the treatments were well tolerated. Selenium was higher in the loin of the supplemented groups than in the control group, whereas selenium concentration in the liver showed a numerical, but nonsignificant, increase in supplemented groups (p = 0.08), and no differences were observed in the kidney. Hepatic antioxidant activity was differentially modulated by dietary treatments. Glutathione peroxidase activity increased in all supplemented groups, whereas catalase activity increased only in piglets receiving selenium-enriched mushroom or selenized yeast, and superoxide dismutase activity increased only in the selenium-enriched mushroom group. Nitrite levels were reduced in all supplemented groups, while plasma antioxidant parameters remained unchanged. These findings indicate that dietary supplementation modulated hepatic antioxidant responses, although the relative contributions of selenium enrichment and mushroom bioactive compounds could not be determined. Trial Registration Number and Date of Registration: 106/2018.
Liver international : official journal of the International Association for the Study of the LiverYuling Zhan, Ying Wang, Tianlong Wei, Yingyuan He, Shiyi Lu, Qianqian Shao, Shasha Ma, Li Zhang, Xiaoqiang Mei, Yu Gao
BACKGROUND AND AIM: Liver fibrosis is a major global health burden with limited treatments. Emerging evidence suggests that metabolic dysregulation can create a state that makes the liver more prone to fibrosis. Carnitine, synthesized by γ-butyrobetaine hydroxylase (BBOX1), is crucial for fat metabolism, but the role of the BBOX1-carnitine axis in liver fibrosis is unclear. This study aimed to elucidate the functional impact of BBOX1 deficiency on hepatic fibrogenesis and to delineate the underlying mechanistic pathway. METHODS: We analysed human liver transcriptomic data. Bbox1 knockout (KO) mice and wild-type (WT) littermates were subjected to thioacetamide (TAA)-induced liver fibrosis, with or without dietary L-carnitine supplementation. Comprehensive analyses included metabolomic and transcriptomic profiling, histopathological evaluation, and focused investigation of calcium-dependent signalling pathways. RESULTS: BBOX1 expression was significantly downregulated in human cirrhotic livers and correlated with reduced systemic carnitine levels. Bbox1-KO mice exhibited profound hepatic carnitine depletion and a metabolically primed state. With TAA challenge, KO mice developed exacerbated liver fibrosis and inflammation compared to WT controls. This susceptibility was driven by the aberrant activation of the TRPC6-Ca2+/CAMK2B-inflammatory signalling axis. Moreover, dietary L-carnitine supplementation completely rescued the aggravated fibrotic phenotype in KO mice. CONCLUSION: BBOX1 is a key regulator of liver carnitine metabolism. Its deficiency creates a pro-fibrotic state by abnormally activating the TRPC6-Ca2+/CAMK2B pathway. Our findings position carnitine as a protector of calcium balance in the liver and identify L-carnitine supplementation as a potential targeted treatment to slow fibrosis progression.
Scandinavian journal of medicine & science in sportsBernardo R Norte, Alex Hickman, Antonio Muñoz Megias, Erick Mosquera-Lopez, Stéphane Bermon, Frédéric Garrandes, Paolo E Adami, Kelsie O Johnson, Elizabeth Mah…
Sodium bicarbonate (SB) ingestion may improve high-intensity exercise performance in efforts that range from 1 to 60 min; however, to date, no studies have investigated the effects of SB supplementation during exercise, nor its potential to attenuate the fatigue-induced decline in parameters of the power-duration curve during prolonged exercise (i.e., durability). This study examined the effects of bicarbonate (BI) and carbohydrate (CHO) co-ingestion via a novel gel format during exercise on subsequent sprint and time-trial (TT) performance in cyclists. Eleven trained cyclists took part in this randomized, crossover study. Following one visit to establish a non-fatigued power profile (3 × 6-s sprints, 2-min TT and 12-min TT cycling performance), participants completed two experimental trials consisting of 3 h cycling at 95% gas exchange threshold and ingested CHO at a rate of 80 g·h-1 with (CHO + BI; 18 g of SB and 2 g of potassium bicarbonate) or without BI co-ingestion (CHO). Participants repeated the same power profiling protocol after the 3 h submaximal exercise. Performance in the 12-min TT was improved in the CHO + BI condition compared with CHO (+12 W; p = 0.01, g = 1.07). Mean power output in the 6-s sprints (+12 W; p = 1.00, g = 0.18) and 2-min TT (+6 W; p = 0.888, g = 0.32) were not significantly different between CHO + BI and CHO. There were no differences in gastrointestinal symptoms between conditions. These data suggest that BI and CHO co-ingestion during prolonged exercise via a novel energy gel format improves subsequent 12-min TT performance in a fatigued state with minimal gastrointestinal discomfort.
A vegetable-based probiotic drink provides an alternative to dairy products for delivering beneficial microorganisms. This study was conducted to develop a fermented probiotic drink using cucumber juice. The probiotic starter culture used was Lacticaseibacillus casei NCDC-17. The fermentation process was optimized to enhance antioxidant activity, total phenolic content, and microbial viability. A rotatable central composite design using response surface methodology was used to set up the experimental design. The independent variables for the optimization were incubation temperature (30-45 °C), pH (5-9), and inoculum size (2-5%). The optimal fermentation conditions were observed to be incubation temperature 37.5 °C, pH 7, and inoculum size 3.5%. The results showed that the pH, total soluble solids, total flavonoids, and total sugar content were decreased after the fermentation. It was observed that the total phenolic content, and antioxidant activity were increased to a significant level after the fermentation. Results revealed that the fermented drink inhibits the key enzymes (alpha-amylase, and alpha-glucosidase) related to diabetes. The volatile compounds were identified using Gas Chromatography-Mass Spectrometry. A total of 54 distinct volatile compounds were identified following the fermentation process, indicating significant biochemical transformation and metabolic activity of the microbial culture. Cell-free supernatant of the drink exhibited antimicrobial activity with the highest and lowest inhibition against Escherichia coli (14 mm), and Staphylococcus aureus (11 mm), respectively. The fermented sample was evaluated for its cytotoxic potential against MCF-7 human breast cancer cell lines. The fermented sample exhibited marked growth inhibitory effects, against MCF-7 cell lines. Sensory evaluation was performed using a 7-point hedonic scale to evaluate attributes such as appearance and colour, mouth feel, aroma and flavor, taste, and overall acceptability. Results showed that the probiotic drink was well accepted.
The Lancet. OncologyAli Moradi, Rahul Winayak, Sumanta Kumar Pal
The gut microbiome is increasingly recognised as a clinically modifiable determinant of efficacy and toxicity across systemic cancer therapies, with the most mature evidence in patients receiving immune checkpoint inhibitors (ICIs). The composition and function of intestinal microbes can influence treatment outcomes by affecting immune priming, antigen presentation, host-microbial co-metabolism, drug biotransformation, and epithelial barrier integrity. In melanoma, non-small-cell lung cancer, and renal cell carcinoma, higher microbial diversity, ecological stability, and enrichment of immunostimulatory pathways have been associated with improved ICI response and survival. By contrast, antibiotics and proton pump inhibitors are linked to inferior outcomes because they disrupt the microbiome. Microbiome-directed interventions, including faecal microbiota transplantation, dietary modifications, prebiotics, probiotics, and live biotherapeutic products, are undergoing clinical testing but remain at the investigational stage. This Review synthesises current evidence linking the intestinal microbiome to anticancer therapy outcomes, evaluates strategies and challenges for therapeutic modulation of the microbiome, and introduces emerging insights into the mycobiome.
Fish physiology and biochemistryQingchao Shi, Jingping Luo, Jiang Xie, Yi Liu, Peng Hu, Qiang Lai, Chuanjie Qin
Feeding oxidized fish oil to cultured fish harms their intestine, but whether pyrroloquinoline quinone (PQQ) can counteract this damage had not been explored. This 56-day study investigated the protective effects of dietary PQQ against oxidized fish oil-induced intestinal injury in juvenile yellow catfish (Pelteobagrus fulvidraco). Four hundred and eighty yellow catfish (initial weight approximately 12 g) were randomly assigned to four groups in triplicate: control (fresh fish oil), PQQ (fresh oil + 5 mg/kg PQQ), OFO (oxidized oil), and PFO (oxidized oil + 5 mg/kg PQQ). Fish fed OFO diet showed significantly reduced intestinal lipase and trypsin activities, lower antioxidant capacity (total antioxidant capacity, superoxide dismutase, catalase), higher malondialdehyde content, shorter and fewer mucosal folds, upregulated pro-inflammatory cytokines (interleukin-1β, interleukin-8, and tumor necrosis factor-α), downregulated transforming growth factor-β, and a disrupted gut microbiota. Dietary PQQ supplementation in the OFO diet largely reversed these adverse effects, restoring most parameters to levels comparable to the control group. PQQ also reversed the OFO-induced increase in Firmicutes and decrease in Proteobacteria and restored the relative abundances of Pseudomonas, Variovorax, Enterobacter, and Candidatus Arthromitus to levels comparable to the control group. Taken together, PQQ effectively protected the juvenile yellow catfish intestine from oxidized fish oil-induced damage by improving digestion, boosting antioxidant defenses, reducing inflammation, and rebalancing the gut microbiota. PQQ is therefore a promising functional feed additive to mitigate lipid oxidation-related problems in aquafeeds.
Journal of the International Society of Sports NutritionRichen Sun, Mingxin Su, Xiaolong Xu, Nan Wang, Zhiyanguan Li, Xiaoning Sun, Weilong Lin, Hengtong Wang
OBJECTIVE: To evaluate the relative effects of dietary supplements, the certainty of evidence, and the robustness of findings within separate networks for peak power (PP), relative peak power (RPP), vertical jump (VJ), and countermovement jump (CMJ). METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were systematically searched, with the final search conducted on September 8, 2026. Eligible studies were randomised parallel-group and crossover controlled trials published in English through August 31, 2026, involving healthy individuals with physical activity or training backgrounds. Four separate Bayesian random-effects networks were constructed. Effects were assessed using mean differences (MDs) in change scores, 95% credible intervals (CrIs), and prediction intervals. Risk of bias and certainty of evidence were assessed using RoB 2 and CINeMA, respectively. Subgroup analyses, network meta-regression, and sensitivity analyses were also conducted. This review was retrospectively registered in PROSPERO (CRD420261283835). RESULTS: A total of 119 studies were included. The PP, RPP, VJ, and CMJ networks comprised 47, 33, 31, and 44 studies, respectively, with some studies contributing to more than one outcome. Compared with placebo, β-hydroxy-β-methylbutyrate (HMB) yielded MDs of 64.70 W (95% CrI: 19.15 to 110.50) for PP and 0.84 W·kg-1 (95% CrI: 0.42 to 1.28) for RPP. Favourable effects were also observed for β-alanine on PP and for creatine and vitamin D on RPP. Iron supplementation yielded an MD of 6.81 cm (95% CrI: 0.84 to 12.83) for VJ, supported by only one direct study. For CMJ, betaine yielded an MD of 3.72 cm (95% CrI: 1.24 to 6.18); the 95% CrIs for palmitoylethanolamide, caffeine combined with Rhodiola rosea, creatine, multi-ingredient supplements, and caffeine also excluded zero. The HMB findings for RPP remained relatively stable across multiple sensitivity analyses, whereas some other favourable comparisons had prediction intervals that included zero or showed attenuated findings in sensitivity analyses. Exploratory associations with training level and sport were observed for RPP, although interpretation was limited by sparse evidence and imbalanced covariate distributions. Of 1,636 pairwise comparisons, 17 were rated as moderate, 55 as low, and 1,564 as very low certainty. The HMB-versus-placebo comparisons for both PP and RPP were rated as moderate certainty. CONCLUSIONS: Some supplements showed favourable effects within their respective networks, with the HMB findings for RPP remaining relatively stable. However, direct evidence was limited, and the certainty of evidence was very low for most comparisons. Findings should be interpreted in the context of the populations and supplementation regimens studied. Differences between networks cannot establish that outcome type modifies supplementation effects, and rankings alone should not be used to guide individualised supplementation regimens.
MicrobiologyOpenMd Moklesur Rahman, Awis Qurni Sazili, Siti Aqlima Ahmad, Khalilah Abdul Khalil, Mohammad Rashedi Ismail-Fitry, Md Sazedul Karim Sarker
The rise of multidrug-resistant (MDR) pathogens presents a major challenge to food safety, particularly in preservation approaches. Lactic acid bacteria (LAB) gain probiotic recognition by effectively controlling MDR pathogens using antimicrobial substances (AMSs) and bacteriocin-like inhibitory substances (BLISs). The study evaluated the probiotic properties and AMS production potential of five LAB strains: Lactiplantibacillus plantarum NBRC 3070 (LP), Lactobacillus acidophilus ATCC 4356 (LA), Lacticaseibacillus casei ATCC 393 (LC), Lacticaseibacillus rhamnosus GG ATCC 53103 (LGG), and Bifidobacterium animalis subsp. lactis ATCC 27673 (BAL). AMS was extracted from neutralized and concentrated cell-free supernatant and tested for antimicrobial activities against common foodborne pathogens using minimum inhibitory concentrations (MICs). All LAB strains showed antagonistic activity, with LP demonstrating the most substantial antagonism. Four strains are resistant to multiple antibiotics but remain susceptible to azithromycin and tetracycline, while LP is resistant to all tested antibiotics. LP and LC demonstrated the highest probiotic potential based on cell surface hydrophobicity and aggregation abilities. Optimal AMS activity (85.36%-91.29%) occurred between 24 and 36 h at 37°C or 28-48 h at 30°C. LGG exhibited the highest AMS activity with the lowest MIC against Salmonella enterica serovar Typhimurium. Enzyme sensitivity confirmed the peptide nature of BLIS produced by BLIS from LP, LA, LC, and LGG. In conclusion, LAB strains demonstrated significant probiotic traits and the ability to produce AMS, especially BLIS, from four strains, with LP and LC showing the most potential. These findings support their application as natural biopreservation against MDR pathogens; however, further validation in the food system is required.
Journal of biomedical materials research. Part AUlvi Suleymanzade, Yağmur Damla Demir, Dilek Tepeli, Tuğba Ezgi Şahin, Nermin Seda Kehr
Hypoxia and chronic inflammation have an interdependent relationship, as they stimulate each other. Under inflammation, hypoxia occurs in tissues and under hypoxia, transcription factors induce overproduction of pro-inflammatory cytokines, causing the chronic inflammatory process. There are very few studies that combine O2 with anti-inflammatory agents to simultaneously reduce the effects of hypoxia and inflammation. However, despite the important role of probiotic metabolites in regulating pro-inflammatory cytokines, none of these studies have addressed the combined use of O2, anti-inflammatory agents, and probiotic metabolites to effectively inhibit the harmful effects of hypoxia and inflammation. In this context, we report a biomaterial (GA-RutPMOF-CAP) consisting of a GelMA-Alginate (GA) hydrogel matrix incorporating rutin-loaded, perfluorocarbon-functionalized periodic mesoporous organosilica (RutPMOF) nanoparticles and probiotic-loaded alginate microcapsules (CAP), capable of delivering sustained O2, probiotic-derived metabolites, and pH-sensitive anti-inflammatory drug release. GA-RutPMOF-CAP, which provides approximately 90% release of the anti-inflammatory drug (Rut) at pH 6.0, > 5% O2 release within the first 5 days under hypoxic conditions, and release of probiotic metabolites over a 7-day incubation period. GA-RutPMOF-CAP does not increase the production of reactive oxygen species (ROS) during 1 and 7 day incubation periods under hypoxic conditions. Furthermore, GA-RutPMOF-CAP supports cell viability under hypoxia and promotes a decrease in TNF-α levels under LPS-stimulated normoxic conditions; this demonstrates that GA-RutPMOF-CAP has beneficial effects on cells under inflammatory-like conditions.
Asia Pacific journal of clinical nutritionQiancheng Cao, Yujie Feng-Gao, Yanan Chen, Wei Li, Chuanshi Hu, Yifei Cao, Xiao Yan, Rong Chen, Xianrong Xu, Fuzhi Lian
BACKGROUND AND OBJECTIVES: Iron is essential but potentially toxic; both deficiency and overload may affect aging. Population-level evidence linking iron exposure to biological aging is limited, and aging-based optimal iron ranges are undefined. We examined associations of total, dietary, and supplemental iron intake and serum iron with three biological age (BA) measures and derived optimal ranges. METHODS AND STUDY DESIGN: We analyzed 13,284 U.S. adults (≥20 years) from NHANES 2007-2010 and 2015-2018. BA deviations (PA, GoldBA, LightBA) were derived from clinical biomarkers. Weighted linear and restricted cubic spline (RCS) models assessed associations; optimal ranges were exposure intervals with significantly beneficial associations. Models adjusted for demographics, lifestyle, comorbidities, and diet quality. Subgroup analyses examined sex, age, menopause, and chronic disease. RESULTS: Dietary iron was associated with younger BA (PA β = -0.07; GoldBA β = -0.09 per 2-fold increase), whereas supplemental iron accelerated aging above 18 mg/day (GoldBA β = 0.35 for >18 mg/day). Serum iron showed the strongest benefit (GoldBA β = -0.25 per 2-fold increase), with a U/J-shaped optimal range of 15.2-18.8 µmol/L. Optimal ranges were also identified for total iron (15.7 - 37.3 mg/day) and dietary iron (≥13.6 mg/day). The optimal serum iron range varied by subgroup (wider in postmenopausal women and those with chronic diseases; interaction p <0.05). CONCLUSIONS: The iron-aging relationship is source-dependent: dietary iron is protective, supplemental iron >18 mg/day is detrimental, and serum iron 15.2-18.8 µmol/L is optimal. Optimal ranges should be stratified by population.