McKenna W Box, Charles Marchese, Troy B Puga, John T Riehl
{"title":"Dietary Supplements (Nutraceuticals) for Improving Adult Fracture Healing Outcomes: A Narrative Review of Current Evidence and Gaps.","authors":"McKenna W Box, Charles Marchese, Troy B Puga, John T Riehl","doi":"10.1080/19390211.2026.2624110","DOIUrl":"10.1080/19390211.2026.2624110","url":null,"abstract":"<p><p>Fracture healing (fracture union) is a central goal of adult orthopedic trauma care. Patients frequently use dietary supplements (nutraceuticals) during fracture recovery to reduce the risk of delayed union and nonunion. However, clinicians have limited guidance from high-quality clinical trials and a large body of preclinical evidence. Malunion and nonunion can cause repeated surgeries, disability, and high costs. Nutraceuticals such as protein, amino acids, collagen, calcium, vitamin D, magnesium, zinc, vitamin C, omega-3 fatty acids, and creatine are considered adjuncts in fracture healing, influencing collagen synthesis, mineralization, inflammation, and muscle health. Animal studies show mixed results but suggest benefits. Human evidence primarily involves proteins, amino acids, vitamin D, and calcium, with mixed effects on healing and radiographic union, and small studies on magnesium, zinc, and vitamin C. Early data on magnesium and zinc suggest potential benefits for early healing, but evidence remains limited. No adult trials directly assess collagen, omega-3s, or creatine, highlighting the need for more well-designed studies with standard outcomes. Evidence regarding the role of these nutraceuticals in fracture prevention or bone density is used as background and for hypothesis development when direct evidence of fracture is scarce. We identify patient groups most likely to benefit, such as older adults with malnutrition, low protein intake, vitamin D deficiency, or fragility fractures. We also discuss practical considerations for perioperative supplement counseling and highlight key evidence gaps to inform future fracture-healing research.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"306-330"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brandon E Davis, Ian Young, Joseph C Giglotti, Jianbo Yao, Janet C Tou
{"title":"The Impact of Whey and Soy Protein Supplementation on Resistance Training in Young Adults: A Systematic Review and Meta-Analysis.","authors":"Brandon E Davis, Ian Young, Joseph C Giglotti, Jianbo Yao, Janet C Tou","doi":"10.1080/19390211.2025.2604679","DOIUrl":"10.1080/19390211.2025.2604679","url":null,"abstract":"<p><p>Protein supplementation, particularly whey and soy protein, are widely used by individuals engaged in resistance exercise training (RET) to enhance lean body mass (LBM) and muscle strength. However, their effectiveness remain unclear due to conflicting study results. This systematic review and meta-analysis evaluated the effect of whey and soy protein supplementation on amino acid bioavailability, LBM, and strength performance in healthy young adults engaged in RET. Database searches were conducted in Cochrane, EBSCO Host, PubMed, and Scopus from inception to October 19, 2024 using a pre-defined search strategy. Initial screening resulted in a total of 1,813 studies that met the eligibility criteria. The inclusion criteria required participants to be trained or untrained young adults aged 18-30 years engaged in RET and taking either whey or soy protein in the form of concentrate or isolate with the primary outcome of LBM and secondary outcomes of bench press, squat, or plasma essential amino acid (EAA). The studies were assessed for risk of bias using the Cochrane RoB 2 tool, and a meta-analysis was conducted using a random-effects model. A total of 12 studies with 261 participants were included after full-text screening with the main reason for exclusion being wrong population. The analysis found no significant effect of either whey or soy protein supplementation on LBM. However, protein supplement increased peak plasma total EAA with whey protein significantly improved bench press (mean difference [MD] 8.87; 95% CI: 5.95-11.79) and squat performance (MD 9.60; 95% CI: 5.61-13.60), with low to no heterogeneity. These findings suggest whey protein supplementation can enhance strength without significantly altering LBM in young adults. However, further large-scale, high-quality randomized controlled trials are needed to establish definitive conclusions on the effects of protein supplementation RET. The review was registered August 30, 2024 in PROSPERO (CRD42024598070).</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"150-174"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nootropic Supplements and Exercise: Patterns and Perceptions of Cognitive Enhancer Use in Physically Active Individuals.","authors":"Joseph T Pastina, Laura K Stewart","doi":"10.1080/19390211.2025.2589784","DOIUrl":"10.1080/19390211.2025.2589784","url":null,"abstract":"<p><p>'Nootropic' describes compounds that enhance cognition. Dietary supplement companies leverage this concept as a descriptor for product marketing. Given that half of all American adults, as well as many active individuals, use a dietary supplement, the purpose of this study was to explore nootropic use in physically active individuals. Nootropic use was evaluated <i>via</i> an online survey. Preferred nootropics, dose, frequency, reasons for use, and perceived effects were evaluated. In total, 152 individuals (men <i>n</i> = 86, women <i>n</i> = 64, other <i>n</i> = 2; mean ± SD age = 27.42 ± 7.66) were eligible for analysis. Means, standard deviations, and percentages were determined, and chi-square (χ<sup>2</sup>) tests of independence were used to determine significant associations related to nootropic type, exercise characteristics, use tendencies, and perceived positive or negative effects (<i>p</i> < 0.05). Thirty-six nootropics were reported, with caffeine (21.7%, <i>n</i> = 122), creatine (9.8%, <i>n</i> = 55), docosahexaenoic acid (DHA, Omega 3) (7.0%, <i>n</i> = 39), L-theanine and nicotine (both 6.6%, <i>n</i> = 37), and ashwagandha (6.1%, <i>n</i> = 34) the most frequently used. The most common reason for use was to increase energy and motivation (34.8%, <i>n</i> = 81). Those who predominantly engaged in weight training were more likely to use amino acids, peptides, and their derivatives (<i>p</i> < 0.001). Those who use their respective nootropics more frequently perceived the nootropic to be more effective (<i>p</i> < 0.001). This survey suggests that nootropic use is common in active individuals for diverse reasons that go beyond cognition enhancement.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"23-41"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai Zheng, Weidi Wang, Jiaohua Dai, Li Jian, Xiujuan Zhao
{"title":"Urine Metabolomics Reveal Quercetin May Improve Metabolic Diseases and Alleviate Brain Inflammation Through Modulation of the NF-κB/NLRP3 Pathway.","authors":"Kai Zheng, Weidi Wang, Jiaohua Dai, Li Jian, Xiujuan Zhao","doi":"10.1080/19390211.2025.2597495","DOIUrl":"10.1080/19390211.2025.2597495","url":null,"abstract":"<p><p>Depression is a mental disorder, and the complexity of its pathogenesis affects the treatment and prevention of depression. Flavonoids possess a variety of biological effects, including antidepressant properties. Quercetin, a natural flavonoid, exhibits antioxidant, antidepressant and anti-inflammatory effects. This research investigated the antidepressant properties of quercetin on rats induced by chronic unpredictable mild stress through untargeted metabolomics. A total of 96 rats were randomly allocated across six groups: control group, quercetin-treated groups receiving distinct dosages (10 and 50 mg/kg bw, respectively), depression model group, and different dosages of quercetin intervention in the depression model. During the 8 wk chronic unpredictable mild stress modeling process, quercetin was administered to the rats via gavage once daily. After 8 wk modeling, rat urine samples and prefrontal cortex were collected for untargeted metabolomics research and related detection, respectively. 19 differential metabolites were identified in the urine of chronic unpredictable mild stress-induced rats, and pathway analysis indicated metabolic disorders in rats, including arachidonic acid metabolism and amino acid metabolism. This study found that the elevation of urinary PGE2 and LTB4 is closely associated with the activation of the NF-κB/NLRP3 pathway in the PFC of chronic unpredictable mild stress-induced rats. Metabolomics reveals that quercetin can ameliorate metabolic disorders induced by chronic unpredictable mild stress through multiple pathways, and inhibit the activation of the NF-κB/NLRP3 pathway in the PFC by exerting anti-inflammatory and antioxidant effects. This study offers novel insights into the role of quercetin for the prevention and management of depression.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"58-75"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ginger (<i>Zingiber Officinale</i>) Supplementation and Biomarkers of Cardiovascular Disease - A Systematic Review.","authors":"Shrin Rjabi, Nasrin Dabirian, Reza Amani-Beni, Masumeh Taghavi, Moein Askarpour","doi":"10.1080/19390211.2025.2583512","DOIUrl":"10.1080/19390211.2025.2583512","url":null,"abstract":"<p><p>Ginger (<i>Zingiber officinale</i>) is one of the most widely used plant extracts and has been associated with improvements in biomarkers relevant to cardiovascular disease. Given the global burden of cardiovascular disease, this systematic review of randomized controlled trials aimed to evaluate the effects of ginger (<i>Zingiber officinale</i>) supplementation on biomarkers of cardiovascular disease. A systematic search of PubMed, Scopus, Web of Science Core Collection, and Google Scholar was performed up to January 2025 to identify eligible RCTs evaluating ginger supplementation. Outcomes included lipid profile, glycemic markers, blood pressure, inflammatory indicators, and liver enzymes. Data were pooled using weighted mean differences (WMDs). Subgroup and meta-regression analyses were conducted. Forty-one RCTs were included. Ginger supplementation was effective in improving FBS (WMD = -12.79 mg/dL; 95% CI = -18.57), insulin (WMD = -1.33 µIU/ml; 95% CI = -1.94, -0.71), HOMA-IR (WMD = -0.51; 95% CI = -0.68, -0.33), HbA1c (WMD = -0.68%; 95% CI = -1.00, -0.36), TG (WMD = -11.98 mg/dL; 95% CI = -23.27, -0.69), LDL (WMD = -4.55 mg/dL; 95% CI = -8.43, -0.68), HDL (WMD = 0.80 mg/dL; 95% CI = 0.01, 1.59), SBP (WMD = -2.72 mmHg; 95% CI = -5.25, -0.19), and ICAM-1 (WMD = -20.26 ng/ml; 95% CI = -40.49, -0.03). Ginger supplementation was not effective on the remaining outcomes. Ginger supplementation may improve several biomarkers of cardiovascular disease, with stronger effects in unhealthy individuals. Further studies are required to establish a clear cutoff for optimal dosage and intervention duration.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"118-149"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chronic Latent Magnesium Deficiency and an Unbalanced Calcium-to-Magnesium Ratio Impact Fetal Development and Maternal Health.","authors":"Deanna J Nelson, Laura J Sommerville","doi":"10.1080/19390211.2026.2624107","DOIUrl":"10.1080/19390211.2026.2624107","url":null,"abstract":"<p><p>During pregnancy, a mother experiences increased metabolic demands to meet the needs of the fetus. A mismatch between these demands and nutrient intake can result in a host of developmental abnormalities to the fetus and health risks to the mother. Several studies have reported strong correlations between deficiency of the essential mineral, magnesium (Mg), and many pregnancy complications, including intrauterine growth restriction, preeclampsia, gestational diabetes, and preterm delivery. Mg also impacts fetal programming and disease presentation in childhood and adulthood, showing that aberrant Mg levels <i>in utero</i> have far-reaching consequences. In this narrative review and commentary, we evaluated recently published data to identify a range of serum Mg concentrations that may reflect chronic latent Mg deficiency (0.7-0.85 mmol/L). We then evaluated independent studies that reported on the relationship between Mg levels and pregnancy outcomes to assess whether this cutoff may help identify patients at risk for adverse events and inform therapeutic strategies. Our analysis showed that chronic latent Mg deficiency coupled with a molar ratio of serum calcium to serum Mg >3 may indicate increased risk to mother or fetus. Given the high social and economic burdens of pregnancy complications, nutritional supplementation that includes Mg at all stages of pregnancy may be a safe and cost-effective way to mitigate the risk of adverse outcomes for mother and child.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"268-289"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zarna Raichura, Kelli L McDonald, Savanna DePriest, Madison Dupre, Meredith Almy, Kristen Hansen, Julia M Salamat, Satyanarayana R Pondugula, Angela I Calderón
{"title":"Evaluation of <i>in Vitro</i> Cytotoxicity and Induction Potential of Açaí (<i>Euterpe oleracea)</i> Extracts in Human Hepatocytes.","authors":"Zarna Raichura, Kelli L McDonald, Savanna DePriest, Madison Dupre, Meredith Almy, Kristen Hansen, Julia M Salamat, Satyanarayana R Pondugula, Angela I Calderón","doi":"10.1080/19390211.2026.2615924","DOIUrl":"10.1080/19390211.2026.2615924","url":null,"abstract":"<p><p><i>Euterpe oleracea</i> Mart. (açaí) is a widely consumed botanical supplement marketed for antioxidant, anti-inflammatory, and antiproliferative properties. Despite its popularity, limited data exist on its ability to modulate drug-metabolizing enzymes and transporters-critical determinants of pharmacokinetic botanical-drug interactions. This study evaluated the cytotoxicity and induction potential of açaí extracts on cytochrome P450 (CYP450) enzymes and drug transporters using physiologically relevant <i>in vitro</i> models. Test samples included aqueous, acidic methanol, methanol, and ethanol extracts of açaí berry powder (Mountain Rose) and commercial capsules (Nature's Way, Natrol), selected to reflect consumer products and enhance translational relevance. Cytotoxicity was assessed using CellTiter-Glo<sup>®</sup> luminescent assay in sandwich-cultured human hepatocytes. Induction of CYP1A2, CYP2B6, CYP3A4, P-glycoprotein (P-gp), and organic anion transporting polypeptides (OATP1B1/B3) was evaluated at the mRNA level <i>via</i> RT-qPCR in the same hepatocyte model. Functional transporter activity was assessed using intracellular probe accumulation assays in LS174T human colon carcinoma cells, a complementary model for preliminary screening. A time- and dose-dependent reduction in hepatocyte viability occurred with specific extracts, notably MRAC (acidic methanol), MRME (methanol), MRET (ethanol), and F4AC (acidic methanol, Natrol). However, none significantly induced CYP450 or transporter expression. Preliminary functional assays also showed minimal impact on P-gp and OATP activity. While preliminary, this study provides a comprehensive evaluation of açaí-mediated modulation of key pharmacokinetic pathways and underscores the need for rigorous assessment of botanical extracts to better predict potential botanical-drug interactions.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"217-239"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blackcurrant Anthocyanin Supplementation Alters Exercise-Induced Substrate Utilization - A Systematic Review and Meta-Analysis.","authors":"Matthew D Cook, James J Bateman, Mark E T Willems","doi":"10.1080/19390211.2026.2624114","DOIUrl":"10.1080/19390211.2026.2624114","url":null,"abstract":"<p><p>Blackcurrant anthocyanins have been investigated for their effects on exercise‑induced substrate utilisation. Previous research has examined the influence of supplementation dose, duration, and exercise modality, with mixed findings. This systematic review and meta-analysis examined the effect of blackcurrant supplementation on exercising substrate utilisation. Electronic searches were conducted in PubMed, Web of Science, and EBSCOhost between the 1st May and 14th November 2025 using a predefined search strategy. Controlled trials investigating the effects of blackcurrant supplementation on fat and carbohydrate oxidation during exercise in physically active adults (18-65 years) were included. All forms, doses, and supplementation durations were eligible, provided outcomes were reported as absolute rates of substrate utilisation during exercise. Two authors independently extracted data and assessed for risk of bias using the Cochrane RoB 2 tool, with a random-effects meta-analysis undertaken on the mean difference between control or placebo and consumption of blackcurrant extract on exercise substrate utilisation. Searches returned 263 articles, with 15 studies included with 226 participants after full-text screening. Meta-analysis demonstrated blackcurrant extract to increase fat oxidation (0.042 g·min-1, <i>P</i> < 0.001) and decrease carbohydrate oxidation (-0.099 g·min-1, <i>P</i> = 0.012). Blackcurrant can increase fat oxidation and decrease carbohydrate oxidation during exercise. However, this finding is not consistent for individuals and factors such as training status, sex, dosage, duration of intake may determine responses. The review was registered on the 28th April 2025 in PROSPERO (CRD420251030222).</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"290-305"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Islam Husain, Mantasha Idrisi, Pankul Kotwal, Ikhlas A Khan, Shabana I Khan
{"title":"Ginger as a Modulator of Drug Metabolizing Enzymes and Transporters: Potential Implications for Herb-Drug Interactions.","authors":"Islam Husain, Mantasha Idrisi, Pankul Kotwal, Ikhlas A Khan, Shabana I Khan","doi":"10.1080/19390211.2025.2606752","DOIUrl":"10.1080/19390211.2025.2606752","url":null,"abstract":"<p><p>Ginger (<i>Zingiber officinale</i>) is one of the most widely used herbs, employed in various food preparations, beverages, and herbal medicines. In recent decades, the demand for commercial formulations of ginger, including herbal medicines, nutraceuticals, and botanical dietary supplements (BDS), has increased significantly, and these products are now readily available. Research indicates that a significant portion of the population regularly consumes ginger and its commercial products, often believing that these products are free from side effects due to their natural origin. However, recent preclinical and clinical studies indicate that ginger can interact substantially with various xenobiotic receptors (e.g. PXR, CAR and AhR), drug-metabolizing cytochrome enzymes (CYP3A4, 2C9, 2D6, 1A2, and GST), and drug transporters (P-gp, BCRP, OATP, and OCT). As a result, over-consumption may lead to herb-drug interactions (HDIs) that are often unnoticed but can sometimes require urgent medical intervention, especially in long-term patients. However, there is limited information available regarding its HDIs. This report outlines the basic concept of HDIs, explores the HDI potential of ginger phytochemicals, and presents clinical cases resulting from the indiscriminate consumption of ginger or its products. We believe this information proves valuable to average consumers, researchers, and policymakers.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"240-256"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of a Cranberry, Probiotic, and Vitamin C Supplement on Recurrent Urinary Tract Infections in Children-A Cohort Study.","authors":"John Dotis, Vasiliki Karava, Antonia Kondou, Vasileia Christodoulaki, Nikolaos Stergiou, Nikoleta Printza","doi":"10.1080/19390211.2026.2615923","DOIUrl":"10.1080/19390211.2026.2615923","url":null,"abstract":"<p><p>Recurrent urinary tract infections (UTIs) are common in children and may lead to long-term renal complications, especially in those with vesicoureteral reflux (VUR). Concerns about antibiotic resistance and side effects of prolonged antibiotic use underscore the need for safe, non-antibiotic alternatives. This prospective, self-controlled observational study evaluated a standardized combination of cranberry extract (36 mg proanthocyanidins daily), probiotics (<i>Lactobacillus rhamnosus</i> and <i>Bifidobacterium longum</i>), and vitamin C (250 mg daily) in 39 children aged 3-16 years, including a subgroup with mild-to-moderate VUR. UTI recurrence was compared before and after the 12-month study period. The supplement was administered for 6 months, followed by a 6-month observation period. Microbiological analyses assessed pathogen distribution. Safety and tolerability were monitored. The intervention significantly reduced UTI recurrence, with median episodes decreasing from 3 to 0 in children without VUR (<i>p</i> < 0.001) and from 2 to 0 in children with VUR (<i>p</i> < 0.05). Overall, 27 of 39 participants (69.2%) remained infection-free throughout follow-up, while the remaining participants experienced a reduced number of UTI episodes compared with the pre-supplementation period. <i>Escherichia coli</i> remained the predominant pathogen, while the diversity of other uropathogens changed minimally, indicating fewer infections rather than microbial shifts. The supplement was well tolerated, with mild gastrointestinal symptoms in 5 of 39 participants (12.8%) and no serious adverse events. Subgroup analyses showed consistent benefit across age and sex, with children having higher baseline UTI frequency experiencing the greatest reduction. A multi-component supplement of cranberry, probiotics, and vitamin C effectively reduced recurrent pediatric UTIs, decreased overall infection burden, preserved <i>E. coli</i> as the main pathogen, and was safe and well tolerated, including in children with mild-to-moderate VUR.</p>","PeriodicalId":15646,"journal":{"name":"Journal of Dietary Supplements","volume":" ","pages":"205-216"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}