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Moringa oleifera , a traditional Indian herb, is widely known for its capacity to induce antioxidant, anti-inflammatory and other chemoprotective effects in a broad range of biomedical models. These perspectives have led to an extensive number of studies using various moringa extracts to evaluate its capacity to protect biological systems from oxidative stress and to explore whether it could be used to slow the onset of numerous age-related conditions and diseases. Moringa extracts have also been applied to prevent damage to plants from oxidative and saline stresses, following hormetic dose–response patterns. The present paper provides the first integrated and mechanistically based assessment showing that moringa extracts commonly induce hormetic dose responses and that many, perhaps most, of the beneficial effects of moringa are due to its capacity to act as an hormetic agent.

Background: Osteoarthritis (OA) is characterized by cartilage and synovial inflammation as well as anomalous lower extremity leading to joint pain, and impairment in lifestyle and epidemic of obesity. This study aimed to use the Jumpstart Nutrition® supplement (JNS) for achieving symmetry of aberrant lower extremity and improving the outcome measures in the management of OA., Methods: This week-twelve registry included 108 patients treated with JNS mainly comprised of calcium, phosphorus, magnesium, vitamin-K 2 , coenzyme-Q 10 , vitamin-C, boswellic acids, and curcumin mixed with soy and whey proteins (experimental group) and 72 were treated with symptomatic slow-acting drugs (control group) for chronic OA confirmed with radiological images. The outcome measures (Visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, Knee-injury Osteoarthritis Outcomes Scale, and Body mass index), and anomalous lower extremity included bilateral: knee gaps between biceps femoris-short head and surface of the bed, diameters of muscles at the calf, the thigh, 4cm above and below the patella, angles of straight leg raising, knee- flexion and-extension in supine were evaluated with appropriate protocol at week-0 and at week-12 for both the groups., Results: After week-12, risk ratios of studied lower extremity, and mean ±standard deviation of all outcome measures were significantly improved (p<0.0001), and Kellgren-Lawrence scale (KLS) was upgraded to ≥2 in experimental group compared to control., Conclusions: This registry study indicates that JNS can be used to achieve symmetry of studied lower extremity and to improve the outcome measures safely as an effective management of OA patients confirmed with radiological images correlated with KLS., Competing Interests: The author declares that there are no conflicts of interest regarding the present study., (© The Author(s).)

Background: Military special operators, elite athletes, and others requiring uninterrupted optimal performance currently lack options for sleep and mood support without performance-inhibiting effects. Kavalactones, derived from the root of the kava plant ( Piper methysticum Forst), have been shown to elevate mood and wellbeing by producing a feeling of relaxation without addiction or cognitive impairment., Methods: In this placebo-controlled, crossover study (NCT05381025), we investigated the effects of 2 weeks of kavalactones use on cortisol (diurnal salivary), sleep (RSQ-W; Restorative Sleep Questionnaire, Weekly), mood (DASS-21; Depression Anxiety Stress Scale-21), and motivation state to expend (Move) or conserve (Rest) energy (CRAVE; Cravings for Rest and Volitional Energy Expenditure, Right Now) in a cohort of 15 healthy, physically fit young males engaged in a rigorous, two-a-day preparation class for special operations forces qualification., Results: Cortisol, sleep, and mood were within normal, healthy parameters in this cohort at baseline. This remained unchanged with kavalactones use with no significant findings of clinical interest. However, a statistically similar, positive slope for within-group Move scores was seen in both groups during kavalactones loading (first group Move slope 2.25, second group Move slope 3.29, p  = 0.299). This trend was seen regardless of order and with no apparent effects on the Rest metric (all p  ≥ 0.05). Moreover, a significant between-group difference appeared after 1 week of kavalactones use in the first phase ( p =  0.044) and persisted through the end of the first loading period ( p  = 0.022). Following the 10-day washout, this between-groups divergence remained significant ( p  = 0.038) but was reversed by 1 week after the crossover ( p =  0.072), with Move scores once again statistically similar between groups and compared to baseline at study end. Furthermore, the group taking kavalactones first never experienced a significant decrease in Move motivation state (lowest mean score 21.0, highest 28.6, all p  ≥ 0.05), while the group receiving kavalactones in the last 2 weeks of the study had Move scores that were statistically lower than baseline (lowest mean score 8.6, highest 25.9, all p  ≤ 0.05) at all time points but the last ( p  = 0.063) after 2 weeks of kavalactones exposure., Conclusions: We report a novel finding that kavalactones may support performance by maintaining or rescuing the desire to expend energy in the context of significant physical and mental strain in well-conditioned individuals, even in a context of already normal cortisol, sleep, and mood.

Objective: Dietary supplements (DSs) are commonly used supplements among children to support disease treatment, however, overuse and inappropriate prescription of outpatient DS can negatively affect health and treatment costs. This study aimed to evaluate DS use in outpatient treatment in children., Methods: The present study used a cross-sectional descriptive retrospective method based on data from 188,579 outpatient prescriptions of children for 1 year., Results: DSs were commonly prescribed in pediatric patients ≤ 5 years old (63.48%) with diagnosing respiratory, infectious, and gastrointestinal diseases (>50%). DS costs account for a high proportion (24.86%) of total outpatient prescription costs. In addition, pediatric prescriptions containing one DS product (88.16%) showed a higher rate than prescriptions containing two DS products (11.84%) with the main ingredients being vitamin D 3 (80.55%), vitamin B 6 (63.01%), vitamin B 1 (60.22%), and vitamin B 2 (59.04%), and calcium (51.0%). The majority of DS products contained multivitamins (69.52%) with DS containing ≥ 5 vitamins of 59.04% and DS containing 2-4 vitamins of 10.48%. Besides, non-compliance with DS prescribing guidelines for age (21.38%), dose (14.13%), and both age and dose (5.54%) was found primarily in highly prescribed DSs (vitamin-amino acid-mineral ingredients), pediatric patients <2 years old, prescriptions containing one DS product or multivitamins, and respiratory disease group (J and R04-09 ICD). The univariate and multivariate regression analyses showed that vitamin-mineral products and groups <2 years old were significantly associated with guideline-adherent DS prescribing for age and/or dose. Meanwhile, foreign DSs and vitamin-mineral ingredients of prescription showed significant associations with guideline-adherent DS prescribing for age or dose., Conclusion: Instructions for DS use regarding recommended age and maximum dosage may not be carefully considered by doctors due to belonging to an over-the-counter medicine group. Therefore, there is a strong need for a national public policy to prevent and control overprescribing and inappropriate prescribing of DS., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: 3,3'-diindolylmethane (DIM) is a phytonutrient derived from cruciferous vegetables that is an often-used supplement in the complementary and alternative medicine space. The most common goal for providers when recommending DIM to their patients is to alter estrogen metabolism, yet research into DIM's effect on the estrogen profile is lacking in the published literature. The objective of this study was to comprehensively evaluate DIM's effect on the urinary estrogen profile., Methods: In this retrospective cohort study, we analyzed data from a clinical laboratory, including urinary estrogen and estrogen metabolite concentrations. Analyte concentrations were determined from dried urine samples using a gas chromatography-tandem mass spectrometry assay. Individuals were separated into two groups, either reporting taking DIM (N = 909) or reporting not taking DIM (N = 18,385). Comparisons between individuals in these two groups were made using the Wilcoxon rank sum test. Additionally, we were also able to explore a subset of women who had laboratory results in the database before and after initiating DIM treatment (N = 53). In this subset, differences were assessed with Wilcoxon signed rank tests., Results: In the larger group that was separated into women reporting either DIM use or no use, significant differences were observed in the concentrations of almost every urinary estrogen and estrogen metabolite (with the only exception being 2-methoxyestrone) in the urinary estrogen profiles of those taking DIM compared to those not taking DIM (all P values < 0.001). In the smaller subset of individuals with results before and after initiating DIM use, differences were only seen in 4 of the urinary estrogens and estrogen metabolites (P < 0.001 for estrone, estradiol, estriol, and 16-hydroxyestrone). Differences in total estrogens were significant in both the larger group and the smaller subset (both with P < 0.001). Additionally, observed differences in the ratios of metabolites followed a similar trend with more significant differences observed in the larger group. Notably, the 2-hydroxyestrone:16-hydroxyestrone ratio increased significantly in both the larger group and the smaller subset with results before and after DIM use., Conclusions: The results of this study provide the most comprehensive evaluation to date of DIM's effect on the urinary estrogen profile. Additionally, the results demonstrate that the dried urine collection and accompanying assay used capture changes that are similar in direction, but not necessarily magnitude, to previous reports in the literature. Considered together, these two things highlight the clinical validity and utility of this approach to the evaluation of DIM supplementation and suggest the need for additional studies using this approach to fully understand the potential clinical utility of DIM., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the National University of Natural Medicine Institutional Review Board, and since all data analyzed in this data mining study were deidentified, the institutional review board determined that written informed consent could be waived. Consent for publication: Not applicable. Competing interests: M.N. is the founder and CEO of Precision Analytical, Inc. J.S. is an employee of Precision Analytical, Inc., (© 2024. The Author(s).)

Background; obesity and nonalcoholic fatty liver disease (NAFLD) reduce life expectancy; nonoperative interventions show poor results. Individually, chitosan (1% w / w ), acetic acid (AA 0.3-6.5% w / w ), and sepiolite clay (5% w / w ) attenuate high-fat-diet-induced obesity (DIO) via reduced energy digestibility and increased energy expenditure. Objectives; therefore, we hypothesized that a chitosan-sepiolite biocomposite suspended in AA would attenuate DIO and NAFLD to a greater extent than AA alone via its more substantial adsorption of nonpolar molecules. Methods; we tested this dietary supplement in C57BL/6J mice fed a high-fat diet (HFD) compared to an unsupplemented HFD and an HFD supplemented with a bile acid sequestrant (cholestyramine) or standalone AA. Results; biocomposite supplementation reduced DIO gain by 60% and abolished hepatic liver accumulation, whereas standalone AA showed mild attenuation of DIO gain and did not prevent HFD-induced hepatic fat accumulation. The biocomposite intake was accompanied by a lower digestibility (-4 point %) counterbalanced by increased intake; hence, it did not affect energy absorption. Therefore, DIO attenuation was suggested to be related to higher energy expenditure, a phenomenon not found with AA alone, as supported by calculated energy expenditure using the energy balance method. Conclusions; these results support further investigation of the biocomposite's efficacy in attenuating obesity and NAFLD, specifically when applied with a restricted diet. Future studies are needed to determine this biocomposite's safety, mechanism of action, and efficacy compared to its components given separately or combined with other ingredients.

Mild and persisting gastrointestinal symptoms (MPGS) as bloating, constipation or diarrhea are widespread in older adults and often accompanied by gut microbiota dysbiosis. Nutritional interventions help to regulate and restore microbiota and gut function. In this non-randomized continuous prospective cohort study, we evaluated the effects of a 21-day intervention using a dietary dairy-based supplement (AGIJOY™) on self-reported gastrointestinal (GI) symptoms, fecal microbiota composition and short chain fatty acids (SCFA) levels in a cohort of Chinese adults (N = 46, age 27-73) suffering from MPGS. Questionnaire data and fecal samples were collected at baseline (D0), on day 7 and 21 of intervention (D7 and D21). The results showed significant improvement in the self-reported GI symptoms on D21 and a gradual shift in the fecal microbiota composition. In the first week of intervention, the relative abundance (RA) of fecal bifidobacteria significantly increased and the RA of Bacteroides and Helicobacter decreased (p < 0.05). The levels of fecal SCFA remained unchanged during the study. To our knowledge, this is the first study testing the effect of this prebiotic and postbiotic containing milk-based supplement blend on gut microbiota and MPGS among Chinese population under a real living environment., Competing Interests: Declarations Competing interests The research being reported in this publication was supported financially by Mead Johnson Nutrition (Hong Kong) LTD. K.B. is employed by Mead Johnson Nijmegen (The Netherlands) and K.B and Y. Zhu are members of the Mead Johnson NHII (Guangzhou, PR China). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Institutional review board The study was conducted in accordance with the Declaration of Helsinki, and approved by the Chinese Academy of Science, Shenzhen Institute of Advanced Technology (SIAT) Institutional Review Board with identifier SIAT-IRB-230915-H0669. Informed consent Written informed consent was obtained from all subjects prior to the initiation of study procedures., (© 2024. The Author(s).)

Background/Objectives: The use of dietary supplements (DSs) has become common among fitness enthusiasts, aiming to enhance performance, recovery, and overall well-being. Methods : A cross-sectional study was conducted in the city of Beni Mellal from April to July 2024, assessed dietary practices, motivations for supplement use, and associated adverse effects among 420 survey participants. Results: The majority of dietary supplement users were aged 25-64 and had higher education levels. Colopathy (67.38%) was the most common eating disorder, followed by digestive (59.46%), inflammatory, and rheumatic diseases (53.50%). Dietary supplementation prevalence was 88.1%, with proteins (60.81%), medicinal plants (45.13%), and vitamins (42.70%) being the most consumed. Key motivations included supporting muscle, bone, and joint strength (musculoskeletal) (83.78%) and enhancing heart and lung function for cardiorespiratory health (82.43%). However, 28% of protein users experienced adverse effects, such as myalgia, gastralgia, palpitations, and insomnia. Multivariate linear regression indicated a significant negative association of creatine with effectiveness (β = -0.485, p = 0.001). Conclusions : Overall, while the benefits of dietary and sports practices are evident, the adverse effects associated with protein supplements highlight the necessity for enhanced nutrivigilance and nutritional education to ensure safe supplements.

To date, the only probiotic yeast with evidence of health-promoting effects is Saccharomyces cerevisiae var. boulardii . The expanded market including dietary supplements and functional foods supplemented with Saccharomyces cerevisiae var. boulardii creates an environment conductive to food adulterations, necessitating rapid testing to verify product probiotic status. Herein, qPCR-HRM analysis was tested for probiotic yeast identification. The effectiveness of the primer pairs' set was examined, designed to amplify heterogeneous regions in (a) rDNA sequences previously designed to identify food-derived yeast and (b) genes associated with physiological and genotypic divergence of Saccharomyces cerevisiae var. boulardii. Preliminary tests of amplicons' differentiation power enabled the selection of interspecies sequences for 18SrRNA and ITS and genus-specific sequences HO , RPB2 , HXT9 and MAL11. The multi-fragment qPCR-HRM analysis was sufficient for culture-dependent Saccharomyces cerevisiae var. boulardii identification and proved effective in the authentication of dietary supplements' probiotic composition. The identification of S. cerevisiae var. boulardii in complex microbial mixtures of kefir succeeded with more specific intragenus sequences HO and RPB2. The predominance of S. cerevisiae var. boulardii in the tested matrices, quantitatively corresponded to the probiotic-enriched food, was crucial for identification with qPCR-HRM analysis. Considering the reported assumptions, qPCR-HRM analysis is an appropriate tool for verifying probiotic-enriched food.

Diabetes is a global public health concern with increasing prevalence worldwide. Chromium (Cr), a trace element found in soil, water, and food, has been proposed to have a possible positive effect in glucose metabolism and diabetes mellitus prevention. However, the relationship between trivalent chromium [Cr(III)] exposure, mainly through the consumption of diet supplements, and type 2 diabetes mellitus (T2DM) remains controversial. An extensive systematic review of the current literature on randomized controlled studies (RCTs) was conducted from 1 January 2000, to January 2024 using the databases PubMed, Scopus, ScienceDirect, and Cochrane, with specific keywords and inclusion as well as exclusion criteria. After close screening of the research studies retrieved from the mentioned websites was conducted, the most related studies were included in the final systematic review. The studies were evaluated for the degree of relevance, quality, and risk bias, using appropriate quality assessment tools. Several of the included RCT studies reported possible benefits of Cr(III) supplementation, mainly in the form of chromium picolinate (CrPic), chromium yeast (CY), chromium chloride (CrCl 3 ), and chromium nicotinate (CrN). The dosage of chromium was between 50 and 1000 μg/day and it was consumed from 2 to 6 months. Glycemic control markers, including FPG, insulin, HbA1C, and HOMA-IR levels, significantly decrease following chromium supplementation, mainly in studies with a longer intervention period. Supplementing with chromium (Cr) indicated that could significantly improve lipid profile by raising high-density lipoprotein and lowering triglyceride and total cholesterol while having little effect on low-density lipoprotein. However, most research findings include significant limitations, such as inconsistent dosage and type of chromium, formulation of supplements, and study duration. Further well-designed and high-quality research is needed to fully understand the role of chromium dietary supplementation and the potential risks related to its mechanisms of action, type, and dose, in the prevention and treatment of type 2 diabetes mellitus., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Rapid growth has been found in the market of dietary supplements (DSs) in China. However, studies about the knowledge level, intentions, and behavior related to DS remained limited in the Chinese population. This study aimed to explore the knowledge level, perception, and practice toward DS among Chinese adults., Methods: This is a cross-sectional design among 1,714 participants aged between 18 and 65 years. A total of 54.1% of participants reported purchasing supplements in the past 6 months. Knowledge levels were assessed with a score from 1 to 10 based on correct answers to 10 binary questions about supplements., Results: Only 29.1% of participants answered seven or more questions correctly, while 7.9% answered three or fewer questions correctly. Participants with high and middle knowledge levels were more likely to seek medical advice when experiencing discomfort symptoms and were less likely to choose DS, with corresponding odd ratios (ORs) of 1.58 (95% CI: 1.16, 2.13) and 0.69 (95% CI: 0.52, 0.91) in high knowledge group and ORs of 1.36 (95% CI: 1.03, 1.80) and 0.96 (95% CI: 0.72, 1.30) in middle knowledge group ( P for trend  = 0.003 and 0.028, respectively). No significant differences were found in the motivation of DS use between knowledge levels. Although higher knowledge levels were associated with less spending on DS (OR high  = 0.69; 95% CI: 0.49, 0.99; OR middle  = 0.88; 95% CI: 0.64, 1.20; P for trend  = 0.038), it did not guarantee better and more accurate awareness toward DS use., Discussion: In conclusion, there is a growing demand for supplements among Chinese adults, but a significant gap between knowledge and behavior exists, affecting decision-making behaviors regarding DS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tan, Wang, Zhao and Zhao.)

Degradation of the endothelial glycocalyx in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to endothelial dysfunction and the development of cardiovascular disease. Herein, we tested the hypothesis that restoration of the endothelial glycocalyx with dietary supplementation of glycocalyx precursors (DSGP, containing glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan) improves endothelial function and other indices of vascular function in T2D. First, in db/db mice, we showed that treatment with DSGP (100 mg/kg/day) for four weeks restored endothelial glycocalyx length, as assessed via atomic force microscopy in aortic explants. Restoration of the glycocalyx with DSGP was accompanied by improved flow-mediated dilation (FMD) and reduced arterial stiffness in isolated mesenteric arteries. Further corroborating these findings, treatment of cultured endothelial cells with that same mixture of glycocalyx precursors promoted glycocalyx growth. Next, as an initial step to investigate the translatability of these findings, we conducted a pilot (n=22) double-blinded randomized placebo-controlled clinical trial to assess the effects of DSGP (3,712.5 mg/day) for eight weeks on endothelial glycocalyx integrity and indices of vascular function, including FMD, in Veterans with T2D. Contrary to the hypothesis, DSGP neither enhanced endothelial glycocalyx integrity nor improved vascular function indices relative to placebo. Together, these findings conceptually support the notion that restoration of the endothelial glycocalyx can lead to improvements in vascular function in a mouse model of T2D; however, DSGP as a therapeutic strategy to enhance vascular function in individuals with T2D does not appear to be efficacious.

Modafinil (brand name Provigil®) is a Schedule IV (U.S.) drug used for the treatment of narcolepsy and sleep disorders. It is also known to be used recreationally. Analogs of modafinil, including adrafinil, remain unapproved and/or unscheduled. The lack of scheduling has made these analogs a popular target for recreational use and inclusion in dietary supplements. However, the use of controlled substances (or their analogs) without the care of a physician presents a public health risk. Preliminary nontargeted analyses in our laboratory revealed the presence of adrafinil in several dietary supplements, highlighting the need for an analytical method to identify modafinil analogs in supplements. A liquid chromatography high resolution mass spectrometry (LC-HRMS) method was developed and validated to quantitate modafinil, plus four novel unscheduled modafinil analogs: adrafinil, CRL-40,940, CRL-40,941, and N-methyl-4,4-difluoromodafinil. This method was then applied to four samples of products marketed as dietary supplements collected via undercover purchase. These four products were marketed as nootropics or cognitive enhancers and labeled to contain adrafinil. Adrafinil was found in all four samples. The identification of modafinil analogs in this context is important so that consumers are not, knowingly or unknowingly, consuming these active pharmaceutical ingredients in products marketed as dietary supplements.

The Dietary Supplement Health and Education Act (DSHEA) of 1994 defined the FDA's statutory authority to regulate dietary supplement products as a category of food in the United States. As we celebrate 30 years post-DSHEA, it is important to reflect on its significance for public health, influence on the continuously evolving and expanding product category, the current regulatory framework, and potential opportunities or modernizing oversight to ensure a strong and well-regulated marketplace. An estimated three-fourths of U.S. consumers report use of dietary supplements, and the product market has grown substantially since the passage of DSHEA, from approximately 4,000 products in 1994 to 80,000+ present day. This growth represents a current $60 billion domestic and $200 billion international market for dietary supplements. Scientists, public health officials, health care providers, patients, consumer advocacy organizations, and the U.S. Food and Drug Administration have all called for reform to what has been described as 'outdated' regulation of dietary supplements. Advancing at an even faster rate is published scientific evidence in the space. This special issue of the Journal of Dietary Supplements comprises a collection of articles authored by academicians, legal scholars, representatives of U.S. government agencies, and industry scientists that critically examine the successes, challenges, and opportunities for improving specific aspects of DSHEA and domestic health policy. This editorial provides historical context and milestones of dietary supplement regulation in the U.S. post-DSHEA and offers an overview of the research contained within the special issue. Advancing toward a more transparent and safer marketplace requires trustworthy supply chains, increased adherence to quality standards, additional labeling requirements, and enhancement of post-market surveillance. This special issue seeks to contribute to the broader understanding of dietary supplement regulation and its future direction.

Purpose: To review the evidence on the effectiveness of dietary supplementation for retinitis pigmentosa (RP)., Methods: A literature search of the PubMed database was last conducted in January 2024 to identify published English-language original research on dietary supplementation for RP. Eligible compounds included products ingested orally containing nutrients intended to supplement the diet. Studies meeting eligibility criteria were assigned a level of evidence rating by the panel methodologist., Results: The search identified 283 citations, 15 of which met the assessment criteria. Two studies were rated level I, 11 studies were rated level II, and 2 studies were rated level III. All were single-center studies and were published between 1993 and 2022. The products evaluated included vitamin A, docosahexaenoic acid (DHA), lutein, vitamin E, goji berry (Lycium barbarum fruit) extract, and chlorogenic acid. Primary outcome measures were most commonly based on electroretinography (n = 7) or perimetry (n = 2) testing. Numerous studies highlighted data suggestive of possible efficacy for vitamin A, DHA, and lutein, yet these findings typically derived from secondary outcomes, evaluations of participant subsets, post hoc analyses, problematic interpretations of the data, or a combination thereof. Additionally, it was often unclear if the study findings represented clinically meaningful outcomes. No prominent safety concerns were reported in any study., Conclusions: No high-quality evidence was found to support the effectiveness of any form of dietary supplementation for RP. The findings underscore the challenges of studying this rare and slowly progressive retinal disease. Future studies should leverage the enhanced recruitment abilities from collaborative research networks to refine eligibility criteria while using novel, clinically meaningful endpoints., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Magnesium (Mg) is a vital element for various metabolic and physiological functions in the human body, including its crucial role in skeletal muscle health. Hypomagnesaemia is frequently reported in many muscle diseases, and it also seems to contribute to the pathogenesis of skeletal muscle impairment in patients with neuromuscular diseases. The aim of this scoping review is to analyze the role of Mg in skeletal muscle, particularly its biological effects on muscle tissue in neuromuscular diseases (NMDs) in terms of biological effects and clinical implications. This scoping review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. From the 305 studies identified, 20 studies were included: 4 preclinical and 16 clinical studies. Preclinical research has demonstrated that Mg plays a critical role in modulating pathways affecting skeletal muscle homeostasis and oxidative stress in muscles. Clinical studies have shown that Mg supplementation can improve muscle mass, respiratory muscle strength, and exercise recovery and reduce muscle soreness and inflammation in athletes and patients with various conditions. Despite the significant role of Mg in muscle health, there is a lack of research on Mg supplementation in NMDs. Given the potential similarities in pathogenic mechanisms between NMDs and Mg deficiency, further studies on the effects of Mg supplementation in NMDs are warranted. Overall, maintaining optimal Mg levels through dietary intake or supplementation may have important implications for improving muscle health and function, particularly in conditions associated with muscle weakness and atrophy.

This study investigated Vietnamese people's behavior and future intention to purchase medicines and functional foods online and their associated factors. From March to May 2023, a Google Form questionnaire was distributed via social networks and online platforms. Convenience and snowballing sampling methods were employed to recruit 1,305 Vietnamese people. In the past year, 50.3% of participants purchased at least one kind of medicine and/or functional foods online (medicines: 27.6%, functional foods: 45.1%). Among 656 buyers, nearly a third bought these products more than three times and only 5.9% felt dissatisfied with their previous experiences. This purchasing behavior was more prevalent among females, those married, having higher education levels, usually shopping online, having longer time of Internet use per day, and seeking health information on the Internet (p < 0.001). In addition, 77.5% of participants intended to purchase these products online in the future and 61.2% would introduce this kind of online purchase to other people. The purchase intention was significantly associated with the participants' previous experiences, area, contracting chronic diseases, and using the Internet for self-medication, while factors associated with the introducing intention included their education level, occupation, and previous experiences in online purchases (p < 0.001)., (© 2024. The Author(s).)

Reduced glutathione (GSH) is an endogenous tripeptide antioxidant which plays a crucial role in a variety of physiological and pathological activities. Although GSH is not present in any FDA-approved drug product, GSH dietary supplement products and compounded GSH drugs are available to patients in the US. Several incidents of toxicity have occurred in recent years due to endotoxin or otherwise contaminated GSH in compounded drugs. Efficient and sensitive analytical methods are needed for assessing and ensuring the quality of GSH substance and associated drug or dietary supplement products. Impurities A (L-cysteinylglycine), B (cysteine), C (oxidized L-glutathione) and D (γ-L-glutamyl-L-cysteine) are the main related impurities for GSH drug substance which have been detected and quantified by capillary electrophoresis and qNMR analytical procedures. However, there are no reported HPLC methods for detecting or quantifying the three main related impurities A, B and D even though numerous HPLC analytical methods have been reported for analyzing GSH and impurity C. In this report, an isocratic HPLC-UV analytical procedure was developed and validated for separating and identifying GSH and related impurities A-D as well as a newly identified degradant, L-pyroglutamic acid (pGlu), within 10 minutes with resolution (R S ) more than 3. The LOD and LOQ were determined to be 0.02 % w/w and 0.05 % w/w, respectively, for impurities A-D and pGlu. Importantly, the optimized HPLC analytical procedure for GSH assay does not have interference from impurities A, B and D, providing highly specific results compared to the commonly used iodine titration method. The newly validated analytical procedure was applied to assess different commercial GSH bulk substance samples. The results suggest that the analytical procedure described in this work is suitable for quality assessment of GSH samples., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Qin Shu reports financial support was provided by US Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Qin Shu reports a relationship with US Food and Drug Administration that includes: employment and funding grants. Mary Schleiff, Jingfan Chen, Cynthia Sommers, Jingyue Yang, Xiaohui Shen, Jason D. Rodriguez, David A. Keire report a relationship with US Food and Drug Administration that includes: employment, (Published by Elsevier B.V.)

Aims: Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over-the-counter turmeric supplements can cause drug-induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements., Methods and Results: We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37-66 years). Six patients (55%) were asymptomatic with abnormal liver function tests, while five patients (45%) presented with malaise and/or jaundice. Ten patients (91%) showed predominant transaminase abnormalities, while one exhibited predominant alkaline phosphatase elevation. Histologically, biopsies showed acute hepatitis (eight cases, 73%, including five pan-lobular and three zone 3-predominant inflammation), scattered lobular aggregates of histiocytes (two; 18%) and a chronic hepatitis pattern of injury (one; 9%). Mild bile duct injury was present in five biopsies (45%). All patients stopped ingesting turmeric supplements after presenting with liver injury, and four patients additionally received steroid therapy; liver function tests normalised in all patients. Roussel Uclaf causality assessment method (RUCAM) analysis estimated the likelihood of turmeric supplement-associated liver injury to be probable (eight cases) and possible (three)., Conclusions: Histological features in the 'possible' cases were consistent with drug-induced injury, highlighting the added benefit of histological analysis relative to RUCAM analysis isolation. This study underscores the need to obtain a full history of over-the-counter medications and supplements when investigating aetiologies for liver injury, including supplements purportedly containing innocuous compounds such as turmeric., (© 2024 John Wiley & Sons Ltd.)

Are all food ingredients, dietary supplement ingredients and even foods, required to meet the same safety standards? Are they all equally safe? If so, then why do the various categories have different expressions describing their safety, such as "reasonable certainty of no harm" for food ingredients and "reasonable expectation of no harm" for dietary supplement ingredients? The basis for these different expressions is that they are not standards of safety, but standards of proof of safety. Just as in criminal vs. civil courts, the threshold for proving guilt or fault is different, so too are there differences between various categories of consumer products regulated by the US Food and Drug Administration. This manuscript describes the threshold requirements for each standard, as well as to the identity of the decision makers on what is safe, their credentials as decision makers and the databases mandated for their use., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite the large number of sheep in Ethiopia, their productivity remains low, mainly due to inadequate and poor-quality feed. Therefore, this systematic review and meta-analysis study was conducted to evaluate the effect of dietary supplements on the growth performance and carcass yield indices of indigenous sheep in Ethiopia. This study included a total of 21 studies that used 533 sheep from 11 breeds. We used Meta-Essentials Version 1.5 to determine the effect sizes in a mixed-effects model at p < 0.05. The current meta-analyses revealed that dietary supplements had a positive and significant effect (p of Z ≤ 0.001) on the total dry matter intake (Hedges' g = 6.84 g/day/head), final body weight (Hedges' g = 3.65 kg/head), average daily gain (Hedges' g = 3.59 g/head), feed conversion efficiency (Hedges' g = 0.72 g/g), slaughter weight (Hedges' g = 2.56 kg/head) and hot carcass (Hedges' g = 2.73 kg/head) of sheep compared to the control. The meta-analysis suggests that sheep of different breeds and sexes that were fed supplemental diets responded differently. In addition, the subgroup analysis declared that dietary supplementation of legumes resulted in a higher magnitude of effect sizes for all response variables in sheep in comparison to sheep supplemented with concentrate and browse. We detected diverse heterogeneity across studies for all response variables that ranged between 0% and 96.65%. It can be concluded that dietary supplements had a positive and significant impact on feed efficiency, growth performance and carcass yield in indigenous sheep, particularly Afar sheep, followed by Arsi Bale and Washera sheep, in Ethiopia., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The potential effects of Astragalus polysaccharides (APS) were evaluated in coral trout ( Plectropomus leopardus ). Five APS levels (0%, 0.05%, 0.10%, 0.15%, and 0.20%) were added to the diet of coral trout, and a 56-day growth trial (initial weight 18.62 ± 0.05 g) was conducted. Dietary APS enhanced growth performance, with the highest improvement observed in fish fed the 0.15% APS diet. This concentration also enhanced the antioxidant capacity and immunomodulation of the fish by regulating the expression of genes associated with antioxidant enzymes and immune responses. Intestinal microbiota analysis revealed that APS supplementation significantly increased the Chao1 index and relative abundance of beneficial bacteria ( Firmicutes and Bacillus ). A high level of APS (0.20%) did not provide additional benefits for growth and health compared to a moderate level (0.15%). These findings indicate that an optimal APS dose promotes growth, enhances antioxidant activity, supports immune function, and improves intestinal microbiota in coral trout. Based on a cubic regression analysis of the specific growth rate, the optimal APS level for the maximal growth of coral trout was determined to be 0.1455%.

Background and Aims: Hypercholesterolemia leads to cardiovascular diseases and atherosclerosis. Previous studies have highlighted the crucial role of gut microbiota in alleviating atherosclerosis progression and reducing plasma cholesterol. However, the protective effects of Houttuynia cordata Thunb (HCT), a well-known fishy Chinese herb, against hypercholesterolemia and vasculopathy remain largely unknown. This study aims to explore the effects of HCT extracts on vascular health and gut microbiota in golden Syrian hamsters with hypercholesterolemia. Methods: The hypercholesterolemia hamster model was established by feeding with a high-cholesterol diet. Aqueous or ethanolic HCT extracts were mixed with diet and concurrently given to hamsters for Six weeks. Plasma lipid profiles were evaluated. Aortas were collected to detect fatty streak areas. Feces were collected to analyze the abundance of microorganisms in the gut microbiota. Results: HCT ethanolic extract treatment remarkedly decreased plasma levels of total cholesterol and high-density lipoprotein cholesterol in hypercholesterolemic hamsters. Notably, both aqueous and ethanolic extracts of HCT reduced atherosclerotic plaques in hamsters fed with a high-cholesterol diet. Strikingly, the effects of HCT ethanolic extract in reducing atherosclerotic plaques are greater than aqueous extract. Furthermore, at the phylum level, the relative abundance of Firmicutes was decreased in hamsters treated with aqueous and ethanolic extracts of HCT. By contrast, the abundance of Bacteroidetes was increased by HCT treatment. At the family level, HCT extract favourably modulated the relative abundance of Porphyromonadaceae and Bacteroidales&#95;S24-7&#95;group . These findings indicate that HCT extracts may facilitate the growth of short-chain fatty acids-producing bacteria to alter gut microbiota composition, contributing to the reduction of plasma lipid levels. Conclusions: This study offers evidence demonstrating the effects of HCT extracts on alleviating atherosclerosis and lowering plasma cholesterol levels in the male hypercholesterolemic hamster model, offering novel insights into the pharmacological effects and promoting the application of HCT. This study highlights the potential of HCT as a dietary supplement to alleviate atherosclerosis, lower plasma cholesterol, and modulate the abundance of microorganisms in gut microbiota.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age, and presents a significant challenge to the global population. This review provides comprehensive evidence of interventions, including food and dietary supplements, aimed at reversing PCOS and improving fertility outcomes. Various dietary supplements are known to cause metabolic changes and hormonal regulation and have a potential impact on increasing pregnancy rates. Although some biochemical alterations have been observed, these metabolic changes do not directly reverse the disorder. Moreover, the lack of sufficient evidence does not convince clinicians to standardize dietary supplements as alternatives to medical or pharmacological interventions. This calls for a study of women with PCOS taking dietary supplements. In addition, unbiased studies of combinations of treatment options for supplements, including large cohort clinical trials, will lead to evidence-based medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Hou, Han, Yuan and Chen.)

Objective: To investigate Vietnamese people's knowledge, attitudes, and experience in purchasing medicines and functional foods online., Methods: Via an online survey, the data of 1,070 participants were collected, including their general characteristics, Internet use, previous experience, knowledge, and attitudes towards purchasing medicines/functional foods online. Factors associated with their knowledge and attitudes were identified via multivariate linear regression models., Results: During 2022-2023, about 97.2% of participants used the Internet to seek health information (self-diagnosis: 65.0%, self-medication: 72.6%). Roughly 52.8% bought medicines and/or functional foods online. Among 565 buyers, 41.8% felt satisfied. Only 19.9% understood that selling medicines online was illegal in Vietnam. The main benefits of purchasing medicines/functional foods online that many people agreed on included convenience (87.1%), freedom from location (84.8%), and being able to order/buy products after opening hours (84.7%). Many people felt worried about the ability to buy counterfeit or substandard products (87.7%), inaccurate product information (85.0%), the lack of supervision of the authorities (83.7%), and increasing risks of drug abuse, self-medication, and treatment non-adherence (82.5%). Roughly 84.3% found distinguishing between legal and illegal online pharmacies difficult. Participants' average knowledge and attitude scores were 6.514 ± 2.461 (range: 0-16) and 89.330 ± 13.720 (range: 23-115), respectively. The main factors associated with people's knowledge and attitudes towards purchasing these products online included their frequency of Internet use, seeking health information online for self-medication, feeling satisfied with previous experience, and having at least one chronic disease., Conclusions: Many Vietnamese people's knowledge about purchasing medicines/functional foods online was limited. With the increasing need for online shopping, enhancing their knowledge is paramount. In the forthcoming years, when the Ministry of Health and relevant authorities publish legal documents and enact laws involving online pharmacies and trading medicines on the Internet, ways to recognize licensed online pharmacies must be widely propagated and disseminated in the community., (© 2024. The Author(s).)

This study examined the effects of incorporating fermented rapeseed meal (FRSM) into the diet of newly weaned piglets on mineral digestibility and bone health. Experimental diets containing varying levels of FRSM (8%, 12%, 15%, and 25%) were introduced to the piglets at 18 days of age, prior to weaning at 28 days. These diets were continued until the piglets were euthanized at 42 days of age. Mineral absorption was assessed using the apparent total tract digestibility (ATTD) method and blood plasma element analysis, while bone mineral content and mechanical properties were evaluated through densitometry and three-point bending tests. The results showed that intermediate levels of FRSM (12-15%) significantly enhanced the digestibility of key minerals, including phosphorus, calcium, magnesium, copper, zinc, and iron. This improvement was linked to increased femoral mineral content and bone stiffness, as well as a higher yield point, likely due to enhanced collagen synthesis. Additionally, there was an increase in bone fracture load and fracture stress, potentially due to changes in the organization of the bone mineral phase, as no changes in bone mid-shaft mineral density or geometry were observed. These findings suggest FRSM as a promising dietary component for improving mineral bioavailability and bone health in piglets.

Dermatan sulfate and chondroitin sulfate are dietary supplements that can be utilized as prophylactics against thrombus formation. Low-molecular-weight dermatan sulfate (LMWDS) is particularly advantageous due to its high absorbability. The enzymatic synthesis of low-molecular-weight dermatan sulfates (LMWDSs) using chondroitin B lyase is a sustainable and environmentally friendly approach to manufacturing. However, the industrial application of chondroitin B lyases is severely hampered by their low catalytic activity. To improve the activity, a semi-rational design strategy of engineering the substrate-binding domain of chondroitin B lyase was performed based on the structure. The binding domain was subjected to screening of critical residues for modification using multiple sequence alignments and molecular docking. A total of thirteen single-point mutants were constructed and analyzed to assess their catalytic characteristics. Out of these, S90T, N103C, H134Y, and R159K exhibited noteworthy enhancements in activity. This study also examined combinatorial mutagenesis and found that the mutant H134Y/R159K exhibited a substantially enhanced catalytic activity of 1266.74 U/mg, which was 3.21-fold that of the wild-type one. Molecular docking revealed that the enhanced activity of the mutant could be attributed to the formation of new hydrogen bonds and hydrophobic interactions with the substrate as well as neighbor residues. The highly active mutant would benefit the utilization of chondroitin B lyase in pharmaceuticals and functional foods.

Background: Urinary incontinence (UI) is a debilitating and common condition that adversely affects quality of life. Prescriptive and surgical approaches for managing UI symptoms may result in undesirable risks and complications. This randomized, double-blind, placebo-controlled, parallel study investigated the efficacy of 2 nonsolvent flower pollen extracts on UI in healthy women., Materials and Methods: One-hundred and fourteen women aged 40-75 years who scored ≥5 on the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) were randomized to receive either Graminex® RCT Fem™ UI, Graminex® PollenBerry®, or placebo for 24 weeks. The primary outcome was the change in the ICIQ-SF score between the trial and placebo groups after 24 weeks of supplementation. The secondary outcomes included changes in the frequency of nocturia (recorded in 3-day void diaries) and 24-hour leakage volume (assessed via pad weight) after 6, 12, 18, and 24 weeks of supplementation and changes in stress-induced urinary leakage volume (after completion of a provocative maneuver challenge) after 24 weeks of supplementation., Results: All the groups demonstrated improvement in ICIQ-SF scores at week 24 ( p < 0.001). The RCT Fem™ UI group had the greatest improvement in ICIQ-SF scores (-4.07 ± 3.4), followed by the PollenBerry® group (-3.34 ± 2.87) and placebo group (-2.61 ± 3.52). The RCT Fem™ UI group had corresponding improvements in 24-hour leakage volume (-17.68 ± 39.84 g) and frequency of nocturia (-0.52 ± 1.26) ( p ≤ 0.05). PollenBerry® supplementation significantly improved stress-induced urinary leakage volume (-7.12 ± 15.64 g) at week 24. The study products demonstrated safe hematological and chemical profiles., Conclusions: RCT Fem™ UI supplementation resulted in significant and clinically meaningful reductions in UI severity, with corresponding improvements in daily urinary leakage volume and frequency of nocturia. PollenBerry® significantly improved stress-induced urinary leakage volume, suggesting that it may be efficacious in women who are prone to stress UI. The study products were safe and well tolerated in this population., Competing Interests: CEM is an employee of Graminex, L.L.C. MM, EDL, DCC, and ME are employees of KGK Science Inc. and have no competing interests to declare., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Dietary supplements containing usnic acid have been increasingly marketed for weight loss over the past decades, even though incidences of severe hepatotoxicity and acute liver failure due to their overuse have been reported. To date, the toxic mechanism of usnic acid-induced liver injury at the molecular level still remains to be fully elucidated. Here, we conducted a transcriptomic study on usnic acid using a novel in vitro hepatotoxicity model employing human induced pluripotent stem cell (iPSC)-derived hepatocytes. Treatment with 20 μM usnic acid for 24 h caused 4272 differentially expressed genes (DEGs) in the cells. Ingenuity Pathway Analysis (IPA) based on the DEGs and gene set enrichment analysis (GSEA) using the whole transcriptome expression data concordantly revealed several signaling pathways and biological processes that, when taken together, suggest that usnic acid caused oxidative stress and DNA damage in the cells, which further led to cell cycle arrest and eventually resulted in cell death through apoptosis. These transcriptomic findings were subsequently corroborated by a variety of cellular assays, including reactive oxygen species (ROS) generation and glutathione (GSH) depletion, DNA damage (pH2AX detection and 8-hydroxy-2'-deoxyguanosine [8-OH-dg] assay), cell cycle analysis, and caspase 3/7 activity. Collectively, the results of the current study accord with previous in vivo and in vitro findings, provide further evidence that oxidative stress-caused DNA damage contributes to usnic acid-induced hepatotoxicity, shed new light on molecular mechanisms of usnic acid-induced hepatotoxicity, and demonstrate the usefulness of iPSC-derived hepatocytes as an in vitro model for hepatotoxicity testing and prediction., (© 2024 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

Background: Dietary supplements can modulate the gut microbial ecosystem and affect the immune system. This has potential implications for autoimmune diseases, including multiple sclerosis (MS). Prior studies explored tolerability, symptomatic improvement, and immunologic effects of probiotics in people with MS (pwMS), but no study has examined prebiotics in this population or compared prebiotics with probiotics., Methods: This is a randomized, open-label trial of participants with relapsing-remitting MS on B-cell depletion therapy from two MS centers. 22 participants enrolled in the original cross-over study in which probiotic (Visbiome, containing Lactobacillus, Bifidobacterium and Streptococcus species) or prebiotic (Prebiotin, containing oligofructose enriched inulin) supplementation for 6 weeks was randomized, each followed by a washout period. Due to pandemic-related interruptions and expiration of the study supply of probiotics, another 15 participants enrolled in a single-arm study to receive prebiotic supplementation for 6 weeks followed by a washout period. We assessed supplement tolerability and patient-reported outcomes (PRO) relevant to MS (disability, fatigue, mood, and bowel symptoms) before and after each supplement administration period and each washout period. We bio-archived plasma, serum, peripheral blood mononuclear cells and stool samples at each timepoint for future multi-omic assessment., Results: Prebiotics and probiotics had comparable adherence rates and both supplements were well tolerated in pwMS. Participants on either supplement reported minor adverse events, most of which were mild and self-limited. There was a subjective preference for prebiotics over probiotics. Comparing supplement-associated changes in PRO scores from baseline to 6 weeks post-supplementation, there were significant difference between prebiotics and probiotics for the change in patient-reported global symptom burden (MSRS-R Total) and bowel control (BWCS), but only probiotics statistically improved bowel control from baseline to post-supplementation., Conclusion: Supplementation with either prebiotics or probiotics is reasonably well-tolerated and safe. Probiotics improved bowel control, but did not improve other PROs in a 6-week time frame. These data regarding feasibility, tolerability, adherence, and adverse events of supplements will inform future clinical trial designs to definitively compare the efficacy and safety of prebiotics and probiotics. The biological data that will be generated from this study in the future will provide mechanistic insights into the effects of these dietary supplements on MS pathophysiology., Competing Interests: Declaration of competing interest No author declared any relevant conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Dietary supplement (DS) use is common and increasing among older adults, though much data available on use frequencies are from surveys and performed cross-sectionally. This paper sought to assess the frequency and pattern of dietary supplement use among older adults over time., Methods: A secondary analysis of data from the AAA LongROAD study, a longitudinal prospective cohort study of older adult drivers, using data from baseline and the first two years of follow up included a total of 2990 drivers aged 65-79 years recruited at five study sites across the US from July 2015 to March 2017. Participants underwent baseline and annual evaluations, which included a "brown bag" medication review. DS were identified and categorized according to type and key components. Prevalence and pattern of DS use over time and relationship to demographics were measured with frequency and Chi squared analyses., Results: 84% of participants took at least one dietary supplement during the 2-year study period, and 55% of participants continually reported use. DS accounted for approximately 30% of the total pharmacologic-pill burden in all years. Participants who were White non-Hispanic, female, 75-79 years of age at baseline, and on more non-supplement medications took significantly more dietary supplements (P < 0.05). Vitamin D, multivitamins, calcium, and omega-3 formulations were the most common supplements, with stable use over time. Use of individual herbal supplements and cannabis products was uncommon (< 1% participants per year)., Conclusions: DS use among older adults is common and relatively stable over time and contributes to polypharmacy. In clinical settings, providers should consider the influence of DS formulations on polypharmacy, and the associated cost, risk of medication interactions, and effect on medication compliance., (© 2024. The Author(s).)

Hydroxycarbodenafil, an analogue of carbodenafil, was detected in a dietary supplement in China in 2020. However, previous reports have not identified some carbon signals from the piperazine ring in nuclear magnetic resonance (NMR) experiments. Because the compound contains an amide bond, the reaction was suggested to be characteristic of compounds with rotational isomers. Variable-temperature NMR is used to determine the rotational barrier between different conformations by changing the measurement temperature. Using this technique, we succeeded in obtaining the first distinct data, including the carbon signals of the piperazine ring in the NMR spectrum of hydroxycarbodenafil. We also confirmed that this technique could be applied to other carbodenafil analogues. Multi-stage mass spectrometry (MS n ) measurements with a high-resolution mass spectrometer specific to the substructures were performed to develop a protocol for the structural determination of the carbodenafil analogues. In addition, hydroxycarbodenafil was analysed using X-ray crystallography, and its inhibitory activity against phosphodiesterase type 5 (PDE5) was measured. The IC 50 value of the inhibitory activity of hydroxycarbodenafil for PDE5A1, a PDE5 isoform, of 2.9 nM was lower than the 4.5 nM for sildenafil, a positive control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is often associated with chronic inflammation exacerbated by hyperglycemia and dyslipidemia. Mung beans have a longstanding reputation in traditional medicine for their purported ability to lower blood glucose levels, prompting interest in their pharmacological properties. This study aimed to explore the impact of mung bean water (MBW) on carbohydrate and lipid metabolism in a T2DM rat model induced by nicotinamide/streptozotocin. Normal and DM rats were supplemented with a stock solution of MBW as drinking water ad libitum daily for 8 weeks. MBW supplementation led to significant reductions in plasma total cholesterol, HDL-C, and VLDL-C + LDL-C levels, and decreased malondialdehyde levels in plasma and liver samples, indicating reduced oxidative stress. MBW supplementation lowered plasma glucose levels and upregulated hepatic hexokinase activity, suggesting enhanced glucose utilization. Additionally, MBW decreased hepatic glucose-6-phosphate dehydrogenase and glutathione peroxidase activities, while hepatic levels of glutathione and glutathione disulfide remained unchanged. These findings underscore the potential of MBW to improve plasma glucose and lipid metabolism in DM rats, likely mediated by antioxidant effects and the modulation of hepatic enzyme activities. Further exploration of bioactive components of MBW and its mechanisms could unveil new therapeutic avenues for managing diabetes and its metabolic complications.

Recent evidence suggests the mechanistic role of mitochondria and oxidative stress in the development of celecoxib-induced cardiotoxicity. On the other, it has reported the positive effects of vitamin D on oxidative stress and the maintenance of mitochondrial functions. This current study examined the cardiac effects of celecoxib, doxorubicin, vitamin D, and a combination of them in rats. The effect of 10 days of celecoxib (100 mg/kg/day), doxorubicin (2.5 mg/kg), vitamin D (60,000 U/kg), and their combination was studied on cardiac function according to serum lactate dehydrogenase (LDH), creatine kinase (CK), glutathione (GSH), and malondialdehyde (MDA) levels as well as mitochondrial succinate dehydrogenases (SDH) activity, reactive oxygen species (ROS) production, mitochondrial swelling, and mitochondrial membrane potential (MMP). Results showed that celecoxib and its combination with doxorubicin led to abnormality in paws and limbs, increased pressure in the eyes, blindness and animal death (in about 75% of the animals under study). Moreover, celecoxib and its combination with doxorubicin significantly increased cardiotoxicity biomarkers, oxidative stress markers (GSH and MDA), and mitochondrial toxicity parameters (SDH, ROS formation, MMP collapse, mitochondrial swelling). However, the combination of vitamin D with celecoxib and celecoxib + doxorubicin caused a significant reversal of deformity in paws and limbs, increased pressure in the eye, blindness, and animal death, as well as cardiotoxicity, oxidative stress, and mitochondrial parameters. This study proved for the first time the beneficial effect of vitamin D on celecoxib-induced cardiotoxicity, which is aggravated in the presence of doxorubicin through the maintenance of mitochondrial functions and its antioxidant potential., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This review provides an in-depth examination of the role that tumor-associated macrophages (TAMs) play in the progression of prostate cancer (PCa), with a particular focus on the factors influencing the polarization of M1 and M2 macrophages and the implications of targeting these cells for cancer progression. The development and prognosis of PCa are significantly influenced by the behavior of macrophages within the tumor microenvironment. M1 macrophages typically exhibit anti-tumor properties by secreting pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), thereby enhancing the immune response. Conversely, M2 macrophages contribute to tumor cell migration and invasion through the production of factors like arginase-1 (Arg1) and interleukin-10 (IL-10). This review not only explores the diverse factors that affect macrophage polarization but also delves into the potential therapeutic strategies targeting macrophage polarization, including the critical roles of non-coding RNA and exosomes in regulating this process. The polarization state of macrophages is highlighted as a key determinant in PCa progression, offering a novel perspective for clinical treatment. Future research should concentrate on gaining a deeper understanding of the molecular mechanisms underlying macrophage polarization and on developing effective targeted therapeutic strategies. The exploration of the potential of combination therapies to improve treatment efficacy is also emphasized. By emphasizing the importance of macrophages as a therapeutic target in PCa, this review aims to provide valuable insights and research directions for clinicians and researchers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Postbiotics could exert different metabolic activities in animal models of non-alcoholic fatty liver disease (NAFLD) and in humans affected by metabolic syndrome. This is a randomized, double-blind, placebo-controlled, parallel-group clinical trial that enrolled a sample of 50 Caucasian healthy individuals with NAFLD, defined as liver steatosis, and metabolic syndrome. After a 4-week run-in, the enrolled individuals were randomized to take a food for special medical purposes with functional release, one tablet a day, containing calcium butyrate (500 mg/tablet), zinc gluconate (zinc 5 mg/tablet), and vitamin D3 (500 IU/tablet), or an identical placebo for 3 months. Liver and metabolic parameters were measured at baseline and at the end of the study. No subject experienced any adverse events during the trial. In both groups, a significant decrease in total cholesterol (TC) and triglycerides (TG) plasma levels was observed at the randomization visit vs. pre-run-in visit ( p < 0.05). Regarding liver parameters, after treatment, the fatty liver index (FLI) improved significantly vs. baseline values ( p < 0.05) and vs. placebo group ( p < 0.05) in the active treatment group, and the hepatic steatosis index (HSI) improved significantly vs. baseline values ( p < 0.05). Moreover, after active treatment, TC, TG, and gamma-glutamyl transferase (gGT) improved significantly vs. baseline values ( p < 0.05), and TC and TG improved vs. placebo group ( p < 0.05), as well. In the placebo group, liver parameters remained unchanged after treatment; only TG improved significantly vs. baseline values ( p < 0.05). In our study, we observed that the butyrate-based formula improved FLI and plasma lipid patterns in individuals affected by liver steatosis and metabolic syndrome.

In modern pig farming, there are many environmental, physiological or social stresses that weaken the immune response and increase susceptibility to disease. Nutritional management has a significant impact on the efficiency of the immune system in pigs. Among the various nutrients, vitamins have been shown to have specific effects on immune system activity. However, the needs of modern genetic types are not met by the dietary recommendations for vitamins in pig diets. The present study therefore summarises the data on dietary integration with supranutritional doses of vitamins in gestating and lactating sows and post-weaning piglets in terms of the immune response. The present data highlight that high doses of dietary vitamins are an effective way to improve the immune system, antioxidant status and gut health. Further studies are needed to deepen the understanding of the role of dietary supplementation with vitamins in pigs on immune system and gut functionality.

Lameness and restricted mobility are a significant concern in companion animals experiencing chronic pain, inflammation, or age-related pathologies. The growing awareness of health risks and side effects associated with the long-term use of prescription analgesics requires different management strategies to address these issues. In this study, we conducted a crossover evaluation of the effect of full spectrum hemp oil dosed orally at 2 mg/kg BID phytocannabinoids for 8 weeks in dogs ( n  = 37) living with pain in common household settings. Owner-reported canine pain, home activity, accelerometer-based activity, walkway-based gait, and tolerability were assessed at each phase of the study. Secondary endpoints included changes in blood biochemistry, liver enzymes, inflammatory biomarkers, and plasma metabolites. The intervention was positively associated with a decrease in pain scores (-46.2%, p  = 0.0016), increased ability to walk up and down the stairs (10.6-14.7%, p  < 0.05), and improved daily activity (25.9%, p  = 0.0038). Decreases in plasma levels of proinflammatory cytokines TNF-α, IL-6, and IL-8 were also observed. Taken together, these findings suggest that the benefits of nutritional supplementation with hemp oil could include control of pain, greater mobility, and an overall improvement in the animal wellbeing., Competing Interests: CP, JG, and BM are employees of Standard Process, a manufacturer of pet whole food dietary supplements. SK consulted and received research grants from Standard Process. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Panda, Rathinasabapathy, Metzger, Dodson, Hanson, Griffiths and Komarnytsky.)

Objectives: The study provides a thorough examination of the rhizomes of Curcuma caesia Roxb., which is a medicinal substance sometimes referred to as black turmeric and has not been well studied., Methods: The study examines the pharmacognostical characteristics, GC-MS profiling, and elemental analysis of the substance to determine its potential for use in medicine. The presence of heavy metal contamination in herbal products is a significant issue, which necessitates the use of Atomic Absorption Spectrophotometry to quantitatively analyze eight elements., Results: The investigation validates the existence of crucial trace elements while guaranteeing that the levels of heavy metals are within the toxicity limits set by the World Health Organization. This indicates that the rhizome is safe for medicinal purposes. The selection of a solvent has a substantial impact on the efficiency of extraction. Acetone has the highest extraction yield, followed by ethanol and ethyl acetate. The GC-MS analysis uncovers a wide range of phytochemicals, such as alkaloids, flavonoids, phenols, tannins, steroids, and proteins. Additionally, particular solvents exclusively detect specific molecules. Epicurzerenone and zederone are chemicals that show promise for use in reducing inflammation and fighting cancer., Conclusions: On the basis of results it can be concluded that rhizome's quality based on acceptable physicochemical characteristics and provides a strong basis for future pharmacological research. The research has potential for the development of novel organic drugs, utilizing the abundant phytochemical composition of C. caesia Roxb. rhizomes., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Elderly people avoid eating red meat and dried meat product due to its texture and stiffness; they deprive them of rich sources of nutrients. In addition, food-related diseases are exponentially increasing due to using synthetic additives in food products. Therefore, this research aimed to develop semi-dried goat meat jerky considering geriatric preferences by using natural tenderizers and nitrate. Four treatments were formulated negative control (NC [synthetic nitrite without tenderizers]), positive control (PC [Swiss chard without tenderizers]), T1 (Swiss chard with pineapple powder), and T2 (Swiss chard with pineapple and tomato powder). T1 and T2 had higher processing yield, and rehydration capacity compared with NC and PC. The fat content of T1 and T2 was lower than the control groups. Moisture was significantly higher in T1, NC, and T2 than in PC ( p < 0.05). T2 showed the lowest water activity (0.87), lowest shear force (4.82 kgf), and lowest total plate count (TPC). The lowest pH and thiobarbituric acid reactive substances (TBARS) were observed in T1 and T2. T1 showed the lowest lightness and the maximum redness ( p < 0.05) while PC showed the lowest yellowness. During the storage period, moisture and pH decreased, and TPC and TBARS significantly increased whereas water activity is stable regardless of the treatment. The results of the myofibrillar fragmentation index (MFI) and sodium dodecyl sulfate-polyacrylamide gel revealed that T1 and T2 more effectively converted protein to polypeptides. In addition, tenderizers positively affected thrombogenicity, atherogenicity, and hypocholesterolemic/hypercholesterolemic indices. T2 observed the highest overall sensory acceptance by reducing goaty flavor. Overall, jerky treated with tenderizers is easily chewable and digestible for the elderly due to its tenderness and essential fatty acids that would be senior-friendly food., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2024 Korean Society of Animal Science and Technology.)

Since usnic acid was first isolated in 1844 as a prominent secondary lichen metabolite, it has been used for various purposes worldwide. Usnic acid has been claimed to possess numerous therapeutic properties, including antimicrobial, anti-inflammatory, antiviral, anti-proliferative, and antipyretic activities. Approximately two decades ago, crude extracts of usnic acid or pure usnic acid were marketed in the United States as dietary supplements for aiding in weight loss as a "fat-burner" and gained popularity in the bodybuilding community; however, hepatotoxicity was documented for some usnic acid containing products. The US Food and Drug Administration (FDA) received numerous reports of liver toxicity associated with the use of dietary supplements containing usnic acid, leading the FDA to issue a warning letter in 2001 on a product, LipoKinetix. The FDA also sent a recommendation letter to the manufacturer of LipoKinetix, resulting in the withdrawal of LipoKinetix from the market. These events triggered investigations into the hepatotoxicity of usnic acid and its mechanisms. In 2008, we published a review article titled "Usnic Acid and Usnea Barbata Toxicity". This review is an updated version of our previous review article and incorporates additional data published since 2008. The purpose of this review is to provide a comprehensive summary of the understanding of the liver toxicity associated with usnic acid, with a particular focus on the current understanding of the putative mechanisms of usnic acid-related hepatotoxicity.

Nutritional interventions to reduce gastrointestinal (GI) permeability are of significant interest to physically active adults and those experiencing chronic health conditions. This in vitro study was designed to assess the impact of AG1, a novel synbiotic, on GI permeability following an inflammatory challenge. Interventions [AG1 (vitamins/minerals, pre-/probiotics, and phytonutrients) and control (control medium)] were fed separately into a human GI tract model (stomach, small intestine, and colon). In the colonic phase, the GI contents were combined with fecal inocula from three healthy human donors. GI permeability was evaluated with transepithelial electrical resistance (TEER) in a Caco-2 (apical)/THP1-Blue™ (basolateral) co-culture model. The apical side received sodium butyrate (positive control) or Caco-2 complete medium (negative control) during baseline testing. In the 24 h experiment, the apical side received colonic simulation isolates from the GI model, and the basolateral side was treated with Caco-2 complete medium, then 6 h treatment with lipopolysaccharide. TEER was assessed at 0 h and 24 h, and inflammatory markers were measured at 30 h in triplicate. Paired samples t -tests were used to evaluate endpoint mean difference (MD) for AG1 vs. control. TEER was higher for AG1 (mean ± SD: 99.89 ± 1.32%) vs. control (mean ± SD: 92.87 ± 1.22%) following activated THP1-induced damage [MD: 7.0% ( p < 0.05)]. AG1 maintained TEER similar to the level of the negative control [-0.1% ( p = 0.02)]. No differences in inflammatory markers were observed. These in vitro data suggest that acute supplementation with AG1 might stimulate protective effects on GI permeability. These changes may be driven by SCFA production due to the pre-/probiotic properties of AG1, but more research is needed.

Background: Dietary restrictions or reductions such as fasting for weight loss are often difficult to adhere to due to increased appetite and food cravings. Recently, gastrointestinal delivery of bitter hops has been shown to be effective at reducing appetite in men. Our aim was to determine the effect of a bitter hop extract on appetite and cravings in women, using a 24 h, water-only fast., Methods: This was a randomized, double-blind, cross-over treatment study. Thirty adult women were recruited and required to fast for 24 h from 1800 h to 1800 h on three occasions and given an ad libitum meal to break each fast. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 125 mg) of a bitter hop-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast., Results: The HD and LD treatment groups exhibited a significant ( p  < 0.05) reduction in appetite and cravings for food when compared to the placebo control. Two participants reported loose stools and one reported heartburn while on the HD treatment, and one participant reported loose stools while on the LD treatment., Conclusion: These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during fasting in women and shows that gastrointestinal delivery of bitter compounds may also be an effective method of reducing cravings for food.This trial received ethical approval from the Northen B New Zealand Human Disability and Ethics committee (Northern B Health and Disability Ethics Committee (2022 EXP 10995) and was prospectively registered with the Australian New Zealand Clinical Trial Registry (ACTRN12622000107729)., Competing Interests: The authors themselves declare no competing financial interests. The New Zealand Institute for Plant and Food Research Limited, a New Zealand government-owned Crown Research Institute, has licensed a hop extract as a dietary supplement to Calocurb Ltd to commercialize and currently holds a minor shareholding in this company., (© 2024 The Authors.)

Objective: Smoking reduction or cessation are critical public health goals, given the well-documented risks of tobacco use to health. Reducing smoking frequency and cessation entirely are challenging due to nicotine addiction and withdrawal symptoms, which can significantly affect mental wellness and overall wellbeing. Previous research has suggested that certain dietary supplements may support smoking cessation and reduction efforts by mitigating these adverse effects. The objective of this study was to assess the effect of supplementation with 900 mg/day of Neuravena ® , a green oat extract (GOE) of Avena sativa L., in enhancing wellness and wellbeing during a smoking reduction or cessation experience., Methods: This was an 8-week randomized, double-blind, placebo-controlled study, ClinicalTrials Identifier: NCT04749017 (https://classic.clinicaltrials.gov/ct2/show/NCT04749017). Participants were assigned to one of the study groups, 72 participants were assigned to GOE and 73 to placebo. The subjects were followed for 8-weeks intervention period as well as an additional 4-week follow-up period. At subsequent visits, they underwent clinical assessments including assessments of quality of life, perceived stress, depression, nicotine dependence, anxiety, cognitive performance, and specific assessments of craving intensity., Results: GOE was associated with greater improvements in elements of the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire as compared with placebo. Similar results were obtained from the SF-36 questionnaire and a visual QoL analogue scale (VAS). Perceived stress levels showed greater decline from baseline among the GOE supplemented participants as compared to placebo. Sleep quality parameters improved with GOE supplementation and worsened in the placebo group. At the end of the intervention period, the percentage of successful reducers (defined as >20% reduction in daily cigarettes) was higher in the GOE group as compared to placebo (66.7% vs. 49.3%, p  = 0.034). The improvements from baseline in QoL measures in the GOE group persisted at 4 weeks after termination of the intervention., Conclusion: GOE supplementation demonstrated greater improvements in quality of life measures, stress and sleep related parameters during a smoking reduction or cessation experience and the product was shown to be safe and well tolerated., Competing Interests: MF, EI, AL, and JJ were employees of IFF Health, which commercializes the Neuravena®. FL-R, FC, AG-M, DV-M, SP-P, and AG-G were part of the Physiology Laboratory staff at Catholic University of Murcia, Murcia, Spain, and were hired by IFF Health to conduct the study. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Friling, García-Muñoz, Lavie, Pérez-Piñero, Victoria-Montesinos, López-Román, García-Guillén, Muñoz-Carrillo, Cánovas, Ivanir and Jalanka.)

Chronic sleep disturbance affects daily functioning, leading to decreased concentration, fatigue, and higher healthcare costs. Traditional insomnia medications are often associated with adverse side effects. This study investigated the efficacy of a novel compound derived from Rhodiola rosea and Nelumbo nucifera extracts (named RNE) in improving sleep quality with fewer side effects. The study included individuals between the ages of 20 and 65 with subthreshold insomnia and evaluated the effects of RNE on sleep, fatigue, and quality of life. Participants took 750 mg of RNE daily at bed-time for two weeks. The study used the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), a sleep diary, the Fatigue Severity Scale (FSS), and the Short Form 36 Health Survey (SF-36) for assessments. Of the 20 participants, 13 completed the study and showed significant improvements in sleep quality. The results showed improvements in ISI and PSQI scores, a 57% reduction in wake-time after sleep onset, and improved sleep efficiency. Although FSS scores remained unchanged, significant improvements were seen in SF-36 physical and mental health scores. The results suggest that RNE is an effective, low-risk option for sleep disturbance, significantly improving sleep quality and overall wellbeing without significant side effects.

Chronic venous insufficiency (CVI) represents a risk factor for cardiovascular events. The first-line treatment includes the use of compression stockings and lifestyle changes. Natural products, such as flavonoids, could be used to improve the effects of compression therapy due to their anti-inflammatory and anti-oxidant properties. This study aims to evaluate the effects of a dietary supplement containing baicalin, bromeline and escin in CVI patients. A retrospective cohort study was performed by using the medical records of CVI affected outpatients. Patients treated with the dietary supplement were defined as "users". A modified Venous Clinical Severity Score (VCSS) was calculated, including pain, inflammation, vessels induration and skin pigmentation. All clinical variables were evaluated at baseline (T0), after 30 (T1) and 90(T2) days in "users" and "non-users". Out of 62 patients, 30 (48.4%) were "users". No difference was observed between groups at baseline. A lower VCSS value was recorded in "users" than that observed in "non-users" at T2 (7.0 (4.0-9.0) vs. 9.0 (5.0-10.0); p = 0.025). Vessels' induration and pain significantly reduced in 53.3% and 43.3% of "users" and in 18.8% and 9.4% of "non-users". Only "users" (33.3%) showed a reduction of the inflammatory signs as well as a decrease in malleolar circumference, from 29.0 (26.5-30.0) to 27.5 (26.0-28.5) ( p < 000.1). A reduction of C-reactive Protein levels was found in "users" compared to "non-users" at T2 (1.0 (0.9-1.2) vs. 1.3 (1.0-1.5); p = 0.006). These findings suggest that implementation of a dietary supplement could improve the clinical outcomes of CVI patients.

Oleuropein, a phenolic compound derived from olives, has known glucoregulatory effects in mammalian models but effects in birds are unknown. We investigated effects of dietary supplementation and exogenous administration of oleuropein on broiler chick feed intake and glucose homeostasis during the first 7 days post-hatch. One hundred and forty-eight day-of-hatch broiler chicks were randomly allocated to one of four dietary treatments with varying oleuropein concentrations (0, 250, 500, or 1,000 mg/kg). Body weight and breast muscle and liver weights were recorded on day 7. In the next experiment, chicks received intraperitoneal (IP) injections of oleuropein at doses of 0 (vehicle), 50, 100, or 200 mg/kg on day 4 post-hatch, with feed intake and blood glucose levels measured thereafter. Lastly, chicks fed a control diet were fasted and administered intracerebroventricular (ICV) injections of oleuropein at doses of 0, 50, 100, or 200 μg, after which feed intake was recorded. Results indicated that IP and ICV injections led to decreased feed intake, primarily at 60 min post-injection, with effects diminishing by 90 min in the IP study. Blood glucose levels decreased 1-h post-IP injection at higher oleuropein doses. These findings suggest that oleuropein acts as a mild appetite suppressant and influences energy metabolism in broiler chickens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sulaiman, Vaughan, Siegel, Liu, Gilbert and Cline.)

Introduction: In recent years, the use of dietary supplements has increased in all age groups. Parents may also use these supplements for their children for different reasons. This study aims to determine the use of dietary supplements by children, the factors affecting this use, and the attitudes of parents about these products., Methods: A total of 1038 children aged 2-18 years without any chronic disease who presented to the pediatric outpatient clinics of Ege University Children's Hospital were included in this study. Parents ( n = 1000) who agreed to participate in the study were interviewed face-to-face, and a comprehensive questionnaire including questions about children's use of dietary supplements, sociodemographic characteristics, and parents' attitudes towards dietary supplements was administered. Analyses were performed with SPSS 25.0., Results: The mean age of the children included in our study was 8.6 ± 4.8 years, and 51% ( n = 510) were male. It was found that 32.5% of the children used nutritional supplements, and vitamin-mineral preparations (23.2%) were the most frequently used. Omega-3 (19.3%) and immune support products (9.4%) were the second and third most frequently used supplements, respectively. A significant relationship was found between the use of dietary supplements and the child's age, body weight, body mass index, parents' educational level, being health worker, and economic status ( p < 0.05). It was found that most of the families thought that vitamin-mineral and omega-3 products were beneficial for growth and development and that they received information from doctors most frequently before taking these products. However, it was found that families followed the media as the second most frequent source of information for these products., Conclusions: Approximately one-third of the children in our study use dietary supplements. It is very important to raise awareness among families about the use of these products when necessary and with the recommendation of a physician. To prevent families from using dietary supplements that are not necessary for their children, especially due to misinformation in the media, pediatricians should provide correct information to parents about these products at every clinic visit. A concerted effort is needed from policy makers, media organizations, and health care providers to guide the safe use of DS. The results obtained from this study will shed light on future randomized controlled prospective studies.

Obesity is a major health problem in dogs and is strongly associated with an increased risk of chronic inflammatory and metabolic diseases. The microaerophilic human gut bacterium Akkermansia muciniphila has been proposed as a potential preventive and therapeutic agent against obesity in both humans and mice; however, the protective effects of human-derived A. muciniphila against canine obesity remain unstudied. We previously demonstrated that the heat-killed A. muciniphila strain EB-AMDK19 (AMDK19-HK) isolated from the faeces of a healthy Korean exerts similar protective effects as the live bacterium in mice with high-fat-diet (HFD)-induced obesity. Here, we evaluated the effects of AMDK19-HK on body weight, body fat mass, haematological and biochemical parameters, and faecal microbiota composition in beagles fed an HFD for 12 weeks. AMDK19-HK supplementation effectively suppressed body weight increase, body fat deposition and serum triglyceride increase in the canine model; however, no significant changes in the overall haematological and biochemical parameters were observed, reflecting the direct anti-obesity effect of AMDK19-HK. Additionally, 16S rRNA gene sequencing revealed that AMDK19-HK supplementation induced significant changes in the faecal bacterial community, with an increased abundance of Firmicutes and a decreased abundance of Bacteroidota . These results suggest that AMDK19-HK can be used as a dietary supplement to counteract diet-induced overweight in dogs.