Dietary Supplements Research Articles

Effect of Vitamin D Supplementation on Human Gut Microbiota: A Systematic Review of Randomized Controlled Trials.

Studies findings have suggested that vitamin D plays a critical role in maintaining overall health, including having a potential impact on gut microbiota composition, which influences various physiological processes. To examine the effects of vitamin D supplementation on human gut microbiota composition and diversity by analyzing findings from randomized controlled trials (RCTs). A comprehensive search of the MEDLINE, Web of Science, Scopus, and the Cochrane Library electronic databases was conducted to identify relevant studies published from January 1, 2015, to November 30, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed. Inclusion criteria were RCTs investigating the impact of vitamin D supplementation on gut microbiota, with outcomes measured using high-throughput sequencing techniques. This review included 14 RCTs encompassing a total of 1458 participants of varying health status and supplementation regimens. Findings demonstrated that vitamin D supplementation modulates gut microbiota composition, with significant increases observed in bacterial taxa associated with anti-inflammatory and gut health-promoting properties, such as Bifidobacterium and Lactobacillus, as well as an increase in the Bacteroidetes to Firmicutes ratio. Some trials reported enhanced microbial diversity (α and β diversity), and others highlighted variability based on dosage, duration, and baseline vitamin D status. Additionally, specific alterations in microbial biomarkers such as calprotectin and trimethylamine N-oxide, which is linked to vitamin D metabolism, were noted. Although promising, the findings underscore the heterogeneity in study designs and methodologies, emphasizing the need for standardized approaches to assess causality and clinical relevance. This review provides valuable insights into the interplay between vitamin D and gut microbiota, offering a foundation for personalized nutritional strategies targeting microbiome modulation. Future research should explore the long-term effects of vitamin D supplementation on gut microbiota and its implications for health outcomes in diverse populations. PROSPERO registration no. CRD42024628080.

Metabolic engineering of Saccharomyces cerevisiae for de novo biosynthesis of hydroxytyrosol and salidroside

ABSTRACT Hydroxytyrosol and salidroside are phenylethanol compounds with significant industrial applications but limited availability due to low-yield natural extraction and complex chemical synthesis. In this study, Saccharomyces cerevisiae was engineered to achieve efficient de novo biosynthesis of these compounds. A tyrosol-producing strain (ZYT1) was optimized to produce 571.8 mg/L tyrosol, which served as the yeast chassis cell for hydroxytyrosol synthesis. By integrating PaHpaB and EcHpaC , strain ZYHT1 produced 304.4 mg/L hydroxytyrosol in shake-flask fermentation, which increased to 677.6 mg/L in a 15 L bioreactor after auxotrophic repair. For salidroside production, glycosyltransferase RrU8GT33 was introduced into ZYT1, yielding strain ZYSAL1 with 48.4 mg/L salidroside. Enhancing UDP-glucose supply using truncated sucrose synthase ( tGuSUS1 ) led to strain ZYSAL9+3, which achieved 1,021.0 mg/L in shake flasks and 18.9 g/L in fed-batch fermentation. This work demonstrates the scalable production of hydroxytyrosol and salidroside in yeast, providing a basis for industrial applications and advancing synthetic biology approaches for natural product biosynthesis. IMPORTANCE Hydroxytyrosol and salidroside are valuable natural compounds with strong antioxidant, anti-inflammatory, and neuroprotective properties, widely used in pharmaceuticals, cosmetics, and health supplements. However, traditional extraction from plants is inefficient, and chemical synthesis is costly and environmentally unfriendly. In this study, we engineered Saccharomyces cerevisiae , a common yeast, to efficiently produce these compounds from simple carbon sources such as glucose and sucrose. By optimizing key biosynthetic pathways, improving cofactor supply, and enhancing sucrose metabolism, we achieved high production levels suitable for industrial applications. Our work provides a sustainable and scalable microbial platform for producing hydroxytyrosol and salidroside, reducing reliance on plant extraction and chemical synthesis. This research advances the field of microbial biotechnology by demonstrating how engineered yeast can serve as a green factory for valuable bioactive compounds, opening new possibilities for large-scale production and commercial use.

Lifestyle Intervention Improves Metabolic Dysfunction-Associated Steatotic Liver Disease in Children with Down Syndrome

Background/Objectives: We evaluated the efficacy of a good lifestyle intervention on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children with Down syndrome (DS). Methods: This retrospective longitudinal study included 31 children with Down syndrome (DS) who were affected by MASLD and attended nutritional counseling based on a nutritional approach (e.g., Mediterranean diet and antioxidant supplements), as well as physical exercise. Clinical parameters, markers of low-grade systemic inflammation, and hepatic steatosis, as assessed by ultrasound, were evaluated at baseline (T0) and after 6 months (T1). Results: Several anthropometric and biochemical parameters, including body mass index, waist circumference, diastolic and systolic blood pressure, aspartate aminotransferase, basal insulin, insulin resistance, pro-inflammatory interleukin-1β, and anti-inflammatory interleukin-10, showed significant improvement after 6 months of a nutritional approach. This study also found a regression of at least one grade of hepatic steatosis in a significant portion of patients, especially in those who received antioxidant supplements. Conclusions: Our study further supports the hypothesis that a healthy lifestyle intervention, based on adherence to the Mediterranean diet, natural supplements with antioxidant properties, and regular physical activity, can be considered a safe therapeutic approach for reducing the risk and severity of MASLD in children with DS.

Deciphering Important Odorants in a Spirulina (Arthrospira platensis) Dietary Supplement by Aroma Extract Dilution Analysis Using Offline and Online Fractionation Approaches

Investigating the volatiles isolated from a commercial spirulina (Arthrospira platensis) dietary supplement by gas chromatography–olfactometry (GC–O) in combination with an aroma extract dilution analysis (AEDA) resulted in 29 odor events with flavor dilution (FD) factors between 8 and 2048. Identification experiments, including various offline and online fractionation approaches, led to the structure assignment of 30 odorants, among which the most potent were sweaty 2- and 3-methylbutanoic acid (FD 2048), roasty, earthy, shrimp-like 2-ethyl-3,5-dimethylpyrazine (FD 2048), vinegar-like acetic acid (FD 1024), and floral, violet-like β-ionone (FD 1024). Static headspace dilution analysis revealed sulfuric, cabbage-like methanethiol (FD factor ≥ 32) as an additional potent odorant. In summary, 31 important spirulina odorants were identified in this study, and 14 were reported for the first time as spirulina constituents. Our data will provide a basis for future odor optimization of spirulina-based food products.

Understanding the research landscape of over-the-counter herbal products, dietary supplements, and medications evaluated for depressive symptoms in adults: a scoping review

BackgroundOver-the-counter (OTC) products such as herbal medical products (HMPs) or dietary supplements are a valued part of preventative and supportive self-care for depressive symptoms, but there is a wide array of products available, with differing levels of clinical evidence. It is unclear what the optimal directions for future research in this field are.AimWe aimed to explore the size and nature of the evidence base available for OTC products for depression in adults aged 18–60.MethodsWe carried out a scoping review following Joanna Briggs Institute guidance. We searched MEDLINE, Embase, PsycINFO, AMED, and CENTRAL from inception to December 2022, and 10% of the results were screened by two authors and the remainder by one author. We included randomised controlled trials of products commonly available OTC in multiple countries in participants with symptoms or a diagnosis of depression. Results were narratively summarised by the product and volume of evidence available.ResultsOut of 23,933 records found, we screened 1,367 full texts and included 209 trials. The largest volume of evidence was for omega-3s, St John’s Wort, saffron, probiotics, and vitamin D. Among a range of herbal medical products with promising evidence, those most commonly used and thus warranting further research were lavender, lemon balm, chamomile, and Echium. For 41 products, we found only single trials. Few products presented safety issues, whether used alone or adjunctively with antidepressants.ConclusionProducts with limited but promising evidence included folic acid, lavender, zinc, tryptophan, Rhodiola, and lemon balm, and future research should focus on these products. There is a need for further evaluation of herbal medical products as adjuncts to antidepressants and for exploring their potential benefits when used adjunctively with psychological therapies to support a more integrative approach. Safety reporting in these trials needs to be further improved.Systematic Review Registration:https://osf.io/rkm57/.

Algal biomass as a food and feed supplement: Process engineering analysis

Background: The global market for algae-based food and feed supplements is well-established and growing rapidly. The sector has grown fivefold since 2000. While microalgae products still hold a modest market share, the large-scale commercial production of microalgae as a primary source of proteins, lipids, carbohydrates, and other compounds remains in its early developmental stages. If successfully mass-produced, microalgae could make a significant contribution to global food and feed security. Objective: The study aims to compare the potential of selected algal strains as sustainable sources of high-value biomass for food and feed using a low-cost, solvent-free analytical method based on Near-infrared spectroscopy. Methods: Green unicellular microalgae Chlorella vulgaris Pa-023, Neochloris oleoabundans Pa-022, and cyanobacterium Limnospira maxima Pc-02 were selected and cultivated in bubble column photobioreactors using nitrogen-rich media under LED illumination with red and blue light spectrums. Near-infrared spectroscopy was applied as a non-destructive method to monitor protein, lipid, and carbohydrate content during cultivation. Results: Quantitative analysis revealed distinct biochemical profiles among C. vulgaris, N. oleoabundans, and L. maxima, with protein contents of 49.2, 40.0, and 59.0 g/100 g dry weight, respectively. L. maxima showed the highest protein content, while N. oleoabundans had the highest lipid content (26.0 g/100 g dry weight), suggesting their suitability for protein-rich products and lipid-based applications. A cost-efficiency assessment of L. maxima cultivation in a 100-L photobioreactor (PUEVIT GmbH, Germany) yielded 98 g dry biomass in 7 days, with production costs estimated at €43.56. Novelty: The study uniquely integrates comparative biochemical profiling of algal and cyanobacterial biomass with a cost-efficiency analysis of semi-industrial biomass production. Key innovations include: (i) species-specific application potential; (ii) the first techno-economic assessment of L. maxima cultivation in a controlled photobioreactor; (iii) a practical demonstration of economically viable microalgal biomass production. Conclusion: Near-infrared spectroscopy has proven to be an effective method for non-destructive biomass analysis. However, improving model accuracy requires a broader calibration set with well-characterized standards. Expanding this dataset will enhance the predictive power and reliability of the method. Keywords: algae, high-value biomass, NIR spectrophotometry, food and feed supplement, cost-efficiency.

Nutritional status and practices among Chinese marathon runners: data from the China marathon nutrition survey (CMNS).

The increasing popularity of marathon running in China highlights the need to better understand the dietary habits and nutritional needs of marathon runners to optimize performance and health outcomes. The study aimed to assess the dietary behaviors, nutritional knowledge, and running-specific nutritional practices of Chinese marathon runners as part of the China Marathon Nutrition Survey (CMNS). This nationwide cross-sectional survey was conducted between January and December 2024. Participants were recruited via official websites, social media, and onsite events. A structured and pre-tested questionnaire, referred to as the China Marathon Nutrition Survey questionnaire, was developed by the research team for the CMNS project. The CMNS questionnaire was used to collect data on demographic characteristics, running experience, and nutrition-related behaviors among Chinese marathon runners across different genders, ages, and performance levels. Descriptive statistics, chi-square tests, and logistic regression were employed to identify factors associated with nutritional practices. A total of 5668 valid questionnaires were included in the analysis, comprising 77.6% male (39.8 ± 10.9 yrs) and 22.4% female (41.0 ± 9.7 yrs) runners, representing a wide distribution across age groups and performance levels. Nearly half of the runners (49.1%) of runners reported no specific dietary habits, while among those with dietary practices, 26.4% adhered to a high-carbohydrate diet. In terms of running-related nutrition, 23.3% of Chinese runners regularly or frequently used dietary supplements, and 31.7% used them occasionally before important races. Carbohydrate-loading strategies were adopted by 57.2% of runners prior to races. However, only 36.7% of participants met the recommended fluid intake (1500-1700 mL/day) set by the Chinese Nutrition Society. Higher nutrition knowledge significantly predicted adherence to recommended hydration practices (p < 0.001), according to logistic regression analysis. Significant variability in the nutritional knowledge of Chinese marathon runners was observed, with 36.6% scoring 6 or higher on a 9-point scale. Male runners (OR = 1.39, 95% CI: 1.22-1.57, p < 0.001) and younger participants (≤34 years) (OR = 1.42, 95% CI: 1.22-1.66, p < 0.001) tended to score higher. This study provides insights into the nutritional knowledge, dietary behaviors, and race-specific nutrition practices of Chinese marathon runners, offering important baseline data for improving endurance nutrition. Common issues were identified in daily macronutrient intake, hydration, and race-day fueling. These findings underscore the gaps between knowledge and practice, emphasizing the need for tailored nutrition education, particularly for recreational runners through race organizers or public platforms.

Magnesium and Zinc Dose-Dependently Stabilize Rat Peritoneal Mast Cells and Enhance the Effects of Adrenaline

Background/Aims: Magnesium and zinc are vital trace elements found in numerous foods and dietary supplements. In addition to their antioxidant, anticancer, antibacterial, and anti-inflammatory effects, clinical research has suggested that they possess anti-allergic properties. Methods: Using differential-interference contrast (DIC) microscopy, we examined the effects of magnesium chloride (MgCl2) and zinc chloride (ZnCl2) on rat peritoneal mast cell degranulation. We also examined their effects in conjunction with adrenaline, the first-choice drug for anaphylaxis treatment. Results: Both MgCl2 and ZnCl2 reduced the number of degranulating mast cells in a dose-dependent manner. MgCl2 significantly decreased the number of degranulating mast cells at concentrations of 50 mM or higher, whereas ZnCl2 achieved similar effects at much lower concentrations of 25 µM or more. These levels of MgCl2 or ZnCl2 enhanced the inhibitory effects of 1 mM adrenaline on mast cell degranulation. Additionally, pharmacological inhibition of the transient receptor potential cation channel subfamily M member 7 (TRPM7) by NS8593 reduced the number of degranulating mast cells in a dose-dependent manner. Conclusion: This study is the first to provide in vitro evidence that magnesium and zinc stabilize mast cells in a dose-dependent manner and also enhance the effects of adrenaline. TRPM7, which has higher permeability to zinc ions than to magnesium ions, may contribute to the stronger mast cell-stabilizing properties of zinc.

Acid-Enzyme Derived Agarotriose Facilitates Anti-Inflammatory Activity for Dextran Sulfate Sodium-Induced Colitis Alleviation as a Food Supplement.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with inadequate therapeutic options and has a significant impact on patient quality of life. We optimized the preparation of agarotriose (A3), a functional oligosaccharide, and assessed its health-promoting potential in a dextran sulfate sodium-induced UC mouse model. The beneficial effects of A3 were evaluated through histopathological, biochemical, immunological, and transcriptomic analyses. The medium dose (200 mg/kg) exhibited the greatest protective effect. A3 effectively restored substantial gut barrier integrity by dose-dependently increasing goblet cell numbers and enhancing the mucus layer thickness through MUC2 upregulation. It also re-established the continuous distribution of tight junction proteins (claudin-1, occludin, and ZO-1), thereby reinforcing gut barrier function. Biochemically, A3 mitigated oxidative stress by reducing malondialdehyde and myeloperoxidase levels, while enhancing antioxidant defenses by boosting total antioxidant capacity and total superoxide dismutase activity. Immunologically, A3 notably suppressed pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β, and IL-6) and increased anti-inflammatory IL-10 levels, promoting a protective immune response. Transcriptomic profiling identified 3871 differentially expressed genes, with A3 downregulating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway─a key regulator of inflammation and cell survival. This was further confirmed by reduced PI3K, Akt, and mTOR phosphorylation, verifying pathway suppression.

Unraveling the role of shrimp hydrolysate as a food supplement in the immune function and fecal microbiota of beagle dogs

Abstract The inclusion of protein hydrolysates from animal by-products in petfood may enhance the industry’s sustainability, while contributing to dogs’ health due to their nutritional and functional properties. However, inconsistent results of protein hydrolysates on gut microbiota, immune responses, among other health parameters, have been observed in dogs. This study aimed to evaluate the effects of diets supplemented with 5% shrimp hydrolysate, compared to non-supplemented diets, on hematological parameters, serum chemistry profile, innate and adaptive immune function, and fecal microbiota composition in adult Beagle dogs during a 12-week feeding trial. Dietary inclusion of shrimp hydrolysate decreased blood eosinophils (P = 0.017) and glucose levels (P = 0.023), while increasing levels of white blood cells (P = 0.002), platelets (P = 0.038), neutrophils (P = 0.036), and CD4+ (P &lt; 0.001) and CD8+ T cells (P &lt; 0.001) single producers of tumor necrosis factor-alpha. It also led to a more extensive proliferation of CD4+ T cells in response to LipL32 antigen (P = 0.020) and to a decrease in superoxide production in stimulated cells (P = 0.002). Additionally, supplemented diets increased Oscillospiraceae (P-adj = 0.005) and Clostridia (P-adj = 0.017) abundance, and decreased such of Sellimonas (P-adj = 0.025). Overall, the results indicate that diet supplementation with shrimp hydrolysate at 5% modulates the immune response and fecal microbiota, highlighting its potential to be included in hypoallergenic and gastrointestinal diets, and in diets for diabetic dogs.

Fisetin as a Promising Agent in Non-Alcoholic Fatty Liver Disease: Insights into Pathogenic Mechanisms and Therapeutic Potential

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver condition characterized by fat accumulation in the liver, with its development involving intricate processes such as inflammation, oxidative damage, and lipid metabolism disturbances. Current treatment options are limited, emphasizing the need for multi-targeted approaches that can simultaneously address these pathogenic pathways to improve liver health. This review synthesizes current evidence on how fisetin impacts molecular pathways relevant to NAFLD. It focuses on its effects in reducing inflammation, oxidative stress, and lipid accumulation, based on experimental and clinical studies examining gene expression, enzyme activity, and signaling pathways involved in hepatic steatosis and injury. This review also explores the mechanisms by which fisetin intervention influences NAFLD management, highlighting its role in glycemic control through postprandial glucose reduction, mitigation of insulin resistance, improvements in pancreatic insulin secretion, and suppression of hepatic gluconeogenesis and glycogenolysis. Additionally, fisetin exerts plasma lipid-lowering effects by enhancing hepatic β-oxidation and reducing lipogenesis. Its anti-inflammatory effects are observed both systemically and locally within the liver. Fisetin also strengthens antioxidant defenses by activating antioxidant enzymes, reducing superoxide levels, chelating metal ions, and scavenging free radicals. Furthermore, fisetin modulates endoplasmic reticulum (ER) stress and promotes autophagy, contributing to the amelioration of NAFLD pathology. Taken together, fisetin exhibits a promising hepatoprotective profile and may serve as a beneficial natural supplement for liver health. Its potential benefits in reducing liver steatosis and supporting NAFLD management, combined with its minimal side effects, make it an attractive candidate for further exploration as a complementary therapy

Curcumin and omega-3 ameliorate experimental osteoarthritis progression in terms of joint pain and mitochondrial dysfunction

Abstract Background Osteoarthritis (OA), a chronic degenerative disorder, induces pain, joint inflammation, and destruction of the articular cartilage matrix. Curcumin and omega-3 have been used as dietary supplements for OA due to their anti-inflammatory and antioxidant properties. However, there is no evidence demonstrating a synergistic effect in OA. The current study aimed to investigate the therapeutic effects and underlying mechanism of a combination of curcumin and omega-3 in the treatment of OA. Methods Wistar rats were injected with monosodium iodoacetate to induce OA. Oral treatments of a vehicle, curcumin, curcumin and omega 3, or celecoxib were administered. Pain was analyzed according to the paw withdrawal latency, paw withdrawal threshold, and weight bearing ability. The joint was isolated from OA rats, and cartilage damage was evaluated using histomorphological techniques, the Mankin scoring system, and micro computed tomography analysis. Protein expression in the joint was examined using immunohistochemistry. The expression levels of catabolic markers were measured in curcumin and omega-3-treated OA chondrocytes. Results The OA animal model revealed diminished pain and cartilage conservation in response to the combined treatment. mRNA levels of matrix metalloproteinase 1 (MMP1), MMP3, and MMP13 were reduced in interleukin-1 beta-simulated human OA chondrocytes. Additionally, mitochondrial markers, cytochrome c oxidase 4, and TOMM20, were increased by the combination treatment. Conclusions These findings suggest promising therapeutic outcomes for the combined treatment of curcumin and omega-3 in OA patients.

Fatality of health supplements– An autopsy case report on iron tablets poisoning

Fatality of health supplements– An autopsy case report on iron tablets poisoning

Awareness of genetic testing and its impact on changing behavior among general population of U.S - Health Information National Trends Survey (HINTS 2022).

This study aims to determine the frequency of genetic testing awareness, the number of individuals who have undergone genetic testing, and the subsequent behavior changes following testing. The analysis utilized recent data from the Health Information National Trends Survey (HINTS) 6, collected between March and September 2022, from a diverse sample of adults aged 18 and older. Logistic regressions were applied to assess predictors of outcome variables. A p-value of < 0.05 was considered statistically significant. Among the 4,631 respondents, 81.6% reported being aware of genetic testing, 28.7% (n = 1,327) had undergone some form of testing, and 16.3% of those tested reported making behavioral changes based on their results. Ancestry-related genetic testing was the most widely recognized and frequently utilized. However, behavioral changes were most commonly reported among individuals who underwent disease-specific genetic testing, especially those who perceived themselves to be at high risk, were motivated to take preventive measures, and received assistance in understanding their results. Within this subgroup, lifestyle modification was the most frequently cited change, followed by adjustments in dietary supplement use, increased health screenings, and changes to medications. Additionally, individuals from racial and ethnic minority groups were more likely than non-Hispanic White respondents to undergo specific types of genetic testing and to report behavior changes in response to the findings. The study highlights an increasing awareness and involvement in genetic testing, though a smaller percentage of individuals have altered their behavior based on the test results. Additionally, the study identifies genetic literacy as a key factor in predicting behavior changes.

Thermodynamic and Structural Evaluation of the Icariside II and Whey Protein Concentrate Complexes

Icariside II (ICS), the main active component of the Herba Epimedii, has attracted abundant interest due to its extensive range of potential health-promoting applications such as cancer prevention, treatment of cardiovascular disease, osteoporosis and erectile dysfunction and delaying the effects of Alzheimer’s disease. However, its great potential as a food supplement is diminished by its poor bioavailability. Although in the case of other flavonoids complexation with whey protein concentrate (WPC) resulted in significant bioavailability improvement, so far, no studies investigated the complex formation with icariside II. This study focuses on understanding the interactions between icariside II and WPC, with a specific focus on β-lactoglobulin (β-lg), its main protein component. The comparison of the performed X-ray powder diffraction, differential scanning calorimetry and Fourier transform infrared spectroscopy measurements between the raw mixture of WPC and ICS and the complex provides evidence of the formation of a new supramolecular ICS-WPC complex. The binding constant, binding number and thermodynamic parameters of the reaction were obtained using fluorescence spectroscopy. Additionally, a molecular docking study was performed to further investigate the interaction between ICS and β-lg. The complex formation of ICS-WPC opens up a new possibility to improve the bioavailability of the icariside II, thus contributing to the prevention and curing of many diseases.

COMPARATIVE CHARACTERISTICS OF MORPHOLOGICAL AND MORPHOMETRIC PARAMETERS OF LIVER SINUSOIDS OF WHITE RATS AFTER 4 AND 8 WEEKS OF EXPERIMENTAL EXPOSURE TO 10% CANNABIDIOL OIL

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid of Cannabis sativa, characterized by a wide range of possible therapeutic effects, including anticonvulsant, anti-inflammatory, antioxidant, anxiolytic, neuroprotective and other properties.The aim of the study was to establish morphological features and conduct a comparative morphometric analysis of liver sinusoids of white rats after 4 and 8 weeks of experimental exposure to 10% cannabidiol oil.Materials and methods. The study was conducted using 40 sexually mature white non-linear male rats weighing 180-230 g, whose age at the beginning of the experiment was 5-7 months. The main group of the experiment was divided into two subgroups (series) of 14 rats each. Rats in the first series were administered 10% cannabidiol oil orally dripped at a dose of 10 mg/kg/day once a day for 4 weeks. Rats in the second series were administered 10% cannabidiol oil orally dripped at a dose of 10 mg/kg/day once a day for 8 weeks (long-term chronic exposure to CBD). The control group consisted of 12 sexually mature white male rats (6 rats each) to compare the two series of the experimental study. All experiments, as well as housing, care, feeding, marking and euthanasia were carried out in compliance with the requirements of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 1986), Council of Europe Directive 2010/63/EU, Law of Ukraine No. 3447-IV “On the Protection of Animals from Cruelty to Animals”. Liver tissue was used as the material for morphological studies. A morphological study of the sinusoids of the hepatic lobule and a morphometric study of the average diameters of the sinusoids with statistical calculation were carried out. The reliability criteria of Pearson (χ2), Mann-Whitney (U), Wilcoxon T-test, McNemar p (McN) were used. The difference was considered statistically significant at a minimum significance level of p&lt;0.05.Results. The morphological study allowed us to establish that the macroscopic structure and microscopic organization of the liver lobule were preserved and did not undergo histopathological changes under the conditions of experimental exposure to 10% CBD oil (10 mg/kg/day) as a dietary supplement for four and eight weeks. Comparative characteristics of morphometric parameters of liver sinusoidal hemocapillaries after four and eight weeks of the experiment demonstrated that the average sinusoidal diameter after 4 weeks did not differ significantly from the control group (p=0.59). In the experimental series after 8 weeks of CBD exposure, i.e. after long-term use of the cannabinoid, the average sinusoidal diameter was 9.72±0.33 μm and significantly differed from the control group (p&lt;0.05) and the experimental series after 4 weeks of CBD exposure. Statistical calculations of single and multiple dilated and hyperemic sinusoids in the respective series, their comparison with the control group and in dynamics indicate that the single dilated and hyperemic sinusoids in both series differed from the control group. The significance of the difference according to the Pearson criterion (χ2) corresponded to the value of p=0.56 in the series after 4 weeks of CBD exposure and p=0.003 in the series after 8 weeks of CBD exposure. Multiple dilated and full-blooded sinusoids were observed only in the experimental series after 8 weeks of CBD exposure, which indicates the vasodilation effect of CBD and increased blood flow after long-term use of the cannabinoid.Conclusions. The results of morphological and morphometric analysis of liver sinusoids after four and eight weeks of experimental exposure to CBD indicate the safety of using 10% CBD oil at a dose of 10 mg/kg/day.

Caffeine as an Ergogenic Aid: A Literature Review of Mechanisms of Action, Performance Effects and Safety Thresholds

Abstract Background: Caffeine is the most widely consumed psychoactive substance worldwide, that can be found in coffee, tea, energy drinks, and dietary supplements. Numerous studies have confirmed caffeine’s potential to decrease fatigue and increase performance. However, optimal dosing strategies and safety profiles across diverse athletic populations remain under active investigation. Aim: This study present the current knowledge on the prevalence of caffeine consumption, its physiological mechanisms, its impact on physical performance, and the potential risks associated with its use. Material and methods. A literature review of studies published in the PubMed and Google Scholar databases was conducted, analyzing the prevalence of caffeine intake, its physiological mechanisms, effects on physical performance, and associated harms. Results. Caffeine supplementation, ingested approximately 60 minutes before exercise enhance endurance performance. In strength assessments, caffeine has been found to enhance 1RM (bench press, squat, deadlift). However caffeine also has adverse effects, including tremors, tachycardia, gastrointestinal discomfort and in some cases, cardiac arrhythmias, that can occur at doses exceeding 7 mg/kg. Caffeine metabolism can affected by genetic polymorphism, hormonal modulators and age-related factors, influence caffeine’s half-life and risk of accumulation. Conclusions. Caffeine supplementation at 3–6 mg/kg is an effective and generally safe ergogenic enhancer for increasing endurance and muscular strength. However, the narrow margin between optimal and toxic doses can be different at various population. Future research should focus on long-term safety of caffeine supplementation, the factors of inter-individual variability to caffeine safety and potential interactions with other performance-enhancing compounds.

Evaluating acceptability and experiences of pregnant women at high risk of developing gestational diabetes who take part in antenatal intervention trials: a qualitative systematic review

BackgroundGestational diabetes mellitus (GDM) is associated with short- and longer-term adverse outcomes for both mother and child. The success of randomised controlled trials (RCTs) assessing interventions to prevent GDM depends in part on participant adherence to and acceptability of the intervention. A review of the nested-qualitative components of antenatal RCTs to prevent GDM is lacking. This qualitative systematic review aimed to evaluate the experiences of pregnant women at higher risk of developing GDM who took part in preconception and/or pregnancy interventions which aimed to reduce GDM.MethodsElectronic databases (MEDLINE, EMBASE, Cochrane Library), and reference and citation lists were searched up to February 2025. Studies were eligible if they included qualitative research methods to examine the experiences of pregnant women following an intervention to reduce GDM. We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework, and the Critical Appraisal Skills Programme (CASP) qualitative checklist was used to assess the quality of the studies.ResultsOf the 38,812 studies initially identified, 102 trials were screened for eligibility, and four met the inclusion criteria and were included. All were pilot RCTs using semi-structured interviews in high-income countries (UK n = 3, USA n = 1). Data were synthesised into three themes: (1) acceptability of the interventions, (2) adherence to the interventions, and (3) perceived change in knowledge, attitude and behaviour. Acceptability of interventions was influenced by awareness of GDM, extra support and antenatal care, and natural pharmacological supplements. Adherence to interventions was facilitated by the intervention content and delivery. Perceived change in knowledge, attitude and behaviour was facilitated by intervention specific components and perceived improvements in health.DiscussionThis review identified factors influencing adherence and acceptability of interventions for pregnant women at high risk of GDM. It also highlighted a lack of embedded qualitative studies exploring women’s experiences of participating in antenatal interventions. The findings suggest that improving the design and implementation of pregnancy interventions requires greater attention to participants’ experiences and support systems. This study highlights the need for nested qualitative studies in RCTs to improve acceptability and adherence to pregnancy interventions.

Metabolomics provides novel understanding of Melissa officinalis mechanism of action ensuring its calming effect on dogs

BackgroundAnimal welfare encompasses both its physical and mental states. This latter could be altered by several psychological-related disorders including stress and anxiety. To address these issues, Melissa officinalis, a Lamiaceae plant, ensuring the anxiolytic-type effects, is widely used. In this study, the main aim was to explore the effect of a commercial hydro-alcoholic Melissa officinalis extract (MOE) and its major compound rosmarinic acid (RA) on dogs’ behavior and metabolome. To do so, twenty healthy beagle dogs were randomly assigned to 4 dietary supplements (5 dogs/group): the first group received a placebo supplemented with maltodextrose (200 mg/kg), the second group was supplemented with MOE (200 mg/kg), the third group received RA at a dose of 10.6 mg/kg, and the fourth group was administered α-casozepine (AC) at a dose of 225 mg in capsule form. Dogs’ behavior was monitored after 4 weeks of treatment using a standardized evaluation grid developed by Oniris. In addition, 4-hydroxybyturic acid (GHB) was quantified to study the effect of the supplementations on the metabolites of γ-aminobutyric acid (GABA) biosynthetic pathway. Moreover, the impact of all supplementations on dogs’ metabolome was assessed using untargeted metabolomics at the end of the supplementation period.ResultsResults demonstrated significant differences between the mean behavioral score of placebo group (-3.4) compared to MOE (2.0), RA (1.4), and AC (0.8) groups. In addition, GHB measurement revealed a decrease in its quantity in all supplemented groups compared to the control. Moreover, untargeted metabolomics uncovered several metabolic pathways, that were impacted by MOE supplementation linked to lipids and bile acids metabolism. Furthermore, RA supplementation impacted fatty acids and lipids metabolism pathways while supplementation with AC affected pathways linked to lysine and sphingolipids metabolism.ConclusionsOur study demonstrated a calming effect of MOE on beagles and proposes a novel hypothesis that sheds new light on its potential mechanism of action. This study underlines metabolomics as an effective tool for gaining deep insights into the metabolic changes associated with supplementation.

Analysis of clinical and epidemiological interactions of phenol and phthalate levels in blood and urine with anamnestic and biochemical health measures during the formation of multisystem organ pathology

Background. Phenol and its derivatives (eg. parabens), phthalates and a number of other aromatic compounds exhibit various toxic effects when entering the human body due to unfavorable ecology, smoking, intake with food and medications. Integrated clinical and epidemiological studies into the clinical consequences of such effects are currently lacking.Objective: To identify patient history parameters that are significantly associated with blood and urine levels of phenols and urine levels of phthalates.Material and methods. The database of the UNESCO Institute for Microelements was used to compile a sample of patient descriptions (n=2746) containing information on the serum and/or urine levels of phenol and urine levels of phthalates. The data sample was analyzed using the methods of Zhuravlev–Rudakov topological and metric data analysis, as well as parametric and nonparametric statistics. The data analysis was carried out in three stages: (1) identification of statistically significant pairwise interactions by the methods of topological data analysis; (2) identification of clusters of pairwise interactions; (3) description of the obtained patterns in the form of metric diagrams, topological “interaction formulas” and “interaction types”.Results. Higher urine levels of phenol were associated with increased levels of bone and cartilage destruction markers, hematopoiesis disorders (decreased hemoglobin and mean corpuscular volume), liver and kidney dysfunction (increased creatinine and albumin levels), decreased systolic blood pressure (hypotension) in the setting of lower intake of fiber, vitamins E, A, C, B2, B6, folates, and magnesium. Higher urine phenol concentrations were correlated with higher levels of a smoking biomarker (cotinine), indicating that smoking is a significant source of phenol and its derivatives in the human body. Higher blood phenol concentrations were associated with a history of smoking, asthma, type 2 diabetes mellitus (T2DM), vasomotor paroxysms (hot flashes), and pain symptoms. Significantly higher blood phenol concentrations were found in participants not taking vitamin and mineral supplements (VMS). Higher urine phthalate levels were found in patients with chronic obstructive pulmonary disease (COPD), alcoholism, pain symptoms (headaches, lower back and leg pain), diabetic polyneuropathy, hematopoiesis disorders (increased erythrocyte distribution width), cartilage homeostasis, liver dysfunction, kidney dysfunction and, in general, a decreased quality of life. Elevated urine phthalate levels corresponded to a lower intake of vitamins A, C, B2, B12, folates, cobalt, iron and lutein n the setting of higher blood concentrations of toxic cadmium, lead and cotinine. This confirms the correlation between smoking and increased concentrations of phenol and its derivatives.Conclusion. Elevated urine levels of phenols and phthalates and blood serum levels of phenols are associated with a number of socially significant chronic pathologies (T2DM, COPD, pain, cartilage, and bone homeostasis disorders) and with lower VMS intakes. Thus, correction of the vitamin and microelement status is an ffective approach to supporting the body's detoxification systems against the negative impact of phenol and its derivatives.