Vitamin C (1000mg)

OBJECTIVE: To critically synthesize evidence on pharmacological and non-pharmacological interventions relevant to nursing practice for the prevention and management of bladder spasms and catheter-related bladder discomfort in adults with indwelling urinary catheters. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases including PubMed, CINAHL, MEDLINE, and Scopus were searched for English-language studies published from 2015 to 2025. Randomized controlled trials, quasi-experimental, and prospective studies involving adult patients with indwelling urinary catheters were included. RESULTS: Ten studies met the inclusion criteria. Both pharmacological and non-pharmacological interventions were effective in reducing bladder spasms and catheter-related bladder discomfort. Non-pharmacological, nursing-led interventions-such as catheter balloon volume adjustment, neuromodulatory techniques, evidence-based targeted nursing care, structured nursing management models, and Traditional Chinese Medicine-based nursing approaches-demonstrated consistent reductions in symptom severity and improvements in patient comfort. Pharmacological therapies, including vitamin C, solifenacin, and ketamine, were primarily effective for short-term symptom relief. Overall, four studies were assessed as having low risk of bias, five as moderate risk, and one as high risk. CONCLUSION: Nursing-led, non-pharmacological interventions play a central role in managing bladder spasms in patients with indwelling urinary catheters and should be prioritized in clinical practice. Further high-quality studies with standardized outcome measures are required to strengthen the evidence base. OBJETIVO. Sintetizar de forma crítica la evidencia sobre las intervenciones farmacológicas y no farmacológicas relevantes para la práctica de la enfermería en la prevención y el tratamiento de los espasmos vesicales y las molestias vesicales relacionadas con el catéter en adultos con catéteres urinarios permanentes. MÉTODOS. Se realizó una revisión sistemática de acuerdo con las directrices Preferred

Glutathione (GSH) is a central regulator of redox homeostasis, melanogenesis, and cellular repair, and has gained increasing attention in dermatology for its potential roles in skin brightening, anti-aging, and tissue regeneration. This systematic review evaluated molecular, clinical, and translational evidence of glutathione's applications and safety across different delivery modalities. The review followed PRISMA guidelines and included studies published between 2000 and 2025. A total of 194 studies met the inclusion criteria, evaluating the effectiveness of glutathione in esthetic dermatology and regenerative medicine. Topical and oral glutathione demonstrated favorable effects on pigmentation, skin brightness, hydration, and oxidative stress markers. Injectable glutathione increases systemic levels rapidly, but is associated with short-lasting effects and potential safety concerns. Glutathione S-transferases facilitate the conjugation of glutathione to electrophilic xenobiotics, thereby protecting proteins and nucleic acids from electrophile-induced damage. Glutathione Peroxidase employs GSH as an electron donor to reduce hydrogen peroxide and lipid hydroperoxides, thus protecting membrane lipids, mitochondrial membranes, and DNA from oxidative damage. Glutathione facilitates the regeneration of other antioxidants, such as vitamin C and vitamin E, through redox cycling. A consistent correlation exists between reduced GSH levels and neuronal dysfunction. Elevated GSH levels enhance cellular resistance to oxidative stress and reduce apoptotic signaling. GSH plays a pivotal role in cutaneous aging and tissue repair through redox regulation, mitochondrial protection, and the modulation of inflammatory and extracellular matrix pathways. To elucidate the clinical significance of glutathione, future research should focus on conducting randomized controlled trials, developing standardized formulations, and performing long-term safety assessments.

OBJECTIVES: To update evidence-based management recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with sepsis or septic shock. DESIGN: A panel of 68 international experts, representing 13 international organizations, as well as six methodologists, was convened. A formal conflict-of-interest policy was developed at the onset of the process and applied throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and subgroup leads as well as within subgroups, served as an integral part of the guideline development process. METHODS: New priority topics and recommendations from the prior guideline iteration were used to identify Population, Intervention, Control, and Outcomes (PICO) questions likely to have new or updated evidence. We conducted a systematic review to identify the best available evidence, summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or conditional, or as a good practice statement. "In our practice," statements were included when evidence was inconclusive to issue a recommendation but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 61 statements on the management of children with sepsis or septic shock. Overall, five were strong recommendations, 24 were conditional recommendations, and ten were good practice statements. For 22 PICO questions, no recommendations could be made, but, for seven of these, "in our practice" statements were provided. Compared with the 2020 guidelines, 20 recommendations were new, 13 were updated for clarity and/or new evidence, six were reviewed but not changed, and 22 were carried forward based on consensus of the panel that new evidence was not available. Only three recommendations were based on high or moderate certainty of evidence. CONCLUSIONS: Updated management guidelines were issued by a panel of international experts for the best care of children with sepsis or sept

Background: Patients undergoing hemodialysis commonly exhibit deficiencies in water-soluble vitamins, primarily as a result of inadequate dietary intake and loss into the dialysate. Given the essential role of vitamin C in numerous metabolic pathways, routine supplementation has been proposed as a potentially beneficial intervention in this population. Aim: We aimed to evaluate the current evidence on vitamin C supplementation in patients undergoing hemodialysis, with particular attention to clinical conditions associated with renal replacement therapy, including anemia, chronic inflammation, restless legs syndrome (RLS), and secondary hyperparathyroidism. Methods: This systematic review was conducted in accordance with PRISMA guidelines. The MEDLINE (via PubMed) and EMBASE databases were searched. The initial search yielded 844 articles, of which 37 studies met the inclusion criteria for this review. Results: Evidence indicates that hemodialysis patients exhibit vitamin C deficiency, both in dietary intake and in plasma or serum concentrations. Despite its intrinsic antioxidant properties and proposed anti-inflammatory effects, vitamin C supplementation has demonstrated inconsistent effects on inflammatory markers. Most clinical studies support a beneficial role of vitamin C supplementation in functional iron deficiency and in alleviating symptoms of RLS within this population. Conclusions: Evidence on vitamin C supplementation for functional iron deficiency and RLS suggests that it might be an effective therapeutic approach. However, despite low serum vitamin C level in hemodialysis patients, current data does not justify the routine use of vitamin C in the hemodialyzed population for other comorbidities, including chronic inflammation and secondary hyperparathyroidism. Further high-quality studies are required to establish the broader clinical utility of targeted vitamin C supplementation.

High-dose intravenous vitamin C (IVC) achieves plasma concentrations that are not attainable by oral administration and has been investigated as an adjunct in sepsis, oncology, and symptom management. To synthesize the evidence regarding the clinical benefits and risks of high-dose IVC, as well as the potential advantages of on-site infusion, a PRISMA-informed search of PubMed/PMC, Scopus, and Web of Science (2010-2025) was conducted, prioritizing randomized controlled trials, systematic reviews, and high-quality observational studies. Pharmacokinetic and mechanistic studies of IVC support plausible physiologic benefits through antioxidant effects, catecholamine biosynthesis, and immune modulation, with recent evidence showing down regulation of pro-inflammatory STAT1/PD-L1 pathways in experimental sepsis. Oncology phase I and II studies demonstrate safety and quality-of-life improvements; a randomized phase II pancreatic trial reported a promising survival benefit when combined with chemotherapy. Some of the major risks include oxalate nephropathy and hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, especially with very large or repeated doses, suggesting pre-screening to avoid these risks. Furthermore, the literature on home infusion and IV therapies is limited; however, the expanding home infusion infrastructure offers an avenue for monitored IVC delivery. In conclusion, evidence does not support routine use of high-dose IVC in sepsis, and its role in oncology remains supportive and exploratory, with potential risks requiring caution. Furthermore, interest in home-based infusion services is increasing in several healthcare systems, although clinical outcome data specific to high-dose IVC in these settings remain limited. © 2026 The Author(s).

Uncertainty persists regarding the estimated effects of vitamin C supplementation on blood pressure, including the strength of the evidence supporting these estimates and the magnitude of the observed effects relative to the minimal important difference. We aimed to provide an overview of the effects of vitamin C supplementation on blood pressure among adults through an umbrella review of randomized controlled trials (RCTs). PubMed, Scopus, and Web of Science, and the Cochrane Library were searched from the earliest date available to 25 December 2024. We identified eligible meta-analyses and included all primary trials, adding any RCTs not included in the largest review. For each trial, we extracted the mean change in blood pressure and its SD for both groups to calculate the mean difference as the effect size. The certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. We identified six meta-analyses involving a total of 17 RCTs reporting systolic blood pressure (SBP) and diastolic blood pressure (DBP) as outcomes. The findings suggest that vitamin C supplementation may reduce SBP by approximately 3.7 mmHg. Although DBP did not decrease overall, a clinically important reduction was observed in patients with diabetes (-2.27 mmHg). These results indicate that vitamin C supplementation may have a meaningful beneficial effect on blood pressure. Nevertheless, the low certainty of evidence highlights the necessity for larger, long-term randomized trials to definitively confirm its efficacy.

BACKGROUND: Scurvy persists as a significant adult medical condition, frequently overlooked due to its mimicry of more common diseases. This review aims to analyse reported adult cases from the twenty-first century to characterize its current epidemiology, clinical presentation, and diagnostic challenges. METHODS: A systematic literature review was conducted across PubMed and MEDLINE for the period 2000-2025, including case reports, case series, and observational studies on adult scurvy. Non-informative texts and paediatric cases were excluded. Artificial intelligence (AI) tools were utilized to assist in translating non-English articles and to extract preliminary data from plain text. To ensure data integrity, all AI-generated variables were rigorously manually verified against the original full-text articles to correct any potential errors or hallucinations. RESULTS: We identified 280 cases of adult scurvy reported from 2000 to 2025. Predominant clinical features included skin lesions, specifically purpura and corkscrew hairs, alongside anaemia and haemorrhage. Social determinants of health played a critical role; many patients presented with restrictive diets, homelessness, or social isolation-risk factors often overlooked at initial presentation. The clinical picture was frequently obscured by nonspecific symptoms, such as general physical deterioration, rheumatological symptoms or oral manifestations leading to diagnostic delays and extensive, unnecessary investigations for autoimmune or haemostatic disorders. CONCLUSION: Despite the varied presentations, early recognition remains crucial for effective management of this misdiagnosed condition mimicking more frequent diseases like autoimmune or haemostatic disorders to prompt rapid and efficacious vitamin C supplementation. Addressing social determinants of health, including poverty, social isolation, and limited access to nutritious food, is essential for preventing and managing scurvy within vulnerable populations.

INTRODUCTION: Exercise-induced oxidative stress and inflammation may impair recovery and performance. Vitamin C, a potent antioxidant, has been proposed to attenuate exercise-induced muscle damage and modulate inflammatory and oxidative biomarkers during recovery. METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD42024594742). Twelve randomized controlled trials involving adult participants exposed to different exercise protocols were included. Vitamin C supplementation, administered in various forms, was compared with placebo. Primary outcomes were inflammatory (CRP, IL-6) and oxidative stress (MDA) biomarkers. Risk of bias was assessed using the RoB 2.0 tool, and certainty of evidence was evaluated using the GRADE framework. RESULTS: Pooled analyses showed no significant effects of vitamin C supplementation on IL-6 (MD = 0.00; 95 % CI: -0.25 to 0.25; p = 1.00; 2 trials, n = 31) or MDA (MD = -0.59; 95 % CI: -1.99 to 0.81; p = 0.41; 3 trials, n = 41). A significant reduction was observed for CRP (MD = -0.44; 95 % CI: -0.66 to -0.22; p = 0.0001; 2 trials, n = 52). Heterogeneity was substantial for MDA (I2 = 80 %) but negligible for IL-6 and CRP (I2 = 0 %). Risk of bias was predominantly rated as "some concerns" or "high." According to GRADE, the certainty of evidence was low for IL-6 and CRP and very low for MDA due to risk of bias and imprecision. CONCLUSION: Based on a very limited number of small randomized trials, vitamin C supplementation does not appear to consistently modify post-exercise inflammatory or oxidative stress biomarkers. However, the available evidence is characterized by low to very low certainty, substantial methodological limitations, and imprecision. Therefore, these findings should be interpreted with caution and considered hypothesis-generating, underscoring the need for larger, high-quality, well-controlled trials.

Endometriosis is a chronic, estrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age worldwide. It is characterized by the presence of endometrial-like tissue outside the uterine cavity, which frequently results in dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. While hormonal medications and surgical procedures are common treatments, they are often constrained by adverse effects and high recurrence rates. The aim was to systematically identify, critically appraise, and synthesize randomized controlled trials evaluating vitamin D, C, and E supplementation in women with endometriosis, focusing on their effects on pelvic pain, dysmenorrhea, dyspareunia, quality of life, oxidative and inflammatory biomarkers, and fertility-related outcomes, and to highlight methodological gaps that can inform future research and integrated therapeutic strategies. Following PRISMA guidelines, seven eligible RCTs were identified from databases including PubMed, Scopus, and ScienceDirect. The quality of these studies was assessed using the Jadad Scoring System and Cochrane RoB 2 tool. High-dose supplementation of vitamin D (50,000 IU) was found to significantly reduce pelvic pain and improve biochemical markers such as hs-CRP and total antioxidant capacity (TAC). Vitamin D appears to modulate endometrial pathways by reducing active β-catenin protein activity, which may disrupt signaling associated with lesion invasion and survival. Additionally, combined Vitamin C and E therapy (typically 1000 mg/day of Vitamin C and 800 IU/day of Vitamin E) acts synergistically to scavenge free radicals. This intervention significantly decreased oxidative stress markers, including malondialdehyde (MDA) and reactive oxygen species (ROS). Patients reported significant improvements in symptoms, including a 43% reduction in daily pelvic pain and a 37% reduction in dysmenorrhea. Despite physiological improvements, there was no statistically significant increase in pregnancy rates observed across the trials. Vitamin supplementation with D, C, and E represents a safe, low-cost adjunct therapy that can effectively mitigate endometriosis-related oxida

INTRODUCTION: Existing guidelines lack comprehensive recommendations for stroke prevention. This network meta-analysis aimed to evaluate the comparative efficacy of non-pharmacological interventions in preventing total stroke and fatal stroke in high-risk adults. METHODS: We pooled only randomized controlled trials (RCTs). Relative risks (RRs), 95% confidence intervals (CIs), and P scores were computed to compare and rank the efficacy of interventions in preventing stroke. RESULTS: 50 RCTs with 673,624 participants were pooled in this study. Compared with the control group, Exercise + Education may decrease stroke risk (RR = 0.23; 95% CI: 0.07-0.73; low strength of evidence [SOE]), followed by Exercise (RR = 0.40; 95% CI: 0.28-0.57; moderate SOE), Mediterranean diet (RR = 0.70; 95% CI: 0.50-0.97; low SOE), and Vitamin B6 combined with B12 and folic acid (Vitamin B6 + B12 + folic acid) (RR = 0.86; 95% CI: 0.77-0.95; moderate SOE). Only Salt substitute showed significantly reduced fatal stroke risk (RR = 0.78; 95% CI: 0.68-0.90; high SOE). Exercise + Education (low SOE) and Exercise alone (moderate SOE) showed short-term benefits on preventing stroke, while Salt substitute had long-term effects on reducing fatal stroke risk (high SOE). Carotid endarterectomy (moderate SOE) and Vitamin C (high SOE) were significantly effective in preventing ischemic stroke, and Salt substitute (high SOE) showed significantly reduced hemorrhagic stroke and fatal hemorrhagic stroke risks. Vitamin B6 + B12 + folic acid may lower hemorrhagic stroke and transient ischemic attack risks (moderate SOE). CONCLUSION: Future studies should prioritize high-quality RCTs with large sample sizes, different follow-up durations and specific stroke types to confirm the efficacy of these non-pharmacological interventions. © 2026 S. Karger AG, Basel.

Nasopharyngeal carcinoma is prevalent in Thailand, with a substantial proportion of cases diagnosed at advanced stages. The standard treatment, concurrent chemoradiotherapy, is associated with considerable adverse effects, which may compromise therapeutic efficacy and diminish patients' quality of life. While vitamin C has shown potential in reducing chemotherapy-induced toxicities in some cancers, its effects in nasopharyngeal carcinoma remain unclear. In this randomized, double-blind, placebo-controlled trial, patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy were assigned to receive either 2 g of intravenous vitamin C or placebo prior to chemotherapy. The incidence of gastrointestinal adverse effects-including nausea, anorexia, mucositis, diarrhea, and dysphagia-did not differ significantly between groups. However, longitudinal analysis demonstrated a significantly attenuated decline in platelet counts in the vitamin C group compared with placebo. Although intravenous vitamin C did not reduce gastrointestinal toxicities, the observed platelet preservation suggests a potential supportive effect that warrants further investigation. Trial registration The study was registered with the Thai Clinical Trial Registry (TCTR20190316003) on March 16, 2019. Copyright: © 2026 Leelasawatsuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

BACKGROUND: Ascorbic acid (AA) has protective and corrective functions critical for counteracting extrinsic and intrinsic skin aging and hyperpigmentation, but it is highly unstable, making it challenging to formulate into skincare products. Tetrahexyldecyl (THD) Ascorbate, a lipid-soluble derivative of AA, has superior stability and skin-mimicking properties. AIMS: To investigate the efficacy and tolerability of a novel antioxidant serum containing 30% THD Ascorbate (THD-AA serum), a patent-pending blend of antioxidants and prebiotics, on photoaged and hyperpigmented skin with respect to long-term skin health. METHODS: Using preclinical models and a randomized, double-blind clinical trial, the antioxidant potential, antimelanogenesis, and antiaging properties of the THD-AA serum were evaluated. RESULTS: Using an in vitro tissue model exposed to blue light, there was an 88% reduction in reactive oxygen species (ROS) formation after 30 min, 87% reduction after 60 min, and an 82% reduction after 120 min compared to the blue light-exposed control. Melanin production was reduced by 24% in vitro tissue co-culture. THD-AA serum improved the structural architecture of the skin, including the epidermis, dermal-epidermal junction, and dermis, and upregulated dermal collagen production 4-fold compared to a controlled moisturizer in an ex vivo model. In the clinical trial, existing damage and hyperpigmentation were visibly corrected on VISIA-CR and Antera 3D photographs, as well as in Clinical Grader results. There were no adverse events, and participants tolerated the serum well. CONCLUSIONS: THD-AA serum has clinical and molecular efficacy in buffering ROS, reducing melanogenesis, and promoting antiaging, providing a safe alternative to hydroquinone products. © 2026 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

BACKGROUND: Salacca zalacca (snake fruit) is rich in antioxidants, polyphenols, organic acids, and vitamin C. This study aimed to evaluate the effectiveness of body massage oil containing snake fruit extract, in conjunction with traditional Thai massage (TTM), on skin quality in healthy individuals. METHODS: Seventy-one participants aged 18-35 years were randomly assigned to one of three groups: (1) control group (n = 23) receiving TTM without oil; (2) Treatment-1 group (n = 23) receiving TTM with pure coconut oil; and (3) Treatment-2 group (n = 25) receiving TTM with snake fruit extract-infused oil. All participants received 60-min massages once weekly for 12 weeks. Skin parameters including elasticity, moisture, melanin, and oiliness were assessed at the neck, back, arm, and leg regions. RESULTS: After 12 weeks, skin elasticity significantly improved at all assessed regions in all groups (p < 0.001), with no significant between-group differences. Skin melanin levels significantly decreased at the back and leg regions across all groups (p < 0.05), with no between-group differences observed. Skin moisture significantly increased at the leg region only in the Treatment-2 group (p = 0.003). Skin oiliness significantly increased at all measured regions in both oil-based groups (Treatment-1 and Treatment-2) (p < 0.05) and was significantly higher than in the control group (p < 0.05), except at the back region in the Treatment-2 group. CONCLUSION: Massage oil containing snake fruit extract demonstrated specific benefits in enhancing skin oiliness and localized moisture. However, it did not confer overall superiority over conventional coconut oil, while improvements in elasticity and melanin appeared to be primarily attributable to the massage technique itself. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06227260.

OBJECTIVE: To explore whether vitamin C supplementation in sepsis patients can reduce the occurrence of acute kidney injury. METHODS: A prospective, randomized and controlled pilot trial was conducted. All individuals participating in the study received comprehensive initial treatment for sepsis. This involved monitoring lactate levels, ensuring appropriate fluid resuscitation, administering empiric broad-spectrum antibiotics, and using vasoactive medications, with a preference for norepinephrine. If the norepinephrine dosage exceeded 20 μg/min, vasopressin was introduced at a rate of 0.03 U/min to sustain a mean arterial pressure of at least 65 mmHg. The experimental group was given vitamin C (1.5 g every 6 h by intravenous infusion) for 3 consecutive days, while the control group was given placebo. RESULTS: A total of 40 patients with sepsis were included in the study following application of the inclusion and exclusion criteria. Patients were randomized into control (n = 20) and experimental (n = 20) groups. No significant differences in baseline characteristics were found between the two groups (all p > 0.05). Among the 40 sepsis patients, 5 (25%) in the experimental group and 14 (70%) in the control group developed acute kidney injury, all of whom required support with continuous renal replacement therapy (RRT). The main site of infection was pulmonary, accounting for 70% of cases in the experimental group and 75% in the control group. The most common pathogenic bacteria were gram-negative bacilli (26/40, 65%). The experimental group had a significantly shorter length of stay in intensive care unit (ICU) compared to the control group (11.8 ± 2.7 days vs. 13.9 ± 2.1 days, p = 0.008), less frequent use of vasoactive drugs (35% vs. 75%, p = 0.011), and less frequent need for RRT within 72 h of admission (25% vs. 70%, p = 0.004). However, the mortality rate in ICU was not significantly different (10% vs. 15%, p = 0.633). CONCLUSION: The use of vitamin C in patients with sepsis is associated with a reduced incidence of acute kidney injury, although a larger sample size is required to confirm this finding. CLINICAL TRIAL REGISTRATION: This trial was registered at

AIMS: Road traffic noise is the dominant source of environmental noise in Europe and a recognized cardiovascular risk factor, yet direct mechanistic evidence from human studies remains limited. This study investigated the acute effects of low-level night-time road traffic noise exposure on cardiovascular parameters in healthy adults. METHODS AND RESULTS: In a randomized, double-blind, crossover design, 74 healthy participants were exposed to three overnight conditions: control (no noise, average sound pressure level (LAeq) 30.70 dB), 30 (LAeq 41.36), and 60 (LAeq 44.13) recorded road traffic noise events (peak level ≈60 dB). The primary endpoint was endothelial function assessed by flow-mediated dilation (FMD) the morning after each night; a subgroup received vitamin C to assess oxidative stress involvement. Secondary endpoints included sleep quality (questionnaires), cardiovascular parameters (blood pressure, heart rate, electrocardiogram), and targeted proteomic analysis (Olink panels). FMD significantly decreased from 9.35% (control) to 8.19% after 30 noise events (Δ = 1.16%, P = 0.005) and 7.73% after 60 events (Δ = 1.63%, P < 0.0001), with the strongest FMD improvement by vitamin C in the 60-event condition (Δ = 1.02%). Noise exposure increased heart rate (mean difference Δ = 1.23 bpm, P = 0.04; max Δ = 7.95 bpm, P < 0.001) and the odds of post-noise heart rate peaks (odds ratio 2.42, 95% confidence interval 2.07-2.83). After noise exposure, self-reported sleep quality and restfulness were significantly impaired across all dimensions. Clinical chemistry blood parameters did not change significantly. Proteomic analysis revealed noise-associated changes in interleukin signalling and chemotaxis in participants with the strongest FMD impairments. CONCLUSION: Acute exposure to night-time road traffic noise leads to measurable changes in cardiovascular health parameters in healthy adults. These effects were linked to activation of molecular pathways of immune signalling. Plasma proteome changes were correlated to FMD changes (responders vs. non-responders), highlighting interindividual biological susceptibility to noise. © The Author(s) 2026. Published by Oxford

Comment in Am J Physiol Heart Circ Physiol. 2026 Apr 1;330(4):H1291-H1292. doi: 10.1152/ajpheart.00219.2026. Chronic anxiety is a highly prevalent condition in young adults that is often associated with irregular sleep patterns, potentially augmenting cardiovascular disease (CVD) risk. Sleep irregularity is significantly associated with elevated oxidative stress and lower vascular function and blood pressure control in individuals with chronic anxiety. This study examined whether these impairments in vascular function and blood pressure control are driven by elevations in oxidative stress. Twenty-five young adults (24 ± 4 yr) with generalized anxiety disorder (GAD) or elevated GAD symptoms were assessed for total sleep time irregularity (TSTI) via wrist-worn accelerometry and separated into high TSTI and low TSTI groups via median split. Precursors to CVD development including oxidative stress (whole blood superoxide levels), vascular function (exercise-induced flow-mediated dilation), and blood pressure control (cardiovagal baroreflex sensitivity) were evaluated in both groups following both acute antioxidant (alpha-lipoic acid, vitamin C, and vitamin E) or placebo (microcrystalline cellulose) supplementation. The high TSTI group displayed significantly greater oxidative stress, significantly lower vascular function, and significantly lower blood pressure control. Following antioxidant supplementation, oxidative stress and blood pressure control were significantly improved in the high TSTI group, whereas vascular function was significantly improved independent of group. Antioxidant supplementation reduced oxidative stress and normalized blood pressure control differences between groups, implicating oxidative stress as a key mechanism linking sleep irregularity and CVD risk in young adults with chronic anxiety.NEW & NOTEWORTHY This study is the first to identify oxidative stress as a mediator of early cardiovascular disease (CVD) risk associated with total sleep time irregularity (TSTI) in young adults with chronic anxiety. Antioxidant supplementation reduced oxidative stress and improved blood pressure regulation in the high TSTI group. These findings suggest

BACKGROUND: Inorganic nitrate from dietary sources has raised health concerns due to its possible conversion into carcinogenic N-nitrosamines, leading to strict regulations on nitrate concentrations in food and drinking water. OBJECTIVES: In this study, which was a part of a larger randomized controlled trial, we evaluated urinary excretion of N-nitrosamines in response to daily dietary nitrate intake over a 5-wk period using 2 different forms of nitrate administration. METHODS: A total of 231 participants with mild hypertension were randomly assigned into 3 groups. Group 1 (n = 78) consumed vegetables low in nitrate along with a placebo capsule (300 mg potassium chloride). Group 2 (n = 77) consumed the same low-nitrate vegetables plus a potassium nitrate supplement (300 mg). Group 3 (n = 77) consumed nitrate-rich leafy green vegetables providing 300 mg nitrate daily plus the placebo capsule. Twenty-four-hour urine samples were collected before and after the intervention. Nitrate was measured with high-pressure liquid chromatography and N-nitrosamine concentrations were quantified using ultra high-pressure liquid chromatography-tandem mass spectrometry. A paired t-test was used for statistical analyses. RESULTS: As expected, urinary nitrate increased ∼5- to 6-fold in participants consuming nitrate-rich vegetables or potassium nitrate compared with those consuming potassium chloride. Total urinary excretion of N-nitrosamines was low across all groups under basal conditions (<5 μg/24 h) and did not significantly change after the intervention. A similar lack of change was observed for each of the 7 individual N-nitrosamine species measured. CONCLUSIONS: These findings suggest that a 5-wk dietary intake of nitrate mostly exceeding the current consensus for upper limit of the acceptable daily intake (3.7 mg/kg/d), whether provided as a vegetable source or as a nitrate salt, does not increase urinary excretion of N-nitrosamines. This study was registered at clinicaltrials.gov as NCT02916615.

BACKGROUND: Low fruit intake is a global risk factor for cardiometabolic diseases. This study sought to investigate vascular and metabolic effects of increasing total and select fruit intake in adults with prediabetes. METHODS: This randomized, 2-arm parallel, partially controlled feeding study provided participants (n=82, aged 45±15 years, 30±6 kg/m2) weekly diets (1500 [women] or 1750 kcal/d [men]) incorporating 1 avocado and 1 cup of mango (avocado-mango diet) daily for 8 weeks or energy-matched low-fat, low-fiber foods (control diet). Flow-mediated vasodilation was the primary end point. Central and brachial blood pressure; pulse-wave velocity; metabolic, inflammatory, and kidney function markers; and dietary intake were secondary end points. Change (Δ) data were analyzed by mixed model ANCOVA or Wilcoxon rank-sum test, and postprandial and dietary intake data by repeated-measures ANOVA using SAS 9.4 (SAS Institute, Cary, NC). RESULTS: Changes in percentage of flow-mediated vasodilation were significantly different between interventions (effect, -2.11±0.77%; P=0.008), increasing ≈1% on the avocado-mango diet and decreasing on the control diet, as were changes in central and brachial diastolic blood pressure (P=0.07 and P=0.03, respectively), specifically in men. Other end points were generally not different between diets (P>0.05), although select lipids and kidney markers were marginally different (P<0.1). Total fruit, dietary fiber, vitamin C, and monounsaturated fat intake significantly increased during the avocado-mango diet compared with the control diet (P<0.05). CONCLUSIONS: In adults with prediabetes, daily inclusion of avocado and mango increases fruit consumption, diversifies nutrient composition, and improves vascular function associated with cardiovascular health. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05353790.

BACKGROUND: In 2020, COVID-19 caused by the SARS-CoV-2 emerged as a global pandemic. Combination therapies for viral illnesses may be more effective than single-agent therapies in reducing symptoms and preventing disease progression. Repurposed drugs may offer cost-effective accessible treatment options while other novel therapies are being developed. STUDY QUESTION: To assess the safety and tolerability of a combination of repurposed drugs and supplements in the early therapy of acute nonhospitalized COVID-19 illness. STUDY DESIGN: A multicenter pilot cohort study was undertaken. Participants older than 40 years and positive for COVID-19 within 4 days of illness onset received telehealth outpatient care. The multimodal therapy of ivermectin, doxycyline, zinc, vitamin C, and vitamin D 3 was given as core therapy (group-1), or core therapy plus famotidine (group-2) for 10 days in a randomized masked controlled fashion. MEASURES AND OUTCOMES: A total of 275 participants, who were either vaccinated (n = 151) or unvaccinated (n = 124) for COVID-19, were randomized into group-1 (n = 137) or group-2 (n = 138). Four participants (1.5%) were hospitalized within the first 28 days. RESULTS: No viral rebound was experienced by any participants who took the 10-day therapy. Symptoms were reported daily until day 10, and at days 14, 28, and 90. The addition of famotidine resulted in less fatigue and nasal symptoms at day 14. These 5-component and 6-component interventions (ie, core therapy with and without famotidine) were equally safe and well tolerated. CONCLUSIONS: The multimodal therapy for acute COVID-19 was safe and well tolerated. The results justify adequately powered trials of the 5- or 6-component intervention on major early and late outcomes of COVID-19 infections.

PURPOSE: Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for hematological disorders but often results in micronutrients deficiency and complications. Vitamin C, a potent antioxidant, may improve endothelial function, tissue protection, and immune recovery. This study evaluated the effects of early high-dose vitamin C supplementation on plasma vitamin C levels and post-HSCT complications. METHODS: In this pilot, triple-blind, placebo-controlled trial, 31 adult allo-HSCT patients were randomized to receive intravenous vitamin C (50 mg/kg/day) or placebo from day + 1 to + 14, followed by oral vitamin C (500 mg/day) or placebo until day + 100. Plasma vitamin C levels were measured at days 0, + 7, + 15, and discharge. Patients were monitored for post-HSCT complications until day + 100. RESULTS: Plasma vitamin C levels were significantly higher in the vitamin C group at all time points (P < 0.001). Trends toward reduced acute graft-versus-host disease (33% vs. 44%), lower oral mucositis severity (46.6% vs. 62.5%), and shorter duration (7.5 ± 3.6 vs. 9.1 ± 3.7 days) were observed, though not statistically significant. No significant adverse events were reported. CONCLUSION: High-dose vitamin C effectively corrected plasma levels, and while trends toward reduced complications were observed in allo-HSCT patients, larger trials are needed to confirm these findings. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Sweet peppers (Capsicum annuum L.) are an important dietary source of antioxidants. Optimizing fruit antioxidant quality under reduced inputs is essential to valorize sustainable pepper production. Here, we evaluated seven Spanish genotypes (traditional/local, derived experimental hybrids and commercial hybrids) across six treatments combining two fertilization (100% and 50%) and irrigation (100% and 75%) regimes, with plant growth-promoting rhizobacteria (PGPR) applied under reduced fertilization treatments. Vitamin C and flavonoids were quantified by HPLC at the green-ripe and fully ripe stages, and carotenoids were determined spectrophotometrically at the fully ripe stage. Several genotypes largely maintained antioxidant content under stress treatments, whereas specific genotype × ripening stage combinations showed maximum increases in vitamin C (+102%), flavonoids (+86% for kaempferol) and carotenoids (+67% for yellow-orange carotenoids) under certain low-input treatments compared to the control. The PGPR effects on vitamin C and carotenoids were generally small, with occasional reductions. However, the PGPR increased total and some individual flavonoids by up to 96% (luteolin) in green-ripe Piquillo and 128% (quercetin) in fully ripe Isabel F1 fruits compared to the corresponding non-inoculated treatments. This multi-genotype, two ripening-stage evaluation identifies Spanish traditional germplasm and derived hybrids with stable or improved antioxidant profiles under low-input conditions and provides insight into PGPR effects. These results support the use of traditional genotypes in breeding for sustainable production.

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

Nitrate-rich vegetables are increasingly recognised as a key subgroup of phytochemical-dense foods that have significant potential for preventing and managing chronic diseases. Although dietary nitrates were historically approached with caution due to concerns about nitrosamine formation, contemporary evidence highlights their beneficial effects on vascular, metabolic and cognitive functions. Ageing is characterised by endothelial dysfunction, impaired nitric oxide (NO) synthesis and increased oxidative stress, which elevates cardiovascular risk. In this context, nitrate-rich vegetables offer a natural way to restore NO bioavailability and support cardiometabolic health. This narrative review provides an integrative overview of nitrate-rich vegetables as sources of bioactive phytochemicals with therapeutic relevance. We summarise the biochemical pathways of nitrate and nitrite metabolism, including the enterosalivary nitrate-nitrite-NO cycle, the role of oral microbiota, and red blood cell-mediated nitrite reduction. Particular emphasis is placed on NOS-independent NO production, which becomes increasingly important with age, and on the synergistic interactions between dietary nitrates and other phytochemicals such as polyphenols, vitamin C, flavonoids and betalains. These compounds enhance NO stability, reduce oxidative stress, modulate inflammatory signalling and support mitochondrial function, thereby amplifying the health benefits of nitrate-rich vegetables. Beetroot, with its high nitrate content and distinctive antioxidant profile, is highlighted as a prime example. Clinical and mechanistic studies suggest that nitrate-rich vegetables may lower blood pressure, improve endothelial function and cerebral perfusion, enhance cognitive performance and muscle oxygenation, and increase exercise efficiency, particularly in older adults. Additional benefits include anti-inflammatory effects, modulation of platelet function and improvements in metabolic parameters, all of which are relevant to the prevention of chronic diseases such as hypertension, type 2 diabetes and atherosclerosis. While dietary nitrate is generally considered low-risk for healthy adults, caution

This study optimized stabilizer type and concentration, and screened natural antioxidant combinations to enhance the stability of a protein beverage fortified with vitamins A, D2, and D3. Three stabilizers-carrageenan, sodium carboxymethyl cellulose (Na-CMC), and microcrystalline cellulose (MCC)-were evaluated at 0.15-0.45% (w/v) during accelerated storage at 45 °C for 21 days. Stability was assessed using Turbiscan analysis, pH, particle size, Zeta potential, and color. MCC at 0.35% demonstrated the best stabilization, with minimal changes in Turbiscan Stability Index, particle size, and Zeta potential. Five natural antioxidants-dl-α-tocopherol, vitamin C, epigallocatechin gallate (EGCG), tea polyphenols (TP), and pyrroloquinoline quinone (PQQ)-were screened for vitamin protection using HPLC. Although vitamin C exhibited the highest in vitro DPPH radical scavenging activity (IC50 = 3.44 μg/mL), TP and EGCG provided superior protection of vitamins in the emulsion system. A synergistic antioxidant blend of EGCG, TP, and dl-α-tocopherol in a 4:4:2 mass ratio was identified as optimal, significantly prolonging vitamin retention over 21 days and yielding the longest predicted shelf-life (>84 days at 25 °C). These findings provide a practical formulation strategy for enhancing the physical and nutritional stability of functional protein beverages.

Male jelly fig (Ficus pumila L. var. awkeotsang) syconia are an underutilized by-product in Taiwan. This study evaluated male fig powder (0-2%, w/v) as a substrate for producing male fig-altered kombucha (FK) using a defined co-culture of Komagataeibacter xylinus and Saccharomyces cerevisiae. Fermentation markedly reshaped FK metabolites. Glucuronic acid increased in a dose-associated manner, reaching 6.63 g/L in 2% FK, whereas vitamin C declined during fermentation but remained highest in 2% FK. Gallic acid increased and peaked at 0.5% FK (320.75 mg/L), while acetic and succinic acids showed formulation-dependent patterns; conversely, caffeine decreased in all male fig-containing groups. FK also exhibited concentration-dependent color divergence from the control at day 9 (ΔE* up to 17.81 at 2% FK). Numerical increases in DPPH and TPC were observed; however, no significant differences were detected among the treatments. Importantly, male fig supplementation substantially enhanced kombucha bacterial cellulose (KBC) yield (0.56 to 7.28 g/L from 0 to 2% FK) without compromising high water content (~96-99%) or swelling (~90-94%). FTIR confirmed retention of the cellulose backbone, SEM showed formulation-dependent fibril diameters, and TGA indicated higher early-stage thermal stability with dose-dependent shifts in main degradation behavior. Collectively, male figs can be valorized to produce FK with altered metabolite profiles and improved KBC productivity.

Background: Electrochemotherapy enhances the intracellular delivery of anticancer agents through electroporation but is traditionally limited to cytotoxic drugs associated with significant side effects. Vitamin C (ascorbic acid) exhibits selective anticancer activity when accumulated at high intracellular concentrations; however, its therapeutic application is restricted by poor membrane permeability and rapid systemic clearance. Methods: In this study, we investigated whether reversible electroporation, applied using a custom-designed variable plate electrode system designed to deliver a uniform electric field, could potentiate the antitumor efficacy of low-dose vitamin C. Numerical simulations were performed to optimize electrode spacing and stimulation voltage, suggesting homogeneous electric field coverage throughout the tumor volume. The proposed approach was evaluated in vitro using MDA-MB-231 and 4T1 breast cancer cell lines and in vivo in a 4T1 murine breast cancer model. Results: Low-dose vitamin C alone produced minimal cytotoxic effects, whereas its combination with electroporation significantly reduced cell viability and increased apoptotic and necrotic cell death in vitro. In vivo, vitamin C-assisted electrochemotherapy resulted in pronounced tumor growth suppression, with tumor volumes reduced to approximately 0.34-fold of baseline by day 15, accompanied by decreased proliferation and marked tissue disruption. Conclusions: These findings demonstrate that uniform-field reversible electroporation markedly enhances the intracellular delivery and antitumor activity of low-dose vitamin C, supporting this technology-driven strategy as a promising, low-toxicity alternative to conventional chemotherapeutic agents in electrochemotherapy for solid tumors.

Low glycemic-index foods may reduce postprandial oxidative stress by reducing postprandial glucose excursions, but the evidence for this is limited by dietary confounders. To determine whether reducing postprandial glucose per se reduces postprandial oxidative stress, overnight-fasted participants (BMI 25.0-39.9 kg/m2, n = 18) consumed four test meals in random order: 75 g dextrose solution (Dex) within 5 min (bolus/noC), Dex slowly over 3.25 h (sipping/noC), bolus with 1 g vitamin C (bolus/C) and sipping with 1 g vitamin C (sipping/C). Venous blood was taken at intervals over 6 h; a standard lunch was consumed at 4 h. Sipping flattened postprandial glucose and insulin and reduced free fatty acid rebound compared to bolus (p < 0.05). Vitamin C raised serum vitamin C from ~20 to ~55 μmol/L. The total peroxyl radical trapping antioxidant potential (TRAP) increments differed after lunch, with a main effect of vitamin C at 5 h (mean ± SEM; C 70 ± 23 vs. noC -29 ± 27; p = 0.016) and main effects of rate (sipping 57 ± 25 vs. bolus -71 ± 28; p = 0.0002) and vitamin C (C 58 ± 25 vs. noC -73 ± 28; p = 0.0003) at 6 h. By multiple regression analysis, the TRAP area under the curve (AUC) was positively associated with the insulin AUC (p < 0.001) and negatively with the glucose and vitamin C AUCs (p < 0.05). The oxidized LDL increments were higher 6 h after sipping than bolus (7 ± 7 vs. -20 ± 7, p = 0.005). The oxidized LDL AUC was negatively associated with the TRAP AUC (p < 0.001). These results support the hypothesis that reducing postprandial glucose reduces postprandial oxidative stress.

BACKGROUND & AIMS: Solute carrier family 23 member 1 (SLC23A1) encodes sodium-dependent vitamin C transporter 1, which mediates intestinal vitamin C absorption. Although SLC23A1 variants are associated with vitamin C bioavailability, their relationship with gut microbiome remains unexplored. We aimed to investigate the associations of SLC23A1 polymorphism with serum vitamin C status and gut microbial profiles in healthy Korean adults. METHODS: We genotyped the SLC23A1 rs6596473 polymorphism in 257 healthy individuals (20-39 years) and measured their serum vitamin C concentrations, which were categorized as optimal (≥50 μM) or suboptimal (<50 μM). Logistic regression analysis was used to evaluate the association between genotypes and suboptimal serum vitamin C status after adjusting for covariates. A subset of 43 participants with suboptimal serum vitamin C status underwent gut microbiota analysis and serum short-chain fatty acid (SCFA) measurements. Microbial profiles and SCFA concentrations were compared across the genotypes. RESULTS: The genotype distributions were 92 CC, 131 CG, and 34 GG, with G as the minor allele. After covariate adjustment, GG carriers had higher odds of suboptimal serum vitamin C status than CC carriers (odds ratio = 2.65; p = 0.03). Among individuals with suboptimal serum vitamin C status, GG carriers (n = 7) exhibited distinct microbial community structures compared with CC (n = 13) and CG (n = 23) carriers, with elevated richness and evenness. GG carriers had higher abundances of Bifidobacterium (vs. CC, p < 0.01; vs. CG, p = 0.054) and Ruminococcaceae incertae sedis (all p < 0.05) compared with CC and CG carriers. In line with these microbial findings, GG carriers had higher propionate and butyrate concentrations than CC and CG carriers (all p < 0.05). CONCLUSIONS: The SLC23A1 rs6596473 variant was associated with reduced vitamin C absorption into systemic circulation in the overall population; however, among individuals with suboptimal serum vitamin C status, it was associated with beneficial gut microbial profiles. Our findings suggest that this genetic variant in the vitamin C transporter has complex health effects that extend bey

BACKGROUND: Monosodium glutamate (MSG), a common food additive, is known to enhance taste and flavour. However, increasing evidence suggests that elevated MSG intake is linked to neuronal pathologies and death. Tabernaemontana stapfiana is a plant traditionally used in Cameroon for multiple purposes, including as a haemostatic, an anthelmintic, and in the treatment of rheumatism, kidney disorders, rickets, and conjunctivitis. Notably, traditional practitioners also use it to address nervous system disorders, drug addiction, and memory impairments, highlighting its potential as a neuroprotective agent. This study aimed to evaluate the neuroprotective effects of the aqueous extract of the stem barks from this plant on MSG-induced neurotoxicity in mice. METHODS: This study was carried out using 49 Swiss albino mice, classified into seven groups of 7 mice each. The negative control group (group 1) received distilled water (10 mL/kg) throughout this experiment. The positive control group received MSG (2 g/kg) and distilled water (10 mL/kg). Reference standard 1 (RS1) received vitamin C (100 mg/kg) and reference standard 2 (RS2) received donepezil (3 mg/kg). Doses 1, 2, and 3 groups received MSG concomitantly with aqueous extract of T. stapfiana (250, 500, and 1000 mg/kg respectively) for 10 days. Monosodium glutamate was administered intraperitoneal (i.p) while treatments were orally administered (p.o). Behavioural parameters such as Y-maze, elevated plus maze, open field and wire suspension tests were evaluated on days 8, 9, and 10 using various tests. After 10 days, biomarkers of oxidative stress and acetylcholinesterase activity were evaluated in the brain. RESULTS: MSG induced oxidative stress, poor muscle coordination, and spatial short-term memory impairment in mice. The T. stapfiana extract prevented these MSG-induced behavioural changes. The extract also alleviated oxidative stress and reduced acetylcholinesterase activity in the brains of the animals. CONCLUSION: Results suggest that T. stapfiana aqueous extract prevents neurotoxicity, possibly through its free radical scavenging ability and the maintenance of acetylcholinesterase activity in a mouse model o

34. IBRO Neurosci Rep. 2026 Apr 22;20:643-652. doi: 10.1016/j.ibneur.2026.04.004. eCollection 2026 Jun. Protective effect of the aqueous extract of Tabernaemontana stapfiana (Apocynaceae) stem bark against monosodium glutamate-induced neurotoxicity in Swiss albino mice. Antoine KS(1), Emégam KN