Association of dietary vitamin C intake with depression in adults: A cross-sectional study of NHANES from 2005 to 2020.

BACKGROUND: The aim of this study was to evaluate the association between dietary vitamin C intake and depression in adults. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) during 2005 to 2020. Logistic regressions and restricted cubic spline (RCS) regression were used to assess the association between dietary vitamin C intake and depression. Additionally, we performed stratified and sensitivity analyses to evaluate the stability of the results. RESULTS: This study included 38,157 participants, with 3448 (9.04 %) of them experiencing depression. The vitamin C intake was negatively associated with depression after adjusting for all covariates (OR = 0.91, 95%CI: 0.88-0.94, P < 0.001). Similar inverse associations were observed when vitamin C intake was transformed into categorical variables. Individuals in higher quartiles of dietary vitamin C intake (Q2, Q3, and Q4) had lower odds ratios (ORs) compared to those in the lowest quartile (Q1), as indicated by adjusted ORs of 0.78 (95 % CI: 0.71-0.87, P < 0.001), 0.74 (95 % CI: 0.67-0.82, P < 0.001), and 0.73 (95 % CI: 0.65-0.81, P < 0.001), respectively. The RCS analysis found an L-shaped nonlinear relationship between dietary vitamin C intake and depression, after adjusting for all covariates (P for non-linearity<0.001). Consumption of vitamin C was inversely associated with depression (OR = 0.994, 95%CI: 0.993-0.996, P < 0.001) for intakes below 93.61 mg, but there was no association between dietary vitamin C intake and depression (P = 0.980) for intakes of 93.61 mg or higher. The inverse associations between vitamin C intake and depression remained robust in stratified and sensitivity analyses. LIMITATIONS: This study was a cross-sectional study, and therefore unable to establish a causal relationship between dietary vitamin C intake and depression. We are unable to fully eliminate the confounding effects resulted from other unmeasured or unknown factors. CONCLUSION: The study revealed a negative association between dietary vitamin C intake and depression, as well as an L-shaped nonlinear relationship between vitamin C intake and depression.

Network pharmacology and molecular docking technology for exploring the effect and mechanism of high-dose vitamin c on ferroptosis of tumor cells: A review.

To investigate the mechanism by which high-dose vitamin C (HVC) promotes ferroptosis in tumor cells via network pharmacology, vitamin C-related and ferroptosis-related targets were obtained from the PharmMapper and GeneCards databases, respectively, and their common targets were compared using the Venn diagram. Common targets were imported into the STRING database for protein-protein interaction analysis, and core targets were defined. Core targets were enriched for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways using the R language packages. A map of the core target-based interaction network and a map of the mechanism by which HVC regulates ferroptosis were constructed. A total of 238 vitamin C-related and 721 ferroptosis-related targets were identified, of which 21 targets were common to both. Furthermore, ALDOA, AHCY, LDHB, HSPA8, LGALS3, and GSTP1 were identified as core targets. GO enrichment analysis suggested that the main biological processes included the extrinsic apoptotic signaling pathway and pyruvate metabolic process. KEGG enrichment analysis suggested that HVC regulates ferroptosis mainly through the amino acid and carbohydrate metabolic pathways. The targets were validated by molecular docking. In conclusion, HVC may promote ferroptosis in tumor cells by regulating metabolic pathways, and there is a synergistic effect between HVC and type I ferroptosis inducers. Glycolysis-dependent tumors may be beneficial for HVC therapy. Our study provides a reference for further clinical studies on HVC antitumor therapy.

Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis.

Community-acquired pneumonia (CAP) poses a significant global health challenge, prompting exploration of innovative treatments. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of vitamin C supplementation in adults undergoing treatment for CAP. A comprehensive search of the MEDLINE, Embase, CINAHL, the Cochrane Central Register of Controlled Trials, and Clinical Trials.gov databases from inception to 17 November 2023 identified six randomized-controlled-trials (RCTs) meeting inclusion criteria. The primary outcome analysis revealed a non-significant trend towards reduced overall mortality in the vitamin C group compared to controls (RR 0.51; 95% CI 0.24 to 1.09; p = 0.052; I2 = 0; p = 0.65). Sensitivity analysis, excluding corona-virus-disease 2019 (COVID-19) studies and considering the route of vitamin C administration, confirmed this trend. Secondary outcomes, including hospital length-of-stay (LOS), intensive-care-unit (ICU) LOS, and mechanical ventilation, exhibited mixed results. Notably, heterogeneity and publication bias were observed in hospital LOS analysis, necessitating cautious interpretation. Adverse effects were minimal, with isolated incidents of nausea, vomiting, hypotension, and tachycardia reported. This meta-analysis suggests potential benefits of vitamin C supplementation in CAP treatment. However, inconclusive findings and methodological limitations warrants cautious interpretation, emphasising the urgency for high-quality trials to elucidate the true impact of vitamin C supplementation in CAP management.

Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The primary challenge encountered by individuals diagnosed with endometriosis is the experience of pain. Emerging research indicates that oxidative stress is implicated in the initiation of pain associated with endometriosis. Vitamins C and E are known for their antioxidative properties. The primary objective of this study is to assess the efficacy of antioxidant supplementation, consisting of these vitamins, in the management of pain associated with endometriosis. METHODS: A comprehensive search was conducted on the ClinicalTrials.gov, Scopus, Europe PMC, and Medline databases up until August 23rd, 2023, utilizing a combination of relevant keywords. This review incorporates literature that examines the relationship between antioxidant supplementation and pain in endometriosis. We employed fixed-effect models to analyze the risk ratio (RR) and present the outcomes together with their corresponding 95% confidence intervals (CI). RESULTS: A total of five RCTs were incorporated. The results of our meta-analysis indicated that antioxidant supplementation with vitamin C and E combination was associated with higher proportion of endometriosis patients reporting reduced chronic pelvic pain (RR 7.30; 95%CI: 3.27-16.31, p<0.00001, I2 = 0%), alleviations of dysmenorrhea (RR 1.96; 95%CI: 1.25-3.07, p = 0.003, I2 = 39%), and dyspareunia (RR 5.08; 95%CI: 2.10-12.26, p = 0.0003, I2 = 0%) than patients only receiving placebo. CONCLUSIONS: This study suggests the potential ability of vitamin C and E in alleviating pain symptoms experienced by individuals with endometriosis.

Managing children with frequent respiratory infections and associated wheezing: a preliminary randomized study with a new multicomponent nasal spray.

BACKGROUND: Preschoolers frequently have respiratory infections (RIs), which may cause wheezing in some subjects. Type 2 polarization may favor increased susceptibility to RIs and associated wheezing. Non-pharmacological remedies are garnering increasing interest as possible add-on therapies. The present preliminary study investigated the efficacy and safety of a new multi-component nasal spray in preschoolers with frequent RIs and associated wheezing. METHODS: Some preschoolers with these characteristics randomly took this product, containing lactoferrin, dipotassium glycyrrhizinate, carboxymethyl-beta-glucan, and vitamins C and D3 (Saflovir), two sprays per nostril twice daily for 3 months. Other children were randomly treated only with standard therapy. Outcomes included the number of RIs and wheezing episodes, use of medications, and severity of clinical manifestations. RESULTS: Preschoolers treated add-on with this multicomponent product experienced fewer RIs and used fewer beta-2 agonists than untreated children (P = 0.01 and 0.029, respectively). CONCLUSIONS: This preliminary study demonstrated that a multicomponent product, administered add-on as a nasal spray, could reduce the incidence of RIs and use of symptomatic drugs for relieving wheezing in children.

The Efficacy of Multivitamin, Vitamin A, Vitamin B, Vitamin C, and Vitamin D Supplements in the Prevention and Management of COVID-19 and Long-COVID: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials.

This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023 to identify randomized clinical trials comparing data on the effects of vitamin supplementation(s) versus placebo or standard of care on the two conditions of interest. Inverse-variance random-effects meta-analyses were conducted to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality between supplemented and non-supplemented individuals. Overall, 37 articles were included: two regarded COVID-19 and long-COVID prevention and 35 records the COVID-19 management. The effects of vitamin D in preventing COVID-19 and long-COVID were contrasting. Similarly, no conclusion could be drawn on the efficacy of multivitamins, vitamin A, and vitamin B in COVID-19 management. A few positive findings were reported in some vitamin C trials but results were inconsistent in most outcomes, excluding all-cause mortality (RR = 0.84; 95% CI: 0.72-0.97). Vitamin D results were mixed in most aspects, including mortality, in which benefits were observed in regular administrations only (RR = 0.67; 95% CI: 0.49-0.91). Despite some benefits, results were mostly contradictory. Variety in recruitment and treatment protocols might explain this heterogeneity. Better-designed studies are needed to clarify these vitamins' potential effects against SARS-CoV-2.

A rare case of methemoglobinemia in a preterm newborn with unclear etiology.

 Cyanosis is a bluish discoloration of the tissues due to increased levels of deoxygenated hemoglobin in capillaries. It is a common finding in newborn infants that can be caused by different diseases, including pulmonary, cardiac, infectious, and hematological disorders. Methemoglobinemia is a rare cause of cyanosis, in which hemoglobin is oxidized, changing its heme iron configuration from the ferrous (Fe2 +) to the ferric (Fe3 +) state, creating methemoglobin (Met-Hb), a form that does not bind oxygen, leading to decreased oxygen delivery to the tissues and cyanosis. We report a rare case of a preterm newborn, who developed cyanosis and worsening hypoxemia on day ten of life, she was found to have elevated Met-Hb percentage in blood gas analysis that required treatment with intravenous methylene blue. Her symptoms resolved after a period of maintenance treatment with oral methylene blue and ascorbic acid, and the etiology of her disease remains unclear.

Co-administration of "L-Lysine, Vitamin C, and Zinc" increased the antioxidant activity, decreased insulin resistance, and improved lipid profile in streptozotocin-induced diabetic rats.

PURPOSE: We previously showed the beneficial effect of L-Lysine (Lys), a chemical chaperone, on reducing diabetic complications in diabetic rats and type 2 diabetic patients. Herein, we evaluated the effect of Lys co-administration with Vitamin C and Zinc (Lys+VC+Zn), in diabetic rats. METHODS: The streptozotocin (50 mg/Kg) was injected into male adult Wistar rats to induce diabetes. Then, different groups of normal and diabetic rats were treated with Lys and Lys+VC+Zn for five months. So, there were 0.1 % Lys in the drinking water of both groups. The control groups received water alone. During the experiment, the body weight, and various parameters were determined in the blood, serum/plasma, and urine of the rats. RESULTS: The determination of biochemical indexes confirmed diabetes induction and its complications in rats. Treatment with either Lys or Lys+VC+Zn resulted in reduced blood glucose and protein glycation (decreasing AGEs and HbA1c), increased insulin secretion, alleviated insulin resistance and HOMA-IR, improved lipid profile and HDL functionality (LCAT and PON1), enhanced antioxidant status (FRAP and AOPP), improved kidney function (decreased microalbuminuria, serum urea, and creatinine), and increased chaperone capacity (HSP70). Lys+VC+Zn showed better effects on these parameters than Lys alone. CONCLUSIONS: The results of this study indicated that co-administration of Lys, a chemical chaperone, with two antioxidants (VC and Zn) potentiates its antidiabetic effects and prevent diabetic complications in rat model of diabetes.

Vitamin C alleviates rheumatoid arthritis by modulating gut microbiota balance.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetric in-flammation. Our previous research revealed an imbalance in the gut flora of RA patients and showed that certain gut microbiota can accelerate RA progression by enhancing vitamin C degradation. However, it is unclear whether vitamin C supplementation could improve the gut microbiota to prevent the development of arthritis by interfering with the gut-joint axis. In this work, we aimed to evaluate the effects of vitamin C in regulating the gut microbiota and to elucidate its potential role in the onset and progression of RA in a mouse model, thus providing a basis for the development of new intervention strategies and treatments for RA. In this study, collagen-induced arthritis (CIA) mouse models, biochemical, histological and 16S rRNA microbiological methods were used to investigate the role and possible mechanism of vitamin C in rheumatoid arthritis. The results showed that treatment of CIA mice with vitamin C effectively rescued the gut mi-crobiota imbalance and suppressed the inflammatory response associated with RA, and effectively alleviated arthritis symptoms in mice in which levels of the pro-inflammatory cytokines IL-6 and TNF-α were specifi-cally reduced. In conclusion, our results demonstrate the potential of vitamin C as a potential therapeutic choice for RA.

Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

Vitamin C Supplementation Among Pregnant Smokers and Airway Function Trajectory in Offspring: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial analyzes the association of vitamin C supplementation in women who smoked during pregnancy with airway function trajectory in their offspring at 4 to 6 years of age.

Dietary Vitamin C Intake and Changes in Frequency, Severity, and Location of Pain in Older Adults.

BACKGROUND: Oral vitamin C supplementation has been associated with lower risk of chronic postsurgical pain. However, the effect of dietary vitamin C on pain in a nonsurgical setting is unknown. We aimed to investigate the association between dietary vitamin C intake and changes over time in chronic pain and its characteristics in community-dwelling adults aged 60 + years. METHODS: We pooled data from participants of the Seniors-ENRICA-1 (n = 864) and Seniors-ENRICA-2 (n = 862) cohorts who reported pain at baseline or at follow up. Habitual diet was assessed with a face-to-face diet history and dietary vitamin C intake was estimated using standard food composition tables. Pain changes over time were the difference between scores at baseline and follow up obtained from a pain scale that considered the frequency, severity, and number of pain locations. Multivariable-adjusted relative risk ratios were obtained using multinomial logistic regression. RESULTS: After a median follow-up of 2.6 years, pain worsened for 696 (40.3%) participants, improved for 734 (42.5%), and did not change for 296 (17.2%). Compared with the lowest tertile of energy-adjusted vitamin C intake, those in the highest tertile had a higher likelihood of overall pain improvement (RRR 1.61 [95% confidence interval 1.07-2.41], p-trend .02). Higher vitamin C intake was also associated with lower pain frequency (1.57 [1.00-2.47], p-trend = .05) and number of pain locations (1.75 [1.13-2.70], p-trend = .01). CONCLUSIONS: Higher dietary vitamin C intake was associated with improvement of pain and with lower pain frequency and number of pain locations in older adults. Nutritional interventions to increase dietary vitamin C intake with the aim of improving pain management require clinical testing.

Vitamins C, E, and ß-Carotene and Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis.

A systematic review and meta-analysis was conducted to assess the relationship between the common dietary antioxidants vitamin C, vitamin E, and ß-carotene and type 2 diabetes (T2D) and related traits. MEDLINE, Embase, and the Cochrane Library were searched for relevant publications up until May 2023. Studies were eligible if they had a cohort, case-control, or randomized controlled trial (RCT) design and examined dietary intake, supplementation, or circulating levels of these antioxidants as exposure, and insulin resistance, ß-cell function, or T2D incidence as outcomes. Summary relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random-effects models. The certainty of the evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluations framework. Among 6190 screened records, 25 prospective observational studies and 15 RCTs were eligible. Inverse associations were found between dietary and circulating antioxidants and T2D (observational studies). The lowest risk was seen at intakes of 70 mg/d of vitamin C (RR: 0.76; CI: 0.61, 0.95), 12 mg/d of vitamin E (RR: 0.72; CI: 0.61, 0.86), and 4 mg/d of ß-carotene (RR: 0.78; CI: 0.65, 0.94). Supplementation with vitamin E (RR: 1.01; CI: 0.93, 1.10) or ß-carotene (RR: 0.98; CI: 0.90, 1.07) did not have a protective effect on T2D (RCTs), and data on vitamin C supplementation was limited. Regarding insulin resistance, higher dietary vitamin C (RR: 0.85; CI: 0.74, 0.98) and vitamin E supplementation (MD: -0.35; CI: -0.65, -0.06) were associated with a reduced risk. The certainty of evidence was high for the associations between T2D and dietary vitamin E and ß-carotene, and low to moderate for other associations. In conclusion, moderate intakes of vitamins C, E, and ß-carotene may lower risk of T2D by reducing insulin resistance. Lack of protection with supplementation in RCTs suggests that adequate rather than high intakes may play a role in T2D prevention. This systematic review and meta-analysis was registered in PROSPERO with registration number CRD42022343482.

High-dose ascorbate exerts anti-tumor activities and improves inhibitory effect of carboplatin through the pro-oxidant function pathway in uterine serous carcinoma cell lines.

OBJECTIVE: Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. METHODS: Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. RESULTS: High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N-acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. CONCLUSIONS: Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring.

Alleviation of radiation combined skin injury in rat model by topical application of ascorbate formulation.

PURPOSE: This research endeavor was undertaken to elucidate the impact of an innovative ascorbate formulation on the regeneration process of full-thickness excision wounds in a rat model exposed to whole-body gamma irradiation, replicating conditions akin to combat or radiation emergency scenarios. MATERIALS AND METHODS: We established a comprehensive rat model by optimizing whole body γ-radiation doses (5-9 Gy) and full-thickness excision wound sizes (1-3 cm2) to mimic radiation combined injury (RCI). The developed RCI model was used to explore the healing potential of ascorbate formulation. The study includes various treatment groups (i.e., sham control, radiation alone, wound alone, radiation + wound, and radiation + wound + formulation). The ascorbate formulation was applied twice daily, with a 12-hour gap between each application, starting 1 hour after the initiation of the wound. The healing potential of the formulation in the RCI context was evaluated over 14 days through hematological, molecular, and histological parameters. RESULTS: The combination of a 5 Gy radiation dose and a 1 cm2 wound was identified as the optimal setting to develop the RCI model for subsequent studies. The formulation was used topically immediately following RCI, and then twice daily until complete healing. Treatment with the ascorbate formulation yielded noteworthy outcomes and led to a substantial reduction (p < .05) in the wound area, accelerated epithelialization periods, and an increased wound contraction rate. The formulation's localized healing response improved organ weights, normalized blood parameters, and enhanced hematopoietic and immune systems. A gene expression study revealed the treatment up-regulated TGF-ß and FGF, and down-regulated PDGF-α, TNF-α, IL-1ß, IL-6, MIP-1α, and MCP-1 (p < .05). Histopathological assessments supported the formulation's effectiveness in restoring cellular architecture and promoting tissue regeneration. CONCLUSION: Topical application of the ascorbate formulation in RCI resulted in a significant improvement in delayed wound healing, leading to accelerated wound closure by mitigating the expression of inflammatory responses.

The association of dietary antioxidants and the inflammatory potential of the diet with poor physical function and disability in older Australian men: the Concord Health and Ageing in Men Project.

Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years (n 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy. The Energy-adjusted Dietary Inflammatory Index (E-DIITM) was used to assess the inflammatory potential of the diet. Physical performance data were collected via handgrip strength and walking speed tests, and activities of daily living (ADL) and instrumental activities of daily living (IADL) questionnaires, at baseline and 3-year follow-up (n 616). Logistic regression analysis was used to identify associations between diet and incident poor physical function and disability. Both poor antioxidant intake and high E-DII scores at baseline were significantly associated with poor grip strength and ADL disability at 3-year follow-up. No significant associations with walking speed or IADL disability were observed. Individual micronutrient analysis revealed a significant association between the lowest two quartiles of vitamin C intake and poor grip strength. The lowest quartiles of intake for vitamins A, C, E and Zn were significantly associated with incident ADL disability. The study observed that poor antioxidant and anti-inflammatory food intake were associated with odds of developing disability and declining muscle strength in older men. Further interventional research is necessary to clarify the causality of these associations.