Ascorbic acid deficiency amongst spondylodiscitis patients.

BACKGROUND: Spondylodiscitis can be a disabling and life-threatening infection. Ascorbic Acid is crucial for neutrophil function and collagen formation. Its association and clinical relevance in spondylodiscitis has not been previously examined. AIMS: To determine the prevalence, characteristics, and clinical outcomes of spondylodiscitis patients with Ascorbic Acid deficiency. METHODS: Sixty-eight consecutive patients admitted with spondylodiscitis, between December 2021 and August 2023 were included. Clinical characteristics, Ascorbic Acid levels and clinical outcomes were evaluated. RESULTS: Thirty-seven patients had Ascorbic Acid levels taken during admission. The median initial Ascorbic Acid level was 15 µmol/L with an IQR 6.5-27 µmol/L. Depletion defined as <28 µmol/L was present in 78% of patients. Deficiency defined as ≤11 µmol/L was present in and 46% of patients. Patients with depletion were more likely to require Intensive Care Admission (absolute risk increase = 24.1%; 2.6%-45.7%). Fifteen patients had repeat serum levels taken during admission with median increase of 17 µmol/L and an IQR 0-26 µmol/L. Patients that received supplementation had a significantly greater increase in Ascorbic Acid levels compared with those that did not receive supplementation (P = 0.002). CONCLUSION: Ascorbic acid deficiency is highly prevalent amongst spondylodiscitis patients. Depletion was associated with worse outcomes. Replacement significantly increased serum levels in comparison to standard hospital diet. The clinical significance of replacement remains to be evaluated.

Severe vitamin C deficiency associated with continuous renal replacement therapy: A case report.

Hypovitaminosis C is prevalent in critically ill patients. Continuous renal replacement therapy (CRRT) clears vitamin C, increasing the risk for vitamin C deficiency. However, recommendations for vitamin C supplementation in critically ill patients receiving CRRT vary widely, from 250 mg/day to 12 g/day. This case report describes a patient who developed a severe vitamin C deficiency after prolonged CRRT despite receiving ascorbic acid (450 mg/day) supplementation in her parenteral nutrition. This report summarizes recent research investigating vitamin C status in critically ill patients receiving CRRT, discusses the patient case, and provides recommendations for clinical practice. In critically ill patients receiving CRRT, the authors of this manuscript suggest providing at least 1000 mg/day of ascorbic acid to prevent vitamin C deficiency. Baseline vitamin C levels should be checked in patients who are malnourished and/or have other risk factors for vitamin C deficiency, and vitamin C levels should be monitored thereafter every 1-2 weeks.

Pseudoparalysis Secondary to Vitamin C Deficiency: A Rare Presentation in a Toddler.

CASE: We present a 17-month-old girl with postencephalitic sequelae only on high-calorie cereal milk through a nasogastric tube. She presented with a 3-week history of swelling and decreased lower limb movements. Synovial fluid analysis ruled out septic arthritis. Plain radiograph and magnetic resonance imaging (MRI) were suggestive of scurvy. She was diagnosed to have pseudoparalysis secondary to scurvy. She was started on vitamin C supplements, after which she showed good clinical improvement. CONCLUSION: This case report is to re-emphasize the need for awareness of the possibility of scurvy in children with poor nutritional status due to feeding difficulties.

The Role of Vitamin C and Vitamin D in the Pathogenesis and Therapy of Periodontitis-Narrative Review.

Periodontitis is a common disorder affecting the bone and soft tissues of the periodontal complex. When untreated, it may lead to severe mobility or even loss of teeth. The pathogenesis of periodontitis is complex, with crucial factors being chronic inflammation in gingival and periodontal tissues and oral microbiome alterations. However, recent studies highlight the alleged role of vitamins, such as vitamin C (VitC) and vitamin D (VitD), in the development of the disease. VitC regulates numerous biochemical reactions, but foremost, it is involved in synthesizing collagen. It was reported that VitC deficiency could lead to damage to the periodontal ligaments. VitC supplementation improves postoperative outcomes in patients with periodontitis. VitD is a steroid derivative that can be produced in the skin under ultraviolet radiation and later transformed into an active form in other tissues, such as the kidneys. VitD was established to decrease the expression of proinflammatory cytokines in gingiva and regulate the proper mineral density of teeth. Moreover, the supplementation of VitD was associated with better results in the nonsurgical treatment of periodontitis. In this review, we summarize recent knowledge on the role of vitamins C and D in the pathogenesis and treatment of periodontitis.

Scurvy-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that results in precapillary pulmonary hypertension. PAH is caused by a group of clinical conditions involving multiple organ systems. Several cases have been reported in the literature demonstrating an association between vitamin C deficiency and PAH. Low endothelial nitric oxide levels in the pulmonary vasculature, combined with the inappropriate activation of hypoxia-inducible transcription factors, seen in patients with ascorbic acid deficiency, are believed to be the main contributors to the pathogenesis of pulmonary vasculopathy and the exaggerated pulmonary vasoconstrictive response seen in patients with scurvy-induced PAH. Vitamin C supplementation is considered the definitive treatment.

[Scurvy still occurs]. / Scheurbuik komt nog steeds voor.

Scurvy is taught in history class and most doctors consider it a disease of the past. However, several studies show that vitamin C deficiency is highly prevalent among alcoholics, but also in elderly, people with low socioeconomic status, mental disorders or a restricted diet (7.1 - 25%). Besides the classical signs of scurvy, individuals exhibit a wide variety of symptoms. We present three recent cases of patients with vitamin C deficiency, with symptoms of bleeding, lethargy and edema, in whom supplementation greatly improved symptoms. As our cases illustrate having a high suspicion of scurvy and starting ascorbic acid might be a low cost and very effective intervention.

Prevalence and prognostic significance of vitamin C deficiency in patients with acute upper gastrointestinal bleeding: a prospective cohort study.

BACKGROUND: Vitamin C is an essential dietary nutrient important for collagen synthesis, including within the gastrointestinal tract. AIM: We aimed to document the prevalence of Vitamin C deficiency (VCD) in patients who present with upper gastrointestinal bleeding (UGIB) and its association with clinical outcomes. METHODS: We conducted a prospective cohort study of patients presenting with UGIB. Fasting Vitamin C levels were collected at admission. Primary outcomes were the prevalence of VCD (Vitamin C level <23 µmol/L, severe VCD < 12 µmol/L) and a composite outcome of adverse events, stratified by VCD status. Secondary outcomes were prolonged hospitalisation and the need for ICU admission. RESULTS: A total of 227 patients were included (mean age 64.5 years, males 63.9%). VCD was identified in 74 (32.6%) and severe deficiency in 32 (14.1%) patients. VCD was associated with a higher composite endpoint of AE (45.9% vs 24.8%, p < 0.01), higher in-hospital mortality (9.5% vs 1.3%, p < 0.01), increased prolonged admissions (62.2% versus 47.1%, p = 0.03) and increased rebleeding (17.6% vs 7.8%, p = 0.03), compared with patients with normal Vitamin C levels. Multivariate logistic regression models showed that VCD was independently associated with the composite endpoint of AE. CONCLUSION: VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding and length of stay. Interventional studies are required to determine the impact of early Vitamin C supplementation on clinical outcomes.

Clinical and molecular characteristics associated with Vitamin C deficiency in myeloid malignancies; real world data from a prospective cohort.

Vitamin C is an essential vitamin that acts as a co-factor for many enzymes involved in epigenetic regulation in humans. Low vitamin C levels in hematopoietic stem cells (HSC) promote self-renewal and vitamin C supplementation retards leukaemogenesis in vitamin C-deficient mouse models. Studies on vitamin C levels in patients with myeloid malignancies are limited. We thus conducted a retrospective analysis on a prospective cohort of patients with myeloid malignancies on whom plasma vitamin C levels were measured serially at diagnosis and during treatment. Baseline characteristics including hematological indices, cytogenetics, and molecular mutations are described in this cohort. Among 64 patients included in our study, 11 patients (17%) had low vitamin C levels. We noted a younger age at diagnosis for patients with myeloid malignancies who had low plasma vitamin C levels. Patients with low plasma vitamin C levels were more likely to have acute myeloid leukemia compared to other myeloid malignancies. Low vitamin C levels were associated with ASXL1 mutations. Our study calls for further multi-institutional studies to understand the relevance of low plasma vitamin C level in myeloid neoplasms, the role of vitamin C deficiency in leukemogenesis, and the potential benefit of vitamin C supplementation.

Rheumatologic manifestations with elevated levels of IL-6, IL-17A, and IL-23 in a patient with scurvy.

Symptomatic vitamin C deficiency, scurvy, is a relatively rare disease in developed countries, but it has been reported in patients with autism spectrum disorder or developmental delay who tend to have selective diets. Patients with scurvy often demonstrate musculoskeletal manifestations with unknown pathophysiology. Herein, we report a case of scurvy in an 11-year-old boy who presented with iron-deficiency anaemia, systemic osteomyelitis, myositis predominantly in the lower extremities, and right ventricular volume overload with mild pulmonary hypertension and was diagnosed with scurvy. He had a mild developmental disorder and a selective diet, which resulted in severe vitamin C deficiency. He received intravenous and oral vitamin C supplementation, which relieved his arthralgia and muscle pain in a week. Following 4 months of vitamin C supplementation, he demonstrated no abnormal manifestations on laboratory or imaging examination and recovered without sequelae. Inflammatory cytokine and chemokine evaluations demonstrated elevated levels of interleukin (IL)-6, IL-17A, and IL-23, which are associated with T-helper (Th) 17 cell activation. This study is the first to suggest the association between the inflammation seen in scurvy, rheumatic manifestations in the patient, and Th17 cell activation. Further analysis of the association between the inflammation and vitamin C supplementation may contribute to new insights for the comprehension and treatment of other inflammatory diseases, such as rheumatic diseases.

Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3ß.

Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence of L-gulono-1,4-lactone oxidoreductase, an essential enzyme for the last step of VC synthesis, VC deprivation resulted in persistent hypoglycemia and subsequent impairment of cognitive functions in female but not male mouse pups. The cognitive disorders caused by VC deprivation were largely reversed when these female pups were given glucose. VC deprivation-induced S-nitrosylation of glycogen synthase kinase 3ß (GSK3ß) at Cys14, which activated GSK3ß and inactivated glycogen synthase to decrease glycogen synthesis and storage under the feeding condition, while VC deprivation inactivated glycogen phosphorylase to decrease glycogenolysis under the fasting condition, ultimately leading to hypoglycemia and cognitive disorders. Treatment with Nω-Nitro-l-arginine methyl ester (l-NAME), a specific inhibitor of nitric oxide synthase, on the other hand, effectively prevented S-nitrosylation and activation of GSK3ß in female pups in response to the VC deprivation and reversed hypoglycemia and cognitive disorders. Overall, this research identifies S-nitrosylation of GSK3ß and subsequent GSK3ß activation as a previously unknown mechanism controlling glucose homeostasis in female pups in response to VC deprivation, implying that VC supplementation in the prevention of hypoglycemia and cognitive disorders should be considered in the certain groups of people, particularly young females.

Scurvy presenting primarily as gingival manifestation in a young child: a diagnostic dilemma.

Vitamin C deficiency, historically known as scurvy, was associated with sailors in the Victorian times, however, a global review in 2020 suggests it still exists in certain at-risk groups.A case is presented of a young non-verbal child with learning difficulties and on a restricted diet, in which the primary symptom was gingival inflammation. It posed a diagnostic dilemma due to the non-specific symptoms, and a delay in the diagnosis, until vitamin C deficiency was confirmed.Gingival inflammation is one of the common findings in vitamin C deficiency and dental professionals may be the first point of contact. The importance of dietary evaluation, identifying and looking for other signs and liaising with the medical colleagues are discussed.This case highlights the role of the dentist in identifying latent cases of vitamin C deficiency and to consider this as a differential diagnosis especially in certain at-risk groups.

High-dose vitamin C therapy for symptomatic deficiency in a patient with myasthenia gravis and Crohn's disease.

Vitamin C (ascorbic acid) is an essential water-soluble antioxidant, and deficiency (ie, plasma level <11 µmol/L) can result in scurvy. People at the highest risk for vitamin C deficiency (ie, scurvy) are those with inadequate intake, such as patients with alcohol abuse disorder, malnutrition, psychiatric disorders, restrictive eating habits, and food insecurity, as well as those with malabsorptive syndromes. We present a case of a 26-year-old woman with Crohn's colitis, myasthenia gravis, and juvenile rheumatoid arthritis who presented with frequent bruising, epistaxis, and excessive bleeding from small cuts and who was found to be deficient in vitamin C. Plasma levels initially normalized with oral vitamin C supplementation, but bleeding symptoms eventually returned despite high-dose oral supplementation with 2000 mg daily. She ultimately required routine intravenous supplementation in the home setting for the normalization of levels and the resolution of symptoms. Case reports of vitamin C deficiency typically involve patients with an inadequate intake of vitamin C-containing foods or inadequate absorption. In contrast, our patient reported a regular intake of vitamin C-containing foods, in addition to oral supplementation, but continued to have difficulty maintaining normal vitamin C levels. Scurvy should be considered for any patient with symptoms of bleeding, petechiae, or ecchymosis and, although it can typically be treated with oral vitamin C, intravenous repletion may be necessary in some cases.

Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study.

BACKGROUND AND AIMS: The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design. METHODS AND RESULTS: Nine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10-8) were used as instrumental variables to predict plasma vitamin C levels. The primary outcomes were coronary artery disease (Ncase = 122,733 and Ncontrol = 424,528), atrial fibrillation (Ncase = 60,620 and Ncontrol = 970,216), heart failure (Ncase = 47,309 and Ncontrol = 930,014), and ischemic stroke (Ncase = 40,585 and Ncontrol = 406,111). Several CVD risk factors were also evaluated in secondary analyses. Two-sample MR analyses were performed using the inverse variance weighted method, with several sensitivity analyses. Genetically determined higher levels of plasma vitamin C were not significantly associated with any of the four examined CVD events. Likewise, there is no convincing evidence for the associations between genetically determined vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. Sensitivity analyses using different analytical approaches yielded consistent results. Additionally, MR assumptions did not seem to be violated. CONCLUSION: This MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention.

Lost-in-Translation of Metabolic Effects of Inorganic Nitrate in Type 2 Diabetes: Is Ascorbic Acid the Answer?

Beneficial metabolic effects of inorganic nitrate (NO3-) and nitrite (NO2-) in type 2 diabetes mellitus (T2DM) have been documented in animal experiments; however, this is not the case for humans. Although it has remained an open question, the redox environment affecting the conversion of NO3- to NO2- and then to NO is suggested as a potential reason for this lost-in-translation. Ascorbic acid (AA) has a critical role in the gastric conversion of NO2- to NO following ingestion of NO3-. In contrast to AA-synthesizing species like rats, the lack of ability to synthesize AA and a lower AA body pool and plasma concentrations may partly explain why humans with T2DM do not benefit from NO3-/NO2- supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO2--to-NO conversion. Here, we hypothesized that the lack of beneficial metabolic effects of inorganic NO3- in patients with T2DM may be at least in part attributed to species differences in AA metabolism and also abnormal metabolism of AA in patients with T2DM. If this hypothesis is proved to be correct, then patients with T2DM may need supplementation of AA to attain the beneficial metabolic effects of inorganic NO3- therapy.

Slipped Capital Femoral Epiphysis Associated With Vitamin C Deficiency in a 7-year-old Boy.

Scurvy is rare in the present world and is mostly found in children with abnormal dietary habits and physical and mental disabilities. Scurvy can present in various forms, mimicking several common diseases, thus making the diagnosis difficult. Spontaneous epiphyseal separation is known to occur in scurvy, although rarely reported. The usual locations of these epiphyseal separations are distal femur and proximal humerus. Our case is unique in that scurvy in a seemingly normal child resulted in proximal femur epiphyseal separation which was not reported previously. We report a case of a 7-year-old boy presenting with pain and swelling in multiple joints for 6 months and later inability to walk. Pseudoparalytic frog-leg posture, dietary history of selective eating, and typical radiologic features made us consider a diagnosis of scurvy which was confirmed by a low serum vitamin C level. He developed epiphyseal separation of proximal femur and was treated with percutaneous screw fixation. Vitamin C supplementation resulted in prompt improvement clinically and radiologically.

Suppressive effects of vitamin C-treated induced-regulatory T cells on heart allograft rejection under vitamin C-deficient or -sufficient conditions.

Foxp3 stability of vitamin C-treated induced-regulatory T cells (V-iTregs) is superior to that of conventional iTregs (C-iTregs). However, the role of V-iTregs in allograft rejection under vitamin C-deficient conditions, such as those seen in humans, remains unclear. We aimed to elucidate the role of vitamin C treatment on generation and maintenance of iTregs from gulo knockout (Gulo-KO) mice as well as wild type (WT) mice, and in vitro and in vivo suppressive effects of V-iTregs on heart allograft rejection in either Gulo-KO or WT recipient mice. Conversion efficiency of iTregs was similar between C- and V-iTregs in both WT and Gulo-KO mice. V-iTregs from WT or Gulo-KO mice showed better in vitro Foxp3 stability than C-iTregs, although there was no difference between WT V-iTregs and Gulo-KO V-iTregs. Furthermore, V-iTregs from WT or Gulo-KO mice suppressed in vitro T cell proliferation better than C-iTregs. Heterotrophic heart transplantation from BALB/c mice to WT or vitamin C-deficient Gulo-KO C57BL/6J mice was performed following adoptive transfer of C- or V-iTregs. V-iTregs as well as C-iTregs prolonged heart allograft survival in WT and Gulo-KO mice. However, there was no difference between the C- and V-iTreg groups. Supplementation of low- or high-dose vitamin C did not induce significant changes in heart allograft survival in Gulo-KO recipients that had received V-iTregs. In conclusion, V-iTregs do not exert better suppressive effects on heart allograft survival than C-iTregs in either WT or vitamin C-deficient recipients.

Vitamin C deficiency as an unusual cause of pulmonary hypertension and refusal to walk.

Vitamin C deficiency has been a historical disease rarely seen nowadays. We illustrate a case of a boy with autism presenting with severe pulmonary hypertension and refusal to walk secondary to vitamin C deficiency. Initiating treatment with high-dose vitamin C reversed his symptoms and he regained full power of his lower limbs with total normalisation of his pulmonary pressures.

Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19.

There are limited proven therapies for COVID-19. Vitamin C's antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6-24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients' vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.

A Pilot Study Examining Vitamin C Levels in Periodontal Patients.

BACKGROUND: Periodontal disease is the leading cause of tooth loss worldwide. Current periodontal treatment is limited by its dependency on patients learning and maintaining good dental habits, and repeated visits to oral health physicians. Vitamin C's role in collagen synthesis and immune function makes it important in wound healing and possibly periodontal healing. Therefore, if some patients are deficient, this may worsen patient outcomes. METHODS: Patients were invited to participate following assessment and treatment at the Westmead Centre of Oral Health Periodontic Clinic, regardless of current disease stage or treatment. Adults were eligible if they gave informed consent and had current periodontal disease. Study involvement consisted of periodontal assessment and care followed by an interview and measurement of serum vitamin C and C-reactive protein (CRP). RESULTS: A total of 6 out of 20 patients had vitamin C levels less than the institutional normal range, of whom 2 had levels <11.4 µmol/L and one <28 µmol/L. Low vitamin C was associated with higher periodontal disease stage (p = 0.03). Elevated CRP was found in 2/3 of people with low vitamin C and CRP was negatively correlated with vitamin C (p < 0.01). Vitamin C did not correlate with patient-reported fruit or vegetable consumption, but high processed meat intake was associated with lower vitamin C. CONCLUSION: Although a small study, this rate of vitamin C deficiency in the periodontal clinic is clinically important and correlations with disease severity and CRP suggests biological importance. This warrants further studies to assess vitamin C and whether supplementation improves periodontal outcomes, particularly in deficient subjects.

Vitamin C deficiency mimicking inflammatory bone disease of the hand.

BACKGROUND: Severe vitamin C deficiency, or scurvy, encompasses a syndrome of multisystem abnormalities due to defective collagen synthesis and antioxidative functions. Among the more common presentations is a combination of oral or subcutaneous hemorrhage with lower extremity pain, the latter often exhibiting inflammatory bone changes on magnetic resonance imaging (MRI). CASE PRESENTATION: A 12-year-old male with anorexia nervosa presented with asymmetric painful swelling of multiple fingers of both hands. Imaging demonstrated soft tissue and bone marrow edema of several phalanges, without arthritis, concerning for an inflammatory process. Extensive imaging and laboratory evaluations were largely unrevealing, with the exception of a severely low vitamin C level and a moderately low vitamin D level. A diagnosis of scurvy was made and supplementation was initiated. Within 3 weeks of treatment, serum levels of both vitamins normalized and the digital abnormalities resolved on physical exam. CONCLUSIONS: This represents the first description of scurvy manifesting with bone and soft tissue changes limited to the hands. There must be a high index of suspicion for scurvy in children with restricted dietary intake or malabsorption who have bone pain, irrespective of location of the lesions.