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Background: Assessment for vitamin C deficiency (VCD) is rarely undertaken in an acute hospital setting in high-income countries. However, with growing interest in VCD in community settings, there is emerging evidence investigating the prevalence and impact of VCD during hospitalization., Objectives: In this scoping review, the prevalence of VCD in adult hospitalized patients is explored, patient characteristics are described, and risk factors and clinical outcomes associated with VCD are identified., Methods: A systematic scoping review was conducted in accordance with the PRISMA-ScR framework. The Ovid MEDLINE, Ovid Embase, Scopus, CINAHL Plus, Allied and Complementary Medicine Database, and the Cochrane Library databases were searched for interventional, comparative, and case-series studies that met eligibility criteria, including adult hospital inpatients in high-income countries, as defined by the Organization for Economic Co-operation and Development, that reported VCD prevalence using World Health Organization reference standards. These standards define VCD deficiency as plasma or serum vitamin C level <11.4 µmol/L, wholeblood level <17 µmol/L, or leukocytes <57 nmol/108 cells., Results: Twenty-three articles were included, representing 22 studies. The cumulative prevalence of VCD was 27.7% (n = 2494; 95% confidence interval [CI], 21.3-34.0). High prevalence of VCD was observed in patients with severe acute illness and poor nutritional status. Scurvy was present in 48% to 62% of patients with VCD assessed in 2 studies (n = 71). Being retired (P = 0.015) and using excessive amounts of alcohol and tobacco (P = 0.0003) were independent risk factors for VCD (n = 184). Age was not conclusively associated with VCD (n = 631). Two studies examined nutrition associations (n = 309); results were inconsistent. Clinical outcomes for VCD included increased risk of frailty (adjusted odds ratio, 4.3; 95%CI, 1.33-13.86; P = 0.015) and cognitive impairment (adjusted odds ratio, 2.93; 95%CI, 1.05-8.19, P = 0.031) (n = 160)., Conclusions: VCD is a nutritional challenge facing the healthcare systems of high-income countries. Research focused on early identification and treatment of patients with VCD is warranted., Systematic Review Registration: Open Science Framework ( https://doi.org/10.17605/OSF.IO/AJGHX )., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Scurvy is caused by vitamin C deficiency and is often thought of as an ancient malady. However, it still afflicts present-day patients with insufficient nutrition, excessive alcohol consumption and disorders of absorption. Scurvy is traditionally characterised by ecchymosis, petechiae, haemorrhages, poor wound healing, myalgias and arthralgias, but it can also present with non-specific symptoms, including mood changes, fatigue, malaise and dyspnoea. Although scurvy can present with signs of excess bleeding, it does not involve blood clotting. We present a case of concurrent scurvy and pulmonary embolism in which clinical presentation and laboratory findings mimicked a coagulation disorder, resulting in delayed diagnosis and excessive resource expenditure. This case underscores the importance of obtaining an early dietary and substance use history in patients with unexplained haematological symptoms. These crucial components of history-taking can significantly reduce invasive and costly tests, resulting in quicker diagnosis and enhanced patient outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Vitamin C deficiency resulting in scurvy, is considered to be a rare nutritional disorder in developed countries, thus leading to underdiagnosis with exposure to unnecessary investigations and delay in appropriate treatment. The wide myriad of clinical signs and symptoms with which vitamin C deficiency can present (including haematological, musculoskeletal and vague constitutional symptoms that overlap with other common medical conditions), also contributes to this diagnostic challenge. Despite scurvy being habitually thought to be present in children with neurodevelopmental conditions such as autism spectrum disorder, other important at-risk groups that frequently tend to be forgotten include children with persistent fussy eating behaviour, and children with abnormal vitamin C metabolism. We hereunder present a case of a 10-year-old boy who presented to an acute general hospital for further investigation with gait disturbance. The lack of detailed nutritional assessment on presentation in the first instance led to a missed diagnosis of vitamin C deficiency, thus exposing the child to a wide array of unnecessary investigations and treatments. The added perplexity to the case resulting from false positive results of investigations performed as part of this child's workup, is also discussed.

Dear Editor, Scurvy is a nutritional disorder which can develop after prolonged (>1-3 months) severe vitamin C deficiency. Vitamin C is a cofactor in several enzyme reactions involved in collagen synthesis. The defect in collagen causes blood vessel fragility, poor wound healing, mucocutaneous bleedings, hair abnormalities, bone pains, and joint contractures due to periosteal and intraarticular bleeding (1,2). Risk factors for scurvy development are undernutrition, low socioeconomic status, older age, male sex, alcoholism, tobacco smoking, and severe psychiatric illnesses (1-3). The required daily intake for vitamin C is ~60 mg, and this amount of vitamin C can be found in only one medium-sized orange. For this reason, the disease is rarely encountered in developed countries and is often underrecognized by healthcare personnel. Herein, we present an illustrative case of scurvy in order to raise the awareness of this disorder. A 61-year-old Caucasian man was admitted to hospital due to fatigue, hypotension (80/50 mmHg), severe normocytic anemia (hemoglobin 76 g/L), kidney failure (estimated glomerular filtration rate of 6 mL/min/1.73m2) and mild elevation in C-reactive protein (30.9 mg/L). Prior medical history included radical cystoprostatectomy with an ileal conduit performed eight years ago due to a bladder tumor and moderate chronic kidney disease with recurrent urinary tract infections. The patient was also an alcoholic and tobacco smoker, with a very low-income and a poor diet. He did not use any medications. Heteroanamnestically, the current clinical state had developed slowly over several weeks. At admission, the patient was afebrile, lethargic, malnourished, and immobile due to generalized weakness, bone pains, and hip and knee contractures. He had generalized edema, mostly related to kidney failure, as well as severe hypoalbuminemia (serum albumin 19 g/L). There were multiple ecchymoses (Figure 1, a) and perifollicular bleedings (Figure 1, b) in the skin. The teeth were defective, and the patient's facial hair had a "corkscrew" appearance (Figure 1, c). The platelet count was normal, as was the serum fibrinogen level and the prothrombin- and activated partial thromboplastin times. Vancomycin-resistant Enterococcus faecium and multi-drug-resistant Acinetobacter baumanii were isolated from the urine. Therefore, hemodialysis, linezolid, and colistin were started. However, the patient continued to be lethargic, immobile, and with prominent skin bleeding. Medical workup excluded the possibility of an underlying malignancy or an autoimmune disorder. Finally, scurvy was suspected and 500 mg daily of oral vitamin C was introduced into therapy. In the following two weeks, the general condition of the patient significantly improved and he was discharged from the hospital in good condition - mobile and with complete resolution of skin lesions (Figure 1, d and e). Three months later, the patient was still under maintenance hemodialysis and had mild anemia (hemoglobin 123 g/L). Interestingly, scurvy was the first disease in the history of medicine for which a randomized trial found a cure (4). The differential diagnosis of scurvy includes skin infections, hematologic disorders, collagen vascular disorders, and anticoagulant/antiplatelet side-effects (1). Pathognomonic skin findings which may help raise suspicion of scurvy are perifollicular bleedings and "corkscrew" hair. Notably, laboratory testing for vitamin C concentration is not necessary to confirm scurvy as it tends to reflect recent dietary intake of vitamin C (2). Nevertheless, it may be useful to identify less typical cases (2). In our case, rapid clinical improvement with the resolution of skin lesions and joint contractures after the introduction of vitamin C confirmed the clinical diagnosis of scurvy. Additionally, vitamin C deficiency could be, at least partly (besides kidney failure and acute infection), responsible for severe anemia at disease presentation (5). This case serves to remind clinicians not to forget scurvy when treating patients at risk for vitamin C deficiency who present with fatigue, anemia, bone pains, and unexplained mucocutaneous bleedings. In suspected cases, vitamin C should be administered without hesitation.

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Scurvy is a well-known clinical condition caused by vitamin C deficiency. Although considered a rare disease in high-income countries, it has been recently increasingly reported in children, especially in those with abnormal dietary habits, mental or physical disabilities. We performed an extensive review of the literature analyzing studies published in the last 20 years focusing on clinical features, differential diagnosis and diagnostic delay. Fifteen articles were selected, collectively reporting a total of 166 children. Because of the wide clinical spectrum (musculoskeletal complaints and/or mucocutaneous lesions or systemic symptoms), scurvy can mimic several conditions, including autoimmune diseases, infections, and neoplasia. In addition, frequent findings such as normal nutritional status, anemia or elevated inflammatory markers may guide clinicians towards the abovementioned misdiagnoses. Scurvy should be considered in patients presenting with musculoskeletal complaints, not only in those with risk factors but also in healthy children. A focused dietary history and a careful physical examination, assessing other signs of vitamin C deficiency, are mandatory in these patients. When suspected, the dosage of serum vitamin C is the diagnostic gold standard; furthermore, imaging studies, performed by an expert radiologist, can reveal the typical features of scurvy. Only early diagnosis can avoid unnecessary investigations and potentially fatal complications of the disease.

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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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.

To date, there are no recommendations about screening plasma vitamin C concentration and adjust its supplementation in patients on long-term home parenteral nutrition (HPN). The aim of this study was to evaluate vitamin C status and determine if a commercial multivitamin preparation (CMVP) containing 125 mg of vitamin C is sufficient in stable patients on HPN. All clinically stable patients receiving HPN or an intravenous fluid infusion at least two times per week for at least 6 months, hospitalized for nutritional assessment, were retrospectively included, for a total of 186 patients. We found that 29% of the patients had vitamin C insufficiency (i.e., <25 µmol/L). In univariate analysis, C-reactive protein (CRP) ( p = 0.002) and intake of only 125 mg of vitamin C ( p = 0.001) were negatively associated with vitamin C levels, and duration of follow-up in our referral center ( p = 0.009) was positively associated with vitamin C levels. In multivariate analysis, only CRP ( p = 0.001) and intake of 125 mg of vitamin C ( p < 0.0001) were independently associated with low plasma vitamin C concentration. Patients receiving only CMVP with a low plasma vitamin C level significantly received personal compounded HPN ( p = 0.008) and presented an inflammatory syndrome ( p = 0.002). Vitamin C insufficiency is frequent in individuals undergoing home parenteral nutrition; therefore, there is a need to monitor plasma vitamin C levels, especially in patients on HPN with an inflammatory syndrome and only on CMVP., Competing Interests: J.G. received lecture fees from Mylan, Baxter, Pfizer, MSD, Elivie, DDS Assistance, Fresenius Kabi, Nutricia, and Nestlé Health Science France. S.A. received lecture fees from Nestlé Health Science France and Shire. C.B. received lecture fess from Takeda, Shire, Abbvie, Fresenius Kabi, Linde Homecare France, Experf Rhone Alpes, Elivie, Janssen-Cilag, Mayoly Spindler, and MSD. T.C. none. E.B. none. C.P. received lecture fees from Takeda and Geistlich Pharma. D.B. received lecture fees from Baxter, Nutricia, Fresenius Kabi, Shire. C.C. received lecture fees from Aguettant, Baxter, B Braun, Coloplast, Fresenius Kabi, Nutricia, Nestlé Clinical Nutrition, Shire, Zealand. M.L. received lecture fees from Shire, Theradial, Fresenius Kabi, Elivie, LVL Medical and Nutricia.

A female patient presented with exertional dyspnea, myalgia, a petechial rash of the lower extremities and pronounced gingivitis. The biochemical test results showed the presence of anemia. The patient had a known eating disorder and on questioning about eating habits admitted that she did not eat any fruit or vegetables. This led to the suspicion of a vitamin C deficiency, which was confirmed by high-pressure liquid chromatography. The patient was subsequently treated with 1000 mg ascorbic acid daily for 1 month whereby the clinical symptoms and anemia improved within a few weeks.

Historically known to be a disease of sailors and soldiers in the seventeenth and eighteenth century, scurvy is a rare nutritional deficiency in the developed world, but it can still be seen among the alcoholics and the malnourished. We present a case of a 39-year-old alcoholic male who presented with progressive fatigue and diffuse purpuric rash with scattered ecchymosis for 2 months. Blood work was remarkable for hemoglobin of 9.1 g/dl, which further dropped to 7 g/dl over the next few days. He was then found to have hemolysis on lab work. After an extensive workup, the common causes of hemolytic anemia were ruled out, vitamin C level was checked, which interestingly resulted as 0 mg/dl. Supplementation with oral vitamin C resulted in the gradual resolution of hemolytic anemia and rash. Hemoglobin improved to 15 g/dl in 4 weeks, with normalization of vitamin C level. The clinical features of scurvy can easily be confused with conditions such as vasculitis, deep venous thrombosis, and systemic bleeding disorders. Therefore, comprehensive workup up is required prior to the diagnosis. Although rare, being a reversible condition, early diagnosis and treatment of scurvy in high-risk populations cannot be stressed enough.

Objectives Vitamin C deficiency is considered extremely rare in modern industrialized countries. This study was performed to assess vitamin C concentrations in the German population. Methods As part of a consultant-patient seminar on nutrition and food intolerances, patients were asked to participate in this study on a voluntary basis. Blood samples were taken for analysis of serum vitamin C concentrations, and all patients were asked to complete a questionnaire. The vitamin C concentration was determined by high-performance liquid chromatography. Results Of approximately 300 patients attending the seminar, 188 (62.6%) consented to vitamin C blood sample analysis and 178 (59.3%) answered the questionnaire. The mean vitamin C concentration was 7.98 mg/L (range, 0.50-17.40; reference range, 5-15 mg/L). A low plasma level with vitamin C insufficiency (<5 mg/L) was found in 31 patients (17.4%), and a potential scorbutogenic deficiency (<1.5 mg/L) was found in 6 (3.3%). Conclusions Potential vitamin C insufficiency and deficiency is common. It is therefore possible, even in modern developed populations, that certain individuals may require a higher intake of vitamin C.

A cohort of 50-year-olds from Canterbury, New Zealand ( N = 404), representative of midlife adults, undertook comprehensive health and dietary assessments. Fasting plasma vitamin C concentrations ( N = 369) and dietary vitamin C intake ( N = 250) were determined. The mean plasma vitamin C concentration was 44.2 µmol/L (95% CI 42.4, 46.0); 62% of the cohort had inadequate plasma vitamin C concentrations (i.e., <50 µmol/L), 13% of the cohort had hypovitaminosis C (i.e., <23 µmol/L), and 2.4% had plasma vitamin C concentrations indicating deficiency (i.e., <11 µmol/L). Men had a lower mean plasma vitamin C concentration than women, and a higher percentage of vitamin C inadequacy and deficiency. A higher prevalence of hypovitaminosis C and deficiency was observed in those of lower socio-economic status and in current smokers. Adults with higher vitamin C levels exhibited lower weight, BMI and waist circumference, and better measures of metabolic health, including HbA1c, insulin and triglycerides, all risk factors for type 2 diabetes. Lower levels of mild cognitive impairment were observed in those with the highest plasma vitamin C concentrations. Plasma vitamin C showed a stronger correlation with markers of metabolic health and cognitive impairment than dietary vitamin C.

Vitamin C (vitC) is essential for normal pregnancy and fetal development and poor vitC status has been related to complications of pregnancy. We have previously shown lower vitC status in diabetic women throughout pregnancy compared to that of non-diabetic controls. Here, we evaluate the relationship between vitC status late in diabetic pregnancy in relation to fetal outcome, complications of pregnancy, diabetic characteristics, and glycemic control based on data of 47 women from the same cohort. We found a significant relationship between the maternal vitC level > or ≤ the 50% percentile of 26.6 μmol/L, respectively, and the umbilical cord blood vitC level (mean (SD)): 101.0 μmol/L (16.6) versus 78.5 μmol/L (27.8), p = 0.02; n = 12/16), while no relation to birth weight or Apgar score was observed. Diabetic women with complications of pregnancy had significantly lower vitC levels compared to the women without complications (mean (SD): 24.2 μmol/L (10.6) vs. 34.6 μmol/L (14.4), p = 0.01; n = 19 and 28, respectively) and the subgroup of women (about 28%) characterized by hypovitaminosis C (<23 μmol/L) had an increased relative risk of complications of pregnancy that was 2.4 fold higher than the one found in the group of women with a vitC status above this level ( p = 0.02, 95% confidence interval 1.2-4.4). No correlation between diabetic characteristics of the pregnant women and vitC status was observed, while a negative association of maternal vitC with HbA1c at delivery was found at regression analysis ( r = -0.39, p < 0.01, n = 46). In conclusion, our results may suggest that hypovitaminosis C in diabetic women is associated with increased risk of complications of pregnancy.

Objectives: Recent studies have highlighted the role of oxidative stress in the pathogenesis of lichen planus (LP). In the present study, the interest of the authors is focused on the investigation of ascorbic acid status in patients with LP and identification of parameters that might influence the level of this vitamin., Material and Method: We analyzed the level of urinary ascorbic acid (reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral LP (OLP)-28 cases) and 50 control subjects. The evaluation of all participants included clinical examination and laboratory and imaging tests., Results: Compared to the control group (19.82 mg/dl) the level of ascorbic acid was significantly lower both in patients with CLP (8.47 mg/dl, p = 0.001) and in those with OLP (8.04 mg/dl, p = 0.001). In patients with LP it was found that the deficiency of ascorbic acid increases with age (r = -0.318, p = 0.032). The urinary concentrations of ascorbic acid were significantly lower in patients with LP associated with infections compared to patients with LP without infections., Conclusions: The urinary ascorbic acid level may be a useful parameter in identifying patients with LP who are at risk of developing viral or bacterial infections.

In Switzerland, vitamin C deficiency is a rare condition. Nonetheless, in clinical practice, there are some patients exhibiting a vitamin C deficiency as a result of an unbalanced diet or intestinal malabsorption. We report the clinical history of a 55-year-old man known for alcoholism and insufficient intake of fresh fruits and vegetables. He was admitted to the intensive care unit, for haemodynamic instability caused by blood loss due to fragile vessels (skin, gastrointestinal). Further analyses revealed a severe lack of vitamin C. The patient received a high dose of intravenous substitutive treatment, leading to a favourable clinical outcome., (2016 BMJ Publishing Group Ltd.)

Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance by the generation of excess levels of reactive oxygen species and induces adipocyte dysfunction and reprogramming, leading to a low grade systemic inflammation and ectopic lipid deposition, e.g., in the liver, hereby promoting a vicious circle in which dietary factors initiate a metabolic change that further exacerbates the negative consequences of an adverse life-style. Large epidemiological studies and findings from controlled in vivo animal studies have provided evidence supporting an association between poor vitamin C (VitC) status and propagation of life-style associated diseases. In addition, overweight per se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA) in NAFLD-patients, suggesting an association between dietary habits, disease and VitC deficiency. In the general population, VitC deficiency (defined as a plasma concentration below 23 μM) affects around 10% of adults, however, this prevalence is increased by an adverse life-style, deficiency potentially playing a broader role in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH.

Background: Researchers suspect that the accepted adequate ascorbic acid plasma concentration is not being met even after dietary intake of the recommended amount of vitamin C. Current dietary intake recommendation in Poland is 60 mg per day for women and 75 mg per day for man (EAR), while in Western Europe and North America is higher and amounts to 75-90 mg per day., Objective: The paper aimed at studying a correlation between composition of nutrients in daily diet and plasma vitamin C levels in university students. Materials and methods. This study examined diet composition and the nutritional status of ascorbic acid in plasma of 120 university students in Szczecin, Poland. Ascorbic acid was determined in blood plasma using HPLC method. The information concerning diet composition was collected using the method of "7-days food record" prior to blood collection., Results: Plasma ascorbic acid deficiency (<40 μmol/L) was observed in 23% of women and 28% of men. The average plasma ascorbic acid concentration was 48.65 μmol/L in women and 45.61 μmol/L in men. The average intake of vitamin C in women with observed deficiency was average 46.55 mg/day, whereas in men it was 48.56 mg/day., Conclusions: The recommendation of dietary intake of vitamin C in Poland is low in comparison to other countries. Population- based studies are necessary to determine the actual demand for vitamin C in various population groups in Poland. Key words: nutrition, vitamins, dietary intake, diet, ascorbic acid, plasma.

Research progress to understand the role of vitamin C (ascorbic acid) in human health has been slow in coming. This is predominantly the result of several flawed approaches to study design, often lacking a full appreciation of the redox chemistry and biology of ascorbic acid. In this review, we summarize our knowledge surrounding the limitations of common approaches used in vitamin C research. In human cell culture, the primary issues are the high oxygen environment, presence of redox-active transition metal ions in culture media, and the use of immortalized cell lines grown in the absence of supplemental ascorbic acid. Studies in animal models are also limited due to the presence of endogenous ascorbic acid synthesis. Despite the use of genetically altered rodent strains lacking synthesis capacity, there are additional concerns that these models do not adequately recapitulate the effects of vitamin C deprivation and supplementation observed in humans. Lastly, several flaws in study design endemic to randomized controlled trials and other human studies greatly limit their conclusions and impact. There also is anecdotal evidence of positive and negative health effects of vitamin C that are widely accepted but have not been substantiated. Only with careful attention to study design and experimental detail can we further our understanding of the possible roles of vitamin C in promoting human health and preventing or treating disease.

Background: Though vitamin C supplementation has shown no observed effects on stroke prevention in several clinical trials, uncertainty remains as to whether long-term, low-dose intake influences the development of stroke among general populations. Furthermore, the association between circulating vitamin C and the risk of stroke is also unclear. For further clarification of these issues, we conducted a meta-analysis of prospective studies., Methods and Results: PubMed and EMBASE databases were searched, and the bibliographies of the retrieved articles were also reviewed to identify eligible studies. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were computed with a random-effects model. The summary RR for the high-versus-low categories was 0.81 (95% CI: 0.74 to 0.90) for dietary vitamin C intake (11 studies), and 0.62 (95% CI: 0.49 to 0.79) for circulating vitamin C (6 studies). The summary RR for each 100 mg/day increment in dietary vitamin C was 0.83 (95% CI: 0.75 to 0.93) (10 studies), and for each 20 μmol/L increment in circulating vitamin C was 0.81 (95% CI: 0.75 to 0.88) (5 studies). Few studies reported results for vitamin C supplements (RR for high-versus-low intake=0.83, 95% CI: 0.62 to 1.10, 3 studies)., Conclusions: This meta-analysis suggests significant inverse relationships between dietary vitamin C intake, circulating vitamin C, and risk of stroke.

Vitamin C is a water soluble vitamin which is mainly fresh fruits and vegetables foodborne. Vitamin C deficiency is most often due to a lack of daily amount. Scurvy is characterized by the occurrence of fatigue, myalgia, arthralgia, purpura, bleeding disorders, and later by dental manifestations. Biological signs are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia. Clinical suspicion is confirmed by the decrease in ascorbic acid level (< 2 mg/L). It must be interpreted in light of the acute phase reactants. The treatment is the administration of 1 g of vitamin C per day for 15 days. Vitamin C depletion (ascorbic acid: 2 to 5 mg/L) could induce long-term complications. The recommended dietary allowance of vitamin C protect from these risks.

A 64-year-old woman presented with a hemorrhagic perifollicular rash on her legs while taking warfarin. After biopsy, vitamin C deficiency was suggested as the diagnosis, which ascorbic acid assays later confirmed. Clinical resolution of the rash followed supplementation with vitamin C. Patients on a vitamin K limited diet may also be limiting their intake of vitamin C. Physicians should be aware of this possible correlation, and consider checking vitamin C levels in patients with a perifollicular hemorrhagic rash or other signs of vitamin C deficiency while on warfarin.

Case: Haven is an 11-year-old primary care patient who you have followed since her birth. She was the 9 lb 6 oz product of a 38-week gestation complicated by maternal hypertension and seizure disorder treated with tegretol. Her delivery and neonatal course were uneventful. She was diagnosed with austistic disorder at age 2 years, at which time she used no functional language or gestures, had repetitive motor mannerisms, and limited eye contact. She had strong tactile sensory aversions. Her diet was very restricted including only banana yogurt and drinking milk and apple juice for the first several years of life. She was followed by a developmental-behavioral pediatrician approximately annually through age 8 years and then more frequently. She was healthy other than lead exposure (maximum serum level 18 at age 3 years) and multiple febrile seizures with other possible absence episodes. Her development remained very delayed with use of single words and short phrases. She developed multiple repetitive, anxious, obsessive behaviors (picking up lint, organizing, cleaning, and freezing in certain postures) that were treated with a selective serotonin reuptake inhibitors fluvoxamine. Sensory issues were ongoing, with restrictive eating (primarily peanut butter and jelly sandwiches, cereal bars, milk, and a kiwi-strawberry drink). She took a liquid multivitamin until age 8.At age 11 years, 3 weeks prior to admission, Haven developed acute loss of ambulation over the course of 1 day, initially dragging her right leg, and then refusing to walk and her parents brought her in to see you. She had fever, vomiting, and general weakness. She developed extensive bruising over her legs, especially in the popliteal fossae. She was also noted to have friability and dark discoloration of her gums. Initially, you suspected a post-viral syndrome and close monitoring. She was seen twice in the next 2 weeks in a local emergency room where her erythrocyte sedimentation rate was reported to be elevated and juvenile rheumatoid arthritis or a reaction to fluvoxamine were suspected. Antibiotics were also prescribed for gingivitis. She was seen by an orthopedist who felt it was not an orthopedic issue and leg films were unremarkable. With her second emergency room visit, she was transferred to a tertiary medical center and admitted for further evaluation. Where would you go from here?

Scurvy is well known since ancient times, but it is rarely seen in the developed world today owing to the discovery of its link to the dietary deficiency of ascorbic acid. It is very uncommon in the pediatric population, and is usually seen in children with severely restricted diet attributable to psychiatric or developmental disturbances. The condition presents itself by the formation of perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We report a case of scurvy in a 10-year-old developmentally delayed boy who had a diet markedly deficient in vitamin C resulting from extremely limited food choices. He presented with debilitating bone pain, inflammatory gingival disease, and perifollicular hyperkeratosis. The diagnosis was made based on clinical and radiographic findings. The importance of diet history is emphasized. We present this case with the aim to help the clinician identify scurvy and implement treatment for a potentially fatal but easily curable disease.

We report the case of the case of a 56 year old female with sepsis on a background of rheumatoid arthritis and steroid use manifesting with overt clinical features of scurvy. Ascorbic acid assays were able to demonstrate severe deficiency and confirm a diagnosis of scurvy. Clinical resolution of signs and symptoms following commencement of vitamin C replacement was rapid. The intensivist and dietitian need to consider this diagnosis even in the first world setting, particularly in the presence of sepsis, inflammatory conditions, steroid use and importantly malnutrition., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Background: Studies from the UK and North America have reported vitamin C deficiency in around 1 in 5 men and 1 in 9 women in low income groups. There are few data on vitamin C deficiency in resource poor countries., Objectives: To investigate the prevalence of vitamin C deficiency in India., Design: We carried out a population-based cross-sectional survey in two areas of north and south India. Randomly sampled clusters were enumerated to identify people aged 60 and over. Participants (75% response rate) were interviewed for tobacco, alcohol, cooking fuel use, 24 hour diet recall and underwent anthropometry and blood collection. Vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid. We categorised vitamin C status as deficient (<11 µmol/L), sub-optimal (11-28 µmol/L) and adequate (>28 µmol/L). We investigated factors associated with vitamin C deficiency using multivariable Poisson regression., Results: The age, sex and season standardized prevalence of vitamin C deficiency was 73.9% (95% confidence Interval, CI 70.4,77.5) in 2668 people in north India and 45.7% (95% CI 42.5,48.9) in 2970 from south India. Only 10.8% in the north and 25.9% in the south met the criteria for adequate levels. Vitamin C deficiency varied by season, and was more prevalent in men, with increasing age, users of tobacco and biomass fuels, in those with anthropometric indicators of poor nutrition and with lower intakes of dietary vitamin C., Conclusions: In poor communities, such as in our study, consideration needs to be given to measures to improve the consumption of vitamin C rich foods and to discourage the use of tobacco.

The purpose of this paper was to report the case of a 2-year-old Caucasian female who was referred with a presumed diagnosis of pediatric rheumatoid arthritis. The patient presented widespread gingival swelling with bleeding, sharp pain, and halitosis. The patient also presented pain and swelling of the right knee joint, and psychomotor restlessness associated with muscular frailty. Little compliance on the part of both the patient and parents was also noted. Oral manifestations, together with an accurate medical history, led to the diagnosis of infantile scurvy, caused by an inadequate dietary supply of vitamin C. Administering 250 mg of ascorbic acid orally twice a day led to the remission of gingival swelling and of the other symptoms. The parents were advised to feed the child appropriate foods. Nutritional problems are traditionally linked to an insufficient availability of food, but can also be associated with child- or family-related psychological problems.

Scurvy, the rare but potentially mortal manifestation of severe and prolonged lack of vitamin C, is often confused with hypovitaminosis C, i.e. the mere definition of vitamin C deficiency. While the latter condition can be diagnosed in millions, the clinical consequences (if they exist) remain largely unknown, since only a tiny fraction of those deficient in vitamin C actually develop clinical scurvy. Is hypovitaminosis C itself a problem at all then? Yes, it may well be in some cases. Recent data from our laboratory suggest that the neonatal brain is particularly susceptible to vitamin C deficiency and that this condition may adversely affect early brain development.

Scurvy is an ancient disease. Over the years, with advances in the understanding of the disease, general improvement in health standards and nutrition, scurvy is now rarely encountered. The few cases of scurvy reported in the 21st century mainly occurred in the neglected elderly, alcoholics and food faddist. We describe scurvy due to food selection in a 37-year-old woman with underlying eating and obsessive-compulsive disorders. With vitamin C replacement, psychiatric medication and cognitive behavioural therapy, there was a dramatic improvement in her condition. This case serves as a reminder to the clinician that, even though rare in today's practice, ascorbic acid deficiency is still encountered, and when recognised, is an easily treatable disease.