A High Vitamin C Micronutrient Supplement Is Unable to Attenuate Inflammation in People with Metabolic Syndrome but May Improve Metabolic Health Indices: A Randomised Controlled Trial.

Chronic low-grade inflammation is a characteristic of people with metabolic syndrome and is thought to contribute to the condition progressing to the more severe type 2 diabetes and cardiovascular disease (CVD). The aim was to carry out a double-blind randomised placebo-controlled trial in people with metabolic syndrome to determine if supplementation with a micronutrient formula containing 1000 mg/d vitamin C could attenuate inflammation in people with metabolic syndrome. We recruited 72 adults aged a median of 52 years with metabolic syndrome, defined as obesity (based on waist circumference or BMI), and at least two of hyperglycaemia, raised triglycerides, lowered HDL cholesterol, hypertension, or taking medications for these conditions. A further inclusion criteria comprised C-reactive protein (CRP) concentrations ≥ 3 mg/L, i.e., high risk of CVD. The participants were randomised to daily micronutrient formula (n = 37) or matched placebo control (n = 35) for 12 weeks. The primary outcome was change in CRP concentrations and secondary outcomes included changes in vitamin C concentrations, pro-inflammatory cytokines (IL-6, TNFα), oxidative stress marker (F2isoprostanes), glycaemic indices (glucose, insulin, HbA1c), lipid markers (triglycerides, LDL and HDL cholesterol), anthropometric parameters (weight, BMI), insulin resistance and insulin sensitivity, and metabolic severity score. The participants had a low median (Q1, Q3) vitamin C status of 29 (15, 41) µmol/L and a high proportion of hypovitaminosis C (38%) and outright deficiency (19%). Following 12 weeks of micronutrient supplementation, at least 70% of the participants reached adequate vitamin C status (≥50 µmol/L), however, there was no change in CRP concentrations relative to the placebo group (Δ-0.3 [95%CI -2.7, 2.1] mg/L, p = 0.8). Similar trends were observed for IL-6, TNFα and F2isoprostanes (p > 0.05). Instead, there were small improvements in BMI, fasting glucose and HbA1c concentrations, insulin sensitivity and metabolic severity score in the micronutrient group relative to placebo (p < 0.05). Overall, 12-week micronutrient supplementation was unable to mitigate systemic inflammation in people with metabolic syndrome but may improve several metabolic health indices.

SunGold Kiwifruit Consumption Restores Adequate to Optimal Vitamin C Status in People with a History of Severe Respiratory Infections.

Severe respiratory infections are characterised by depleted vitamin C and elevated inflammation and oxidative stress. The aim of this study was to recruit people with a history of severe respiratory infections to undergo a six-week intervention with SunGold kiwifruit to determine if this could restore adequate vitamin C status. Secondary outcomes included changes in inflammatory and oxidative stress biomarkers, self-reported fatigue and subjective mood, and the incidence, duration and severity of respiratory symptoms. The total cohort comprised 20 adults (65% female, age range 31-84 years). The participants had a low median fruit and vegetable intake of 2.3 servings/day and a correspondingly low vitamin C intake of 46 mg/day. Circulating vitamin C status was a median of 45 µmol/L and was in the hypovitaminosis range in 25% of the cohort. Following intervention with two SunGold kiwifruit/day (equivalent to ~300 mg vitamin C), there was an increase in plasma vitamin C concentrations to >60 µmol/L (p < 0.05). Approximately 20% of the participants were unable to reach adequate vitamin C status (≥50 µmol/L), possibly due to current smoking, which enhances vitamin C turnover, and a strong inverse correlation between body weight and vitamin C status (r = -0.734, p < 0.05). Following the intervention, there were indications towards decreases in the inflammatory biomarkers C-reactive protein and TNFα (p > 0.05), but no changes in oxidative stress biomarkers (F2isoprostanes, protein carbonyls). There were decreases in fatigue and depression (p < 0.05) and a lower number of individual respiratory symptoms reported during the kiwifruit intervention phase (8.5 vs. 10, p = 0.05). Overall, the consumption of two SunGold kiwifruit per day for six weeks was able to restore adequate to saturating vitamin C status in ~80% of the participants. Smokers and people with higher body weight may need larger doses and/or longer duration of supplementation. The contribution of vitamin C to reducing fatigue, depression, and number of respiratory symptoms warrants further investigation.

Estimating Vitamin C Intake Requirements in Diabetes Mellitus: Analysis of NHANES 2017-2018 and EPIC-Norfolk Cohorts.

Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus, suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017-2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four-parameter logistic) curves. The NHANES cohort (n = 2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥ 6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs. 44 [25, 61] µmol/L, p < 0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs. 53 [24, 104] mg/d, p = 0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had a lower BMI than the NHANES cohort (26 [24, 28] kg/m2 vs. 29 [25, 34] kg/m2, p < 0.0001). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes had 1.4 to 1.6 fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes, equating to a total daily intake of at least 125 mg/d.

Low Vitamin C Concentrations in Patients with Community-Acquired Pneumonia Resolved with Pragmatic Administration of Intravenous and Oral Vitamin C.

Community-acquired pneumonia (CAP) is characterized by elevated markers of inflammation and oxidative stress and depleted circulating concentrations of the antioxidant nutrient vitamin C. A feasibility trial of intravenous and oral vitamin C supplementation, matched to the timing of intravenous and oral antibiotic formulations, was carried out and changes in vitamin C status were monitored to determine whether saturating status could be achieved throughout the administration period. Patients with moderate and severe CAP (CURB-65 ≥ 2; n = 75) who were receiving intravenous antimicrobial therapy were randomized to placebo (n = 39) or intravenous vitamin C (2.5 g per 8 h; n = 36) before moving to oral vitamin C (1 g three times daily) when prescribed oral antimicrobials. Blood samples were collected at baseline and then daily whilst in the hospital. Vitamin C concentrations were determined by high-performance liquid chromatography. The inflammatory and infection biomarkers C-reactive protein and procalcitonin were elevated at baseline (158 (61, 277) mg/L and 414 (155, 1708) ng/L, respectively), and vitamin C concentrations were depleted (15 (7, 25) µmol/L). There was an inverse association between vitamin C and C-reactive protein concentrations (r = -0.312, p = 0.01). Within one day of intervention initiation, plasma vitamin C concentrations in the vitamin C group reached median concentrations of 227 (109, 422) µmol/L, and circulating concentrations remained at ≥150 µmol/L for the duration of the intervention, whilst median vitamin C concentrations in the placebo group remained low (≤35 µmol/L). There was a trend toward decreased duration of hospital stay (p = 0.07) and time to clinical stability (p = 0.08) in the vitamin C group. In conclusion, patients with moderate to severe CAP have inadequate plasma vitamin C concentrations for the duration of their hospital stay. The administration of intravenous or oral vitamin C, titrated to match the antimicrobial formulation, provided saturating plasma vitamin C concentrations whilst in the hospital. There were trends toward shorter duration of hospital stay and time to clinical stability. Thus, larger trials assessing the impact of intravenous and oral vitamin C intervention on CAP clinical outcomes are indicated.

Factors Affecting the Vitamin C Dose-Concentration Relationship: Implications for Global Vitamin C Dietary Recommendations.

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to investigate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations, and the possible extent of these additional requirements. The final cohort comprised 2828 non-supplementing adult males and females (aged 18-80+ years) with both vitamin C serum concentrations and dietary intake data available. The data were subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: ≤1.35, 1.36-3.0, >3.0), weight tertiles (<72, 72-91, >91 kg), BMI tertiles (<26, 26-32, >32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach 'adequate' serum vitamin C concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heavier weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes > 75 mg/day, at intakes < 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population should consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach comparable vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

Inflammation and Vitamin C in Women with Prenatal Depression and Anxiety: Effect of Multinutrient Supplementation.

Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (p < 0.05), including the Edinburgh Postnatal Depression Scale, the Clinical Global Impressions-Severity Scale, the Montgomery and Åsberg Depression Rating Scale, the Depression Anxiety Stress Scale 21, and the Generalized Anxiety Disorder-7 (GAD-7). CRP correlated weakly with GAD-7 (p = 0.05). There was an inverse correlation between CRP and the vitamin C status of the cohort (p = 0.045), although there was no association of the latter with the mood scales (p > 0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (p = 0.007) but did not affect the inflammatory biomarker concentrations (p > 0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes.

People with diabetes and hypovitaminosis C fail to conserve urinary vitamin C.

Background: Hypovitaminosis C has negative health consequences. People with diabetes and hypovitaminosis C may fail to conserve vitamin C in the urine, thereby displaying evidence of inappropriate renal leak of vitamin C. This study describes the relationship between plasma and urinary vitamin C in diabetes, with a focus on the clinical characteristics of participants with renal leak. Methods: Retrospective analysis of paired, non-fasting plasma and urine vitamin C, and also clinical characteristics, from participants with either type 1 or type 2 diabetes, recruited from a secondary care diabetes clinic. Plasma vitamin C thresholds for renal leak have been defined previously as 38.1 µmol/L for men and 43.2 µmol/L for women. Results: Statistically significant differences in clinical characteristics were seen between those with; i) renal leak (N = 77) and; ii) hypovitaminosis C but no renal leak (N = 13) and; iii) normal plasma vitamin C levels (n = 34). Compared to participants with adequate plasma vitamin C levels, participants with renal leak tended to have type 2 (rather than type 1) diabetes, a lower eGFR and a higher HbA1c. Conclusion: In the diabetes population studied, renal leak of vitamin C was common. In some participants, it may have contributed to hypovitaminosis C.

Does Aging Affect Vitamin C Status Relative to Intake? Findings from NHANES 2017-2018.

The aging population is growing and fueling a global increase in chronic diseases and healthcare expenditure. In this study, we examine vitamin C dose-concentration relationships based on data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 to identify a possible age-dependent change in intake vs. concentration relationship among non-supplemented individuals (n = 2828). The vitamin C intake was similar between the younger (18-36 years), middle (37-58 years) and older (59-80+ years) age groups; however, circulating vitamin C concentrations were significantly lower in the middle and older age groups (p < 0.001). For intakes above 75 mg/day, no significant difference in the intake vs. serum concentration relationship was identified between younger and older individuals. However, for intakes below 75 mg/day, we found significantly lower serum concentrations relative to intake for the older compared to younger individuals, despite smoking being more prevalent in the younger compared to older adults (p < 0.001). This effect persisted among non-smokers and was further exacerbated by smoking in older people. Collectively, the present study suggests that healthy aging in non-institutionalized individuals does not increase requirements for vitamin C. In contrast, the lower serum concentrations relative to intake observed in older individuals at intakes < 75 mg/day may suggest that older individuals are more sensitive to a low vitamin C intake, perhaps due to the increased impact of long-term smoking and increased chronic disease prevalence in older adults. This finding may have implications for future intake guidelines in countries with low RDAs and for WHO/FAO, but requires further investigation.

Does Aging Have an Impact on Vitamin C Status and Requirements? A Scoping Review of Comparative Studies of Aging and Institutionalisation.

The global healthcare burden of an aging population continues to increase, with nearly a quarter of the total global burden of disease attributable to people aged ≥60 years. Older people are at greater risk of micronutrient deficiencies, including immune-supportive vitamin C, which is both a contributor to and a consequence of acute and chronic illnesses. However, whether healthy aging, per se, is associated with depleted vitamin C status and increased requirements for the vitamin is less certain. A systematic scoping review was carried out to assess comparative studies that reported the vitamin C status and prevalence of deficiency in older versus younger people and in older people relative to residential status. Furthermore, vitamin C requirements were assessed through comparative studies reporting vitamin C status and pharmacokinetics in older people relative to younger people. Overall, there was limited evidence to suggest that healthy aging, per se, is related to lower vitamin C status or higher requirements for the vitamin. However, institutionalised elderly had lower vitamin C status and enhanced vitamin C requirements, primarily as a result of low intakes and/or chronic illnesses, which were not being met by hospital or residential diets. Because institutionalised elderly are vulnerable to malnutrition and micronutrient deficiencies, it is imperative that appropriate nutritional interventions are instigated to provide optimal micronutrient intake to support healthy aging.

Vitamin C - a scoping review for Nordic Nutrition Recommendations 2023.

Vitamin C has multiple metabolic functions in the body, but the available information on the exact relationship between these functions and the intake necessary to maintain them is very limited. However, most attempts to objectively measure adequacy of vitamin C status, including, for example, replacement of metabolic turnover, chronic disease prevention, urinary excretion, and saturation of immune cells and body compartment, currently point toward 50 µmol/L as a reasonable target plasma concentration. As a strong correlation between body weight and vitamin C status exists, recommended intakes (RIs) for other age groups may be extrapolated from the adult RI based on weight. However, as body weights above 70 kg are becoming increasingly common - also in the Nordic region - an RI of 140 mg/day for individuals weighing 100 kg or more should be considered to compensate for the larger volume of distribution. Finally, smoking continues to be a common contributor to poor vitamin C status; therefore, it is proposed that people who smoke increase their daily vitamin C intake by 40 mg/day to compensate for the increased metabolic turnover induced by smoking.

Critically ill septic patients have elevated oxidative stress biomarkers: lack of attenuation by parenteral vitamin C.

Patients with septic shock are under an intense inflammatory burden, which is closely associated with increased oxidative stress and depletion of antioxidants such as vitamin C. We hypothesized that patients with septic shock would present with elevated oxidative stress (assessed as F2-isoprostanes) and that administration of parenteral vitamin C to these patients would attenuate F2-isoprostane concentrations. We recruited 40 critically ill patients with septic shock into a randomized placebo-controlled trial and assessed the effect of short-term (4-day) parenteral vitamin C administration (100 mg/kg/d) on 8-isoprostane F2α concentrations, which were measured using enzyme-linked immunosorbent assays. Sources of sepsis and intensive care unit severity scores were recorded. Smokers (n = 20) and nonsmoking controls (n = 50) were assessed for comparison. The median baseline 8-isoprostane F2α concentration in the septic patients was 3.95 (interquartile range [Q1, Q3] 2.1, 6.63) ng/mg creatinine; this was higher than smokers 1.61 [1.25, 2.82] P = .007 ng/mg creatinine; P = .005) and nonsmoking controls 1.12 [0.76, 1.57] ng/mg creatinine; P < .0001). The 8-isoprostane F2α concentrations in the placebo group did not vary significantly over the duration of the study. Although parenteral vitamin C administration significantly increased the vitamin C status of the patients within 24 hours, this did not affect their 8-isoprostane F2α concentrations. In conclusion, patients with septic shock have elevated 8-isoprostane F2α excretion, which short-term parenteral vitamin C administration is unable to attenuate. If vitamin C is to work by antioxidant mechanisms, then early administration, before the development of shock, may be required. This trial was registered at anzctr.org.au (ACTRN12617001184369).

Supplementation with Oral Vitamin C Prior to and during Myeloablative Chemotherapy and Autologous Haematopoietic Stem Cell Transplantation: A Pilot Study.

Chemotherapy-related side effects are common in patients undergoing myeloablative chemotherapy and haematopoietic stem cell transplantation. Some, such as oral mucositis, are believed to be due to enhanced oxidative stress and inflammation. Vitamin C, a potent antioxidant with anti-inflammatory properties, becomes severely depleted following myeloablative chemotherapy. The aim of our study was to assess the feasibility and efficacy of oral vitamin C supplementation to restore and maintain adequate vitamin C concentrations in patients undergoing myeloablative chemotherapy and stem cell transplantation. We carried out a pilot randomized controlled trial in 20 patients with myeloma and lymphoma. Placebo or vitamin C tablets (1 g twice daily) were initiated one week prior to transplantation and continued for 4 weeks post-transplantation. Blood samples were collected weekly for analysis of plasma vitamin C concentrations using high-performance liquid chromatography. The patients' symptoms and quality of life parameters were monitored using the World Health Organization oral toxicity scale and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Pre-supplementation with oral vitamin C doubled vitamin C concentrations relative to placebo by day 0 (median 61 vs. 31 µmol/L), with 60% of those in the vitamin C group achieving concentrations ≥ 50 µmol/L, compared with only 10% in the placebo group. Following chemotherapy and transplantation, significance between the vitamin C and placebo groups was lost by day 7, with only 30% of the patients in the vitamin C group having plasma concentrations ≥ 50 µmol/L. This was partly due to intolerance of the oral intervention due to nausea/vomiting and diarrhoea (40% of the participants in each group). Oral mucositis was also observed in 40% of the participants at day 7 or 14. Overall, our study showed that whilst short-term oral vitamin C pre-supplementation was able to restore adequate vitamin C status by day 0, ongoing supplementation could not maintain adequate vitamin C concentrations following chemotherapy and transplantation. Thus, intravenous vitamin C should be trialled as this bypasses the gastrointestinal system, negating intolerance issues and improving bioavailability of the vitamin.

Estimation of Vitamin C Intake Requirements Based on Body Weight: Implications for Obesity.

Higher body weight is known to negatively impact plasma vitamin C status. However, despite this well-documented inverse association, recommendations on daily vitamin C intakes by health authorities worldwide do not include particular reference values for people of higher body weight. This suggests that people of higher body weight and people with obesity may be receiving insufficient vitamin C in spite of ingesting the amounts recommended by their health authorities. The current preliminary investigation sought to estimate how much additional vitamin C people with higher body weights would need to consume in order to attain a comparable vitamin C status to that of a lower weight person consuming an average Western vitamin C intake. Data from two published vitamin C dose-concentration studies were used to generate the relationship: a detailed pharmacokinetic study with seven healthy non-smoking men and a multiple depletion-repletion study with 68 healthy non-smoking men of varying body weights. Our estimates suggest that an additional intake of 10 mg vitamin C/day is required for every 10 kg increase in body weight to attain a comparable plasma concentration to a 60 kg individual with a vitamin C intake of ~110 mg/day, which is the daily intake recommended by the European Food Safety Authority (EFSA). Thus, individuals weighing e.g., 80 and 90 kg will need to consume ~130 and 140 mg vitamin C/day, respectively. People with obesity will likely need even higher vitamin C intakes. As poor vitamin C status is associated with increased risk of several chronic diseases including cardiovascular disease, these findings may have important public health implications. As such, dose-finding studies are required to determine optimal vitamin C intakes for overweight and obese people.

Multi-Level Immune Support by Vitamins C and D during the SARS-CoV-2 Pandemic.

Vitamins C and D have well-known immune supportive roles, with deficiencies in both vitamins predisposing to increased risk and severity of respiratory infections. Numerous studies have indicated that administration of these vitamins, particularly to people who are deficient, can decrease the risk and severity of respiratory infections. This has stimulated an interest in the potential efficacy of these vitamins in people with novel coronavirus (SARS-CoV-2) infection and its more severe disease (COVID-19). In this overview, we highlight the current research evidence around the multiple levels of immune support provided by vitamins C and D in the context of general respiratory infections and with a focus on the current SARS-CoV-2 pandemic. These include: prevention of infection; attenuating infection symptoms and severity; adjunctive therapy for severe disease; attenuating ongoing sequelae (long COVID); and immunisation support. Although some of these topics have not yet been investigated in great depth concerning SARS-CoV-2 and COVID-19, extensive research into the role of these vitamins in general respiratory infections has highlighted directions for future research in the current pandemic.

Vitamin C Status in People with Types 1 and 2 Diabetes Mellitus and Varying Degrees of Renal Dysfunction: Relationship to Body Weight.

Diabetes mellitus is a chronic metabolic disorder and is associated with depleted vitamin C status. The underlying aetiologies and pathogeneses responsible for this association are poorly understood. This retrospective study explored the vitamin C status of 136 adult outpatients with types 1 and 2 diabetes mellitus (T1DM/T2DM), with a focus on indices of renal function and metabolic health, including body weight. In the T1DM group (n = 73), the median plasma vitamin C concentration was 33 (18, 48) µmol/L, with 37% hypovitaminosis C and 12% deficiency. In the T2DM group (n = 63), the median plasma concentration was 15 (7, 29) µmol/L, with 68% hypovitaminosis C and 38% deficiency. Lower vitamin C was associated with macroalbuminuria (p = 0.03), renal dysfunction (p = 0.08), and hypertension (p = 0.0005). Inverse associations were also observed between plasma vitamin C and various other metabolic health parameters (p < 0.05), especially body weight (p < 0.0001), which was higher in those with hypovitaminosis C (<23 µmol/L; p = 0.0001). The association with bodyweight remained, even after multivariable analysis. In summary, body weight was a significant predictor of low vitamin C status in people with diabetes. This suggests that people with both diabetes and a high body weight may have greater than average vitamin C requirements.

Intravenous vitamin C administration to patients with septic shock: a pilot randomised controlled trial.

BACKGROUND: Intravenous vitamin C administration in septic shock may have a sparing effect on vasopressor requirements, and vitamin C's enzyme cofactor functions provide a mechanistic rationale. Our study aimed to determine the effect of intravenous vitamin C administration on vasopressor requirements and other outcomes in patients with septic shock. METHODS: This was a double-blind, randomised placebo-controlled trial in 40 patients with septic shock who were randomised (1:1) to receive intravenous vitamin C (at a dose of 25 mg/kg of body weight every 6 h) or placebo (intravenous 5% dextrose) for up to 96 h, or until death or discharge. The primary outcome was intravenous vasopressor requirements (dose and duration), and secondary outcomes included Sequential Organ Failure Assessment (SOFA) scores, intensive care unit (ICU) and hospital length of stay, and mortality. In addition, blood samples were collected to determine vitamin C kinetics and inflammatory marker concentrations. RESULTS: Median plasma vitamin C concentrations were deficient at baseline (9.2 [4.4, 12] µmol/L) and increased to 408 (227, 560) µmol/L following 72 h of intervention. The mean duration of intravenous vasopressor infusion in the vitamin C group was 48 (95% CI 35-62) hours and in the placebo group was 54 (95% CI 41-62) hours (p = 0.52). The dose of vasopressor delivered over time was comparable between the two groups, as were SOFA scores (p > 0.05). The median ICU length of stay in the intervention group was 3.8 (2.2, 9.8) days versus 7.1 (3.1, 20) days in the placebo group (p = 0.12). The median hospital length of stay for the vitamin C group was 18 (11, 35) days versus 22 (10, 52) days for the placebo group (p = 0.65). Mortality was comparable between the two groups (p > 0.05). Of the inflammatory markers, neutrophil counts were elevated in the vitamin C group relative to placebo by 72 h (p = 0.01). C-reactive protein and myeloperoxidase concentrations were elevated at baseline, however, the two groups were comparable over time (p > 0.05). CONCLUSIONS: Our pilot study indicated that intravenous vitamin C did not provide significant decreases in the mean dose or duration of vasopressor infusion. Further research that takes into account the potential impact of intervention timing, dose and duration, and location of trial, may provide more definitive evidence. TRIAL REGISTRATION: ACTRN12617001184369 (11/8/2017).

Effect of intravenous vitamin C on arterial blood gas analyser and Accu-Chek point-of-care glucose monitoring in critically ill patients.

Background: Intravenous vitamin C is known to interfere with some point-of-care blood glucose meters. We aimed to determine the concentrations at which ascorbate interferes with glucose concentrations measured using a point-of-care blood glucose meter. We also compared the point-of-care meter and an arterial blood gas (ABG) analyser in the intensive care unit with laboratory glucose monitoring in septic patients receiving intravenous vitamin C infusions. Methods: Blood samples containing normal, depleted and supplemented glucose and increasing concentrations of ascorbate (0.1-1.0 mmol/L) were tested using an Accu-Chek Inform II (Roche Diagnostics, USA) glucometer. For the in vivo study, 41 individual blood samples were drawn daily from septic patients (n = 16) receiving infusions of 25 mg/kg of vitamin C every 6 hours. The glucose values of matched blood samples were assessed using Accu-Chek, ABG and laboratory glucose methods. Results: For every 1 mmol/L of ascorbate added, the glucose concentration measured by the point-of-care monitor increased by 1.4 mmol/L (95% CI, 1.0-1.8; P < 0.001). Analysis of matched blood samples collected following intravenous vitamin C infusion indicated that 98% of the ABG and 83% of the Accu-Chek values met the International Organization for Standardization (ISO) 15197:2013 accuracy criteria. One patient had severe renal impairment, which contributed to elevated plasma vitamin C concentrations (median, 0.95 mmol/L; range, 0.64-1.10 mmol/L), resulting in elevated Accu-Chek readings and presenting a moderate clinical risk for the highest value. Conclusions: Vitamin C concentrations < 0.8 mmol/L do not interfere with point-of-care glucose monitoring. Intravenous vitamin C infusion of 25 mg/kg every 6 hours does not interfere with point-of-care glucose monitoring unless the patient has renal impairment, in which case laboratory glucose tests should be used.