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Background Reduced plasma vitamin C (vitC) concentrations in human immunodeficiency virus (HIV) may result from abnormal urinary excretion: a renal leak. VitC renal leak indicates underlying nutritional dysregulation independent of diet. We hypothesized that increased renal leak prevalence in HIV would be associated with deficient vitC concentrations. Methods We conducted an outpatient cross-sectional study of 96 women (40 HIV [PWH] and 56 without HIV [PWOH]) at the National Institutes of Health and Georgetown University. Renal leak was defined as abnormal urinary vitC excretion at fasting plasma concentrations <43.2µM, 2 SDs below vitC renal threshold in healthy women. To determine the primary outcome of renal leak prevalence, matched urine and plasma samples were collected the morning after overnight fast. Secondary outcomes assessed group differences in mean plasma vitC concentrations and prevalence of vitC deficiency. Exploratory outcomes assessed clinical parameters associated with renal leak. VitC was measured by high-performance liquid chromatography with coulometric electrochemical detection. Results PWH had significantly higher renal leak prevalence (73%vs14%; OR (odds ratio):16; P <.001), lower mean plasma vitC concentrations (14µMvs50µM; P <.001), and higher prevalence of vitC deficiency (43%vs7%; OR:10; P <.001) compared with PWOH, unchanged by adjustments for confounding factors. Significant predictors of renal leak included antiretroviral therapy (ART), Black race, older age, and metabolic comorbidities but not viral load or CD4 count. When compared with other chronic disease cohorts, PWH had the highest prevalence of renal leak and vitC deficiency (P <.001). Conclusions High prevalence of vitC renal leak in HIV was associated with vitC deficiency, ART use, and race/ethnicity differences. [ABSTRACT FROM AUTHOR]

Purpose: Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1–100 g. Methods: A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1–100 g; oncology participants received IVC infusions of 25–100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study. Results: In both cohorts, IVC exhibited first-order kinetics at doses up to 75 g. At 100 g, maximum concentration (Cmax) plateaued in both groups, whereas area under the concentration–time curve (AUC) only plateaued in the healthy group. IVC was primarily excreted through urine. No saturation of clearance was observed; however, the mean 24-h total IVC excretion in urine for all doses was lower in oncology participants (89% of dose) than in healthy participants at 100 g (99%). No significant adverse events were observed; thus, maximum tolerated dose (MTD) was not reached. Conclusion: IVC followed first-order pharmacokinetics up to 75 g and at up to 100 g had complete renal clearance in 24 h. IVC up to 100 g elicited no adverse effects or significant physiological/biochemical changes and appears to be safe. These data can be used to rectify existing misinformation and to guide future clinical trials. Registration: ClinicalTrials.gov identifier number NCT01833351. [ABSTRACT FROM AUTHOR]

Background Diabetes is associated with low plasma vitamin C concentrations. Objectives We investigated the contribution of dysregulated vitamin C renal physiology, its prevalence, and associated clinical characteristics. Methods An essential prerequisite was determination of normal vitamin C renal threshold, the plasma concentration at which vitamin C first appears in urine. Using data from 17 healthy participants who underwent vitamin C depletion–repletion studies with a vitamin C dose range of 15–1250 mg daily, renal threshold was estimated using physiology-based pharmacokinetics modeling. Applying renal threshold 95% CIs, we estimated the minimal elimination threshold, the plasma concentration below which no vitamin C was expected in urine of healthy people. Renal leak was defined as abnormal presence of vitamin C in urine with plasma concentrations below the minimal elimination threshold. Criteria were tested in a cross-sectional cohort study of individuals with diabetes (82) and nondiabetic controls (80) using matched plasma and urine samples. Results Vitamin C renal thresholds in healthy men and women were [mean (SD)] 48.5 (5.2) µM and 58.3 (7.5) µM, respectively. Compared with nondiabetic controls, participants with diabetes had significantly higher prevalence of vitamin C renal leak (9% compared with 33%; OR: 5.07; 95% CI: 1.97, 14.83; P  < 0.001) and 30% lower mean plasma vitamin C concentrations (53.1 µM compared with 40.9 µM, P  < 0.001). Fasting plasma glucose, glycosylated hemoglobin A1c, BMI, micro/macrovascular complications, and protein/creatinine ratio were predictive of vitamin C renal leak. Conclusions Increased prevalence of vitamin C renal leak in diabetes is associated with reduced plasma vitamin C concentrations. Glycemic control, microvascular complications, obesity, and proteinuria are predictive of renal leak. [ABSTRACT FROM AUTHOR]

The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen. We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, Svct2 (ref. 4). Cultured embryonic fibroblasts from homozygous Slc23a1-/- mice had less than 5% of normal ascorbic-acid uptake. Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1-/- mice. Prenatal supplementation of pregnant females did not elevate blood ascorbic acid in Slc23a1-/- fetuses, suggesting Slc23a1 is important in placental ascorbic-acid transport. Slc23a1-/- mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage. Lungs showed no postnatal expansion but had normal surfactant protein B levels. Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1-/- mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content. We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta. Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period. [ABSTRACT FROM AUTHOR]

Presents a study which determined the ideal Vitamin C intake in healthy young male subjects. Methods; Results; Discussion.

Considers how recommendations for vitamin C intake are under revision by the Food Nutrition Board of the United States National Academy of Sciences. Vitamin C and human metabolic processes; Ingestion criteria; Dietary availability; Food sources of vitamin C; Bioavailability; Urinary excretion of vitamin C; Adverse effects; Benefits; Prevention of deficiency; Other issues.

Abstract: Although vitamin C (ascorbate) is present in whole blood, measurements in red blood cells (RBCs) are problematic because of interference, instability, limited sensitivity, and sample volume requirements. We describe a new technique using HPLC with coulometric electrochemical detection for ascorbate measurement in RBCs of humans, wild-type mice, and mice unable to synthesize ascorbate. Exogenously added ascorbate was fully recovered even when endogenous RBC ascorbate was below the detection threshold (25nM). Twenty microliters of whole blood or 10μl of packed RBCs was sufficient for assay. RBC ascorbate was stable for 24h from whole-blood samples at 4°C. Processed, stored samples were stable for >1month at −80°C. Unlike other tissues, ascorbate concentrations in human and mouse RBCs were linear in relation to plasma concentrations (R =0.8 and 0.9, respectively). In healthy humans, RBC ascorbate concentrations were 9–57μM, corresponding to ascorbate plasma concentrations of 15–90μM. Mouse data were similar. In human blood stored as if for transfusion, initial RBC ascorbate concentrations varied approximately sevenfold and decreased 50% after 6weeks of storage under clinical conditions. With this assay, it becomes possible for the first time to characterize ascorbate function in relation to endogenous concentrations in RBCs. [Copyright &y& Elsevier]

Background. Reactive oxygen species generated by ultraviolet light result in photocarcinogenic and photoaging changes in the skin. Antioxidants protect skin from these insults. Objective. This study defines formulation characteristics for delivering L-ascorbic acid into the skin to supplement the skin's natural antioxidant reservoir. Methods. L-ascorbic acid or its derivatives were applied to pig skin. Skin levels of L-ascorbic acid were measured to determine percutaneous delivery. Results. L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin. Maximal concentration for optimal percutaneous absorption was 20%. Tissue levels were saturated after three daily applications; the half-life of tissue disappearance was about 4 days. Derivatives of ascorbic acid including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid did not increase skin levels of L-ascorbic acid. Conclusions. Delivery of topical L-ascorbic acid into the skin is critically dependent on formulation characteristics. [ABSTRACT FROM AUTHOR]