Serum Ascorbic Levels Research Articles

A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer

BackgroundPatients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor 5-year survival. Pharmacological ascorbate (P-AscH-, high dose, intravenous, vitamin C) has shown promise as an adjunct to chemotherapy. We hypothesized adding P-AscH- to gemcitabine and nab-paclitaxel would increase survival in patients with metastatic PDAC. MethodsPatients diagnosed with stage IV pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC, control) or to SOC with concomitant P-AscH−, 75 g three times weekly (ASC, investigational). The primary outcome was overall survival with secondary objectives of determining progression-free survival and adverse event incidence. Quality of life and patient reported outcomes for common oncologic symptoms were captured as an exploratory objective. Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023. ResultsIntravenous P-AscH- increased serum ascorbate levels from micromolar to millimolar levels. P-AscH- added to the gemcitabine + nab-paclitaxel (ASC) increased overall survival to 16 months compared to 8.3 months with gemcitabine + nab-paclitaxel (SOC) (HR = 0.46; 90 % CI 0.23, 0.92; p = 0.030). Median progression free survival was 6.2 (ASC) vs. 3.9 months (SOC) (HR = 0.43; 90 % CI 0.20, 0.92; p = 0.029). Adding P-AscH- did not negatively impact quality of life or increase the frequency or severity of adverse events. ConclusionsP-AscH− infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to quality of life or added toxicity (ClinicalTrials.gov number NCT02905578).

Ascorbate Deficiency Is Associated with Severity of Cytokine Release Syndrome Following Therapy with Chimeric Antigen Receptor T-Cells

The therapy of hematologic malignancies has been revolutionized by the development of therapies using chimeric antigen receptor modified T-cells (CAR-T). However, CAR-T cell therapy is often associated with cytokine release syndrome (CRS), characterized by fevers, hypotension, and hypoxia, as well as immune effector cell-associated neurotoxicity syndrome (ICANS). Severe cases of CRS can result in significant morbidity and mortality. Although disease features such as tumor burden may predict for more severe CRS and ICANS, other clinical features and biomarkers predictive of CRS and ICANS remain lacking, with the exception of measurements of serum cytokines following cell infusion (PMID: 27076371, PMID: 24553386). Experimental models have implicated elaboration of inflammatory cytokines such as IL-1 and IL-6 by monocytes in the pathogenesis of CRS and ICANS (PMID: 29808007, PMID: 29808005). Accordingly, the severity and duration of CRS and ICANS can be mitigated in part by IL-6 receptor blockade with tocilizumab and treatment with corticosteroids such as dexamethasone. Recent work has implicated ascorbate in the regulation of the activity of TET enzymes in hematopoietic cells (PMID: 28825709, PMID: 28823558). Given that TET2 deficiency has been associated with increased elaboration of inflammatory cytokines such as IL-6 and IL-1 by macrophages (PMID 3026882, PMID: 28104796, PMID: 28636844), we reasoned that ascorbate deficiency might predict for more pronounced cytokine release in patients leading to more severe CRS or ICANS.We identified 13 patients receiving CAR-T cell therapy for hematologic malignancies at the University of Texas Southwestern. Plasma specimens were collected from patients at baseline prior to receipt of lymphodepleting chemotherapy and/or at two weeks following CAR-T cell infusion. Given the poor reliability of clinical ascorbate measurements due to oxidation, we used an optimized protocol incorporating a C13-labeled ascorbate internal standard to obtain highly precise serum measurements using liquid-chromatography mass spectrometry. The incidence and severity of CRS and ICANS was classified using standardized grading criteria as per the American Society for Transplantation and Cellular Therapy.We measured serum ascorbate in 7 baseline and 12 post CAR-T cell infusion specimens obtained from 13 patients, with a median age of 65 (range 53 to 77). The cohort included eight patients with diffuse large B-cell lymphoma and two patients with mantle cell lymphoma receiving CD19-targeted CAR-T cells, as well as three patients with multiple myeloma receiving BCMA-targeted CAR-T cells. Eight patients developed grade one CRS, three patients developed grade two CRS, and two patients did not develop CRS. One patient developed grade one ICANS, one developed grade two ICANS, and one developed grade three ICANS. Eight patients received dexamethasone for CRS or ICANS, and eight patients received tocilizumab. Five patients only received one dose of tocilizumab, while two received two doses and one received three doses.Taking all pre- and post-CAR-T cell infusion ascorbate measurements into account, a significant correlation was found between having low serum ascorbate levels and a higher maximal grade of CRS or ICANS (Figure 1A, r 2=-0.64, p=0.0039). Post-infusion ascorbate measurements also demonstrated a significant correlation between low serum ascorbate levels and higher maximal CRS or ICANS (Figure 1B, r 2=-0.78, p=0.0035), while there was no correlation between pre-infusion ascorbate measurements and CRS or ICANS. Finally, we noted a significant decrease in serum ascorbate levels when comparing pre-infusion to post-infusion specimens (Figure 1C, p=0.048), including five paired specimens. There was no significant correlation between serum ascorbate levels and the number of doses of tocilizumab or dexamethasone administered.Low serum ascorbate levels may be associated with an increased risk for developing severe CRS and ICANS following CAR-T cell therapy. Although follow-up studies with a larger cohort of patient are necessary to substantiate this correlation, these data provide preliminary evidence that serum ascorbate levels may serve as a useful biomarker to predict severity of CRS and ICANS. Furthermore, they suggest ascorbate supplementation as a promising future strategy to mitigate these common complications of CAR-T cell therapy. [Display omitted] DisclosuresKansagra: Alynylam, Celgene/BMS, Cota Health, GSK, Janssen, Karyopharm, Oncopeptide, Pfizer, Takeda, Sanofi: Membership on an entity's Board of Directors or advisory committees. Anderson: Celgene, BMS, Janssen, GSK, Karyopharm, Oncopeptides, Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Awan: Abbvie: Consultancy; Dava Oncology: Consultancy; Johnson and Johnson: Consultancy; Incyte: Consultancy; BMS: Consultancy; Astrazeneca: Consultancy; ADCT therapeutics: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy; Beigene: Consultancy; Merck: Consultancy; Gilead sciences: Consultancy; Cardinal Health: Consultancy; Verastem: Consultancy; MEI Pharma: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Kite pharma: Consultancy; Genentech: Consultancy. Madanat: Stem line pharmaceutical: Honoraria; Blue Print Pharmaceutical: Honoraria; Onc Live: Honoraria; Geron Pharmaceutical: Consultancy. Patel: Agios: Membership on an entity's Board of Directors or advisory committees; PVI: Honoraria; Celgene-BMS: Membership on an entity's Board of Directors or advisory committees. Sweetenham: EMA Wellness: Membership on an entity's Board of Directors or advisory committees.

Vitamin C Differentially Impacts the Serum Proteome Profile in Female and Male Mice.

A suboptimal blood vitamin C (ascorbate) level increases the risk of several chronic diseases. However, the detection of hypovitaminosis C is not a simple task, as ascorbate is unstable in blood samples. In this study, we examined the serum proteome of mice lacking the gulonolactone oxidase (Gulo) required for the ascorbate biosynthesis. Gulo-/- mice were supplemented with different concentrations of ascorbate in drinking water, and serum was collected to identify proteins correlating with serum ascorbate levels using an unbiased label-free liquid chromatography-tandem mass spectrometry global quantitative proteomic approach. Parallel reaction monitoring was performed to validate the correlations. We uncovered that the serum proteome profiles differ significantly between male and female mice. Also, unlike Gulo-/- males, a four-week ascorbate treatment did not entirely re-establish the serum proteome profile of ascorbate-deficient Gulo-/- females to the optimal profile exhibited by Gulo-/- females that never experienced an ascorbate deficiency. Finally, the serum proteins involved in retinoid metabolism, cholesterol, and lipid transport were similarly affected by ascorbate levels in males and females. In contrast, the proteins regulating serum peptidases and the protein of the acute phase response were different between males and females. These proteins are potential biomarkers correlating with blood ascorbate levels and require further study in standard clinical settings. The complete proteomics data set generated in this study has been deposited to the public repository ProteomeXchange with the data set identifier: PXD027019.

A COMPARATIVE STUDY OF SERUM ASCORBATE BETWEEN NEWLY DIAGNOSED TYPE 2 DIABETICS AND LONG STANDING TYPE 2 DIABETICS ON TREATMENT

Introduction: diabetes mellitus is a metabolic disorder prevalent worldwide . Oxidative stress has been the Cause of complications which arises gradually due to prolonged hyperglycemia. Vitamin c being a potent antioxidant is well consumed in diabetes mellitus. Methods: Serum samples of diabetes mellitus type 2 patients from jorhat medical college of Assam were tested to estimate ascorbate levels using spectrophotometer. Whole blood samples were tested to estimate glycated hemoglobin levels in d-10 biorad hplc machine. A total of 58 patients and equal numbers of age and sex matched apparently healthy controls were included. Results: significantly lower levels of ascorbate were recorded in diabetic cases compared to controls. Newly diagnosed cases had lesser serum ascorbate levels compared to patients who were on treatment with oral hypoglycemic drugs and insulin. Conclusion: the study was done to look for any alteration in serum ascorbic acid levels in diabetes mellitus patients. Patients newly diagnosed had lesser vitamin c levels compared to patients already on medications. It is found that vitamin c is significantly lower in diabetic patients with or without medications compared to healthy controls.

Comparative analysis of dietary pattern, anthropometry and serum ascorbate status of persons living with or without non-Hodgkin's lymphoma.

Recent upsurge of cancer cases across the globe is of concern to all and many studies shows the relationship between nutrient and the immune system and consequently cancer. This work aims to compare the dietary pattern, anthropometry and serum ascorbate status of the persons living with and those living without non-Hodgkin’s lymphoma (NHL). A case-control study was conducted using blood samples of eight patients diagnosed for NHL at the University College Hospital (UCH) Ibadan, while eight (8) volunteers were the control group. Socio-economic characteristics, medical history, food preferences, anthropometric indices were retrieved from questionnaires. Ascorbic Serum assay done with ultraviolet absorption spectrophotometry method using Klett-summerson photoelectric. Students’ t-test and Chi-square were used to test the educational levels fruit consumption. 25% of the respondents suffering from NHL skipped lunch and dinner, but none skipped breakfast. 66.67% of the cases and 100% of the control have their weight normally distributed. Cases had 11.11% slightly underweight and 11.11% obese. 25% of the population of the respondents had normal range of 0.4 mg/100 of serum ascorbate, while six had low serum ascorbate levels.

A Randomized Steady-State Bioavailability Study of Synthetic versus Natural (Kiwifruit-Derived) Vitamin C

Whether vitamin C from wholefoods has equivalent bioavailability to a purified supplement remains unclear. We have previously showed that kiwifruit provided significantly higher serum and tissue ascorbate levels than synthetic vitamin C in a genetically vitamin C-deficient mouse model, suggesting a synergistic activity of the whole fruit. To determine if these results are translatable to humans, we carried out a randomized human study comparing the bioavailability of vitamin C from kiwifruit with that of a vitamin C tablet of equivalent dosage. Thirty-six young non-smoking adult males were randomized to receive either half a gold kiwifruit (Actinidia Chinensis var. Hort 16A) per day or a comparable vitamin C dose (50 mg) in a chewable tablet for six weeks. Ascorbate was monitored weekly in fasting venous blood and in urine, semen, leukocytes, and skeletal muscle (vastus lateralis) pre- and post-intervention. Dietary intake of vitamin C was monitored using seven day food and beverage records. Participant ascorbate levels increased in plasma (P < 0.001), urine (P < 0.05), mononuclear cells (P < 0.01), neutrophils (P < 0.01) and muscle tissue (P < 0.001) post intervention. There were no significant differences in vitamin C bioavailability between the two intervention groups in any of the fluid, cell or tissue samples tested. Overall, our study showed comparable bioavailability of synthetic and kiwifruit-derived vitamin C.

The Effect of Supplemental Ascorbate on Defersirox Iron Chelation In the Iron-Loaded Gerbil

AbstractAbstract 2059 Introduction:Iron dextran injections are often used to induce iron overload in rodents, for the purposes of assessing iron chelation therapy. In gerbils, we have previously described that deferasirox therapy preferentially clears hepatocellular iron when compared with reticuloendothelial stores. Ascorbate deficiency, which is common in humans with iron overload, produces similar profound disparities between reticuloendothelial and parenchymal iron stores. We postulated that iron-induced ascorbate deficiency might be exaggerating reticuloendothelial iron retention in gerbils receiving deferasirox therapy. This study examined the effect of supplemental ascorbate on spontaneous iron loss and deferasirox chelation efficiency in the iron-dextran loaded gerbil. Methods:48 female gerbils underwent iron dextran loading at 200 mg/kg/week for 10 weeks. Sixteen animals were sacrificed at 11 weeks to characterize iron loading; eight were on standard rodent chow and eight had chow supplemented with 2250 ppm of ascorbate. 32 additional animals that were not ascorbate supplemented during iron loading transitioned into the chelation phase. Half were subsequently placed on ascorbate supplemented chow and both groups were assigned to receive either deferasirox 100 mg/kg/day five days per week or sham chelation. Animals received iron chelation for twelve weeks. Liver histology was assessed using H & E and Prussian blue stains. Iron loading was ranked and graded on a five-point scale by an experienced pathologist screened to the treatment arm. Iron quantitation in liver and heart was performed by atomic absorption. Results:Table 1 one summarizes the findings. During iron dextran loading, ascorbate supplementation lowered wet weight liver iron concentration but not liver iron content suggesting primarily changes in tissue water content. Spontaneous iron losses were insignificant, regardless of ascorbate therapy. Deferasirox lowered liver iron content 56% (4.7% per week) in animals without ascorbate supplementation and 48.3% (4.0% per week) with ascorbate supplementation (p=NS).Cardiac iron loading, unloading and redistribution were completely unaffected by ascorbate supplementation. Spontaneous iron redistribution was large (1.9% – 2.3% per week). Deferasirox chelation did not lower cardiac iron to a greater degree than spontaneous cardiac iron redistribution.Histologic grading paralleled tissue wet weight iron concentrations. Ascorbate treatment lowered the rank and absolute iron score in liver during iron loading (p=0.003) and there was a trend toward lower iron scoring in sham treated animals (p=0.13). Ascorbate had no effect on histological score or relative compartment distributions of iron in deferasirox chelated animals (p=0.5).Ascorbate supplementation was sufficient to increase total plasma ascorbate levels from 25 ± 12.2 uM to 38.4 ± 11 uM at 10 weeks (p=0.03). In the liver, ascorbate increased from 1203 ± 212 nmol/g of tissue to 1515 ± 194 nmol/g of tissue (p=0.01) with supplementation. No significant change in total ascorbate was observed in the heart. Discussion:We hypothesized that ascorbate supplementation might improve reticuloendothelial iron accessibility to deferasirox by facilitating redox cycling. Although gerbils synthesize their own ascorbate, supplementation was able to raise both serum and hepatic total ascorbate levels. However, increasing ascorbate did not change either the amount or distribution of tissue iron in deferasirox-treated animals. Disclosures:Nick:Novartis: Employment. Wood:Novartis: Research Funding; Ferrokin Biosciences: Consultancy.

β-Catenin Regulates Vitamin C Biosynthesis and Cell Survival in Murine Liver

Because the Wnt/beta-catenin pathway plays multiple roles in liver pathobiology, it is critical to identify gene targets that mediate such diverse effects. Here we report a novel role of beta-catenin in controlling ascorbic acid biosynthesis in murine liver through regulation of expression of regucalcin or senescence marker protein 30 and L-gulonolactone oxidase. Reverse transcription-PCR, Western blotting, and immunohistochemistry demonstrate decreased regucalcin expression in beta-catenin-null livers and greater expression in beta-catenin overexpressing transgenic livers, HepG2 hepatoma cells (contain constitutively active beta-catenin), regenerating livers, and in hepatocellular cancer tissues that exhibit beta-catenin activation. Interestingly, coprecipitation and immunofluorescence studies also demonstrate an association of beta-catenin and regucalcin. Luciferase reporter and chromatin immunoprecipitation assays verified a functional TCF-4-binding site located between -163 and -157 (CTTTGCA) on the regucalcin promoter to be critical for regulation by beta-catenin. Significantly lower serum ascorbate levels were observed in beta-catenin knock-out mice secondary to decreased expression of regucalcin and also of L-gulonolactone oxidase, the penultimate and last (also rate-limiting) steps in the synthesis of ascorbic acid, respectively. These mice also show enhanced basal hepatocyte apoptosis. To test if ascorbate deficiency secondary to beta-catenin loss and regucalcin decrease was contributing to apoptosis, beta-catenin-null hepatocytes or regucalcin small interfering RNA-transfected HepG2 cells were cultured, which exhibited significant apoptosis that was alleviated by the addition of ascorbic acid. Thus, through regucalcin and L-gulonolactone oxidase expression, beta-catenin regulates vitamin C biosynthesis in murine liver, which in turn may be one of the mechanisms contributing to the role of beta-catenin in cell survival.

Ascorbate, not urate, modulates the plasma antioxidant capacity after strawberry intake

The consumption of antioxidant-rich foods has already been associated with acute significant increases in plasma total antioxidant capacity (TAC) in humans, but there is no consensus among different literature reports. Furthermore, the acute rise in plasma TAC observed after consumption of several non-berry fruits seems not to be necessarily related to the absorption of dietary antioxidants, such as micronutrients and phenolic substances, but is attributed to the relevant increase of endogenous urate in serum. In this study, we first compared the nutritional quality of strawberry fruits from different genotypes, all cultivated in the same experimental field. Significant genotype-to-genotype differences were observed in the antioxidant capacity and in the vitamin C, folate and phenolic contents of the fruits. Second, in order to investigate the individual effects of the selected strawberry genotypes on the post-prandial plasma antioxidant status in humans, we assessed the acute effects of a single dose of strawberries in healthy subjects. The variation of plasma TAC through the FRAP and TEAC assays, and any eventual changes in ascorbate and urate levels in serum, were measured during the three hours following the strawberry intake. The acute intake of strawberries resulted in a significant increase in plasma FRAP values in all the subjects, independently of the individual TAC baseline levels. Interestingly, the lowest increases in plasma TAC and in serum ascorbate levels were associated with consumption of the nutritionally-poorest cultivars. In addition, significant increases in ascorbate, but not in urate, concentrations were observed in serum. These findings suggested that the fructose-dependent hyperuremic effect, observed after the intake of non-berry fruits, is not responsible for the plasma antioxidant changes following strawberry consumption.

Oxidative stress in blood of camels (Camelus dromedaries) naturally infected with Trypanosoma evansi

Oxidant stress is an imbalance between radical-generating and radical-scavenging activity, resulting in oxidation products and tissue damage. The present study aimed to estimate oxidation and antioxidant status in blood of camels naturally infected with Trypanosoma evansi. Blood samples from T. evansi-infected and healthy (control) female camels were used to determine the free radical nitric oxide (NO) generation in serum, malondialdehyde production in serum (sMDA) and erythrocyte (eMDA) as a biomarker of lipid peroxidation, blood methemoglobin formation (MetHb, a biomarker of hemoglobin oxidation), the antioxidants serum ascorbate and albumin levels, erythrocytic glutathione concentration (GSH), superoxide dismutase (SOD) and catalase (CAT) activities. The infected camels were characterized by macrocytic hypochromic anemia. Trypanosomiasis in camels resulted in significant (P<0.001) stimulation of serum NO (78.93%), eMDA (110.04%), sMDA (67.39%) and MetHb (1.5-fold) coupled with significant reduction (P<0.001) of albumin (27.6%), ascorbate (25.38%), GSH (43.36%), SOD (32.47%) and non-significant increase in CAT (7.06%, P=0.322) compared to control values. In infected camels, a significant positive correlation of NO with eMDA (r=0.546, P=0.009) and MetHb (r=0.490, P=0.021) was detected. By contrast, NO was inversely correlated with RBC (r=−0.546, P=0.009), PCV (r=−0.427, P=0.048) and Hb (r=−0.612, P=0.002). On the other hand, eMDA was inversely correlated with RBC (r=−0.596, P=0.003), PCV (r=−0.516, P=0.014) and Hb (r=−0.613, P=0.002). In addition, methemoglobinemia was negatively correlated with RBC (r=−0.560, P=0.007), PCV (r=−0.470, P=0.027) and Hb (r=−0.585, P=0.004). Our results suggest that chronic T. evansi infection in camels is associated with a state of oxidative process.

Is homocysteine a mediator of atrial dysfunction or just another marker of endothelial dysfunction?

Atrial fibrillation (AF) is a common and increasingly prevalent arrhythmia that is associated with a significant increase in risk for stroke (five- to seven-fold) and mortality (two-fold). Stroke risk is a primary concern in the management of AF patients. Structural factors contribute to increased stroke risk. Left atrial enlargement, reflecting either mitral regurgitation or impaired left ventricular (LV) function, promotes persistent AF as a result of increased area for re-entrant electrical activity. Left atrial enlargement and AF are associated with endocardial changes that lead to increased risk of left atrial thrombus formation, with the consequent increment in risk for thrombo-embolism and stroke, 1 and thus is a strong predictor of a poor clinical prognosis. 2 Left atrial enlargement occurs in response to LV dysfunction as a result of both haemodynamic influences and active remodelling of the atrial wall. Matrix metalloproteinases (MMPs) facilitate the disruption of collagen filaments that hold myocytes closely together. Several of the MMPs (MMP2, MMP9) are activated in response to oxidant stress. There is accumulating evidence of increased oxidant stress in patients with AF. 3–5 Oxidant stress is associated with oxidation and depletion of circulating and cellular reducing agents, including glutathione and ascorbate. In an epidemiological study, serum ascorbate levels were inversely related with stroke incidence. Homocysteine (Hcy) is an amino acid metabolite of cysteine or methionine; circulating Hcy levels are elevated in patients with coronary artery disease. Hyperhomocysteinaemia occurs under conditions of oxidant stress, and much of the circulating Hcy is oxidized and protein-bound, as a result of depletion of circulating reduced glutathione. 6 In 2004, Marcucci et al. 7

High prevalence of ascorbate deficiency in an Australian peritoneal dialysis population

An adequate total body pool of ascorbate is essential for optimum health in humans. Requirements for ascorbate are increased in peritoneal dialysis (PD) patients most likely due to a combination of poor nutrition and increased dialysate losses. We measured serum ascorbate levels in 45 clinically stable PD patients to assess the prevalence of ascorbate insufficiency (level between 2 and 4 mg/L) and deficiency (level <2 mg/L). We also assessed the efficacy of subsequent supplementation and patients' adherence to the prescribed supplementation. All patients were advised on commencement of dialysis to take a multivitamin tablet containing 100-120 mg ascorbate. Eighteen (41%) PD patients were regularly taking ascorbate-containing multivitamins, while 27 (59%) patients did not take ascorbate supplements. Serum ascorbate levels ranged from <0.2 to 41 mg/L, with wide variations in serum ascorbate at any given intake level. Ascorbate deficiency was present in 1/3 of the current PD population (44% of patients not taking supplements and in 16% of those on supplements), although none of the patients demonstrated clinical manifestations of scurvy. Targeted supplementation of ascorbate insufficient patients increased the median serum ascorbate level from 1.7 mg/L (IQR 1.2-2.2) to 22.5 mg/L (IQR 16.7-32.9). Our results show that, in PD patients, ascorbate deficiency is common and can readily be identified with serum ascorbate measurements. Oral supplements in the form of inexpensive multivitamin preparations restore adequate serum ascorbate levels in the majority of these patients. We therefore suggest measurement of ascorbate levels in all PD patients at the commencement of dialysis with a target level in the normal range (4-14 mg/L).

Role of Vitamin C (Ascorbic Acid) on Human Health- A Review

Vitamin C, also known as ascorbic acid, abounds in nature and is highly labile. It is a water-soluble vitamin that is lost in large amounts during food processing. It is a vitamin whose prescribed requirement across cultures is not uniform. For example , the prescribed requirement of vitamin C in Great Britain is 30mg/day, while in the U.S.A., it is 60mg/day and 100mg/day in Japan. These variations are unusual and point to the need for further research to establish the acceptable RDAs for diverse populations. The RDA for vitamin C should be more than the amount needed to prevent the occurrence of disease. Vitamin C plays significant functions in the body that enhance its role in the health status of the human body. The biochemical functions of vitamin C include: stimulation of certain enzymes, collagen biosynthesis, hormonal activation, antioxidant, detoxification of histamine, phagocytic functions of leukocytes, formation of nitrosamine, and proline hydroxylation amongst others. These functions are related to the health effects of vitamin C status in an individual. In human health, vitamin C has been associated with reduction of incidence of cancer, blood pressure, immunity, and drug metabolism and urinary hydroxyproline excretion, tissue regeneration. This vitamin is needed for the proper metabolism of drugs in the body through adequate hepatic mixed function oxidase system. Epidemiological data have revealed the preventive and curative role of vitamin C on certain disease conditions in the body though controversies still persist. Vitamin C is effective in protecting against oxidative damage in tissues and also suppresses formation of carcinogens like nitrosamines. There is an inverse relationship with blood pressure and both plasma vitamin C and Vitamin C. Vitamin C has a lowering effect on blood pressure, especially on systolic pressure more than a diastolic pressure. Low levels of plasma vitamin C are associated with stroke and with an increased risk of all cause mortality. Increased consumption of ascorbic acid raises serum ascorbic levels and could decrease the risk of death.

Serum ascorbic acid concentration in patients with acute Falciparum malaria infection: possible significance

Falciparum malaria infection is associated with significant destruction of erythrocytes. This leads to the release of toxic metabolic products, including oxidant compounds. We measured the serum concentration of the antioxidant, ascorbic acid, in 129 patients presenting with acute falciparum malaria infection and in 65 healthy individuals. None of the study subjects administered any form of ascorbic acid supplementation within one week prior to participation in this study. The mean serum ascorbate concentration in infected adult males (n = 49, age range 18-50 years) was found to be 2.02 +/- 0.20 mg/dL, and it was 2.03 +/- 0.24 mg/dL in infected adult females (n = 56, age range 18-50 years). These values were significantly greater than the serum ascorbate levels (1.54 +/- 0.10 mg/dL) in healthy adult males (n = 28) and females (n = 28) (p < 0.05). In children (age range 3 to 5 years), the serum ascorbate concentration was significantly lower (1.95 +/- 0.20 mg/dL) during infection (n = 25) than in their healthy counterparts (2.9 +/- 0.24 mg/dL, n = 9) (p < 0.05). It is evident therefore that ascorbic acid plays a significant role in the pathogenesis of acute falciparum malaria in adults. Infected children also need to be given supplemental doses of ascorbate in view of the weakness of their immune system.

Supplementation with α-tocopherol or a combination of α-tocopheroland ascorbic acid protects the gastrointestinal tract of iron-deficientrats against iron-induced oxidative damage during iron repletion

Recently we have shown the susceptibility of Fe-deficient rat intestine to oxidative damage during Fe repletion. The role of dietary antioxidants like ascorbic acid, alpha-tocopherol and a combination of both in counteracting the oxidative stress was tested in this study. Five groups of thirteen weanling WKY female rats were fed with an Fe-deficient diet for a period of 5 weeks. Another set of thirteen rats received an Fe-sufficient diet and served as the control group (Con). Oral administration of either vehicle (D), 8 mg Fe alone (D+) or in the presence of 24 mg ascorbic acid (D+ + C), 40 mg alpha-tocopherol (D+ + E) or a combination of both (D+ + C + E) per d for 15 d was carried out in Fe-depleted rats. The impact of this treatment protocol on Fe status, oxidative stress and antioxidant status at the site of Fe absorption was assessed. It was observed that though the indicators of Fe status were normalised on Fe supplementation, the oxidative stress as reflected by the levels of both thiobarbituric-acid reactive substances (TBARS) and protein carbonyls were significantly greater in D+ and D+ + C compared to D+ + E, D+ + C + E and Con groups. The mucosal cell DNA damage was seen in D+, D+ + C and D+ + E groups on electrophoresis. Functional integrity as assessed by the activities of alkaline phosphatase and lys-ala-dipeptidyl aminopeptidase were normalized in all the groups treated with the antioxidant(s). There were significant positive alterations in some of the endogenous antiperoxidative systems and in serum caeruloplasmin activity in D+ + E and D+ + C + E groups. Paradoxically, serum ascorbate levels were significantly lower in D+ + C than in D+ + E and D+ + C + E groups. This could be due to the protection offered by alpha-tocopherol in the presence of Fe. It is concluded that supplementation of alpha-tocopherol alone or in combination with ascorbic acid protects the gastrointestinal tract of Fe-deficient rats against Fe-mediated oxidative damage during Fe repletion. However, ascorbic acid alone does not protect the gastrointestinal tract against Fe-induced oxidative stress.

Agreement among indicators of vitamin C status.

Agreement among three indicators of vitamin C status--serum ascorbate level, a 24-hour recall, and the frequency of fruit and vegetable consumption--was examined using data from the Second National Health and Nutrition Examination Survey conducted between 1976 and 1980. Agreement between pairs of these indicators was good when assessed at the group level but inconsistent at the individual level. These indicators, when classified as continuous measures, had moderately good agreement (r = 0.45-0.54), whereas agreement was poor when classified as quartiles (kappa = 0.17-0.23). Agreement between clinically based categories of serum ascorbate and total intake levels was poorer than expected (kappa = 0.25) as was agreement between low or deficient levels of both of these indicators (kappa = 0.3). Disagreement between low or deficient serum and intake levels was greater in participants who were younger, African American compared with white and other races, less educated, current smokers, nonsupplement users, and examined in the winter compared with in the summer or fall. These findings suggest that the indicators cannot be used interchangeably to assess vitamin C status because they distinguish between different aspects of status, intake level versus serum level, an indicator of available pool. Moreover, depending upon how these indicators are used in statistical analyses, they may classify individuals differently.

Serum carotene, vitamin A, and vitamin C levels in breast cancer and cancer of the uterine cervix.

Levels of carotene, vitamin A, and vitamin C measured in the serum of patients with cancer of the breast and uterine cervix were compared with levels in healthy controls and patients with benign diseases of the breast and cervix. Serum ascorbate levels were significantly lower in patients with benign diseases of the breast and cervix than in controls. In cancer patients, there was a significant trend of lower serum vitamin levels with increasing stage of the disease.

Studies on the ascorbic acid metabolism of callitrichid monkeys by14C isotope excretion technique

Recently it has been found that the two monkey species Callithrix jacchus and Saguinus fuscicollis, both belonging to the same New World monkey family Callitrichidae and held in the same colony under identical conditions, had extremely different serum ascorbate levels. To examine the ascorbic acid metabolism the 14C-excretion of orally given 1-14C-ascorbic acid was studied under conditions of marginal and abundant vitamin C supply and under intentional stress. There were large differences in the mode of 14C excretion between low and high ascorbate supply. The differences were smaller between stress/no stress conditions intraindividually than between the two species, but they were in the same manner. In comparable trials S. fuscicollis reacted such that a higher status of stress can be supposed in this species.

Modelling cortical cataractogenesis. XI. Vitamin C reduces γ-crystallin leakage from lenses in diabetic rats

Normal and streptozotocin diabetic female Wistar rats were given vitamin C (VC) at 0·3% or 1·0% ( w w ) in the diet: 1% dietary VC resulted, in 12–24 hr, in significant increases in serum ascorbate levels and lens ascorbate concentrations in normal rats. The increase was biphasic, with VC concentrations falling to a lower level which was still significantly elevated compared to controls in the period of 1·7–4 days for serum and 1·7–5 days for lenticular VC. At the end of 10 weeks the rats were examined for weight gain or loss, general body condition and cataracts. At the time of killing, blood was collected for measurement of serum glucose. Alpha-crystallin levels were determined in vitreous and aqueous humours using a radioimmunoassay. One lens from each rat was fixed for either scanning electron microscopy or light microscopy; the other lens was homogenized in 8 m guanidinium chloride for adenosine triphosphate analysis. In normal rats, a small amount of γ-crystallin was found in the vitreous humour, and an even smaller amount in the aqueous humour. Diabetes caused a five-fold increase in the vitreous humour and a 2·5-fold increase in γ-crystallin in the aqueous humour. Diabetes also led to a significant worsening in general body condition, loss of body weight, formation of cataracts, and decrease in lens adenosine triphosphate levels. Addition of VC to the diet of diabetic animals resulted in reduction in cataracts and a decrease of γ-crystallin leakage into the aqueous and vitreous humours. VC had no effect on lens adenosine triphosphate levels. Neither streptozotocin diabetes nor VC in the diet appeared to affect the weight of the lenses.

Ascorbic acid requirement and assessment of ascorbate status in the common marmoset (Callithrix jacchus).

Marmosets can tolerate an ascorbic acid (AA) deficiency for several weeks without clinical symptoms. After being fed an AA-free diet for 3 months, nonspecific deficiency symptoms became obvious. Different dietary levels of AA resulted in corresponding serum ascorbate levels. The kidney threshold of AA in marmosets is comparable to that in humans. When the minimal AA requirement is defined as the amount that is necessary to maintain a serum AA level above the kidney threshold, then about 20 mg AA/kg body weight is needed. This intake was achieved in our trial with a diet containing 500 ppm AA. Thus, the AA requirement of marmosets is severalfold higher than the AA requirement of humans.