Cytotoxic activity of high dose ascorbic acid is enhanced by 2-deoxy-d-glucose in glycolytic melanoma cells.

Although, numerous in vitro studies showed that cancer cells are killed after exposure to pharmacological doses of ascorbic acid (AA), significant clinical data proving the efficacy of AA is still absent. A hallmark of most tumor cells is an altered glucose metabolism characterized by an upregulation of glycolysis despite normoxic conditions (Warburg effect). Since pyruvate is capable of detoxifying hydrogen peroxide (H2O2), the alleged mediator of AA-induced toxicity, it seems likely that enhanced glycolysis and subsequent higher pyruvate formation might be an explanation for the attenuated effect of pharmacological AA in vivo. Therefore, inhibition of glycolysis might be a promising approach to enhance the anticancer effect of AA by diminishing the generation of pyruvate. Considering the altered metabolism of cancer cells, we examined the cytotoxic potential of 2-DG and/or AA using SRB assay in two different cell lines: a glycolytic human melanoma (451Lu) and a non-glycolytic breast cancer (MCF-7) cell line. Inhibition of glycolysis increased AA cytotoxicity in 451Lu cells, whereas same treatment had a marginal effect on MCF-7 cells. We also investigated the influence of glycolysis inhibition on H2O2 generation. H2O2 concentrations were higher in presence of 451Lu cells when pretreated with 2-DG, but not in MCF-7 cells. Treatment with 10 mM 2-DG decreased pyruvate and lactate concentrations in both cell lines in a concentration-dependent manner. In summary, 2-DG enhances the cytotoxic effect of AA in glycolytic 451Lu cells by increasing AA-induced H2O2 concentration. This result indicates that lower pyruvate levels, as a result of glycolysis inhibition, may be responsible for the enhanced effect of 2-DG on AA toxicity. Further experiments are needed to clarify the underlying mechanism and the potential use in cancer therapy.

Vitamin C Deficiency in Blood Samples of COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is the most notable pandemic of the modern era. A relationship between ascorbate (vitamin C) and COVID-19 severity is well known, whereas the role of other vitamins is less understood. The present study compared the blood levels of four vitamins in a cohort of COVID-19 patients with different severities and uninfected individuals. Serum concentrations of ascorbate, calcidiol, retinol, and α-tocopherol were measured in a cohort of 74 COVID-19 patients and 8 uninfected volunteers. The blood levels were statistically compared and additional co-morbidity factors were considered. COVID-19 patients had significantly lower plasma ascorbate levels than the controls (p-value < 0.001), and further stratification revealed that the controls had higher levels than fatal, critical, and severe COVID-19 cases (p-values < 0.001). However, no such trend was observed for calcidiol, retinol, or α-tocopherol (p-value ≥ 0.093). Survival analysis showed that plasma ascorbate below 11.4 µM was associated with a lengthy hospitalization and a high risk of death. The results indicated that COVID-19 cases had depleted blood ascorbate associated with poor medical conditions, confirming the role of this vitamin in the outcome of COVID-19 infection.

Preoperative Ascorbic Acid Levels in Proximal Femur Fracture Patients Have No Postoperative Clinical Impact, While Ascorbic Acid Levels upon Discharge Have a Major Effect on Postoperative Outcome.

Proximal femur fractures show a high prevalence in elderly patients and are associated with an elevated risk of multimorbidity and early mortality. Recovery is impaired by malnutrition and oxidative stress, which is affected by antioxidants such as ascorbic acid (AA). This study monitored AA levels during hospitalization of patients with a proximal femur to investigate the influence of AA status to the clinical outcome. AA levels of 25 elderly patients with a proximal femur fracture were measured during hospitalization using high performance liquid chromatography. Plasma samples were collected preoperatively, on the first day after surgery, on the third day after surgery and on the day of discharge. Nutritional Risk Screening 2002 (NRS) and Mini Nutritional Assessment (MNA) were assessed to evaluate the nutritional status. In patients with proximal femoral fractures, preoperative AA concentrations were significantly lower compared to elderly patients without an acute fracture. A significant decrease of 33.8% in AA plasma level was measured on the day after surgery with a significant recovery up to the time of discharge. The preoperative AA status did not have any significant effect on clinical outcome. However, inadequate AA levels (<50 µmol/L) upon discharge significantly increased the incidence and the severity of postoperative complications. These results indicate that the AA status upon discharge has a greater impact on clinical outcome than assumed, and therefore, AA supplementation during hospitalization should be considered.