Ascorbic acid

Sci Rep . 2018 Jul 27;8(1):11372

Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression[Pubmed: 30054560]

Abstract L-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of L-Ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of L-Ascorbic acid. In this study, we demonstrate that L-Ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of L-Ascorbic acid from 10 μM -2 mM. However, in low SVCT-2 expressing cell lines, high-dose L-Ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose L-Ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of L-Ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that L-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.

Nutr Res. 2013 Oct;33(10):868-75.

α-Tocopherol, ascorbic acid, and β-carotene protect against oxidative stress but reveal no direct influence on p53 expression in rats subjected to stress.[Pubmed: 24074745]

We hypothesized that α-tocopherol, Ascorbic acid, and β-carotene, either applied individually or in combination, would modulate redox homeostasis and affect the regulation of genes involved in DNA repair under stress conditions.
METHODS AND RESULTS:
To test this hypothesis, we analyzed the influence of these vitamins, either supplied individually or in combination, on the plasma lipid peroxide level and the hepatic level of 8-hydroxy-2'-deoxyguanosine in rats. We also evaluated the expression of p53 and Mdm2 protein in the intestinal epithelium, as these proteins are involved in the cellular regulation of DNA damage repair. Male Wistar rats (n = 112) were supplemented with α-tocopherol (2 mg), Ascorbic acid (12 mg), and β-carotene (1 mg), both individually and in combination, for 14 days; 32 control rats were treated with placebo. Half of the animals in each group (n = 8) were subjected to 15-minute treadmill running at 20 m/min to cause exercise-induced oxidative stress. A statistically significant reduction in lipid peroxide levels was observed in the plasma of rats subjected to exercise and given 2 or 3 of the antioxidants (P < .0001). Exercise, as well as coadministration of the antioxidants, had no significant effect on the amount of DNA damage. Downward trends in the level of p53 protein expression were observed both in exercised and nonexercised animals, especially when the studied vitamins were administered in combination.
METHODS AND RESULTS:
Our findings suggest that α-tocopherol, Ascorbic acid, and β-carotene, when given concurrently, have primarily antioxidant effects on lipids under stress but do not significantly affect the regulation of p53 gene expression.

Am J Kidney Dis. 2006 Apr;47(4):644-54.

Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia.[Pubmed: 16564942 ]

Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis patients most commonly results from iron deficiency, the contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We conducted an open-label prospective study to assess the effect of vitamin C(Ascorbic acid), an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia.
METHODS AND RESULTS:
Forty-six of 262 patients in an inner-city hemodialysis center met the inclusion criteria (administration of intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk, average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%). Patients were excluded if they had a clear explanation for the EPO hyporesponsiveness. Four patients refused to participate. The remaining patients were randomly assigned; 20 patients to receive standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 22 patients to receive standard care only (group 2). Study duration was 6 months. During the study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from final analysis. Monthly assessment included Hb level, mean corpuscular volume, iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive protein (CRP), and liver enzymes were measured every 3 months. Age, sex, race, and time on dialysis therapy were similar in both groups. At 6 months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased significantly in group 1, but not in controls. Changes in Hb content in reticulocytes and ferritin level also were statistically significant in group 1. There was no change in biointact parathyroid hormone levels. Although serum iron levels and intravenous iron doses changed within each group, changes were equal between the 2 groups.
CONCLUSIONS:
In hemodialysis patients with refractory anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either by augmenting iron mobilization from its tissue stores or through antioxidant effects.

Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1999 Nov;124(3):233-7.

Enhanced testicular antioxidant system by ascorbic acid in alloxan diabetic rats.[Pubmed: 10661714]

The diabetic subject is at significantly increased risk of developing testicular changes. Its etiology may involve oxidative damage by free radicals and protection against such damage can be offered by antioxidant supplementation.
METHODS AND RESULTS:
Alloxan elicited significant inhibition of antioxidants including superoxide dismutase, catalase and glutathione reductase activities and decreased glutathione content in testis. These effects were accompanied by significant elevation of testicular lipid peroxidation, decreased plasma testosterone level and a drop in copper and zinc concentrations in testis. The administration of Ascorbic acid after alloxan treatment interfered and prevented alloxan action. Ascorbic acid blunted the increased testicular lipid peroxidation and the decreased plasma testosterone level probably by protecting antioxidants and the loss of copper and zinc from testes.
CONCLUSIONS:
The data suggested that Ascorbic acid has a protective effect on alloxan-induced damage by maintaining the activity of cellular antioxidants.

Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11003-6.

Ascorbic acid protects against endogenous oxidative DNA damage in human sperm.[Pubmed: 1763015]

Damage to the DNA of germ cells can lead to mutation, which may result in birth defects, genetic diseases, and cancer. The very high endogenous rate of oxidative DNA damage and the importance of dietary Ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA.
METHODS AND RESULTS:
The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxo-7,8-dihydro-2'-deoxyguanosine; oxo8dG), 1 of approximately 20 major products of oxidative damage to DNA, was measured in DNA isolated from human sperm provided by healthy subjects and compared to the seminal fluid AA levels. This relationship was studied in two groups. In a group of 24 free-living individuals 20-50 years old high levels of oxo8dG were correlated with low seminal plasma AA. The endogenous level of oxo8dG in this group was 13 fmol per microgram of DNA or approximately 25,000 adducts per sperm cell. The second group of individuals was maintained on a controlled diet that varied only in AA content. When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%.
CONCLUSIONS:
These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers.

Circulation. 1996 Mar 15;93(6):1107-13.

Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease.[Pubmed: 8653830]

In the setting of atherosclerosis, endothelial vasomotor function is abnormal. Increased oxidative stress has been implicated as one potential mechanism for this observation. We therefore hypothesized that an antioxidant, Ascorbic acid, would improve endothelium-dependent arterial dilation in patients with coronary artery disease.
METHODS AND RESULTS:
Brachial artery endothelium-dependent dilation in response to hyperemia was assessed by high-resolution vascular ultrasound before and 2 hours after oral administration of either 2 g Ascorbic acid or placebo in a total of 46 patients with documented coronary artery disease. Plasma Ascorbic acid concentration increased 2.5-fold 2 hours after treatment (46+/-8 to 114+/-11 micromol/L, P=.001). In the prospectively defined group of patients with an abnormal baseline response (<5% dilation), Ascorbic acid produced marked improvement in dilation (2.0+/-0.6% to 9.7+/-2.0%), whereas placebo had no effect (1.1+/-1.5% to 1.7+/-1.5%, P=.003 for Ascorbic acid versus placebo). Ascorbic acid had no effect on hyperemic flow or arterial dilation to sublingual nitroglycerin.
CONCLUSIONS:
Ascorbic acid reverses endothelial vasomotor dysfunction in the brachial circulation of patients with coronary artery disease. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in patients with atherosclerosis and that endothelial dysfunction may respond to antioxidant therapy.

Aquaculture, 1998, 161(1–4):453-61.

Dietary ascorbic acid needs of common carp (Cyprinus carpio) larvae.[Reference: WebLink]

As some controversy seem to exist regarding the dietary essentiality of Ascorbic acid (AA) for larval cyprinids, a study was conducted to determine the dietary AA requirements with first-feeding larvae of common carp.
METHODS AND RESULTS:
Six semi-purified diets were formulated to contain graded levels (0, 10, 30, 90, 270, 810 mg kg−1) of AA supplied as ascorbyl polyphosphate. Triplicate groups of 250 larvae each were fed one of the experimental diets using automatic feed dispensers over the light hours of the day (temperature: 24±1°C; photoperiod 16L:8D). A duplicate group was kept unfed. Survival, body length and weight increments were recorded. At the end of the 21 day trial, samples were withdrawn for analyses of whole body vitamin C content.
CONCLUSIONS:
The results indicate that common carp larvae have a dietary requirement for Ascorbic acid. The required level for maximum tissue storage is higher than that needed for survival and maximum growth. Based on growth performance, a dietary requirement of about 45 mg AA equivalent kg−1 was established. Maximal body vitamin C concentration (104–115 μg g−1 wet weight) was observed in larvae fed 270 mg AA equivalent kg−1 or more.