- Human dermal fibroblasts: enhances elastic fiber and collagen deposition via sodium-dependent vitamin C transporters (SVCTs), reduction of intracellular ROS, activation of c-Src kinase, and enhancement of IGF-1 receptor phosphorylation. [1]
- Neuronal T-type calcium channels: selectively inhibits Cav3.2 (α1H) subtype via metal-catalyzed oxidation of histidine 191 in domain I, with no effect on Cav3.1 or Cav3.3. [3]

- Ascorbate (Sodium L-ascorbate) (50–200 μM) significantly stimulated deposition of immuno-detectable elastic fibers and collagen fibers in 72 h cultures of normal human dermal fibroblasts and fat-derived fibroblasts. Higher concentrations (400 μM) did not further stimulate, and 800 μM inhibited elastogenesis. NaCl or a mixture of NaCl and ascorbic acid (AA) had no effect. [1]
- Combination of 100 μM SA with the prolyl hydroxylase inhibitor DMOG inhibited collagen deposition but did not diminish enhanced elastogenesis; 7-day cultures with daily SA showed more elastin, and SA+DMOG further increased elastic fibers and insoluble elastin. [1]
- SA (100 μM) up-regulated tropoelastin mRNA (18 h), intracellular tropoelastin (24 h), and insoluble elastin (72 h). The SVCT inhibitor probenecid (400 μM) eliminated these elastogenic effects. [1]
- SA (100 μM, 2 h) significantly decreased intracellular reactive oxygen species (ROS) levels in fibroblasts, as detected by CM-H₂DCFDA fluorescent probe and flow cytometry. This effect was blocked by probenecid. [1]
- SA enhanced elastogenesis only in cultures with 5% FBS (containing IGF-1). In serum-free medium, SA alone did not induce elastogenesis, but SA enhanced IGF-1-induced tropoelastin synthesis. SA enhanced IGF-1 receptor phosphorylation; this was blocked by c-Src inhibitor PP2 or IGF-1R kinase inhibitor PPP. SA did not enhance insulin receptor phosphorylation. [1]
- In fibroblasts from dermal stretch marks, SA (200 μM) up-regulated collagen and elastic fiber deposition, whereas AA selectively inhibited elastogenesis. [1]
- Ascorbate (ascorbic acid) inhibited native T-type Ca²⁺ currents in acutely dissociated rat dorsal root ganglion (DRG) neurons with an IC₅₀ of 6.5 ± 3.9 μM and maximal inhibition of 70.2 ± 2.1% (Hill coefficient 0.56 ± 0.12). Ascorbate shifted the voltage dependence of activation to more depolarized potentials (V₅₀ from -49.0 to -44.1 mV) and steady-state inactivation to more hyperpolarized potentials (V₅₀ from -75.0 to -80.4 mV), and slowed activation and inactivation kinetics. [3]
- Ascorbate (100–300 μM) reversibly inhibited recombinant human Cav3.2 T-type channels expressed in HEK293 cells, but had no effect on Cav3.1 or Cav3.3 channels. The inhibition was concentration-dependent. [3]
- Site-directed mutagenesis identified histidine 191 (H191) in the extracellular loop between S3 and S4 of domain I as critical for ascorbate sensitivity. Mutations H191Q or H191C abolished ascorbate inhibition. The H191Q mutation also reduced Cu²⁺ sensitivity (>40-fold). [3]
- Ascorbate inhibition was prevented by the metal chelator DTPA, the H₂O₂-decomposing enzyme catalase, and the ROS scavenger c-PTIO. Addition of 300 nM Cu²⁺ increased ascorbate inhibition. [3]

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The B16F10 cell conditioned medium has a relative molecular mass of less than 5,000 for the active components, and it strongly reduces apoptosis induced by Sodium L-ascorbate (10 mM) [4].

Compared to Tg rats not treated with sodium L-ascorbate (Sodium L-ascorbate), Tg rats treated with sodium L-ascorbate (15.4%) had a greater incidence of cancer (29.6%). Transgenic rats showed several organ cancers, even in the absence of L-ascorbic acid sodium salt therapy [5]. All animals experienced simple hyperplasia and papillary or nodular (PN) hyperplasia following 12 weeks of PEITC treatment; however, most lesions subsided by 48 weeks, irrespective of the administration of sodium salt (L-ascorbic acid) treatment. By week 48, after 24 weeks of PEITC treatment, the same lesions had progressed to dysplasia and cancer in a few cases; however, the rats' simple hyperplasia and PN hyperplasia were the only conditions in which the treatment with L-ascorbic acid sodium salt showed an enhancement impact. [6].

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Sodium L-ascorbate (Na-AsA) is well recognized as a promoter of bladder carcinogenesis in rats, yet it yields negative results in standard two‑year bioassays. To further investigate its tumorigenic potential, the present study utilized Hras128 transgenic rats, which are highly susceptible to bladder cancer. A total of 40 male transgenic (Tg) rats (7 weeks old) and 42 non‑transgenic (Non‑tg) littermates were divided into four groups and fed a powdered MF diet with or without 5% Na-AsA for 57 weeks. Regardless of Na-AsA treatment, Tg rats had significantly shorter survival than Non‑tg rats. Among Tg rats, the incidence of carcinoma was slightly higher in the Na-AsA‑treated group (29.6%) compared to the untreated group (15.4%), but this difference was not statistically significant. Moreover, overall bladder tumor incidence, including papillomas, did not differ significantly between the two Tg groups (37.0% with Na-AsA vs. 30.8% without). No bladder tumors were detected in any Non‑tg rats. Various other lesions were observed in multiple organs of Tg rats, both with and without Na-AsA, but no intergroup differences were apparent. In conclusion, Na-AsA did not exhibit tumorigenicity in the highly bladder‑cancer‑susceptible Hras128 transgenic rat model. These findings indicate that Na-AsA acts as a pure promoter rather than a complete carcinogen in rats. [5]

- For elastogenesis studies: Immuno-staining, Western blot, RT-PCR, and quantitative assay of metabolically labeled insoluble elastin using [³H]valine were performed as described. ROS levels were measured using CM-H₂DCFDA fluorescent probe and flow cytometry. [1]
- For T-type calcium channel studies: Whole-cell patch-clamp recordings were performed on acutely dissociated DRG neurons, thalamic slices, and HEK293 cells expressing recombinant channels. External solution contained 10 mM Ba²⁺ as charge carrier. Concentration-response curves were fitted to Hill-Langmuir equation. Voltage dependence of activation and inactivation were fitted to Boltzmann distributions. [3]

- Human dermal fibroblasts and fat-derived fibroblasts (passages 2-4) were cultured in DMEM with 5% FBS. Cells were treated with SA (50–800 μM) for 18–72 h. Immuno-staining for elastin and collagen I, Western blot for tropoelastin, RT-PCR for tropoelastin mRNA, and [³H]valine incorporation for insoluble elastin were performed. [1]
- For ROS measurement, cells were loaded with 10 μM CM-H₂DCFDA for 30 min, then treated with SA (100 μM) for 2 or 24 h, and fluorescence was visualized by microscopy or flow cytometry. [1]
- For IGF-1R phosphorylation studies, cells were lysed and immunoprecipitated with anti-IGF-1R β-subunit antibody, then Western blotted with anti-phosphotyrosine. [1]
- For T-type channel studies: Acutely dissociated rat DRG neurons, thalamic slices, and HEK293 cells transiently expressing Cav3.1, Cav3.2, or Cav3.3 channels were used. Whole-cell voltage-clamp recordings were performed at room temperature. Ascorbate was applied via perfusion. [3]

At 6 weeks of age, animals were divided into six groups (Fig. 1). To examine the development of proliferative lesions in the urinary bladder at the end of different periods of PEITC exposure, animals in groups 1 and 2 were fed basal diet (control) or 0.1% PEITC for up to 48 weeks, and sacrificed at 12, 24, and 48 weeks (7–8 animals per time point). To examine the enhancing effect of Na‑AsA on the development of proliferative lesions induced by PEITC, animals of groups 4 and 6 were fed 0.1% PEITC for the initial 12 and 24 weeks, respectively, and then fed 5% Na‑AsA until week 48 (16 animals/group). Animals of groups 3 and 5 served as Na‑AsA negative controls for groups 4 and 6, respectively, and were fed basal diet instead of Na‑AsA after PEITC treatment (16 animals/group). Food and tap water were available ad libitum. Body weight and food consumption were recorded at least once every 2 weeks after the first 8 weeks. At the sacrifice points, all animals were euthanized under ether anesthesia. At autopsy, the liver, kidneys and urinary bladder were removed, and the liver and kidneys were weighed. The urinary bladder was inflated with 10% neutral buffered formalin (pH 7.4) before immersion in the fixative. Urinary bladders at terminal sacrifice were weighed after fixation and six slices were prepared from each. They were paraffin‑embedded together with slices of liver and kidneys, sectioned at 3 μm, and stained with hematoxylin and eosin. The lesions observed in the urinary bladder were histopathologically classified into simple hyperplasia, PN hyperplasia, dysplasia, and transitional cell carcinoma according to criteria described previously.[6]

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Rat Tissue Preparation:** Acutely dissociated dorsal root ganglion (DRG) cells and thalamic slices were prepared from adolescent rats. [3]

Absorption, Distribution and Excretion
Ascorbic acid, the reduced form of vitamin C, is a potent antioxidant and plays a role in cell differentiation. Mammalian cells absorb ascorbic acid via specific sodium/ascorbic acid cotransporters SVCT1 and SVCT2. Although skeletal muscle contains approximately 50% of the body's vitamin C, the expression of SVCT transporters in this tissue has not been clearly studied. …This study… used chicken embryos as a model system to analyze the expression pattern of SVCT2 during embryonic myogenesis. Immunohistochemical analysis showed that SVCT2 is preferentially expressed in type I slow-twitch muscle fibers during chicken embryonic myogenesis and is also expressed in postnatal skeletal muscle in various species, including humans… Humans utilize two sodium-ascorbic acid cotransporters (hSVCT1 and hSVCT2) to transport the dietary essential micronutrient ascorbic acid, the reduced active form of vitamin C. Although the human liver plays a crucial role in regulating and maintaining vitamin C homeostasis, the physiology of vitamin C transport and the regulatory mechanisms of the hSVCT system in this organ remain poorly elucidated. Therefore, this study used the human hepatocyte line (HepG2) to validate some results from primary human hepatocytes and determined that the initial rate of ascorbic acid uptake is dependent on the Na(+) gradient, pH, and concentration saturation in both low and high micromolar ranges. Furthermore, the expression levels of hSVCT2 protein and mRNA were high in HepG2 cells and native human livers, and the cloned hSVCT2 promoter was more active in HepG2 cells. Results using short interfering RNA showed that in HepG2 cells, reducing hSVCT2 mRNA levels was more effective than reducing hSVCT1 mRNA levels in reducing overall ascorbic acid uptake. Activation of intracellular PKC regulatory pathways led to downregulation of ascorbic acid uptake, but this downregulation was not mediated by any single predicted PKC-specific amino acid phosphorylation site in hSVCT1 or hSVCT2. However, PKC activation leads to hSVCT1 internalization but not hSVCT2 internalization. Studies on other intracellular ascorbic acid uptake regulatory pathways have shown that PKA, PTK, and Ca(2+)/calmodulin may also be involved in regulation, but the nitric oxide-dependent pathway is not involved…

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Metabolism/Metabolites
…The adrenal cortex is closely related to ascorbic acid metabolism…It has been reported that hydrocortisone…can stimulate gluconolactone synthesis of ascorbic acid, while deoxycorticosterone or aldosterone leads to…increased ascorbic acid excretion in normal or adrenalectomized rats…

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Vitamin C is a normal component of breast milk and an important antioxidant. It is recommended that breastfeeding women consume 120 mg of vitamin C daily, and infants 6 months and under consume 40 mg daily. High doses of up to 1000 mg daily will increase the vitamin C content in breast milk, but this is insufficient to cause health problems for breastfed infants and is not a reason to discontinue breastfeeding. Breastfeeding women may need to supplement their diet to reach the recommended intake or correct any known vitamin C deficiency. When pregnant women take prenatal vitamins, intake at or near the recommended intake will not change the vitamin C content in breast milk.
For hospitalized mothers of full-term and premature infants, freezing freshly expressed mature breast milk (at -20°C) for at least 3 months will not change the vitamin C content. After freezing (at -20°C) for 6 to 12 months, the vitamin C content will decrease by 15% to 30%. Storing at -80°C preserves vitamin C content for 8 months, with a 15% loss after 12 months.
◉ Effects on breastfed infants
60 healthy lactating women aged 1 to 6 months postpartum, exclusively breastfeeding infants, received either 500 mg of vitamin C and 100 IU of vitamin E once daily for 30 days, or no supplementation. Infants born to mothers receiving supplementation showed elevated urinary antioxidant activity biochemical indicators. No clinical results were reported.
18 preterm infants (7 of whom had a gestational age of less than 32 weeks) fed mixed, pasteurized donor breast milk for the first three days after birth experienced a decrease in mean plasma ascorbic acid concentration from 15.5 mg/L at birth to 5.4 mg/L at 1 week postpartum, and a further decrease to 4.1 mg/L at 3 weeks postpartum. The authors considered the ascorbic acid levels at 1 and 3 weeks to be below therapeutic levels (<6 mg/L), indicating insufficient intake, which may affect postnatal growth and development. Although this study was conducted prior to advances in parenteral nutrition and enteral fortified milk for preterm infants, contemporary research suggests that insufficient vitamin C intake from mixed pasteurized donor milk may be a potential health problem for preterm infants receiving donor milk.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.
Interactions

When different concentrations of calcium chloride were added to a bath containing acetylcholine but without Ca2+ ions, tissues exposed to sodium ascorbate showed a stronger response than untreated muscle.
In vitro, the effects of sodium ascorbate (with or without vitamin K3) at concentrations ranging from 0.198 μg/mL to 1.98 mg/mL were investigated using cultured human tumor cell lines MCF-7 (breast cancer), KB (oral epidermal carcinoma), and AN3-CA (endometrial adenocarcinoma). Culture media without sodium ascorbate and vitamin K3 served as controls. When cell confluence reached 50%, sodium ascorbate and vitamin K3 were added to the culture in different proportions and incubated for 1 hour. DNA assays were then performed. The medium supplemented with sodium ascorbate only showed growth inhibition at high concentrations (5 x 10⁻³ mol/L). Combined administration showed synergistic inhibition of cell growth even at concentrations reduced by 10 to 50 times. These results apply to all three cell types…
Male and female Wistar rats (n=5 per group) were administered sodium ascorbate and/or sodium nitrite for 6 consecutive months. The control group was fed only a basal diet and water. The treatment groups were given the following solutions: 0.075%, 0.15%, or 0.3% sodium nitrite aqueous solution; 1%, 2%, or 4% sodium ascorbate; or a combination of two chemicals at low + low, medium + medium, and high + high doses. The combined high-dose group showed a significantly reduced increase in body weight. The high-dose combination also showed a significant decrease in serum total protein, a significant increase in blood urea nitrogen (BUN), and a significant increase in relative kidney weight. Histopathological examination revealed moderate to severe squamous cell hyperplasia in the forestomach of the high-dose combination group, while mild hyperplasia was observed in the medium-dose combination group. No gender differences were observed. The minimum toxic dose was 0.15% sodium nitrite + 2% sodium ascorbate…

[1]. Sodium L-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin. J Dermatol Sci. 2014 Sep;75(3):173-82.

[2]. Sodium L-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin. J Dermatol Sci. 2014 Sep;75(3):173-82.

[3]. Molecular mechanisms of subtype-specific inhibition of neuronal T-type calcium channels by ascorbate. J Neurosci. 2007 Nov 14;27(46):12577-83.

[4]. Mouse melanoma cell line B16F10-derived conditioned medium inhibits sodium L-ascorbate-induced B16F10 cell apoptosis. Nan Fang Yi Ke Da Xue Xue Bao. 2012 Feb;32(2):146-50.

[5]. Lack of urinary bladder carcinogenicity of sodium L-ascorbate in human c-Ha-ras proto-oncogene transgenic rats. Toxicol Pathol. 2005;33(7):764-7.

[6]. Limited tumor-initiating activity of phenylethyl isothiocyanate by promotion with sodium L-ascorbate in a rat two-stage urinary bladder carcinogenesis model. Cancer Lett. 2005 Mar 10;219(2):147-53.

Tiny crystals or white powder. The pH of its aqueous solution is 5.6 to 7.0 or higher (e.g., a 10% solution prepared from a commercially available product may have a pH of 7.4 to 7.7). (NTP, 1992)
Sodium ascorbate is an organic sodium salt formed by the substitution of a sodium ion for the proton on the 3-hydroxyl group of ascorbic acid. It is used as a food antioxidant, flour treatment agent, coenzyme, plant metabolite, human metabolite, large flea metabolite, and reducing agent. It is an organic sodium salt and also vitamin C. It contains L-ascorbic acid.
A six-carbon compound associated with glucose. It is naturally found in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient for the human body and is crucial for maintaining connective tissue and bones. Its biologically active form—vitamin C—acts as a reducing agent and coenzyme in various metabolic pathways. Vitamin C is considered an antioxidant.
See also: Ascorbic acid (with active fraction)...See more...

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Mechanism of Action
The mechanism of action of ascorbic acid is the scavenging of superoxide radicals.
...Sodium ascorbate reduces iron uptake in melanoma cells in a dose- and time-dependent manner, suggesting that intracellular iron levels may be a key factor in sodium ascorbate-induced apoptosis. In fact, the iron chelator deferoxamine (DFO) enhances sodium ascorbate-induced apoptosis, while the iron donor ferric ammonium citrate (FAC) inhibits this process. Furthermore, the addition of transferrin blocks the inhibitory effect of sodium ascorbate on intracellular iron levels, suggesting that sodium ascorbate may regulate iron uptake through a transferrin receptor (TfR)-dependent pathway. Cells exposed to sodium ascorbate exhibit downregulated transferrin receptor (TfR) expression, and this downregulation precedes sodium ascorbate-induced apoptosis. In summary, sodium ascorbate-mediated apoptosis appears to be initiated by decreased TfR expression, leading to reduced iron uptake and subsequently inducing apoptosis…
The human body utilizes two sodium-ascorbate cotransporters (hSVCT1 and hSVCT2) to transport the dietary essential micronutrient ascorbic acid, the reduced active form of vitamin C. Although the human liver plays a crucial role in regulating and maintaining vitamin C homeostasis, the physiology of vitamin C transport in this organ and the regulatory mechanisms of the hSVCT system remain largely unclear. Therefore, this study used the human hepatocyte cell line (HepG2) to validate some of the findings from primary human hepatocyte studies and determined that the initial rate of ascorbic acid uptake is correlated with the Na⁺ gradient, pH-dependent, and saturates across both low and high micromolar concentrations. Furthermore, the expression levels of hSVCT2 protein and mRNA were higher in HepG2 cells and native human liver tissue, and the cloned hSVCT2 promoter exhibited stronger activity in HepG2 cells. Results using short interfering RNA (siRNA) showed that in HepG2 cells, reducing hSVCT2 mRNA levels was more effective than reducing hSVCT1 mRNA levels in reducing overall ascorbic acid uptake. Activation of intracellular PKC regulatory pathways led to downregulation of ascorbic acid uptake, but this downregulation was not mediated by a single predicted PKC-specific amino acid phosphorylation site in hSVCT1 or hSVCT2. However, PKC activation led to hSVCT1 internalization but not hSVCT2 internalization. Studies of other intracellular ascorbic acid uptake regulatory pathways have shown that PKA, PTK, and Ca(2+)/calmodulin may also be involved in regulation, but the nitric oxide-dependent pathway is not involved…

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Therapeutic Uses
Antioxidant; Free Radical Scavenger
Ascorbic acid, as well as calcium ascorbate and sodium ascorbate, are used as antioxidants in the pharmaceutical and food industries.
Of 20 patients with acute asthma attacks, 16 recovered rapidly after intravenous administration of 6 grams of sodium ascorbate. Of 25 asthma patients, 18 received long-term oral sodium ascorbate (0.6-1 g/day for 60 days) which prevented asthma symptoms. Eight patients with hyphema received intravenous glycerol in combination with sodium ascorbate. Results showed that the combined use of glycerol and sodium ascorbate reduced ocular hemorrhage within 12-24 hours. For more complete data on the therapeutic uses of sodium ascorbate (6 types), please visit the HSDB record page. Drug Warnings: Each gram of sodium ascorbate contains approximately 5 milliequivalents of sodium; this should be considered when using this medication in patients on a low-sodium diet.

C6H7NAO6

198.11

198.014

C, 36.38; H, 3.56; Na, 11.60; O, 48.46

134-03-2

L-Ascorbic acid;50-81-7;L-Ascorbic acid (GMP Like);50-81-7

23667548

Off-white to light yellow solid powder

1.799 g/cm3

552.7ºC at 760 mmHg

220 °C (dec.)(lit.)

238.2ºC

1.62E-14mmHg at 25°C

105.5 ° (C=10, H2O)

3

6

2

13

237

2

[Na+].O1C(C(=C([C@@]1([H])[C@]([H])(C([H])([H])O[H])O[H])[O-])O[H])=O

PPASLZSBLFJQEF-RXSVEWSESA-M

InChI=1S/C6H8O6.Na/c7-1-2(8)5-3(9)4(10)6(11)12-5;/h2,5,7-10H,1H2;/q;+1/p-1/t2-,5+;/m0./s1

sodium;(2R)-2-[(1S)-1,2-dihydroxyethyl]-4-hydroxy-5-oxo-2H-furan-3-olate

Ascorbate; Vitamin C sodium; SODIUM ASCORBATE; 134-03-2; L-Ascorbic acid sodium salt; Sodium L-ascorbate; Vitamin C sodium; Sodium Ascorbate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~504.77 mM)
DMSO : ~1 mg/mL (~5.05 mM)

Solubility in Formulation 1: 50 mg/mL (252.39 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)