Korean J Physiol Pharmacol.  2018 Jan;22(1):35-42. 10.4196/kjpp.2018.22.1.35.

Alleviation of ascorbic acid-induced gastric high acidity by calcium ascorbate in vitro and in vivo

Affiliations
  • 1Department of Physical Pharmacy, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea. eicosa@cnu.ac.kr
  • 2Department of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea. cm8r@cnu.ac.kr
  • 3PHARMCROSS Co., Ltd., Chuncheon 24398, Korea.

Abstract

Ascorbic acid is one of the most well-known nutritional supplement and antioxidant found in fruits and vegetables. Calcium ascorbate has been developed to mitigate the gastric irritation caused by the acidity of ascorbic acid. The aim of this study was to compare calcium ascorbate and ascorbic acid, focusing on their antioxidant activity and effects on gastric juice pH, total acid output, and pepsin secretion in an in vivo rat model, as well as pharmacokinetic parameters. Calcium ascorbate and ascorbic acid had similar antioxidant activity. However, the gastric fluid pH was increased by calcium ascorbate, whereas total acid output was increased by ascorbic acid. In the rat pylorus ligation-induced ulcer model, calcium ascorbate increased the gastric fluid pH without changing the total acid output. Administration of calcium ascorbate to rats given a single oral dose of 100 mg/kg as ascorbic acid resulted in higher plasma concentrations than that from ascorbic acid alone. The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the C(max) value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml). However, their T(max) values were similar. Thus, although calcium ascorbate showed equivalent antioxidant activity to ascorbic acid, it could attenuate the gastric high acidity caused by ascorbic acid, making it suitable for consideration of use to improve the side effects of ascorbic acid. Furthermore, calcium ascorbate could be an appropriate antioxidant substrate, with increased oral bioavailability, for patients with gastrointestinal disorders.

Keyword

Antioxidant; Ascorbic acid; Bioavailability; Calcium ascorbate; Gastric pH

MeSH Terms

Animals
Ascorbic Acid
Biological Availability
Calcium*
Fruit
Gastric Juice
Humans
Hydrogen-Ion Concentration
In Vitro Techniques*
Models, Animal
Pepsin A
Plasma
Pylorus
Rats
Ulcer
Vegetables
Ascorbic Acid
Calcium
Pepsin A

Figure

  • Fig. 1 Effect of calcium ascorbate on the pH and total acid output of human simulated gastric fluid (hSGF).After the addition of ascorbic acid or calcium ascorbate to the hSGF, the changes in hSGF pH and total acid were measured until 240 min. pH (A) and total acid (B) of hSGF; pH (C) and total acid (D) of hSGFw/P (hSGF with pepsin). Data are expressed as the mean±SEM (n=5). ***p<0.001 vs. distilled water (DW).

  • Fig. 2 Effect of calcium ascorbate on the pH and total acid output of rat simulated gastric fluid (rSGF).After the addition of ascorbic acid or calcium ascorbate to the rSGF, the changes in rSGF pH and total acid were measured until 240 min. pH (A) and total acid (B) of rSGF; pH (C) and total acid (D) of rSGFw/P (rSGF with pepsin). Data are expressed as the mean±SEM (n=5). ***p<0.001 vs. distilled water (DW).

  • Fig. 3 Effect of calcium ascorbate on gastric juice volume and pH in the rat pylorus ligation-induced ulcer model.After oral administration of distilled water (DW; as a control), ascorbic acid (105.96 mg/kg), or calcium ascorbate (135.24 mg/kg) to rats processed by pylorus ligation, the stomach was removed immediately following animal sacrifice and the gastric contents were collected at designated times. After the centrifugation of the gastric contents (1,800×g for 5 min), the volume (A) and pH (B) were measured. Data are expressed as the mean±SEM (n=5). **p<0.01, ***p<0.001 vs. distilled water (DW); ##p<0.01, ###p<0.001 vs. ascorbic acid.

  • Fig. 4 Effect of calcium ascorbate on total acid output and pepsin secretion in the rat pylorus ligation-induced ulcer model.After oral administration of distilled water (DW; as a control), ascorbic acid (105.96 mg/kg), or calcium ascorbate (135.24 mg/kg) to rats processed by pylorus ligation, the stomach was removed immediately following animal sacrifice and the gastric contents were collected at designated times. After centrifugation of the gastric contents (1,800×g for 5 min), the total acid output (A) and amount of secreted pepsin (B) were measured. Data are expressed as the mean±SEM (n=5). **p<0.01, ***p<0.001 vs. distilled water (DW); ##p<0.01, ###p<0.001 vs. ascorbic acid.

  • Fig. 5 Blood concentration of ascorbic acid after oral administration.Plasma concentration versus time profiles obtained after the administration of ascorbic acid (105.96 mg/kg) and calcium ascorbate (135.24 mg/kg). Values for each time point are expressed as the mean±SEM (n=6).


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