Safety and tolerance of ester-C compared with regular ascorbic acid

Adv Ther. Jan-Feb 2006;23(1):171-8. doi: 10.1007/BF02850358.


The goal of this randomized, double-blind crossover clinical trial in 50 healthy volunteers sensitive to acidic foods was to evaluate whether Ester-C calcium ascorbate causes fewer epigastric adverse effects than are produced by regular ascorbic acid (AA). Volunteers were randomly separated into 2 groups of 25. The study comprised an observation period of 9 days (phase 1 medication for 3 consecutive days, washout phase for 3 consecutive days, phase 2 medication for 3 consecutive days). Participants took 1000 mg vitamin C as Ester-C during phase 1 of the study followed by 1000 mg of vitamin C as AA during phase 2, or vice versa. During the course of the study, 3 examinations for the evaluation of epigastric adverse effects were performed (on days 0, 3, and 9). Participants used a diary to record epigastric adverse effects on a daily basis. In total, 28 (56%) of 50 participants reported 88 epigastric adverse effects of mild to moderate intensity. Of these 88 adverse effects, 33 (37.5%) occurred after intake of Ester-C and 55 (62.5%) were noted after intake of AA. The tolerability of Ester-C was rated "very good" by 72% of participants, whereas AA was rated "very good" by only 54%. This difference is statistically significant (P<.05). Investigators concluded that Ester-C compared with AA caused significantly fewer epigastric adverse effects in participants sensitive to acidic foods and that Ester-C is much better tolerated.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antioxidants / adverse effects*
  • Antioxidants / chemistry
  • Ascorbic Acid / adverse effects*
  • Ascorbic Acid / chemistry
  • Cross-Over Studies
  • Dehydroascorbic Acid / adverse effects
  • Dehydroascorbic Acid / chemistry
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Threonine / adverse effects*
  • Threonine / chemistry


  • Antioxidants
  • Drug Combinations
  • calcium ascorbate
  • Threonine
  • Ascorbic Acid
  • Dehydroascorbic Acid