Effects of Ester‐C ® and Ascorbic Acid on Gastrointestinal Outcomes: A Randomized, Double‐Blind Trial
Abstract
Background Optimum vitamin C intake is not always attainable solely via food consumption, therefore supplementation may be desirable. However, vitamin C supplementation is not without notable gastrointestinal discomfort resulting from its acidic nature, which may affect overall quality of life. Objective To compare the effects of Ester‐C ® (EC) and Ascorbic Acid (AA) on gastrointestinal symptoms and quality of life in subjects with acid‐sensitivity. Methods In this double‐blind, cross‐over study, 50 healthy adults with acid‐sensitivity were randomized to receive vitamin C (1000 mg for Day 1‐5, 2000 mg for Day 6‐10) provided by either AA or EC. Gastrointestinal side effects as measured by Gastrointestinal Symptom Rating Scale (GSRS) and the associated changes in quality of life as measured by Medical Outcomes Short Form‐36 (SF‐36) were assessed. Results An intention‐to‐treat analysis was conducted on 50 subjects (11 males, 39 females). After ten days of treatment, AA resulted in significant worsening of Abdominal pain (p=0.02), Diarrhea (p=0.047), and total GSRS score (p=0.019), while there were no significant changes in EC group. The Role Physical and Bodily Pain scores were significantly better in EC group compared to AA group over the ten‐day period (p = 0.004 and 0.008, respectively). Conclusion Ester‐C ® is better tolerated than Ascorbic Acid in individuals with acid‐sensitivity.
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In participants with acid sensitivity using higher dosages (1000 mg daily day 1-5, 2000 mg daily day 6-10), no significant changes were observed in gastrointestinal symptoms of those taking Calcium ascorbate EC.
“Finally, even when using higher dosages and in participants with acid sensitivity (1000 mg daily for day 1–5, 2000 mg daily for day 6–10), no significant changes were observed in the gastrointestinal symptoms of those taking Calcium ascorbate EC, whereas ascorbic acid was associated with increases in abdominal pain (p = 0.02), diarrhea (p = 0.047), and worsening of the overall Gastrointestinal Sym”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [34]
In the same study, ascorbic acid was associated with increases in abdominal pain (p=0.02), diarrhea (p=0.047), and worsening of overall Gastrointestinal Symptom Rating Scale score (p=0.019).
“Finally, even when using higher dosages and in participants with acid sensitivity (1000 mg daily for day 1–5, 2000 mg daily for day 6–10), no significant changes were observed in the gastrointestinal symptoms of those taking Calcium ascorbate EC, whereas ascorbic acid was associated with increases in abdominal pain (p = 0.02), diarrhea (p = 0.047), and worsening of the overall Gastrointestinal Sym”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [34]
Over the 10-day period, Role Physical and Bodily Pain scores were significantly improved in the Calcium ascorbate EC group compared to the ascorbic acid group (p=0.004 and p=0.008).
“Additionally, over the 10-day period, the Role Physical and Bodily Pain scores were significantly improved in the Calcium ascorbate EC group compared to the ascorbic acid group (p = 0.004 and p = 0.008, respectively).”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [34]
Cited by
Sorted by citations
Mitmesser, S. H., Ye, Q., Evans, M., & Combs, M. (2016) · SpringerPlus · doi:10.1186/s40064-016-2605-7 · Cited by 34 · see citing works
“Phagocytes consume extracellular vitamin C when activated during an immune challenge, causing plasma and leukocyte vitamin C concentrations to decline rapidly during an infection and/or stress (Stankova et al.”
BackgroundSelf-citationCalder, P. C., Kreider, R. B., & McKay, D. L. (2025) · Nutrients · doi:10.3390/nu17020279 · Cited by 12 · see citing works
Dickerson, B., Gonzalez, D. E., Sowinski, R., Xing, D., Leonard, M., Kendra, J., Jenkins, V., Gopalakrishnan, S., Yoo, C., Ko, J., et al. (2024) · Nutrients · doi:10.3390/nu16193358 · Cited by 1 · see citing works
“Participants rested passively for 32 h while undergoing blood donation and receiving standardized diets.”
Method
- Authors
- Ye, Q., Combs, M., & Mitmesser, S.
- Affiliations
- Department of Nutrition Research NBTY, Inc Ronkonkoma NY United States
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2015-04
- Volume
- 29
- Issue
- S1
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1010845280
- Cited by
- 3
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2016: 1
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- vitamin C, vitamin C supplementation, gastrointestinal adverse effects, acid sensitivity, abdominal pain, diarrhea, quality of life, tolerability, Gastrointestinal Symptom Rating Scale, SF-36
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