A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress
Abstract
Rationale Physiological responses to stress are considered disruptive to health. High-dose ascorbic acid has reduced indices of stress in laboratory animals.Methods We conducted a randomized double-blind, placebo-controlled 14-day trial of sustained-release ascorbic acid (60 healthy young adults; 3 x1000 mg/day Cetebe) and placebo (60 healthy young adults) for reduction of blood pressure, cortisol, and subjective response to acute psychological stress (Trier Social Stress Test, TSST, consisting of public speaking and mental arithmetic). Six subjects from each group were excluded.Results Compared to the placebo group, the ascorbic acid group had less systolic blood pressure (an increase of 23 versus 31 mmHg), diastolic blood pressure, and subjective stress responses to the TSST; and also had faster salivary cortisol recovery (but not smaller overall cortisol response). Cortisol response to 1 microg ACTH, and reported side-effects during the trial did not differ between groups. Plasma ascorbic acid level at the end of the trial but not pre-trial was associated with reduced stress reactivity of systolic blood pressure, diastolic blood pressure, and subjective stress, and with greater salivary cortisol recovery.Conclusions Treatment with high-dose sustained-release ascorbic acid palliates blood pressure, cortisol, and subjective response to acute psychological stress. These effects are not attributable to modification of adrenal responsiveness.
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Both studies with sustained-release vitamin C as the intervention were placebo-controlled.
“Both studies with sustained-release vitamin C as the intervention were placebo-controlled [29,31].”
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 [29]
From the NICE checklist quality assessment of thirteen RCTs, ten (77%) showed low risk of bias, two (15%) high risk, and one (8%) unclear risk.
“From the assessment of the methodological quality of thirteen RCTs, ten (77%) showed a low risk of bias [12,16,27,28,29,30,31,32,35,37,38], two (15%) showed a high risk of bias [33,36] and one (8%) showed an unclear risk of bias [34].”
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 [29]
A study of sustained-release vitamin C (3000 mg daily for 14 days) found no significant differences in adverse events between intervention and placebo groups.
“The study on sustained-release vitamin C (3000 mg daily for 14 days) did not find significant differences in adverse events between the intervention and placebo groups [29].”
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 [29]
In that study, upset stomach was reported by 19% of participants taking sustained-release vitamin C vs 15% placebo; diarrhea by 22% vs 24%; and all other minor complaints by 39% vs 37%.
“An upset stomach was reported by 19% of participants taking sustained-release vitamin C in comparison with 15% in the placebo group; diarrhea was reported by 22% vs. 24%; and all other minor complaints by 39% vs. 37%, 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 [29]
The studies on sustained-release vitamin C were all against placebo, disabling any conclusion on its benefits over ascorbic acid or other advanced formulations such as Ester-C®.
“The studies on sustained-release vitamin C were all against placebo, disabling any conclusion to be made on its benefits over ascorbic acid or other, advanced formulations such as Ester-C®, etc. [29,31].”
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 [29]
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- Authors
- Brody, S., Preut, R., Schommer, K., & Schürmeyer, T. H.
- Affiliations
- Universität Trier (DE)
- ORCID
- Brody, Stuart
- Venue
- Psychopharmacology
- Published
- 2001-11-20
- Volume
- 159
- Issue
- 3
- Pages
- 319-324
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2131218255
- Cited by
- 127
- References
- 44
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 14 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universität Trier
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- high-dose ascorbic acid, vitamin C, blood pressure, cortisol, acute psychological stress, stress reactivity, Trier Social Stress Test, plasma ascorbic acid levels, ACTH response, young adults
- MeSH terms
- Adult, Analysis of Variance, Antioxidants, Ascorbic Acid, Blood Pressure, Delayed-Action Preparations, Double-Blind Method, Female, Humans, Hydrocortisone, Male, Stress, Psychological, Chi-Square Distribution
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