Phase I clinical trial of i.v. ascorbic acid in advanced malignancy
Open accessAbstract
Background Ascorbic acid is a widely used and controversial alternative cancer treatment. In millimolar concentrations, it is selectively cytotoxic to many cancer cell lines and has in vivo anticancer activity when administered alone or together with other agents. We carried out a dose-finding phase I and pharmacokinetic study of i.v. ascorbic acid in patients with advanced malignancies.Patients and methods Patients with advanced cancer or hematologic malignancy were assigned to sequential cohorts infused with 0.4, 0.6, 0.9 and 1.5 g ascorbic acid/kg body weight three times weekly.Results Adverse events and toxicity were minimal at all dose levels. No patient had an objective anticancer response.Conclusions High-dose i.v. ascorbic acid was well tolerated but failed to demonstrate anticancer activity when administered to patients with previously treated advanced malignancies. The promise of this approach may lie in combination with cytotoxic or other redox-active molecules.
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A phase I study found that infusing 100 g of vitamin C intravenously safely produced ascorbate levels of 25-30 mM.
“a phase I clinical study revealed that ascorbate concentrations could safely reach 25–30 mM with intravenous infusion of 100 g of vitamin C98.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [98]
That study kept plasma levels near 10 mM for at least four hours, which preclinical work suggests is enough to slow cancer cell growth.
“plasma concentrations around 10 mM were sustained for at least 4 hours, which, on the basis of preclinical studies, is sufficient to slow the growth of cancer cells.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [98]
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Self-citation
- Authors
- Hoffer, L. J., Levine, M., Assouline, S., Melnychuk, D., Padayatty, S. J., Rosadiuk, K., Rousseau, C., Robitaille, L., & Miller, W. H.
- Affiliations
- Jewish General Hospital (CA)
- National Institutes of Health (US)
- Corresponding author
- Hoffer, L.J.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 19
- Issue
- 11
- Pages
- 1969-1974
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2133373817
- Cited by
- 375
- References
- 36
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 19 · 2023: 18 · 2022: 30 · 2021: 19 · 2020: 28 · 2019: 27 · 2018: 31 · 2017: 20 · 2016: 15 · 2015: 29 · 2014: 27 · 2013: 28 · 2012: 15
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Lotte and John Hecht Memorial Foundation
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- vitamin C, advanced cancer, hematologic malignancies, dose escalation, pharmacokinetics, toxicity, anticancer activity, redox-active molecules, combination therapy
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antioxidants, Ascorbic Acid, Dose-Response Relationship, Drug, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Neoplasms
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