Vitamin C fails to protect amino acids and lipids from oxidation during acute inflammation
Abstract
The observation that antioxidant vitamins fail to confer protective benefits in large, well-designed randomized clinical trials has led many to question the role of oxidative stress in the pathogenesis of disease. However, there is little evidence that proposed antioxidants actually scavenge reactive intermediates in vivo. Ascorbate reacts rapidly with oxidants produced by activated neutrophils in vitro, and neutrophils markedly increase their oxidant production when mice are infected intraperitoneally with the gram-negative bacterium Klebsiella pneumoniae. To explore the antioxidant properties of ascorbate in vivo, we therefore used K. pneumoniae infection as a model of oxidative stress. When mice deficient in L-gulono-gamma-lactone oxidase (Gulo(-/-)), the rate-limiting enzyme in ascorbate synthesis, were depleted of ascorbate and infected with K. pneumoniae, they were three times as likely as ascorbate-replete Gulo(-/-)mice to die from infection. Mass spectrometric analysis of peritoneal lavage fluid revealed a marked increase in the levels of oxidized amino acids and of F2-isoprostanes (sensitive and specific markers of lipid oxidation) in infected animals. Surprisingly, there were no significant differences in the levels of the oxidation products in the ascorbate-deficient and -replete Gulo(-/-)mice. Our observations suggest that ascorbate plays a previously unappreciated role in host defense mechanisms against invading pathogens but that the vitamin does not protect amino acids and lipids from oxidative damage during acute inflammation. To examine the oxidation hypothesis of disease, optimal antioxidant regimens that block oxidative reactions in animals and humans need to be identified.
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The involvement of vitamin C as an endogenous antioxidant (e.g., scavenger of ROS) is still a matter of debate.
“The involvement of vitamin C as an endogenous antioxidant, e.g., scavenger of ROS, is still a matter of debate.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [155]
The role of vitamin C as an antioxidant has been clearly and repeatedly demonstrated in vitro, but in vivo the situation is less clear.
“Its role has been clearly and repeatedly demonstrated in vitro, but in vivo, the situation is less clear [5,6,154,155,156].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [155]
Patients with infections have lower levels of vitamin C.
“Patients with infections have lower levels of vitamin C”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [155]
Animal models have largely shown a protective effect of vitamin C on different infections or intoxications with bacterial toxins.
“and animal models have largely shown a protective effect of vitamin C on different infections or intoxications with bacterial toxins [155,195].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [155]
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“A mouse study demonstrated that after challenge with the bacteria Klebsiella pneumonia to induce a sepsis-like state, a 3-fold higher mortality is observed in ascorbate-deficient animals compared to controls [89].”
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Vitamin C Deficiency Fails to Protect Mice from Malaria
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A REVIEW ON ANTIOXIDANT VITAMIN C AND ITS IMPACT ON SKIN HEALTH
Behera, P., Sharma, A., BISWAL, S., MOHARANA, S., Biswal, P. K., & Panda, B. B. (2025) · Innovare Journal of Medical Sciences · doi:10.22159/ijms.2025v13i5.55899
- Authors
- Gaut, J. P., Belaaouaj, A., Byun, J., Roberts, L. J., Maeda, N., Frei, B., & Heinecke, J. W.
- Affiliations
- Washington University in St. Louis (US)
- Inserm (FR)
- University of Washington (US)
- Vanderbilt University (US)
- University of North Carolina at Chapel Hill (US)
- Oregon State University (US)
- Corresponding author
- Heinecke, Jay W.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 40
- Issue
- 9
- Pages
- 1494-1501
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W1972038765
- Cited by
- 48
- References
- 47
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 6 · 2013: 3
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Federation for Aging Research
- National Institutes of Health
- National Institute on Aging (AG021191, R01AG021191)
- National Heart, Lung, and Blood Institute (P50HL073996, P01HL030086, P01HL060886, P01 HL60886)
- National Institute of General Medical Sciences (R37 GM42056, R37GM042056)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 02456)
- National Institute of Environmental Health Sciences (ES007033, P30ES007033)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- vitamin C, oxidative stress, acute inflammation, neutrophils, Klebsiella pneumoniae infection, L-gulono-γ-lactone oxidase, ascorbate deficiency, F2-isoprostanes, lipid oxidation, host defense against infection, antioxidants
- MeSH terms
- Amino Acids, Animals, Antioxidants, Ascorbic Acid, Inflammation, Klebsiella Infections, Klebsiella pneumoniae, Oxidation-Reduction, Lipid Peroxidation, Mice, Knockout, Sepsis, L-Gulonolactone Oxidase, Mice
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