Plasma-Saturating intakes of vitamin C confer maximal antioxidant protection to plasma
Abstract
OBJECTIVE: Supplemental vitamin C has been shown to reduce oxidative damage in vivo, yet the dose-response relationship between vitamin C intake and antioxidant protection is not known. This report examined blood indicators of oxidative stress in subjects consuming graded doses of vitamin C, from 75 to 2,000 mg/day. METHODS: Ten healthy, non-smoking men and women (26.1 +/- 2.1 years) were recruited from a campus population. During the ten-week study, subjects limited fruit and vegetable consumption (< or = 3 servings/day) and consumed a multivitamin and mineral pill daily. Beginning at week 3, subjects ingested either a vitamin C (n = 8) or placebo (n = 2) capsule, which were identical in appearance and taste. The content of the vitamin C capsule increased every two weeks (from 250 mg at weeks 3-4 to 500 mg, 1,000 mg. and 2,000 mg at weeks 5-6. 7-8. 9-10, respectively). Fasting blood samples were collected at two-week intervals and analyzed for vitamin C, total lipid hydroperoxides and Heinz bodies in packed erythrocytes incubated 24 hours at 37 degrees. RESULTS: Plasma vitamin C rose 55% in vitamin C-supplemented subjects by the end of the ten-week treatment (p < 0.05), and measures of oxidative stress decreased 60% to 90% (8.1 +/- 0.6 to 3.5 +/- 0.4 nmol/mL and 69.1 +/- 7.8% to 6.7 +/- 6.0% for total lipid hydroperoxides and Heinz bodies, respectively). Significant decreases in markers of oxidative stress were noted at the 500 mg, 1,000 mg and 2,000 mg dosages versus placebo. Antioxidant protection was similar at the 1,000 mg and 2,000 mg dosage. CONCLUSIONS: These data indicate that the antioxidant protection afforded by short-term vitamin C supplementation is maximal at the 500-1,000 mg dosage range.
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Higher doses of vitamin C can behave as a prooxidant.
“Higher doses of vitamin C can behave as a prooxidant [156,168,169]”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [156]
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 [156]
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 [156]
A single oral dose of vitamin C of 5-10 g produces transient osmotic diarrhea and/or abdominal bloating with pain but, otherwise, even such a high dose is considered to be safe.
“A single oral dose of vitamin C of 5–10 g produces transient osmotic diarrhea and/or abdominal bloating with pain but, otherwise, even such a high dose is considered to be safe.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [156]
Cites
Oxidants, antioxidants, and the degenerative diseases of aging.
Ames, B. N., Shigenaga, M. K., & Hagen, T. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7915 · Cited by 5,958 · see citing works
[1] Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids
Omaye, S. T., Turnbull, J. D., & Sauberlich, H. E. (1979) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(79)62181-x · Cited by 1,815 · see citing works
Carr, A. C., & Frei, B. (1999) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.6.1086 · Cited by 940 · see citing works
Correa, P. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.23.1881 · Cited by 734 · see citing works
Simple Assay for the Level of Total Lipid Peroxides in Serum or Plasma
Yagi, K. (2003) · Humana Press eBooks · doi:10.1385/0-89603-472-0:101 · Cited by 540 · see citing works
Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins
Abuja, P. M., & Albertini, R. (2001) · Clinica Chimica Acta · doi:10.1016/s0009-8981(01)00393-x · Cited by 454 · see citing works
Christen, W. G., Gaziano, J. M., & Hennekens, C. H. (2000) · Annals of Epidemiology · doi:10.1016/s1047-2797(99)00042-3 · Cited by 377 · see citing works
Oxidative stress and antioxidants in epilepsy
Sudha, K., Rao, A. V., & Rao, A. (2001) · Clinica Chimica Acta · doi:10.1016/s0009-8981(00)00337-5 · Cited by 355 · see citing works
GEY, K. F., Moser, U., Jordan, P., Stähelin, H., Eichholzer, M., & Lüdin, E. (1993) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/57.5.787s · Cited by 305 · see citing works
Relationships between plasma measures of oxidative stress and metabolic control in NIDDM
Nourooz-Zadeh, J., Rahimi, A., Tajaddini-Sarmadi, J., Tritschler, H., Rosen, P., Halliwell, B., & Betteridge, D. J. (1997) · Diabetologia · doi:10.1007/s001250050729 · Cited by 303 · see citing works
Allard, J. P., Aghdassi, E., Chau, J. F. L., Tam, C., Kovacs, C. M., Salit, I. E., & Walmsley, S. L. (1998) · AIDS · doi:10.1097/00002030-199813000-00013 · Cited by 275 · see citing works
Effects of Vitamin E on Lipid Peroxidation in Healthy Persons
Meagher, E. A. (2001) · JAMA · doi:10.1001/jama.285.9.1178 · Cited by 269 · see citing works
Vitamin E and Alzheimer disease: the basis for additional clinical trials
Grundman, M. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.2.630s · Cited by 267 · see citing works
Lykkesfeldt, J., Christen, S., Wallock, L. M., Chang, H., Jacob, R. A., & Ames, B. N. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.2.530 · Cited by 230 · see citing works
Rehman, A., Collis, C. S., Yang, M., Kelly, M., Diplock, A. T., Halliwell, B., & Rice-Evans, C. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8592 · Cited by 202 · see citing works
Lehr, H. A., Frei, B., & Arfors, K. E. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7688 · Cited by 167 · see citing works
The Linxian trials: mortality rates by vitamin-mineral intervention group
Blot, W., Li, J., Taylor, P., Guo, W., Dawsey, S., & Li, B. (1995) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.6.1424s · Cited by 148 · see citing works
Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia
Sinclair, A. J., Bayer, A. J., Johnston, J., Warner, C. A., & Maxwell, S. R. J. (1998) · International Journal of Geriatric Psychiatry · doi:10.1002/(sici)1099-1166(1998120)13:12 · Cited by 143 · see citing works
Vitamin E and vascular homeostasis: implications for atherosclerosis
Keaney, J. F., Simon, D. I., & Freedman, J. E. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.9.965 · Cited by 141 · see citing works
The Effects of Vitamin C Supplementation on Protein Oxidation in Healthy Volunteers
Carty, J. L., Bevan, R. J., Waller, H. L., Mistry, N., Cooke, M. S., Lunec, J., & Griffiths, H. R. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3014 · Cited by 134 · see citing works
Long-term vitamin C supplement use and prevalence of early age-related lens opacities
Jacques, P. F., Taylor, A., Hankinson, S., Willett, W. C., Mahnken, B., Lee, Y., Vaid, K., & Lahav, M. (1997) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/66.4.911 · Cited by 133 · see citing works
Marchioli, R. (1999) · Pharmacological Research · doi:10.1006/phrs.1999.0480 · Cited by 130 · see citing works
Vitamin C elevates red blood cell glutathione in healthy adults
Johnston, C. S., Meyer, C. G., & SRILAKSHMI, J. C. (1993) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/58.1.103 · Cited by 125 · see citing works
Self-citationJain, S. K., McVie, R., & Smith, T. (2000) · Diabetes Care · doi:10.2337/diacare.23.9.1389 · Cited by 123 · see citing works
A secondary prevention trial of antioxidant vitamins and cardiovascular disease in women
Manson, J. E., Gaziano, J. M., Spelsberg, A., Ridker, P. M., Cook, N. R., Buring, J. E., Willett, W. C., & Hennekens, C. H. (1995) · Annals of Epidemiology · doi:10.1016/1047-2797(94)00091-7 · Cited by 121 · see citing works
Vitamin C prevents cigarette smoke–induced oxidative damage in vivo
Panda, K., Chattopadhyay, R., Chattopadhyay, D. J., & Chatterjee, I. B. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00297-5 · Cited by 103 · see citing works
Why Does Ethnicity Affect Prevalence of Gestational Diabetes? The Underwater Volcano Theory
Yue, D. K., Molyneaux, L. M., Ross, G. P., Constantino, M., Child, A., & Turtle, J. R. (1996) · Diabetic Medicine · doi:10.1002/(sici)1096-9136(199608)13:8 · Cited by 102 · see citing works
Biomarkers for Establishing a Tolerable Upper Intake Level for Vitamin C
Johnston, C. S. (1999) · Nutrition Reviews · doi:10.1111/j.1753-4887.1999.tb06926.x · Cited by 76 · see citing works
Self-citationAscorbic acid intake and plasma levels in healthy elderly people
VanderJagt, D. J., Garry, P. J., & BHAGAVAN, H. N. (1987) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/46.2.290 · Cited by 72 · see citing works
Lipid Peroxidation and Antioxidant Status in Human Cervical Carcinoma
Ahmed, M. I., Fayed, S. T., Hossein, H., & Tash, F. (1999) · Disease Markers · doi:10.1155/1999/963176 · Cited by 51 · see citing works
Vitamin C prevents the acute atherogenic effects of passive smoking
Valkonen, M. M., & Kuusi, T. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00260-9 · Cited by 41 · see citing works
Ascorbic acid and erythorbic acid metabolism in nonpregnant women
Sauberlich, H. E., Kretsch, M. J., Taylor, P. C., Johnson, H., & Skala, J. H. (1989) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/50.5.1039 · Cited by 38 · see citing works
Blomberg, A. (2000) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.2000.00814.x · Cited by 38 · see citing works
Antioxidants and Oxidative Stress in Health and Disease: Introduction
Bray, T. Μ. (1999) · Proceedings of The Society for Experimental Biology and Medicine · doi:10.1046/j.1525-1373.1999.d01-135.x · Cited by 36 · see citing works
González, C., D, M. P. S. M., González, E., Rivera, D., Simón, J., Islas, S., & Haffner, S. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1999.tb01792.x · Cited by 29 · see citing works
Antioxidant Vitamins and Coronary Artery Disease Risk in South African Males
Delport, R., Ubbink, J., Human, J. A., Becker, P., Myburgh, D. P., & Vermaak, W. J. H. (1998) · Clinica Chimica Acta · doi:10.1016/s0009-8981(98)00131-4 · Cited by 23 · see citing works
Use of in vitro methaemoglobin generation to study antioxidant status in the diabetic erythrocyte
Coleman, M. D. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(00)00333-6 · Cited by 21 · see citing works
Contribution of epidemiology to understanding relations of diet to age-related cataract
Mares-Perlman, J. A. (1997) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/66.4.739 · Cited by 19 · see citing works
Sato, H., & Miwa, S. (1971) · PubMed · Cited by 3 · see citing works
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Cited by
Sorted by citations
Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination
Doseděl, M., Jirkovský, E., Macáková, K., Krčmová, L., Javorská, L., Pourová, J., Mercolini, L., Remião, F., Nováková, L., Mladěnka, P., et al. (2021) · Nutrients · doi:10.3390/nu13020615 · Cited by 553 · see citing works
Vitamins E and C are safe across a broad range of intakes1,2
Hathcock, J. N., Azzi, A., Blumberg, J. B., Bray, T. Μ., Dickinson, A., Frei, B. B., Jialal, I., Johnston, C. S., Kelly, F. J., Kraemer, K., et al. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.4.736 · Cited by 307 · see citing works
Self-citationMozaffarian, D., Lemaitre, R. N., King, I. B., Song, X., Huang, H., Sacks, F. M., Rimm, E. B., Wang, M., & Siscovick, D. S. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-158-7-201304020-00003 · Cited by 283 · see citing works
Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality
Wu, J. H. Y., Lemaître, R. N., King, I. B., Song, X., Psaty, B. M., Siscovick, D. S., & Mozaffarian, D. (2014) · Circulation · doi:10.1161/circulationaha.114.011590 · Cited by 203 · see citing works
Korantzopoulos, P. G., Kolettis, T. M., Kountouris, E., Dimitroula, V., Karanikis, P., Pappa, E. C., Siogas, K., & Goudevenos, J. A. (2005) · International Journal of Cardiology · doi:10.1016/j.ijcard.2004.12.041 · Cited by 148 · see citing works
Vitamin C: Overview and Update
Schlueter, A. K., & Johnston, C. S. (2011) · Journal of Evidence-Based Complementary & Alternative Medicine · doi:10.1177/1533210110392951 · Cited by 112 · see citing works
Self-citationHigh-Dose Vitamin C in Advanced-Stage Cancer Patients
Zasowska‐Nowak, A., Nowak, P. J., & Ciałkowska-Rysz, A. D. (2021) · Nutrients · doi:10.3390/nu13030735 · Cited by 69 · see citing works
Atrial Fibrillation After Cardiac Surgery: Clinical Update on Mechanisms and Prophylactic Strategies
Raiten, J. M., Ghadimi, K., Augoustides, J. G., Ramakrishna, H., Patel, P. A., Weiss, S. J., & Gutsche, J. T. (2015) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2015.01.001 · Cited by 67 · see citing works
Ghalibaf, M. H. E., Kianian, F., Beigoli, S., Behrouz, S., Marefati, N., Boskabady, M., & Boskabady, M. H. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01169-1 · Cited by 60 · see citing works
Hu, X., Yuan, L., Wang, H., Li, C., Cai, J., Hu, Y.-H., & Ma, C. (2016) · International Journal of Surgery · doi:10.1016/j.ijsu.2016.12.009 · Cited by 55 · see citing works
Ascorbic acid mitigates the myocardial injury after cardiac arrest and electrical shock
Tsai, M., Huang, C., Tsai, C.-Y., Chen, H., Lee, H., Cheng, H., Hsu, C.-Y., Wang, T., Chang, W., & Chen, W. (2011) · Intensive Care Medicine · doi:10.1007/s00134-011-2362-6 · Cited by 48 · see citing works
Nutritional assessment and support during pregnancy
Hamaoui, E., & Hamaoui, M. (2003) · Gastroenterology Clinics of North America · doi:10.1016/s0889-8553(02)00132-2 · Cited by 42 · see citing works
The biochemical basis of antioxidant therapy in critical illness
Eaton, S. D. (2006) · Proceedings of The Nutrition Society · doi:10.1079/pns2006501 · Cited by 40 · see citing works
Moore, A., & Khanna, D. (2023) · Cureus · doi:10.7759/cureus.33740 · Cited by 34 · see citing works
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Mj, G., & Smith, K. (2015) · Cited by 21 · see citing works
Vitamin C and its therapeutic potential in the management of COVID19
Neethu, R. S., Reddy, M. V. N. J., Batra, S., Srivastava, S. K., & Syal, K. (2022) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2022.05.026 · Cited by 22 · see citing works
(EFSA), E. F. S. A. (2004) · EFSA Journal · doi:10.2903/j.efsa.2004.59 · Cited by 17 · see citing works
Atrial Remodeling And Atrial Fibrillation: Mechanistic Interactions And Clinical Implications.
Ghamdi, B. A., & Hassan, W. (2009) · Europe PMC (PubMed Central) · doi:10.4022/jafib.125 · Cited by 15 · see citing works
Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment
Wang, L., Zhu, Y., Huang, C., Pan, Q., Wang, J., Li, H., Huang, Y., Yi, G., Li, Z., Qi, S., et al. (2025) · Genes & Diseases · doi:10.1016/j.gendis.2025.101678 · Cited by 14 · see citing works
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Omae, T., & Inada, E. (2018) · Journal of Anesthesia · doi:10.1007/s00540-018-2478-8 · Cited by 13 · see citing works
Palasuwan, A., Soogarun, S., Wiwanitkit, V., Luechapudiporn, R., Pradniwat, P., & Lertlum, T. (2006) · PubMed · Cited by 9 · see citing works
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Ordman, A. R. (2010) · Health · doi:10.4236/health.2010.28123 · Cited by 6 · see citing works
Project GLEAN: Evaluation of a School-Based, Gleaned-Food Distribution Project
Hampl, J. S., Levinson, S. L., Garcia, L. W., & Johnston, C. S. (2005) · Journal of Sustainable Agriculture · doi:10.1300/j064v25n02_03 · Cited by 5 · see citing works
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Moser, L. R., & Ordman, A. B. (2006) · AGE · doi:10.1007/s11357-006-9000-1 · Cited by 5 · see citing works
Karandish, M., Rahideh, S. T., & Moghaddam, A. (2008) · Journal of Biological Sciences · doi:10.3923/jbs.2008.1333.1337 · Cited by 1 · see citing works
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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
- Johnston, C. S., & Cox, S. K.
- Affiliations
- Arizona State University (US)
- Corresponding author
- Johnston, Carol S.
- ORCID
- Johnston, Carol S.
- Venue
- Journal of the American College of Nutrition
- Publisher
- Informa UK Limited
- Published
- 2001-12
- Volume
- 20
- Issue
- 6
- Pages
- 623-627
- ISSN
- 0731-5724 (ISSN-L)
- 1541-1087
- OpenAlex
- W2050361512
- Cited by
- 31
- References
- 39
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American College of Nutrition (publishedVersion)
- PubMed (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 › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- vitamin C, vitamin C supplementation, dose-response relationship, oxidative stress, antioxidant defense, plasma vitamin C, lipid hydroperoxides, Heinz bodies, erythrocytes, oxidative damage
- MeSH terms
- Adult, Analysis of Variance, Antioxidants, Ascorbic Acid, Female, Heinz Bodies, Humans, Lipid Peroxides, Male, Reference Values, Diet Records, Oxidative Stress, Dietary Supplements
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