Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum
Abstract
We investigated whether circulating ascorbic acid in humans is protein bound or free and whether ascorbic acid exists in its reduced form alone as ascorbic acid or in its reduced and oxidized forms as ascorbic acid and dehydroascorbic acid, respectively. Ascorbic acid and dehydroascorbic acid were determined by using HPLC with coulometric electrochemical detection, and protein binding was determined by centrifugal ultrafiltration. Ascorbic acid was free in plasma and serum of normal, healthy volunteers, 10 men and 10 women. Ascorbic acid was detectable only in its reduced form. However, dehydroascorbic acid could be made to appear in samples processed under oxidizing conditions. Because circulating ascorbic acid is free and is detected only as reduced vitamin, ascorbic acid may be available without intermediates for peripheral utilization. Dehydroascorbic acid may not be present in plasma and serum of normal humans unless assay conditions permit ascorbic acid oxidation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is no difference between serum and plasma vitamin C levels.
“There is no difference between serum and plasma [59,60,61,62,63].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [62]
The plasma levels of dehydroascorbic acid are very low in healthy humans, while ascorbyl radical is undetectable.
“The plasma levels of dehydro-ascorbic acid are very low in healthy humans, while that of an ascorbyl radical are undetectable [6,53,54,62,67].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [62]
Vitamin C is not bound to plasma proteins.
“Vitamin C is not bound to plasma proteins [62].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [62]
Cites
New Concepts in the Biology and Biochemistry of Ascorbic Acid
Flier, J. S., Underhill, L. H., & Levine, M. (1986) · New England Journal of Medicine · doi:10.1056/nejm198604033141407 · Cited by 646 · see citing works
Self-citationAn improved method for determination of l-ascorbic acid and l-dehydroascorbic acid in blood plasma
Masato, O. (1980) · Clinica Chimica Acta · doi:10.1016/0009-8981(80)90144-8 · Cited by 353 · see citing works
Bergsten, P., Amitai, G., Kehrl, J. H., Dhariwal, K. R., Klein, H. G., & Levine, M. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39841-2 · Cited by 199 · see citing works
Self-citationAscorbic Acid Transport and Accumulation in Human Neutrophils
Washko, P., Rotrosen, D., & Levine, M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47256-6 · Cited by 193 · see citing works
Self-citationAscorbic acid metabolism in diabetes mellitus
Som, S., Basu, S., Mukherjee, D., Deb, S., Choudhury, P. R., Mukherjee, S., Chatterjee, S. N., & Chatterjee, I. B. (1981) · Metabolism · doi:10.1016/0026-0495(81)90133-5 · Cited by 191 · see citing works
McLaren, D. S. (1982) · Biochemical Society Transactions · doi:10.1042/bst0100435a · Cited by 173 · see citing works
Vitamin C: Its Molecular Biology and Medical Potential
Scrutton, M. C. (1977) · FEBS Letters · doi:10.1016/0014-5793(77)80679-0 · Cited by 166 · see citing works
Lunec, J., & Blake, D. (1985) · Free Radical Research Communications · doi:10.3109/10715768509056534 · Cited by 144 · see citing works
Washko, P. W., Hartzell, W. O., & Levine, M. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90243-1 · Cited by 105 · see citing works
Self-citationEnhancement of norepinephrine biosynthesis by ascorbic acid in cultured bovine chromaffin cells.
Levine, M., Morita, K., & Pollard, H. B. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38816-6 · Cited by 78 · see citing works
Self-citationUPTAKE AND REDUCTION OF OXIDIZED AND REDUCED ASCORBATE BY HUMAN LEUKOCYTES
Bigley, R. H., & Stanková, L. (1974) · The Journal of Experimental Medicine · doi:10.1084/jem.139.5.1084 · Cited by 73 · see citing works
THE MECHANISM OF THE EXCRETION OF VITAMIN C BY THE HUMAN KIDNEY 1
Ralli, E. P., FRIEDMAN, G. J., & Rubin, S. H. (1938) · Journal of Clinical Investigation · doi:10.1172/jci101006 · Cited by 69 · see citing works
FRIEDMAN, G. J., Sherry, S., & Ralli, E. P. (1940) · Journal of Clinical Investigation · doi:10.1172/jci101171 · Cited by 65 · see citing works
Dhariwal, K. R., Washko, P. W., & Levine, M. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90037-a · Cited by 57 · see citing works
Self-citationRegulation of peptide amidation in cultured pituitary cells.
May, V., & Eipper, B. A. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36224-5 · Cited by 52 · see citing works
Ascorbic acid within chromaffin granules
Dhariwal, K. R., Washko, P., Hartzell, W. O., et al. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84842-1 · Cited by 46 · see citing works
Self-citationBlood Dehydroascorbic Acid and Diabetes Mellitus in Human Beings
Banerjee, A. (1982) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/000456328201900201 · Cited by 43 · see citing works
The effect of cortisone and adrenocorticotropic hormone on the dehydroascorbic acid of human plasma
Stewart, C. P., Horn, D. B., & Robson, J. S. (1953) · Biochemical Journal · doi:10.1042/bj0530254 · Cited by 40 · see citing works
The measurement of dehydroascorbic acid and diketogulonic acid in normal and diabetic plasma
Cox, B. D., & Whichelow, M. J. (1975) · Biochemical Medicine · doi:10.1016/0006-2944(75)90110-6 · Cited by 27 · see citing works
Human Utilization of Dehydroascorbic Acid
Sabry, J. H., Fisher, K. H., & Dodds, M. L. (1958) · Journal of Nutrition · doi:10.1093/jn/64.3.457 · Cited by 26 · see citing works
Ramu, A., Levine, M. A., & Pollard, H. B. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.8.2107 · Cited by 22 · see citing works
Self-citationPlasma Levels of Vitamin C Components in Normal and Diabetic Subjects
Newill, A., Habibzadeh, N., Bishop, N., & Schorah, C. J. (1984) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/000456328402100608 · Cited by 15 · see citing works
A SIMPLE ULTRAFILTRATION APPARATUS
Coolidge, T. B. (1940) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)73123-2 · Cited by 12 · see citing works
Heinemann, M. (1941) · Journal of Clinical Investigation · doi:10.1172/jci101240 · Cited by 10 · see citing works
FAILURE TO FIND BOUND ASCORBIC ACID IN PLASMA
Sargent, F., & Golden, R. L. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77751-5 · Cited by 7 · see citing works
Blood Plasma Ascorbic Acid Levels on Controlled Intakes of Ascorbic Acid
Dodds, M. L., & MacLeod, F. L. (1947) · Science · doi:10.1126/science.106.2742.67.a · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance
Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K. R., Park, J. B., Lazarev, A., Graumlich, J. F., King, J., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3704 · Cited by 1,325 · see citing works
Self-citationA family of mammalian Na+-dependent L-ascorbic acid transporters
Tsukaguchi, H., Tokui, T., Mackenzie, B., Berger, U. V., Chen, X.-Z., Wang, Y., Brubaker, R. F., & Hediger, M. A. (1999) · Nature · doi:10.1038/19986 · Cited by 882 · see citing works
Vitamin C: The known and the unknown and Goldilocks
Padayatty, S., & Levine, M. (2016) · Oral Diseases · doi:10.1111/odi.12446 · Cited by 753 · see citing works
Self-citationVitamin C function in the brain: Vital role of the ascorbate transporter SVCT2
Harrison, F. E., & May, J. M. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.12.018 · Cited by 661 · see citing works
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
Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin
Shindo, Y., Witt, E., Han, D., Epstein, W., & Packer, L. (1994) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12371744 · Cited by 546 · see citing works
A new recommended dietary allowance of vitamin C for healthy young women
Levine, M., Wang, Y., Padayatty, S. J., & Morrow, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171318198 · Cited by 496 · see citing works
Carr, A. C., Rosengrave, P. C., Bayer, S., Chambers, S., Mehrtens, J., & Shaw, G. M. (2017) · Critical Care · doi:10.1186/s13054-017-1891-y · Cited by 413 · see citing works
Phase I clinical trial of i.v. ascorbic acid in advanced malignancy
Hoffer, L. J., Levine, M., Assouline, S., Melnychuk, D., Padayatty, S. J., Rosadiuk, K., Rousseau, C., Robitaille, L., & Miller, W. H. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn377 · Cited by 375 · see citing works
Self-citationShindo, Y., Witt, E., & Packer, L. (1993) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12469048 · Cited by 363 · see citing works
Role of Vitamin C in the Function of the Vascular Endothelium
May, J. M., & Harrison, F. E. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5205 · Cited by 358 · see citing works
Sotiriou, S., Gispert, S., Cheng, J., Wang, Y., Chen, A., Hoogstraten-Miller, S., Miller, G. F., Kwon, O., Levine, M., Guttentag, S. H., et al. (2002) · Nature Medicine · doi:10.1038/0502-514 · Cited by 367 · see citing works
Self-citationRhie, G.-E., Shin, M. H., Seo, J. Y., Choi, W. W., Cho, K. H., Kim, K. H., Park, K. C., Eun, H. C., & Chung, J. H. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01469.x · Cited by 274 · see citing works
Vitamin C transport systems of mammalian cells
Liang, W.-J., Johnson, D., & Jarvis, S. M. (2001) · Molecular Membrane Biology · doi:10.1080/09687680110033774 · Cited by 255 · see citing works
Erythrocyte Glut1 Triggers Dehydroascorbic Acid Uptake in Mammals Unable to Synthesize Vitamin C
Montel-Hagen, A., Kinet, S., Manel, N., Mongellaz, C., Prohaska, R., Battini, J.-L., Delaunay, J., Sitbon, M., & Taylor, N. (2008) · Cell · doi:10.1016/j.cell.2008.01.042 · Cited by 243 · see citing works
Shindo, Y., Witt, E., Han, D., & Packer, L. (1994) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12373027 · Cited by 234 · see citing works
Fuchs, J., & Kern, H. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00132-4 · Cited by 200 · see citing works
Potential Mechanisms of Action for Vitamin C in Cancer: Reviewing the Evidence
Vissers, M. C. M., & Das, A. B. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00809 · Cited by 188 · see citing works
Vitamin C transport and its role in the central nervous system
May, J. M. (2012) · Subcellular Biochemistry · doi:10.1007/978-94-007-2199-9_6 · Cited by 186 · see citing works
Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion
Graumlich, J. F., Ludden, T. M., Conry-Cantilena, C., Cantilena, L. R., Wang, Y., & Levine, M. (1997) · Pharmaceutical Research · doi:10.1023/a:1012186203165 · Cited by 172 · see citing works
Self-citationCorpe, C. P., Tu, H., Eck, P., Wang, J., Faulhaber-Walter, R., Schnermann, J., Margolis, S., Padayatty, S., Sun, H., Wang, Y., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39191 · Cited by 162 · see citing works
The sodium-dependent ascorbic acid transporter family SLC23
Bürzle, M., Suzuki, Y., Ackermann, D., Miyazaki, H., Maeda, N., Clémençon, B., Burrier, R., & Hediger, M. A. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.12.002 · Cited by 158 · see citing works
Regulation of vitamin C homeostasis during deficiency
Lindblad, M., Tveden-Nyborg, P., & Lykkesfeldt, J. (2013) · Nutrients · doi:10.3390/nu5082860 · Cited by 151 · see citing works
Determination of optimal vitamin C requirements in humans
Levine, M., Dhariwal, K., Welch, R., Wang, Y., & Park, J. (1995) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.6.1347s · Cited by 149 · see citing works
Self-citationThiele, J. J., Traber, M. G., Tsang, K., Cross, C. E., & Packer, L. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00617-x · Cited by 138 · see citing works
Synthetic or food-derived vitamin C—Are they equally bioavailable?
Carr, A., & Vissers, M. (2013) · Nutrients · doi:10.3390/nu5114284 · Cited by 137 · see citing works
6-Bromo-6-deoxy-l-ascorbic Acid
Corpe, C. P., Lee, J.-H., Kwon, O., Eck, P., Narayanan, J., Kirk, K. L., & Levine, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412925200 · Cited by 95 · see citing works
Self-citationKARLSEN, A., BLOMHOFF, R., & GUNDERSEN, T. (2005) · Journal of Chromatography B · doi:10.1016/j.jchromb.2005.07.008 · Cited by 94 · see citing works
Pullar, J., Bayer, S., & Carr, A. (2018) · Antioxidants · doi:10.3390/antiox7020029 · Cited by 92 · see citing works
A simple method for plasma total vitamin C analysis suitable for routine clinical laboratory use
Robitaille, L., & Hoffer, L. J. (2015) · Nutrition Journal · doi:10.1186/s12937-016-0158-9 · Cited by 88 · see citing works
Mechanisms of ascorbic acid recycling in human erythrocytes
May, J. M., Qu, Z.-C., & Morrow, J. D. (2001) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(01)00188-x · Cited by 81 · see citing works
Erichsen, H. C., Engel, S. A. M., Eck, P. K., Welch, R., Yeager, M., Levine, M., Siega-Riz, A. M., Olshan, A. F., & Chanock, S. J. (2006) · American Journal of Epidemiology · doi:10.1093/aje/kwj035 · Cited by 79 · see citing works
Self-citationBozonet, S. M., & Carr, A. C. (2019) · Nutrients · doi:10.3390/nu11061363 · Cited by 63 · see citing works
Tu, H., Wang, Y., Li, H., Brinster, L. R., & Levine, M. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.08.017 · Cited by 35 · see citing works
Self-citationErichsen, H. C., Peters, U., Eck, P., Welch, R., Schoen, R. E., Yeager, M., Levine, M., Hayes, R. B., & Chanock, S. (2008) · Nutrition and Cancer · doi:10.1080/01635580802033110 · Cited by 36 · see citing works
Self-citationAssociations among plasma vitamin C, epidermal ceramide and clinical severity of atopic dermatitis
Shin, J., Kim, Y. J., Kwon, O., Kim, N.-I., & Cho, Y. (2016) · Nutrition Research and Practice · doi:10.4162/nrp.2016.10.4.398 · Cited by 35 · see citing works
Effects of erythorbic acid on vitamin C metabolism in young women
Sauberlich, H., Tamura, T., Craig, C., Freeberg, L., & Liu, T. (1996) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/64.3.336 · Cited by 22 · see citing works
Ascorbic acid and reaction kinetics in situ: A new approach to vitamin requirements
LEVINE, M., DHARIWAL, K. R., WASHKO, P., WELCH, R., WANG, Y.-H., CANTILENA, C. C., & Yu, R. (1992) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.38.special_169 · Cited by 13 · see citing works
Self-citation
- Authors
- Dhariwal, K., Hartzell, W., & Levine, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Levine, M
- ORCID
- Levine, M
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 1991-10
- Volume
- 54
- Issue
- 4
- Pages
- 712-716
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W1835099507
- Cited by
- 262
- References
- 26
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 10 · 2014: 11 · 2013: 8 · 2012: 7
- FWCI
- 11.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Clinical 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 › Rheumatology › Folate and B Vitamins Research
- Keywords
- vitamin C, dehydroascorbic acid, plasma, serum, protein binding, vitamin C metabolism
- MeSH terms
- Adult, Ascorbic Acid, Blood Proteins, Chromatography, High Pressure Liquid, Dehydroascorbic Acid, Electrochemistry, Female, Humans, Male, Middle Aged, Oxidation-Reduction, Protein Binding, Ultrafiltration
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
