The Pharmacokinetics of Vitamin C
Open accessAbstract
The pharmacokinetics of vitamin C (vitC) is indeed complex. Regulated primarily by a family of saturable sodium dependent vitC transporters (SVCTs), the absorption and elimination are highly dose-dependent. Moreover, the tissue specific expression levels and subtypes of these SVCTs result in a compartmentalized distribution pattern with a diverse range of organ concentrations of vitC at homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. The homeostasis of vitC is influenced by several factors, including genetic polymorphisms and environmental and lifestyle factors such as smoking and diet, as well as diseases. Going from physiological to pharmacological doses, vitC pharmacokinetics change from zero to first order, rendering the precise calculation of dosing regimens in, for example, cancer and sepsis treatment possible. Unfortunately, the complex pharmacokinetics of vitC has often been overlooked in the design of intervention studies, giving rise to misinterpretations and erroneous conclusions. The present review outlines the diverse aspects of vitC pharmacokinetics and examines how they affect vitC homeostasis under a variety of conditions.
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Most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations and compared to other vitamins.
“Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 2.1 reports intracellular vitamin C concentrations of about 0.5–10 mM, versus 50–80 µM in the plasma of healthy individuals. It does not compare those concentrations with other vitamins, so that part of the sentence is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredErythorbic acid, a poor substrate of SVCT1, reaches similar plasma concentrations as vitamin C.
“This can be supported by the fact that its isomer, erythorbic acid, which is a poor substrate of SVCT1, reaches similar plasma concentrations as vitamin C [52].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 2.1 (Oral Route of Administration; page not provided) says erythorbic acid is poorly transported by epithelial SVCT1. It reports similar times to maximal plasma concentration after oral administration, not similar plasma concentrations; that part of the claim is unsupported. (LLM, conf=0.90)
Experimental — accuracy not yet measuredDehydroascorbic acid can be transported through the basolateral membrane of GIT cells by glucose transporters.
“Dehydroascorbic acid can be again transported through the basolateral membrane of these cells by glucose transporters [52].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
The Oral Route of Administration section says DHA can be transported by glucose transporters. It does not establish transport across the basolateral membrane of intestinal cells; instead, it says efflux to the blood through glucose transporters is unlikely to contribute significantly because intracellular vitamin C is kept reduced. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSmoking decreases vitamin C plasma levels on average by 25-50%.
“Smoking decreases the plasma level of vitamin C on an average by 25–50% [52,61,63].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 3.2 (Smoking; page unavailable) says active smoking typically depletes the vitamin C pool by 25–50% compared with never-smokers. That supports the magnitude and direction, but the passage does not specify a 25–50% decrease in plasma levels. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe Michaelis constant Km for vitamin C transport by SVCT1 was reported to be in a wide range from 10 to 200 μM, suggesting a large capacity to absorb dietary vitamin C.
“The Michaelis constant Km, i.e., the concentration of vitamin C transported by half of the maximal transport velocity, was reported to be in a wide range from 10 to 200 µM, suggesting a large capacity to absorb dietary vitamin C.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
The Oral Route of Administration section describes SVCT1 as a high-capacity intestinal vitamin C transporter, supporting the absorption point. It reports a Km of about 65–252 µM, however, not the claimed 10–200 µM range. (LLM, conf=0.88)
Experimental — accuracy not yet measured
The need for vitamin C in smokers is higher, but available studies suggested different recommendations ranging from 35 to 200 mg of additional vitamin C/day.
“The need for vitamin C in smokers is higher, but the available studies suggested different recommendations ranging from 35 to 200 mg of additional vitamin C/day needed for smokers [52].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 3.2 (Smoking) reports that smokers have poorer vitamin C status and cites estimates of 35 mg and 130 mg *additional* vitamin C per day. It also reports recommendations of at least 200 mg per day, but those are for total intake, not 200 mg additional per day. The upper end of the claimed range is therefore not supported as stated. (LLM, conf=0.90)
Experimental — accuracy not yet measuredEx-smoking seems to slightly decrease vitamin C plasma levels as well.
“Ex-smoking seems to slightly decrease the levels as well [52,60].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
The Smoking section reports a difference in vitamin C levels between ex-smokers and never-smokers and says cessation restores only part of the depletion associated with smoking. It does not specify the size of the ex-smoker difference or identify those levels as plasma measurements, so the claim’s ‘slightly’ and ‘plasma’ qualifiers are not established. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThere are reports that vitamin C can pass through the blood-brain barrier in the form of dehydroascorbic acid through the glucose transporter GLUT1.
“There are also reports that vitamin C can pass through the blood-brain barrier in the form of dehydroascorbic acid through the glucose transporter GLUT1 [52,53,73].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 2.1 states that glucose transporters, including GLUT1, can transport dehydroascorbic acid. But it describes vitamin C entry into the brain as occurring primarily through SVCT2 in the choroid plexus; it does not report dehydroascorbic acid crossing the blood-brain barrier through GLUT1. (LLM, conf=0.84)
Experimental — accuracy not yet measuredVitamin C reaches a concentration between 0.5-5 mM in most cells, except erythrocytes, which do not express SVCT2 and have cytosolic levels reflecting plasma levels of about 50 μM.
“Vitamin C reaches a concentration between 0.5–5 mM in most cells with the exception of erythrocytes, which do not express SVCT2, and, hence, their cytosolic levels reflect plasma levels and are about 50 µM [52,55,68,71].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 2.1 (Oral Route of Administration; page unavailable) says intracellular vitamin C concentrations range from about 0.5 to 10 mM, not 0.5 to 5 mM. It also says erythrocytes lack SVCTs and maintain intracellular concentrations similar to plasma, reported as 50–80 µM. The erythrocyte exception is supported, but the stated range for other cells does not match. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe elimination half-life of vitamin C is generally about 2 h.
“The elimination half-life of vitamin C is generally about 2 h [52].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 2.2.2 (Metabolism and Excretion) reports an elimination half-life of about 2 hours specifically after high-dose intravenous infusion is discontinued. The claim omits that condition and presents the figure as generally applicable; Section 2.1.5 describes vitamin C pharmacokinetics as nonlinear and dose-dependent. (LLM, conf=0.90)
Experimental — accuracy not yet measuredDehydroascorbic acid is absorbed likely through glucose transporters, and glucose decreases absorption of dehydroascorbic acid.
“The oxidized form of vitamin C, dehydroascorbic acid, is absorbed likely through glucose transporters, and glucose decreases absorption of dehydroascorbic acid.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Vitamin C is taken up by cells via SVCT2.
“Vitamin C is taken up by the cells via SVCT2 (SLC23A2, Figure 2C), which is a close analogue of SVCT1 with which it shares 65% sequence homology.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Erythrocytes are very active in mediating the reduction of dehydroascorbic acid.
“Erythrocytes are very active in mediating this reduction [6,52].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Passive diffusion of vitamin C in urine was suggested but apparently plays a minor, if any, role.
“Since the pH of urine is also lower, passive diffusion was suggested but apparently plays a minor, if any, role at all [52,53].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
SVCT1 activity is highest at a neutral pH and drops markedly with increasing acidity.
“Its activity is highest at a neutral pH. It drops markedly with increasing acidity [51,52,53,54].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 2.1 describes SVCT1-mediated vitamin C uptake and discusses how pH changes the ionization of ascorbic acid and its possible passive diffusion. It does not say that SVCT1 activity peaks at neutral pH or declines with acidity (searched for neutral pH and pH-dependent SVCT1 activity). (LLM, conf=0.72)
Experimental — accuracy not yet measuredThe contribution of dehydroascorbic acid to total vitamin C absorption is probably low.
“In any case, the contribution of dehydroascorbic acid to the total vitamin C absorption is probably low [52].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [52]
Section 2.1.1 (Absorption; page unavailable) says DHA and ascorbate have similar bioavailability as vitamin C sources and that intestinal DHA concentrations may be relatively high. It does not estimate DHA’s share of total vitamin C absorption or say that share is probably low (searched for DHA’s contribution and dietary amounts). (LLM, conf=0.74)
Experimental — accuracy not yet measured
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- Authors
- Lykkesfeldt, J., & Tveden-Nyborg, P.
- Affiliations
- University of Copenhagen (DK)
- Faculty of Health and Medical Sciences, Department of Veterinary and Animal Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark
- Corresponding author
- Lykkesfeldt, Jens
- ORCID
- Lykkesfeldt, Jens
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2019-10-09
- Volume
- 11
- Issue
- 10
- Pages
- 2412
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC6835439
- OpenAlex
- W2979508643
- Cited by
- 344
- References
- 123
- Citations by year
- 2026: 43 · 2025: 46 · 2024: 46 · 2023: 63 · 2022: 64 · 2021: 53 · 2020: 29
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- vitamin C, pharmacokinetics, sodium-dependent vitamin C transporters, dose-dependent absorption, tissue distribution, genetic polymorphism, smoking, diet, cancer therapy, sepsis treatment, dosing regimen
- MeSH terms
- Ascorbic Acid, Ascorbic Acid Deficiency, Diffusion, Female, Homeostasis, Humans, Intestinal Absorption, Nutritional Requirements, Pregnancy, Smoking, Tissue Distribution, Sodium-Coupled Vitamin C Transporters
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