NDLI: Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic $Discoveries^{1,2}$

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Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic $Discoveries^{1,2}$

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Levine, Mark Padayatty, Sebastian J. Espey, Michael Graham
Description	Country affiliation: United States Author Affiliation: Levine M ( Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USA. MarkL@mail.nih.gov.)
Abstract	A concentration-function approach to vitamin C (ascorbate) has yielded new physiology and pharmacology discoveries. To determine the range of vitamin C concentrations possible in humans, pharmacokinetics studies were conducted. They showed that when vitamin C is ingested by mouth, plasma and tissue concentrations are tightly controlled by at least 3 mechanisms in healthy humans: absorption, tissue accumulation, and renal reabsorption. A 4th mechanism, rate of utilization, may be important in disease. With ingested amounts found in foods, vitamin C plasma concentrations do not exceed 100 μmol/L. Even with supplementation approaching maximally tolerated doses, ascorbate plasma concentrations are always <250 μmol/L and frequently <150 μmol/L. By contrast, when ascorbate is i.v. injected, tight control is bypassed until excess ascorbate is eliminated by glomerular filtration and renal excretion. With i.v. infusion, pharmacologic ascorbate concentrations of 25–30 mmol/L are safely achieved. Pharmacologic ascorbate can act as a pro-drug for hydrogen peroxide $(H_{2}O_{2})$ formation, which can lead to extracellular fluid at concentrations as high as 200 μmol/L. Pharmacologic ascorbate can elicit cytotoxicity toward cancer cells and slow the growth of tumors in experimental murine models. The effects of pharmacologic ascorbate should be further studied in diseases, such as cancer and infections, which may respond to generation of reactive oxygen species via $H_{2}O_{2}.$
File Format	HTM / HTML
ISSN	21618313
e-ISSN	21565376
DOI	10.3945/an.110.000109
Journal	Advances in Nutrition: An International Review Journal
Issue Number	2
Volume Number	2
Language	English
Publisher	Oxford University Press
Publisher Date	2011-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Nutritional Sciences Ascorbic Acid Pharmacokinetics Vitamins Absorption Animals Administration & Dosage Blood Hydrogen Peroxide Metabolism Mice Mice, Knockout Neoplasms Research Support, N.i.h., Intramural
Content Type	Text
Resource Type	Article
Subject	Nutrition and Dietetics Medicine Food Science

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Time course of vitamin C distribution and absorption after oral administration in SMP30/GNL knockout mice.

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Attenuation of sepsis-induced organ injury in mice by vitamin C.

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Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic $Discoveries^{1,2}$

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Time course of vitamin C distribution and absorption after oral administration in SMP30/GNL knockout mice.

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