Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries
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...
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| Veröffentlicht in: | Advances in nutrition (Bethesda, Md.) Md.), 2011-03, Vol.2 (2), p.78-88 |
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| creator | Levine, Mark Padayatty, Sebastian J. Espey, Michael Graham |
| description | 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 |
| doi_str_mv | 10.3945/an.110.000109 |
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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 (H2O2) 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. 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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 (H2O2) 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 H2O2.</description><subject>Absorption</subject><subject>Animals</subject><subject>Ascorbic Acid - administration & dosage</subject><subject>Ascorbic Acid - blood</subject><subject>Ascorbic Acid - pharmacokinetics</subject><subject>Female</subject><subject>Humans</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neoplasms - metabolism</subject><subject>Vitamins - administration & dosage</subject><subject>Vitamins - blood</subject><subject>Vitamins - pharmacokinetics</subject><issn>2161-8313</issn><issn>2156-5376</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LAzEURYMotmiXbiV_YGoy-ejUXRmtCgVdVEEQQiZ5YyOdzJBMC_33poy6c_Uuj8PlchC6omTK5lzcaD-lKRNCKJmfoHFOhcwEm8nTY5Y0KxhlIzSJ8SsxROTFTLJzNMpzxnLC5Bh9vLleN87j8hYvcNl6A74Punetz5Y7b44BL7outNps8LuDrY34ZaNDo027bT8PWHuL1xsIuoNd7wy-c9G0ewgO4iU6q_U2wuTnXqDX5f26fMxWzw9P5WKVGc5Fn1FbWGOhkLWRUlIrjbRE5zq9COcGRMG1qYUliahqSSrGqBAVNzUIPq8lu0DZ0GtCG2OAWnXBNTocFCXqKEppr5IoNYhK_PXAd7uqAftH_2pJwGwAIK3eOwgqGgfJjXUBTK9s6_6p_gZtIXcJ</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Levine, Mark</creator><creator>Padayatty, Sebastian J.</creator><creator>Espey, Michael Graham</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20110301</creationdate><title>Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries</title><author>Levine, Mark ; Padayatty, Sebastian J. ; Espey, Michael Graham</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-1d8dcde86fc6661d6c6d0a2ade8044ce584acf5d086fbf60b33155b4cfe549f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Absorption</topic><topic>Animals</topic><topic>Ascorbic Acid - administration & dosage</topic><topic>Ascorbic Acid - blood</topic><topic>Ascorbic Acid - pharmacokinetics</topic><topic>Female</topic><topic>Humans</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neoplasms - metabolism</topic><topic>Vitamins - administration & dosage</topic><topic>Vitamins - blood</topic><topic>Vitamins - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Levine, Mark</creatorcontrib><creatorcontrib>Padayatty, Sebastian J.</creatorcontrib><creatorcontrib>Espey, Michael Graham</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Advances in nutrition (Bethesda, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Levine, Mark</au><au>Padayatty, Sebastian J.</au><au>Espey, Michael Graham</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries</atitle><jtitle>Advances in nutrition (Bethesda, Md.)</jtitle><addtitle>Adv Nutr</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>2</volume><issue>2</issue><spage>78</spage><epage>88</epage><pages>78-88</pages><issn>2161-8313</issn><eissn>2156-5376</eissn><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 (H2O2) 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 H2O2.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22332036</pmid><doi>10.3945/an.110.000109</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Advances in nutrition (Bethesda, Md.), 2011-03, Vol.2 (2), p.78-88 |
| issn | 2161-8313 2156-5376 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Absorption Animals Ascorbic Acid - administration & dosage Ascorbic Acid - blood Ascorbic Acid - pharmacokinetics Female Humans Hydrogen Peroxide - metabolism Male Mice Mice, Knockout Neoplasms - metabolism Vitamins - administration & dosage Vitamins - blood Vitamins - pharmacokinetics |
| title | Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries |
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