Mark A. Levine, M.D.

Section Chief: Molecular and Clinical Nutrition Section, Digestive Disease Branch

Scientific Focus Areas: Cancer Biology, Clinical Research, Molecular Biology and Biochemistry, Molecular Pharmacology

mark.levine@nih.gov 301-402-5588 Add to Contacts

Publications

A selection of recent and significant publications can be viewed below.

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Vitamin E sequestration by liver fat in humans.

Violet PC, Ebenuwa IC, Wang Y, Niyyati M, Padayatty SJ, Head B, Wilkins K, Chung S, Thakur V, Ulatowski L, Atkinson J, Ghelfi M, Smith S, Tu H, Bobe G, Liu CY, Herion DW, Shamburek RD, Manor D, Traber MG, Levine M.

JCI Insight (2020 Jan 16) 5. Abstract/Full Text

Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly.

Shenoy N, Creagan E, Witzig T, Levine M.

Cancer Cell (2018 Nov 12) 34:700-706. Abstract/Full Text

Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial.

Sevransky JE, Rothman RE, Hager DN, Bernard GR, Brown SM, Buchman TG, Busse LW, Coopersmith CM, DeWilde C, Ely EW, Eyzaguirre LM, Fowler AA, Gaieski DF, Gong MN, Hall A, Hinson JS, Hooper MH, Kelen GD, Khan A, Levine MA, Lewis RJ, Lindsell CJ, Marlin JS, McGlothlin A, Moore BL, Nugent KL, Nwosu S, Polito CC, Rice TW, Ricketts EP, Rudolph CC, Sanfilippo F, Viele K, Martin GS, Wright DW, VICTAS Investigators.

JAMA (2021 Feb 23) 325:742-750. Abstract/Full Text

Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid.

Tu H, Li H, Wang Y, Niyyati M, Wang Y, Leshin J, Levine M.

EBioMedicine (2015 Nov) 2:1735-50. Abstract/Full Text

Vitamin C Urinary Loss and Deficiency in Human Immunodeficiency Virus (HIV): Cross-sectional Study of Vitamin C Renal Leak in Women With HIV.

Ebenuwa I, Violet PC, Michel K, Padayatty SJ, Wang Y, Tu H, Wilkins KJ, Kassaye S, Levine M.

Clin Infect Dis (2023 Oct 13) 77:1157-1165. Abstract/Full Text

Additional Publications

Temporo-spacial microanatomical distribution of the murine sodium-dependent ascorbic acid transporters Slc23a1 and Slc23a2 in the kidney throughout development.

Eck PK, Corpe C, Levine MA.

Biochem Cell Biol (2017 Jun) 95:421-427. Abstract/Full Text

Pharmacologic Ascorbate in Myeloma Treatment: Doses Matter.

Violet PC, Levine M.

EBioMedicine (2017 Apr) 18:9-10. Abstract/Full Text

Vitamin C: the known and the unknown and Goldilocks.

Padayatty SJ, Levine M.

Oral Dis (2016 Sep) 22:463-93. Abstract/Full Text

Synergistic effects of ascorbate and sorafenib in hepatocellular carcinoma: New insights into ascorbate cytotoxicity.

Rouleau L, Antony AN, Bisetto S, Newberg A, Doria C, Levine M, Monti DA, Hoek JB.

Free Radic Biol Med (2016 Jun) 95:308-322. Abstract/Full Text

Antitumor effect of pharmacologic ascorbate in the B16 murine melanoma model.

Serrano OK, Parrow NL, Violet PC, Yang J, Zornjak J, Basseville A, Levine M.

Free Radic Biol Med (2015 Oct) 87:193-203. Abstract/Full Text

High-dose ascorbate with low-dose amphotericin B attenuates severity of disease in a model of the reappearance of candidemia during sepsis in the mouse.

Leelahavanichkul A, Somparn P, Bootprapan T, Tu H, Tangtanatakul P, Nuengjumnong R, Worasilchai N, Tiranathanagul K, Eiam-ong S, Levine M, Chinampon A, Srisawat N.

Am J Physiol Regul Integr Comp Physiol (2015 Aug 1) 309:R223-34. Abstract/Full Text

Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer.

Padayatty SJ, Levine M.

Ann Intern Med (2014 May 6) 160:654. Abstract/Full Text

Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics.

Parrow NL, Leshin JA, Levine M.

Antioxid Redox Signal (2013 Dec 10) 19:2141-56. Abstract/Full Text

The human sodium-dependent ascorbic acid transporters SLC23A1 and SLC23A2 do not mediate ascorbic acid release in the proximal renal epithelial cell.

Eck P, Kwon O, Chen S, Mian O, Levine M.

Physiol Rep (2013 Nov) 1:e00136. Abstract/Full Text

Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8.

Corpe CP, Eck P, Wang J, Al-Hasani H, Levine M.

J Biol Chem (2013 Mar 29) 288:9092-101. Abstract/Full Text

Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial.

Welsh JL, Wagner BA, van't Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, Yee NS, Bodeker KL, Du J, Roberts LJ 2nd, Drisko J, Levine M, Buettner GR, Cullen JJ.

Cancer Chemother Pharmacol (2013 Mar) 71:765-75. Abstract/Full Text

Standard-dose vs high-dose multivitamin supplements for HIV.

Padayatty SJ, Levine M.

JAMA (2013 Feb 13) 309:545-6. Abstract/Full Text

Vitamin C in mouse and human red blood cells: an HPLC assay.

Li H, Tu H, Wang Y, Levine M.

Anal Biochem (2012 Jul 15) 426:109-17. Abstract/Full Text

Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.

Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, Pillai MV, Newberg AB, Deshmukh S, Levine M.

PLoS One (2012) 7:e29794. Abstract/Full Text

Prostate imaging modalities that can be used for complementary and alternative medicine clinical studies.

Dusing RW, Drisko JA, Grado GG, Levine M, Holzbeierlein JM, Van Veldhuizen P.

Urol Clin North Am (2011 Aug) 38:343-57. Abstract/Full Text

Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer.

Espey MG, Chen P, Chalmers B, Drisko J, Sun AY, Levine M, Chen Q.

Free Radic Biol Med (2011 Jun 1) 50:1610-9. Abstract/Full Text

Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries.

Levine M, Padayatty SJ, Espey MG.

Adv Nutr (2011 Mar) 2:78-88. Abstract/Full Text

Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects.

Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, Levine M.

PLoS One (2010 Jul 7) 5:e11414. Abstract/Full Text

Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer.

Pollard HB, Levine MA, Eidelman O, Pollard M.

In Vivo (2010 May-Jun) 24:249-55. Abstract/Full Text

Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice.

Corpe CP, Tu H, Eck P, Wang J, Faulhaber-Walter R, Schnermann J, Margolis S, Padayatty S, Sun H, Wang Y, Nussbaum RL, Espey MG, Levine M.

J Clin Invest (2010 Apr) 120:1069-83. Abstract/Full Text

Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer.

Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang SH, Taghiyev AF, Du C, Knudson CM, Cullen JJ.

Clin Cancer Res (2010 Jan 15) 16:509-20. Abstract/Full Text

Comment re: Vitamin C antagonizes the cytotoxic effects of chemotherapy.

Espey MG, Chen Q, Levine M.

Cancer Res (2009 Nov 15) 69:8830; author reply 8830-1. Abstract/Full Text

Vitamin C: working on the x-axis.

Levine M, Eck P.

Am J Clin Nutr (2009 Nov) 90:1121-3. Abstract/Full Text

Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment.

Levine M, Espey MG, Chen Q.

Free Radic Biol Med (2009 Jul 1) 47:27-9. Abstract/Full Text

Antioxidant supplements and cardiovascular disease in men.

Padayatty SJ, Levine M.

JAMA (2009 Apr 1) 301:1336; author reply 1336-7. Abstract/Full Text

Oxalic acid excretion after intravenous ascorbic acid administration.

Robitaille L, Mamer OA, Miller WH Jr, Levine M, Assouline S, Melnychuk D, Rousseau C, Hoffer LJ.

Metabolism (2009 Feb) 58:263-9. Abstract/Full Text

Phase I clinical trial of i.v. ascorbic acid in advanced malignancy.

Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, Rousseau C, Robitaille L, Miller WH Jr.

Ann Oncol (2008 Nov) 19:1969-74. Abstract/Full Text

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice.

Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M.

Proc Natl Acad Sci U S A (2008 Aug 12) 105:11105-9. Abstract/Full Text

Dehydroascorbate and glucose are taken up into Arabidopsis thaliana cell cultures by two distinct mechanisms.

Horemans N, Szarka A, De Bock M, Raeymaekers T, Potters G, Levine M, Banhégyi G, Guisez Y.

FEBS Lett (2008 Aug 6) 582:2714-8. Abstract/Full Text

Hypoxia-inducible factor-1alpha stabilization in nonhypoxic conditions: role of oxidation and intracellular ascorbate depletion.

Pagé EL, Chan DA, Giaccia AJ, Levine M, Richard DE.

Mol Biol Cell (2008 Jan) 19:86-94. Abstract/Full Text

Genetic variation in sodium-dependent vitamin C transporters SLC23A1 and SLC23A2 and risk of advanced colorectal adenoma.

Erichsen HC, Peters U, Eck P, Welch R, Schoen RE, Yeager M, Levine M, Hayes RB, Chanock S.

Nutr Cancer (2008) 60:652-9. Abstract/Full Text

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo.

Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, Choyke PL, Pooput C, Kirk KL, Buettner GR, Levine M.

Proc Natl Acad Sci U S A (2007 May 22) 104:8749-54. Abstract/Full Text

Inhibition of the intestinal glucose transporter GLUT2 by flavonoids.

Kwon O, Eck P, Chen S, Corpe CP, Lee JH, Kruhlak M, Levine M.

FASEB J (2007 Feb) 21:366-77. Abstract/Full Text

Intravenously administered vitamin C as cancer therapy: three cases.

Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M.

CMAJ (2006 Mar 28) 174:937-42. Abstract/Full Text

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues.

Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M.

Proc Natl Acad Sci U S A (2005 Sep 20) 102:13604-9. Abstract/Full Text

6-Bromo-6-deoxy-L-ascorbic acid: an ascorbate analog specific for Na+-dependent vitamin C transporter but not glucose transporter pathways.

Corpe CP, Lee JH, Kwon O, Eck P, Narayanan J, Kirk KL, Levine M.

J Biol Chem (2005 Feb 18) 280:5211-20. Abstract/Full Text

Vitamin C pharmacokinetics: implications for oral and intravenous use.

Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M.

Ann Intern Med (2004 Apr 6) 140:533-7. Abstract/Full Text

Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival.

Sotiriou S, Gispert S, Cheng J, Wang Y, Chen A, Hoogstraten-Miller S, Miller GF, Kwon O, Levine M, Guttentag SH, Nussbaum RL.

Nat Med (2002 May) 8:514-7. Abstract/Full Text

A new recommended dietary allowance of vitamin C for healthy young women.

Levine M, Wang Y, Padayatty SJ, Morrow J.

Proc Natl Acad Sci U S A (2001 Aug 14) 98:9842-6. Abstract/Full Text

Criteria and recommendations for vitamin C intake.

Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y.

JAMA (1999 Apr 21) 281:1415-23. Abstract/Full Text