Mark A. Levine, M.D.

Senior Investigator

Molecular and Clinical Nutrition Section, Digestive Disease Branch

NIDDK

Building 10, Room 4D52
10 Center Drive
Bethesda, MD 20814

301-402-5588

markl@mail.nih.gov

Research Topics

Current Research

Research conducted in my laboratory aims to determine optimal nutrition in health, disease, and treatment.  Our research focuses on vitamin C (ascorbic acid) as a model nutrient.  We determine how specific vitamin C functions relate to nutrient concentration in vitro and in vivo.  We seek a functional basis for nutrient recommendations, rather than relying on preventing deficiency—the previous method used for many years.  Facilitated glucose transporters mediate transport of the oxidation product of ascorbic acid, dehydroascorbic acid.  Therefore, our work includes investigation of these transporters by themselves and in relation to dehydroascorbic acid.

Our laboratory conducts basic, translational, and clinical research in the following areas:

  • ascorbic acid function in relation to concentration in cells and subcellular organelles
  • mechanisms of ascorbic acid transport and accumulation
  • ascorbic acid pharmacokinetics (dose-concentration relationships) in animals and people
  • pharmacologic ascorbic acid as a prodrug for hydrogen peroxide formation in vivo and for treatment of cancer and infectious diseases
  • ascorbic acid and free radical biology
  • regulation of glucose transport in vitro and in vivo
  • function of ascorbic acid in red blood cells in health and disease, with special attention to diabetes

Many countries base, in large part, recommended dietary allowances (RDAs) for vitamin C on this work.

Need for Further Study

Our research may benefit the public by providing new ways to: (1) prevent disease and optimize health through nutrition; (2) treat cancer with minimal side effects; (3) slow glucose absorption as an added treatment for obesity and diabetes; (4) prevent or delay complications of diabetes; and (5) improve the collection or storage of red blood cells for transfusion.

Biography

  • NIH Fellowship in Endocrinology and Metabolism, Interinstitute Endocrinology Training Program, 1980-1983
  • Internship and Residency, Osler Medical Service, Johns Hopkins Hospital, 1977-1980
  • M.D., Harvard Medical School, 1977
  • B.A., Brandeis University, 1973

Selected Publications

  1. Parrow NL, Leshin JA, Levine M. Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics. Antioxid Redox Signal. 2013;19(17):2141-56.

  2. 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. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol. 2013;71(3):765-75.

  3. Corpe CP, Eck P, Wang J, Al-Hasani H, Levine M. Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8. J Biol Chem. 2013;288(13):9092-101.

  4. Li H, Tu H, Wang Y, Levine M. Vitamin C in mouse and human red blood cells: an HPLC assay. Anal Biochem. 2012;426(2):109-17.

  5. Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014;6(222):222ra18.


This page was last updated on March 31st, 2015