Mark A. Levine, M.D. : NIDDK

Mark A. Levine, M.D.

Chief, Molecular and Clinical Nutrition Section,
Digestive Diseases Branch

NIDDK, National Institutes of Health
Building 10, Room 4D52
10 Center Dr.
Bethesda, MD 20892
Tel: 301-402-5588
Fax: 301-402-6436

Education / Previous Training and Experience:
B.A., Brandeis University, 1973
M.D., Harvard Medical School, 1977

Research Statement:
Goals are to determine optimal nutrition in health, disease, and disease treatment, using vitamin C (ascorbic acid) as a model nutrient. We determine how specific nutrient function occurs in relation to nutrient concentration, in vitro (in cells and organelles) and in vivo (animals and people). We seek a functional basis for nutrient recommendations, rather than reliance on preventing deficiency as has been used for many years.

The laboratory conducts basic, translational, and clinical research in these areas:

A. Ascorbic acid function in relation to concentration in cells and subcellular organelles.

B. Ascorbic acid transport and accumulation mechanisms.

C. Ascorbic acid pharmacokinetics (dose concentration relationships) in animals and people.

D. Pharmacologic ascorbic acid as a pro-drug for hydrogen peroxide formation in vivo, for treatment of cancer and infectious diseases.

E. Ascorbic acid and free radical biology.

F. Regulation of glucose transport in vitro and in vivo.

Recommended Dietary Allowances for vitamin C in many countries are based in part on this work.

Selected Publications:

Chen Q., Espey M.G., Sun A., Poupot C., Kirk K., Cherukuri M., Khosh D.B., Drisko J., Levine M. (2008) Pharmacologic doses of ascorbate act as a pro oxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci USA. 105:11105-9.

Hoffer L.J., Levine M., Assouline S., Melnychuk D., Padayatty S.J., Rosadiuk K., Rousseau C., Robitaille L., Miller W.H. Jr. (2008) Phase I clinical trial of intravenous ascorbate in advanced malignancy Annal Oncol 19: 1969-74

Padayatty S., Doppman J.L., Chang, R., Wang Y., Gill J., Papanicolau D., Levine M. (2007) Adrenal glands secrete vitamin C in response to ACTH in humans. American Journal of Clinical Nutrition 86, 145-9.

Chen Q., Espey M.G., Cherukuri M.K., Sun A., Buettner G.R., Shacter E., Poupot C., Kirk K., Levine M. (2007) Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci USA 107, 8749-54.

Kwon O., Eck P., Chen S., Corpe C., Lee J-h., Kruhlak M., Levine M. (2007) Inhibition of the intestinal glucose transporter GLUT 2 by flavonoids. FASEB Journal 21, 366-77.

Chen Q., Espey M.G., Cherukuri M.K., Mitchell J.B., Corpe C.P., Buettner G.R., Shacter E., Levine M. (2005) Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA. 102: 13604-13609.

Corpe C., Lee J-H., Kwon O., Eck P., Narayanan J., Kirk K., Levine M. (2005) 6-bromo-6-deoxy-L-ascorbic acid: an ascorbate analog specific for Na+dependent vitamin C transporter but not glucose transporter pathways. J Biol. Chem. 280:5211-5220.

Eck P., Erichsen H.C., Taylor J.G., Yeager M., Hughes A.L., Levine M. , Chanock S.J.(2004) Comparison of the genomic structure and variation in the two human sodium dependent vitamin C transporters, SLC23A1 and SLC23A2. Human Genetics, 115:285-294.

Padayatty S.J., Sun H., Wang Y., Riordan H.D., Hewitt S.M., Katz A., Wesley R.A., Levine M. (2004) Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Annals of Internal Medicine 140: 533-7.

Song J., Kwon O., Chen S., Daruwala R., Eck P., Park J.B., Levine M. (2002) Flavonoid inhibition of SVCT1 and GLUT2, intestinal transporters for vitamin C and glucose. J. Biol. Chem. 277, 15252-60.

Sotiriou S., Gispert S., Chen A., Cheng J., Wang Y., Hoogstraten-Miller S., Miller G.F., Kwon O., Levine M., Guttentag S.H., Nussbaum R.L. (2002) Ascorbic acid transporter slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nature Medicine 8, 514-17.

Levine M., Wang Y., Padayatty S.J., Morrow J.D. (2001) A new recommended dietary allowance of vitamin C for healthy young women. Proc Natl Acad Sci USA. 98; 9842-46.

Page last updated: January 07, 2009

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