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Research Newsletter-Fall/Winter 2007

LINUS PAULING INSTITUTE PRIZE FOR HEALTH RESEARCH



Mark Levine, M.D.

The 2007 LPI Prize for Health Research, consisting of a medal and $50,000, was awarded at the Diet and Optimum Health Conference on May 18th to Mark Levine, M.D. Dr. Levine is Chief of the Molecular and Clinical Nutrition Section of the Digestive Diseases Branch of the National Institute of Diabetes & Digestive & Kidney Diseases in Bethesda, Maryland. He earned his B.A. degree in biology at Brandeis University and his M.D. degree at Harvard Medical School. He has been at the NIH since 1980, conducting clinical research and seeing patients, and has published over 125 scientific papers. Dr. Levine joins Drs. Bruce Ames (2001), Walter Willett (2003), and Paul Talalay (2005) as recipients of the LPI Prize.

Dr. Levine became interested in research while in medical school. When he learned that the conversion of dopamine to norepinephrine is dependent on vitamin C, he became particularly interested in vitamin C and was shocked to find that its RDA was based solely on the prevention of scurvy, not on function or optimum levels. For many years, Dr. Levine has worked on the pharmacokinetics of vitamin C—how much of different doses is absorbed into the blood from the gastrointestinal tract and how that influences blood levels and excretion. He has also carefully documented differences in blood concentrations of vitamin C following oral or intravenous infusion, finding that such concentrations are 70 times greater after intravenous infusion. These observations have rekindled interest in the therapeutic use of vitamin C in cancer. Dr. Ewan Cameron, Linus Pauling's clinical collaborator in vitamin C and cancer studies, began treating terminal cancer patients with high-dose intravenous and oral vitamin C in 1971 and reported favorable responses. The infamous Mayo Clinic studies in the 1970s and 1980s failed to replicate Cameron's work but used only oral vitamin C. Consequently, vitamin C in the blood of those patients was unlikely to have attained sufficient concentrations to kill cancer cells.


Dr. Levine gives his plenary lecture on vitamin C.
Photo from the Diet and Optimum Health Conference

Dr. Levine's recent papers have described elegant studies on the molecular mechanism responsible for the cancer cell toxicity of vitamin C. He and his co-workers found that high concentrations of vitamin C in the extracellular fluid—but not in blood—attained by intravenous infusion, generate the ascorbate free radical, which then stimulates the formation of hydrogen peroxide. Hydrogen peroxide then diffuses into cancer cells and kills them via several mechanisms, including the depletion of ATP—a molecule critical in cellular energy—in the mitochondria. In the anaerobic metabolism of cancer cells, mitochondria may be especially sensitive to hydrogen peroxide, whereas mitochondria in normal cells exhibiting aerobic metabolism are not. Dr. Levine found that cancer cells exposed to high concentrations of vitamin C die by necrosis or apoptosis (programmed cell death), whereas normal cells are unaffected. Dr. Levine believes that the anticancer mechanism elucidated for vitamin C may also be useful in treating viral and bacterial infections.

Dr. Levine's pharmacokinetic studies in healthy young men and women led to the observation that circulating cells in blood reach their highest concentration of vitamin C after a dose of about 400 mg, which also results in near maximum plasma concentrations. However, vitamin C is excreted fairly rapidly, and Dr. Levine's recent pharmacokinetic model proposes that the concentration in blood can be maintained at its maximum by taking vitamin C several times a day.

LPI Prize for Health Research Medal

Dr. Levine has also studied the transport of vitamin C into cells. He characterized one of the vitamin C transporters that gets the vitamin into the brain and lung and discovered the critical role of vitamin C in fetal development. His vitamin C transport studies also found that flavonoids, a class of polyphenolic phytochemicals found in fruit and vegetables, inhibit the absorption of vitamin C.

As one nomination letter noted, "Without a doubt, Dr. Levine is one of the leading scientists in the fields of vitamin research." Another nominator stated that "his work has had such a major impact that he is truly considered the world's expert on vitamin C and its potential for treatment of disease. Thus, he has provided solid justification for... Linus Pauling's proposals for the use of vitamin C against cancer and infections."

Last updated December 2007