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Research Newsletter-Fall/Winter 2008

FROM THE DIRECTOR



Balz Frei, Ph.D.
LPI Director and Endowed Chair
Professor of Biochemistry and Biophysics

The Linus Pauling Institute continues to expand its Healthy Aging Program with the recent recruitment of Dr. Adrian "Fritz" Gombart, who joined us in September from the Cedars-Sinai Medical Center and the David Geffen School of Medicine at the University of California, Los Angeles. Dr. Gombart holds B.S. and M.S. degrees in Biology and Genetics, respectively, from Oregon State University, and a Ph.D. in Microbiology from the University of Washington in Seattle. Dr. Gombart will work closely with Dr. Tory Hagen, director of LPI's Healthy Aging Program and recently endowed Jamieson Chair in Healthspan Research. Dr. Gombart's research program focuses on understanding the role of vitamin D in innate immunity and immunosenescence. He also has done work on vitamin A and has a general interest in the biological mechanisms affecting the immune system and its decline during aging. On behalf of all of us at LPI, a warm welcome to Dr. Gombart and his family!

We are also getting ready for our fifth LPI conference on "Diet and Optimum Health," which will be held in May 2009 in Portland, Oregon. As in previous years, the conference will emphasize dietary and lifestyle approaches to improving human health and preventing or treating disease, including dietary supplements, micronutrients, and phytochemicals; and the role of oxidative stress and dietary antioxidants in human health and disease. In addition to the LPI Prize for Health Research and a public session by Dr. Marion Nestle from New York University on "What to eat?," the program features scientific sessions on metabolic syndrome, healthy aging, immune function, epigenetics, and vitamin K.

Finally, two intriguing scientific articles were published recently, and picked up by the popular press, on the role of vitamin C in cancer therapy, a topic of great interest to us. The first was a paper in the prestigious journal, Proceedings of the National Academy of Sciences USA (PNAS), by the group of Dr. Mark Levine at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. They showed that intraperitoneal injection (into the abdominal cavity) of large, "pharmacologic doses" of vitamin C into mice decreased by about half the growth and weight of human, rat, and mouse tumor xenografts (implanted cancer cells growing into tumors). This work followed a number of publications by the same group showing that millimolar concentrations of extracellular vitamin C in the fluid surrounding cells and tissues kill cancer cells but not normal cells by a pro-oxidant mechanism, involving the production of hydrogen peroxide by vitamin C and a yet-to-be-identified metalloprotein. Interestingly, such millimolar concentrations of vitamin C can be achieved in humans only by intravenous infusion, not by diet or oral vitamin C supplementation. This finding may explain the discrepant results by Drs. Linus Pauling and Ewan Cameron in the 1970s, showing that intravenous vitamin C is of substantial benefit in terminal cancer patients, and the "repeat" of those studies at the Mayo Clinic published in 1979 and 1985, which used only oral vitamin C and did not find a benefit in cancer patients. The Editor-in-Chief of PNAS invited me to write a commentary on Dr. Levine's paper, in which Stephen Lawson and I concluded that the new data provide a compelling rationale for revisiting the still-controversial issue of vitamin C and cancer and that the potential anticancer value of vitamin C should be vigorously pursued in randomized, double-blind, placebo-controlled clinical trials of high-dose intravenous vitamin C.

The second study was published in a leading cancer journal, Cancer Research, by Dr. Mark Heaney's group at the Memorial Sloan-Kettering Cancer Center in New York City. The paper carried the rather alarmist title "Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs." A closer look at this paper reveals that they did not use vitamin C in any of their experiments but instead used its oxidized form called dehydroascorbic acid (DHA). Dehydroascorbic acid is not available as a dietary supplement, and any DHA formed in the human body by oxidation of vitamin C is quickly disposed of by known chemical and biological mechanisms. What's more, the studies by Heaney and colleagues were performed on two cancer cell lines in Petri dishes, and the single study in animals used DHA doses known to be toxic. Under these conditions, the authors found that DHA may very modestly lower the effectiveness of the anticancer drug doxorubicin. In sharp contrast, in reviewing the current scientific evidence from human studies, other researchers have concluded that the relationship between vitamin C and chemotherapy is promising in terms of increased survival times and decreased toxicity (adverse side effects) of chemotherapeutic drugs. They cautioned, however, that the interaction between vitamin C and chemotherapy or radiation therapy should be further addressed in large, well-designed, clinical studies before any conclusions can be drawn. It is likely that vitamin C, by itself or in combination with standard therapy, will show substantial benefit in the treatment of certain types of cancer.

Last updated January 2009