Recent Publications by LPI Scientists

Developments

Oxygen Club of California 2006 World Congress

The XIIth Annual Meeting of the Oxygen Club of California on Oxidants and Antioxidants in Biology, co-sponsored by the Linus Pauling Institute and the Society for Free Radical Research International, will be held on March 15-18, 2006, at Fess Parker’s Doubletree Resort, Santa Barbara, California, USA. The meeting highlights will include a symposium and sessions devoted to: Obesity, Oxidative Stress, and the Metabolic Syndrome; Obesity, Uncoupling Proteins, and Micronutrient Action; Dietary Modulation of Cell Signaling Pathways; and Mitochondrial Function, Aging, and Degenerative Diseases. The meeting will also feature keynote lectures by Arne Holmgren and Sten Orrenius, posters and young investigator awards, the Science and Humanity Prize, established investigator prizes, and a concert by a renowned Japanese artist followed by a banquet and award ceremony. For more information, visit www.oxyclubcalifornia.org, or contact Dr. Cesar Fraga, Chief Communications Officer, at cgfraga@ucdavis.edu.

Vitamin C and Cancer—Renewed Interest

Over 35 years ago, Dr. Ewan Cameron, a Scottish surgeon, began collaborating with Dr. Linus Pauling on the use of vitamin C in cancer therapy. Cameron typically administered 10 grams/day of vitamin C intravenously to terminal cancer patients for about 10 days, followed by an equivalent oral dosage continued indefinitely. Cameron and Pauling reported that patients given high-dose vitamin C reported an increased sense of well-being and lived longer than matched patients who were not supplemented with vitamin C. Subsequently, the Mayo Clinic conducted two randomized, placebo-controlled, double-blind clinical studies that failed to show any benefit for vitamin C in cancer treatment. According to Cameron and Pauling, the Mayo Clinic studies were seriously flawed, and their protocol differed significantly from that used by Cameron, especially the mode of vitamin C administration. The Mayo Clinic gave only oral vitamin C, which produces plasma concentrations of vitamin C much lower than intravenous vitamin C.

Dr. Mark Levine and his colleagues at the National Institutes of Health have published insightful pharmacokinetic studies on vitamin C showing how much of orally ingested and intravenous doses gets into the blood and how quickly it is excreted. According to these studies, the plasma concentration achieved with intravenous vitamin C is over 25 times higher than oral vitamin C and could reach 70-fold higher concentrations. These very high concentrations are similar to those that have been reported to kill cancer cells in culture. In addition to the results reported by Pauling and his two medical collaborators, Cameron and Dr. Abram Hoffer, anecdotal clinical evidence supports the selective cytotoxicity of vitamin C for cancer cells, including a report from the University of Kansas on the beneficial effect of intravenous vitamin C in two women with stage III ovarian carcinoma.

A new paper by Levine’s group published in the September 20th issue of the Proceedings of the National Academy of Sciences USA offers more evidence that pharmacological concentrations of vitamin C preferentially kill cancer cells. Ten human cancer cell lines and four normal cell types were studied. Vitamin C at concentrations easily achieved by intravenous administration effectively killed cancer cells by apoptosis (programmed cell death) and necrosis, but did not harm normal cells. The investigators found that cell death was absolutely dependent on the presence of serum proteins and the generation of hydrogen peroxide, but the mechanism by which vitamin C generates hydrogen peroxide is still obscure. Extracellular, but not intracellular, vitamin C was responsible for the cytotoxicity, which was independent of metal ions. Metals like iron and copper are involved in reactions that generate free radicals capable of damaging cells. Previous studies at the Linus Pauling Institute also determined that certain structural characteristics of the vitamin C molecule and its derivatives exhibit selective toxicity to cancer cells. Levine previously called for a re-evaluation of vitamin C as cancer therapy, especially intravenous vitamin C, and his paper concluded with the news that a phase I safety trial with intravenous vitamin C in humans is under way.

Talk of the Nation/Science Friday

Several of the speakers from the Diet and Optimum Health Conference appeared on Ira Flatow’s live radio program, “Talk of the Nation/Science Friday,” on National Public Radio on May 20th. Drs. Balz Frei, George Brooks, Janet King, and Meir Stampfer discussed the new Food Guide Pyramid and fielded questions from the national radio audience. Three main messages emerged from committee deliberations on the new Food Guide Pyramid: 1) balance food intake with physical activity, 2) eat a variety of foods, and 3) choose nutrient-rich foods. Dr. King said that many Americans have low intakes of important micronutrients, so the consumption of fruits, vegetables, and whole grains— sources of these micronutrients and associated with protection from disease—is now re-emphasized. Milk is included in the guidelines as a source of calcium and potassium, but some experts prefer to consume other foods and supplements to get these essential minerals. Dr. Brooks discussed the inclusion of physical activity as a new component of the dietary guidelines. Emphasis on the maintenance of an appropriate weight is especially important as Americans adopt even more sedentary lifestyles and exhibit an alarming trend toward obesity. About 60 minutes of brisk walking or other physical activity each day adequately raises energy expenditure. Dr. Frei made the case for supplementation with a daily multivitamin/mineral and, for some populations, with single micronutrients, such as vitamin B12, folic acid, and vitamins C, D, and E. He also mentioned that high dose vitamin C shortens the duration and severity of colds and that supplemental vitamin E helps prevent upper respiratory infections in the elderly. Dr. Stampfer suggested that the new Pyramid is difficult to interpret and doesn’t give enough advice on what foods to avoid, such as refined carbohydrates and trans fats. He said that the emphasis on dairy products was problematic and that most people around the world consume very little dairy products and have few bone problems. He also noted that fish oil might help prevent sudden death from heart disease by preventing fibrillation. The USDA website, MyPyramid.gov, allows an individual to get a customized Food Guide Pyramid based on age, gender, and amount of daily physical activity, but, as Dr. Stampfer noted, doesn’t take into account body height or weight. In response to callers, much discussion involved the need for education and the relationship between the food industry, government, and school districts. The federal government subsidizes many food crops that end up in unhealthful foods, and schools often depend on money from vending machines that dispense unhealthful foods and beverages to support programs.