I recently finished reading a marvelous book by David Grann, “The Wager.” It recounts the story of the Wager, a British man-of-war in the 1740s that was dispatched on a mission from England around the tip of South America. The long voyage from Britain to the Pacific took months, and during its course there was an outbreak of scurvy from a deficiency of vitamin C or ascorbic acid, which resulted from the lack of fresh fruits and vegetables. Vitamin C deficiency was a major cause of death on such voyages, and it was not until 1753 that Jeremy Lind discovered that citrus fruits could prevent or cure it. Years later, the British Navy routinely began dispensing lime juice to its sailors who, as a result, became known as Limeys.
In the 1920s and early 1930s, the actual vitamin was isolated and then synthesized. Albert Szent-Gyorgi of Hungary is given the main credit for this and was awarded the Nobel Prize in Medicine in 1937.
This brings us to Linus Pauling, a chemistry professor at Caltech and also a Nobel laureate in Chemistry although not for anything to do with vitamin C. Actually, Pauling is one of five individuals who have won the Nobel Prize twice—for our trivia aficionados, I will list the five in next week’s column. Pauling became a strong proponent of the salutary effects of megadoses of vitamin C for various medical ailments. He advocated its use as a remedy for the common cold and later also suggested it would help prevent cardiovascular disease. Studies of this never showed any evidence of benefit for these two conditions and its use became discredited.
Vitamin C is an antioxidant, like vitamin E or selenium. Antioxidants bind to free radicals, molecules in the body that are unstable and bind to DNA or other macromolecules and are thought to harm health. Thus, it is thought that antioxidants are beneficial for health; one way in which this is thought to be a positive contribution is in cancer prevention. Thus, a number of studies explored their efficacy in cancer prevention, but they came to naught.
Ultimately Pauling came around to proposing a megadose (10 grams/day) vitamin C for late-stage cancer as well. A study was published by two physicians that described the treatment of 50 patients with this treatment of whom five had objective tumor regression. Pauling subsequently joined one of the authors, a Scottish physician named Ewan Cameron, and expanded the study to 100 patients. With some further manipulation of the patient population, they described a mean survival time of 293 days versus 38 days for a historical control group. Historical control groups always arouse skepticism, but this study and result for a relatively nontoxic treatment coming from a Nobel laureate generated widespread attention and use by many cancer patients.
All of this engendered the involvement of our hero skeptic, Charles Moertel. He and his colleagues undertook a study of advanced colorectal cancer—this tumor was selected because this was the main tumor type in the Cameron and Pauling study, and their study had claimed an impressive improvement in survival with the vitamin C treatment.
To be eligible, subjects had to have histologically proven advanced colorectal adenocarcinoma, be ambulatory, and without prior chemotherapy, and to have measurable disease (a standard requirement for most chemotherapy trials). After informed consent, each was randomized to either 10 grams of vitamin C daily or placebo. The study was designed to be double-blind—the patients, physicians and all the other health care personnel were unaware of the treatment assignment. Treatment was continued as long as the patient could tolerate it or until progression of disease—a greater than 50% increase in the product of two diameters in any measurable area of disease, the appearance of a new metastatic lesion, worsening of symptoms, or a loss of 10% or more of body weight.
One hundred patients were randomized, 51 to vitamin C and 49 to placebo. Most patients tolerated therapy very well. In terms of results, no patient had objective evidence of regression in either arm of the study. Most of the patients were asymptomatic at study entry; of 11 patients with symptoms in the intervention arm, seven claimed some degree of symptomatic relief (64%) while 11 of 17 symptomatic patients in the placebo arm claimed relief (65%). For patients taking vitamin C, the median time to progression was 2.9 months while for the placebo group it was 4.1 months. The one-year survival was 49% in the vitamin C arm versus 47% in the placebo group.
This study, published in the New England Journal of Medicine in 1985, very clearly discredited the putative benefits of high-dose vitamin C for cancer. Nonetheless, vitamin C is a vitamin and therefore its regulation is quite a bit looser by the FDA than that of true drugs. It cannot be made illegal and thus is available for doctors or clinics to treat patients using it for cancer. This is still frequently done today in clinics throughout the country and abroad.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.