Vitamin C and magnesium used as placebo in chelation study - Letters to the Editor

Townsend Letter for Doctors and Patients, Feb-March, 2003

Editor:

"Would it surprise you to learn that drug companies make their own placebo pills for research purposes? And that they choose the ingredients? And sometimes they purposely put ingredients into the placebos that match those in the drug and will affect the outcome of the trial. And they are not required to disclose the ingredients they use." Jenny Thompson, Health Sciences Institute. See: http//www.hsibaltimore.com/ea2002/ea_020725.shtml

The Houston-based Vitamin C Foundation has applied to the National Institutes of Health (NIH), National Center for Complementary and Alternative Medicine (NCCAM), for a grant to study 6 g vitamin C and 6 g lysine as a therapy for heart disease. If funded, the study would be the first-ever clinical trial in humans of the oral vitamin C and lysine intervention, first suggested by Linus Pauling in 1994.

The Foundation has asked the NIH/NCCAM to fund an 18-month pilot study of 30-40 subjects. More than 100 persons in Silver Springs, Florida have already volunteered to participate. The investigators cannot deprive patients of vitamin C for a lengthy period and therefore the pilot will not be a placebo-controlled double-blind trial. Instead, the design will monitor Lp(a) and other assessments for all study participants during a two-month baseline period without any intervention. These two months will act as the control on which to base the statistical analysis. The study proposal can be read at http://vitaminCfoundation.org/NCCAMgrant/

In this design, we hope to overcome some of the more obvious objections to a long-term trial, i.e., subjects having to take a 'useless' placebo for 6 to 18 months. This design also overcomes many of the difficulties that A. Hoffer and others have written about, ethical and otherwise, such as the difficulty preparing a proper placebo for megadose therapies, the fact that patients do not like to cooperate in double-blind experiments leading to the high drop-out rates, the lack of physician time to perform realistic monitoring, patient placebo "switching," etc.

A. Hoffer, one of the pioneers of the double-blind method, having run one of the very first trials beginning in 1953, wrote in Vitamin C and Cancer: In Sum, I believe that the validity of the double-blind method has been grossly overvalued. It has only limited utility. In my opinion it does not reliably prove that effective treatments are effective or that ineffective ones are ineffective. Elsewhere I have examined the reasons why it is such a limited method. The main reason is that it violates the doctor-patient relationship and therefore creates a model that is too far removed from the real clinical relationships."

We do not believe that the lack of a "placebo controlled group" will lessen the value of the Pauling therapy study. First, two competing formulas will be evaluated head-to-head, as drugs often are. There is anecdotal evidence, and thus some reason to believe, that the elevated Lp(a) levels in the Pauling Therapy group can be lowered to zero (less than 3 mg/dl). Dr. Robert Feminella (New Jersey) reported to us on his personal experiment. He added 2 g lysine and .5 proline after a blood test revealed elevated Lp(a). This was the only change he made in his daily regimen, which already included supplements and vitamin C. Feminella reported that after six months his Lp(a) dropped by 40% and that after 18 months there was no detectable Lp(a) in his blood serum. If this effect could be monitored in a controlled setting, perhaps across some or most of the entire study group, it would be an outstanding result that we hope would merit further investigation by the National Institutes of Health (NIH) and other medical au thorities and researchers.

This study should also give, an interesting result. The Pauling high-dose vitamin Cllysine therapy will be directly compared, and thus quantitatively measured in terms of ASI and serum Lp(a) against the use of a major 'alternative' therapy, i.e., vitamins B6, B12, folate, etc. Before and after video interviews with each subject will also be conducted.

Placebos in the JAMA

Chelation Trial

It is interesting that organized medicine may have already run a similar trial on one-half of the so-called Pauling Therapy, i.e., (5 g vitamin C). During this 'placebo' controlled trial, both groups were given IV vitamin C and magnesium. While ethical, this approach (giving multivitamins and the vitamin C IV to the placebo group) did affect the conclusion. Evidently, the fact that a statistically significant result supporting the Pauling/Rath theory was produced was obscured. This is not an argument for inert placebos but one for making fully correct and less sweeping conclusions in papers.

In the JAMA study being referred to (Chelation Therapy for Ischemic Heart Disease: A Randomized Controlled Trial, Knudtson, et al. JAMA, Jan 23/30, 2002 - Vol. 287, No 4. pp. 481-486), 5 g of vitamin C and 750 mg of magnesium were given intravenously to both the EDTA and the control (placebo) groups. The study paper, seemingly written to debunk EDTA chelation for heart disease, concluded that there is "no benefit of EDTA chelation over placebo," yet from the text in JAMA we read that the sample size was chosen as follows: