VITAMIN C AND MAGNESIUM USED AS PLACEBO IN CHELATION STUDY
New Study Based on Pauling/Rath Theory submitted to NIH
© Owen R. Fonorow 2002
Revision 43 01/18/03
“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
The Houston-based Vitamin C Foundation has applied to the U. S. National Institutes of Health (NIH), National Center for Complimentary 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 high oral vitamin C and lysine intervention, first suggested by Linus Pauling in 1994.
The study design is somewhat unusual in that will be one study group with elevated serum Lp(a), but there will be no placebo. Because the Vitamin C Foundation and its investigators cannot deprive patients of vitamin C for a lengthy period, the pilot study will first 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.
This method is designed to overcome some of the more obvious objections to a long-term trial. These objections include the subjects having to take a 'useless' placebo for 6 to 18 months. Also, this design overcomes many of the problems that A. Hoffer and others have written – both ethical and otherwise. These problems referred to are: The patient being deprived of a therapy that may work; the difficulty of 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; the fact that patients may “switch” formulas with each other, etc.
Doctor 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; iIt 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 relationships and therefore creates a model that is too far removed 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. In the proposed study, serum Lp(a), homocysteine and ordinary lipids will be monitored (as often as funds allow). Brachial arterial stiffness (ASI) and blood pressure will be measured weekly using FDA-approved CardioVision®. 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 proposal can be read at http://vitamincfoundation.org/NCCAMgrant/
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). A biochemist, Dr. R. F. (New Jersey) reported to us regarding his personal experiment: He added 2 g lysine and .5 proline when 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. Doctor R.F. reported that after six months his Lp(a) dropped by 40% and that after 14 months there was no detectable Lp(a) in his blood serum.
Other physicians familiar with the Pauling therapy, report similar effects. Warren Levin, MD, has written a letter to the Journal of the American Medical Association (JAMA) about lowering Lp(a) with high-doses of vitamin C, lysine and proline.
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 which we hope would merit further investigation by the National Institutes of Health (NIH) and other medical authorities and researchers.
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.
The fact was obscured, evidently, that a statistically significant result supporting the Pauling/Rath theory had been produced. 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:
“A sample size of 40 per group was chosen to provide 90% power to detect a 60-second difference in mean change in exercise time from the baseline to the 27-week follow-up.”
The study was designed to detect a 60-second improvement in treadmill exercise time in a statistically significant way.
Again from the paper, “The 500-ml. infusion solution of 5% dextrose in water… Each treatment solution also contained 750 mg of magnesium sulfate, 5 g of ascorbic acid, and 5 g of sodium bicarbonate…”
Vitamin C and magnesium were given to both groups.
According to their own paper, and I quote, “Both study groups were able to significantly (P<.001) increase their exercise time to ischemia at the 27-week treadmill test.”
Thus, using vitamin C and magnesium in the placebo obscured the statistically significant increase in treadmill exercise time - in both groups, including the EDTA group. Unfortunately, the JAMA author’s conclusions overlook this statistically significant benefit and called it a "placebo effect." (The possibility that it was a placebo effect is unlikely, based on a meta-review of other Time to Ischemia treadmill studies in MEDLINE. See references.)
While I agree with Hoffer that therapies and interventions are not “proven” by a double-blind placebo controlled trial, on the basis of generally accepted medical terminology, this trial “proves” the significant value of vitamin C in heart patients.
As alternative doctors know, “spontaneous remission” usually means that the patient did not tell the doctor about the supplements that were taken. We now know that 5 g of vitamin C is quite the "placebo" for ischemic heart disease. (Several drugs evaluated in a similar manner showed no increase in Time to Ischemia.) In my opinion, based on the JAMA study, which said little about the value of EDTA for CVD (did the EDTA bind with something else given to both groups inactivating it?) and said nothing about the long-term benefits of EDTA, Chelation/ACAM doctors now have a moral obligation to add vitamin C and magnesium to their EDTA (if not doing so already) based on this “proven” result of the unified theory.
Not all ischemia is calcium-based; however, EDTA has a proven affinity for calcium. If a patient receives the contents of an IV bag for three hours, they ought to receive EDTA as well as ascorbate.
The air we breathe contains lead; our teeth are full of mercury; our foods and water contain aluminum and other metal and heavy metal toxins. EDTA detoxification has many proven beneficial effects. We now know that EDTA is even a better idea for heart patients when combined with supplements, especially vitamin C and magnesium. (Maybe Knudtson, et al. can be encouraged to add 5 g of lysine to the IV in their next study?)
For more information, or to contribute to the Vitamin C Foundation’s sponsored clinical trial, please contact:
PO Box 73172 Houston, Texas 77273
1-888-443-3634 Toll Free
630-416-1438 Fax: 630-416-1309 firstname.lastname@example.org
1) Circulation 2000 Oct 17;102(16):1906-11, Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK.
2) Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. Rosano GM, Webb CM, Chierchia S, Morgani GL, Gabraele M, Sarrel PM, de Ziegler D, Collins P. Department of Cardiology, Ospedale San Raffaele, Rome, Italy.
3) Am Heart J 2002 Jul;144(1):60-7. Randomized comparison of T-type versus L-type calcium-channel blockade on exercise duration in stable angina: results of the Posicor Reduction of Ischemia During Exercise (PRIDE) trial. Lee DS, Goodman S, Dean DM, Lenis J, Ma P, Gervais PB, Langer A; PRIDE Investigators. St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Indian Heart J 2002
Mar-Apr;54(2):170-5, Bharani A, Ganguli A, Mathur LK, Jamra Y, Raman
PG.Department of Medicine, MGM Medical College and MY Hospital, Indore, MP.
email@example.com Nowak Z, Petelenz T, Wos S, Lowczynski S.
Am J Cardiol 2002 Apr
1;89(7):822-4, Effects of enhanced external counterpulsation on stress
radionuclide coronary perfusion and exercise capacity in chronic stable
angina pectoris. Stys TP, Lawson WE, Hui JC, Fleishman B, Manzo K, Strobeck
JE, Tartaglia J, Ramasamy S, Suwita R, Zheng ZS, Liang H, Werner D.
6) Vasc Med 2001;6(3):151-6, Effects of cilostazol on resting ankle pressures and exercise-induced ischemia in patients with intermittent claudication. Mohler ER 3rd, Beebe HG, Salles-Cuhna S, Zimet R, Zhang P, Heckman J, Forbes WP. University of Pennsylvania School of Medicine, Philadelphia 19104, USA. firstname.lastname@example.org
Randomized trial of a
medical food for the dietary management of chronic, stable angina. Maxwell
AJ, Zapien MP, Pearce GL, MacCallum G, Stone PH.
8) J Cardiovasc Pharmacol 2001 Sep;38(3):356-64, A randomized, double-blind comparison of the efficacy and tolerability of once-daily modified-release diltiazem capsules with once-daily amlodipine tablets in patients with stable angina. Chugh SK, Digpal K, Hutchinson T, McDonald CJ, Miller AJ, Lahiri A. Department of Cardiac Research, Northwick Park Hospital, Harrow, Middlesex, UK
9) Ter Arkh 2001;73(1):38-41, Comparison of carvedilol and atenolol efficacy in patients with stable effort angina, Martsevich SIu, Koniakhina IP, Alimova EV, Kutishenko NP, Lerman OV