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The conclusions of the paper by Tousoulis et al, which compares the effects on inflammatory processes of atorvastatin with those of 2g doses of vitamin C, are invalid. In concluding that atorvastatin (but not vitamin C) improved endothelial function, the authors state that,
“All studies were conducted between 08:00-10:00 AM after a 12 hours fasting period, and the last medication was administered th...
“All studies were conducted between 08:00-10:00 AM after a 12 hours fasting period, and the last medication was administered the night before the follow-up visit.”
The half-life of high dose vitamin C is half an hour. This means that subjects would have excreted the 2g dose of vitamin C before experimental measurements took place. Even allowing for delay in absorption of an oral dose, the interval between dose and measurement was too large. Basic
pharmacokinetics suggests that the vitamin C condition in this experiment would not differ from the control condition.
By comparison, the mean plasma elimination half-life of atorvastatin in humans, according to Pfizer, is approximately 14 hours. They add that the half-life of inhibitory activity for HMG-CoA reductase is 20 to 30
hours, due to the contribution of active metabolites. The dosage interval of the Tousoulis study was similar to the half-life, allowing plasma atorvastatin levels to accumulate over the four weeks, in a quasi-steady condition. A pharmacological heuristic is that, to sustain levels, the dose interval should be less than five times the half-life. Dose equivalence in this experiment would require vitamin C to be given about every hour (dynamic flow level).
Ascorbate acts as an antioxidant by donating electrons. At the time measurements were taken, the plasma ascorbate concentration would have been at baseline (60-70microG/L). Since, under these experimental conditions, there was no supplemental vitamin C present in plasma to act as an antioxidant, the authors’ conclusions are invalid.
The authors’ conclusions regarding non-transient responses, such as cholesterol levels, are also faulty. With their protocol, a 2g dose of vitamin C will cause only a marginal increase in median daily blood plasma levels. Because of the way it is absorbed, the effect of a 2g dose of vitamin C on average plasma levels in a healthy adult approximates to that of a single 500mg dose. It produces a short-lasting increase, followed by a return to baseline over most of the day. The appropriate supplementation
for a study such as this requires achievement of a quasi-steady state, known as dynamic flow.[2,3]
Scientific knowledge of the action of high doses of vitamin C has been hindered by ignorance of the pharmacokinetics. This error pervades the literature on clinical studies of vitamin C at doses above 200mg. It
has been described with reference to the NIH pharmacokinetic measurements, used for the US RDA.[4,5] Similarly, most attempts to refute claims that high-dose vitamin C might prevent or cure the common cold contain the same mistake. Such claims by Linus Pauling and others remain unchallenged by clinical data, accumulated in the intervening three decades, since the hypotheses have not been tested appropriately. Indeed, almost all clinical
higher dose studies of vitamin C have this flaw. As a result, possible benefits of vitamin C in prevention and therapy have been overlooked.[2,3]
We can only hope that future studies, purporting to show negative responses for vitamin C supplementation, will consider the pharmacokinetics when selecting appropriate doses and dose intervals.
1. Pfizer Ireland Pharmaceuticals (2005) Lipitor (Atorvastatin Calcium) Tablets, Prescribing Information, September.
2. S. Hickey and H. Roberts, Ascorbate: the Science of Vitamin C, Lulu Press, 2004.
3. S. Hickey and H.J. Roberts (2005) Dynamic flow, JOM, 20(4), 237-244.
4. Levine M. Conry-Cantilena C. Wang Y. Welch R. W. Phillip W. Washko P.W. Dhariwal K.R. Park J.B. Lazarrev A. Graumlich J.F. King J. Cantilena L.R. (1996) Vitamin C pharmacokinetics in healthy volunteers: Evidence for
a recommended dietary allowance, Proc. Natl. Acad. Sci. USA, 93, 3704–3709.
5. Levine M. Wang Y. Padayatty S.J. Morrow J. (2001) A new recommended dietary allowance of vitamin C for healthy young women Proc. Natl. Acad. Sci. USA, 14, 98 (17), 9842-9846.
6. S. Hickey (2005) Misleading information on the properties of vitamin C, PLOS Medicine, 2(9), e307.