High doses of vitamin C lower indinavir levels

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Taking high doses of vitamin C reduces indinavir concentrations in the blood, according to research conducted amongst HIV-negative volunteers and presented as a poster to the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago on 17th September.

It has been suggested that large doses of vitamin C (one gramme or more a day) could have an effect on the P-450 enzymes, particularly CYP3A, which play a key role in the metabolising of protease inhibitors. As vitamin C is a widely used nutritional supplement by patients taking HAART, this could have implications for the success of their therapy. Other nutritional and herbal supplements, most notably St John’s wort and large doses of garlic have been shown to reduce concentrations of several anti-HIV drugs.

Seven healthy volunteers took 800mg of indinavir every eight hours, receiving a total of four doses in a day. Blood samples were obtained pre-dose, and at the following intervals after receiving indinavir: thirty minutes, one hour, and then at hours two, three, four and five hours after the fifth dose.

Glossary

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

confounding

Confounding exists if the true association between one factor (Factor A) and an outcome is obscured because there is a second factor (Factor B) which is associated with both Factor A and the outcome. Confounding is often a problem in observational studies when the characteristics of people in one group differ from the characteristics of people in another group. When confounding factors are known they can be measured and controlled for (see ‘multivariable analysis’), but some confounding factors are likely to be unknown or unmeasured. This can lead to biased results. Confounding is not usually a problem in randomised controlled trials. 

chemotherapy

The use of drugs to treat an illness, especially cancer.

washout period

The time it takes for a drug to be completely cleared from the body after its use is discontinued. In cross-over trials, participants typically have a washout period after they have completed a course of treatment with one study drug before beginning the course with a second study drug. 

After a wash out period the procedure was repeated for seven days, except that all the volunteers received a daily one gramme dose of vitamin C concluding on the day that blood was collected for indinavir concentrations. Diet was controlled for the duration of the study to ensure that there were no nutrition-related confounding factors.

It was found that vitamin C caused a fall of 20% in maximum indinavir concentrations (p=0.04) and a 14% reduction in steady-state eight hour concentrations (p

On the basis of these data, the investigators conclude that vitamin C can cause a reduction in indinavir concentrations and recommend that doctors caution patients about the dangers of taking vitamin C and indinavir together.

References

Slain D et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. 43rd ICAAC, abstract A-1610, Chicago, September 14 – 17th, 2003.