It’s been increasingly clear that the widespread marketing of antioxidants as vital health-giving nutrients is often mistaken. Taking antioxidants reduces the cellular effects of exercise, and interferes with many forms of cancer treatment (both of which effects are exactly the opposite of the popular conceptions of what should be happening). And now comes word that the same problem seems to exist with the leading tuberculosis drug in the world, isoniazid.
A recent clinical trial in South Africa pointed out some potential trouble. This was a study of a popular dietary supplement (Sutherlandia), a botanical preparation which is apparently widely used in many parts of Africa for infections and general health. It’s widely taken by HIV-positive patients in South Africa, but this is apparently the first controlled trial to see if it has any effect. Unfortunately, it appears to do nothing for HIV at all (viral loads and T-lymphocyte counts did not change). But what did happen was that two of the participants developed active tuberculosis, even though they were taking isoniazid as preventative therapy. The authors proposed that the antioxidant effects of the supplement interfere with isoniazid’s mechanism of action, which is widely believed, on a great deal of evidence, to be oxidative activation with release of nitric oxide and other reactive species. They also suggested that other antioxidant supplements should be studied to see if they have similar effects.
Here’s a paper from a group at Missouri following up on this. Sutherlandia extracts do indeed seem to reduce the production of reactive oxygen species, and reduce gene expression markers of oxidative stress. According to the labels on the juice bottles and nutrition bars, the end-caps in the vitamin aisles, and the blurbs on the popular magazine covers, these should all be great things. But they’re not, or certainly not always – your response to infection and other kinds of cellular stress depends on reactive oxygen species and signaling thereof, and just blocking it wholesale is a bad idea. This certainly doesn’t seem to have penetrated into the popular culture, which is apparently All Antioxidants, All The Time, but it should.
Update: a colleague points out that Sutherlandia is also a known CYP3A4 inducer. In rats it shows a definite interaction with nevirapine via this mechanism, and in humans it increases the clearance of atazanavir. Not what you want among patients taking antiretroviral cocktails, for sure. . .