Reply to James Whitehead 3 January 2005
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Nicholas Bennett,
Infectious Disease Postdoc/Clinician
Department of Pediatrics, University Hospital, Syracuse NY

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Re: Reply to James Whitehead

My personal take on the GSH issue is hinted at in the post Mr Whitehead made. Pre-HAART HIV-infected patients appear to have lower levels of GSH and (interestingly enough) the stereotypical "antioxidant" vitamins. It seems clear that HIV itself induces GSH reduction itself, either directly or through the chronic overstimulation of the cellular immune system (a hyper-catabolic state).

As such, it may very well be true that mere CD4 counts alone are not the whole story, and furthermore the situation may be a double-edged sword. The lower the CD4 count, the greater the progression and (presumably) the worse the GSH situation. They may be no need to choose between the hypotheses, since they're not mutually exclusive!

As such, in the HIV model of infection the use of PIs in controlling the virus will explain the benefits both in terms of improved CD4 cell count and function, and improved GSH/antioxidant levels. The fact that virologic treament failure correlates with worse Vit C levels supports the view that control of the virus leads to less immune-stimulation and subsequent GSH reduction, rather than an effect of the drugs directly. But this perhaps argues for the kind of additional supplementation that Mr Whitehead is taking.

I appreciate Mr Whitehead bringing these studies, and other similar ones in the past, to light. In vitro interventions do seem to make a difference to the cellular function, and I do wonder if Mr Whitehead's personal experiences will be translated to a proper study sometime soon - and that the results are given proper prominence.

I'm unable to find the study in question, but I note that a PubMed search of "glutamine supplementation HIV" throws up a number of articles which I'm sure Mr Whitehead, and others, will find interesting.

On another note, I learnt today that Pneumocystis is unable to produce a certain metabolite (S-adenosylmethionine) which may be involved in GSH production. It therefore scavenges the chemical from the host organism, resulting is significant systemic depletion (which is reversible with treatment) [1]. It may well be that the immune deficiency due to HIV, if it results in PCP, may then result in subsequent further deterioraton of immune function and HIV control.

On a cynical note, one wonders when the first "pharmaceutical" version of GSH will be on the market...

I sincerely wish Mr Whitehead all the best with his latest strategy!

Nick Bennett njb35@cantab.net

1. Skelly et al Lancet. 2003 Apr 12;361(9365):1267-8. "S- adenosylmethionine concentrations in diagnosis of Pneumocystis carinii pneumonia."

Competing interests: None declared