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HIV NUTRITION UPDATE
VOLUME 6, ISSUE 2
N-Acetylcysteine
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USES IN HIV

The role of NAC in HIV has been examined since 1989 in 15 peer-reviewed publications. (2,3,7,8,11,16,17,28,32,35, 38,42,49,56,58) Due to its history of safe use as a therapeutic agent, NAC has been suggested as a potential supplement for GSH replenishment in HIV since 1991. (21,27,41) Early clinical studies on the use of NAC in HIV were compromised due to their small size, inability to classify disease progression or lack of therapies to provide some control over viral replication. 
 

"Unlike cysteine, NAC is not found in foods but serves as a delivery form of cysteine."
In pharmacokinetic studies examining the ability of NAC to affect cysteine and GSH concentrations, both positive (16) and negative (58) effects of NAC on GSH replenishment were described. In the de Quay study, nine persons with HIV (PWHIV) and six controls received about 2100 milligrams (mg) NAC as a single, oral dose. This dose of NAC increased the plasma concentration of NAC from undetectable at time 0 to 8.7 and 10.7 µmol/L at two hours in PWHIV and controls, respectively. In four hours, nearly all of the NAC had disappeared from plasma. Increases in plasma cysteine were three- to four-fold in all subjects, also returning to baseline at 4 hours. GSH content of peripheral blood mononuclear cells (PBMC) was moderately, but significantly (P=0.02) increased in PWHIV, but was unchanged in the controls. In the Witschi study, six PWHIV were given 1.8 grams NAC per day for two weeks. During treatment, the plasma concentration of cysteine increased, but there was no increase in GSH in plasma or in PBMC. (58)
 
INTERVENTION STUDIES 

One partially blinded and three blinded (neither the researchers nor the participants knew who got the treatment or the placebo) NAC intervention studies reported a positive effect of supplementation on survival and immunologic functioning in HIV. The partially blinded study was (1) double-blinded, placebo-controlled for four months and (2) single-blinded with the investigators knowing the treatments, for the remaining two years. In a partially blinded study, the Herzenberg group (28) reported on the supplementation of PWHIV with median doses of 4400 mg NAC for up to eight months. They showed that (1) NAC supplementation replenishes GSH concentrations in T cells; (2) GSH concentrations in T cells predict survival in PWHIV and; (3) GSH replenishment affects survival in PWHIV. Following 44 subjects, 25 who had taken a median dose of 4400 mg of NAC for 8 to 32 weeks, over a two to three year period demonstrated a marked difference in survival between the groups. At the time when survival of the No NAC group was only 50 percent, more than 80 percent of the NAC group was still alive. 

In a double-blinded, placebo controlled trial, a sub-group of the Herzenberg study of 246 PWHIV, 81 relatively healthy PWHIV were stratified into two groups based upon CD4 T-cells counts of (1) 200 to 500 cells per µL or (2) less than 200 cells per µL. (17) The subjects received 8000 mg of NAC per day for eight weeks followed by an optional open-label period for up to 24 weeks. Whole blood GSH levels in the NAC arm subjects increased from 0.88 mM to 0.98 mM (P=0.03), with no change in the placebo group. This increase brought the NAC-treated subjects to 89 percent of the uninfected controls. Additionally, T cell GSH also increased in the NAC-treated PWHIV (P=0.04).
 

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9/30/2001