Pulse Administration Of The Drug N-Acetylcysteine in Comparison with the

Feeding of a Specially Prepared Whey Protein Isolate: a Natural Cysteine

Delivery System
By Gustavo Bounous, MD
N-Acetylcysteine (NAC)
NAC is commonly and effectively used as an antidote for acetaminophen toxicity in humans when
rapid restoration of glutathione level in the liver cells is needed. Most of the adverse reaction to
NAC can be attributed to the non utilized cysteine either for glutathione (GSH) synthesis or the
sulfate pathway. The most common reaction associated with therapeutic dosage of NAC consists
of skin manifestations alone and occasionally bronchospasm and hypotension. It is suspected
that they are anaphylactic in nature (1-4). More recently Herzenberg (5) reported the oral
administration of NAC to 200 AIDS patients (3200-8000 mg per day, median 4.4) with GSH
replenishments. Nine patients left the trial, mainly within a week, citing symptoms such as
nausea and rash which were similar to symptoms reported by subjects who completed the trial
(legend of Fig. 6, ref. 5)
Another danger of pulse administration of NAC is its paradoxical effect on HIV-1 replication: NAC
at 2.5 m M enhances the self sustained HIV-1 replication in monocyte-derived
macrophages. This effect was inhibited by

OH scavenger which agrees with the observation that

NAC can reduce Fe
3+
to Fe
2+
thereby catalyzing

OH generation from H
2
O
2
(6)
More severe and even lethal effects are related to the neurotoxicity of NAC. For example, Dr.
Paul Cheney Director of the Cheney Clinic in Charlotte N.C. observed 12 patients treated with
oral NAC (1 g a day). Two of these patients developed severe encephalopathy (7)
Immunocal
The whey protein isolate, Immunocal, was administered to children with AIDS and wasting for a
6 month period. No adverse effect was noted and peripheral blood mononuclear cell GSH was
restored to normal values when it was below normal at the onset of the study (8) The effect on
cellular GSH were comparable to that obtained in Herzenberg study with NAC (5) but without the
reported side effects. Immunocal was also effectively administered to seven patients with
metastatic carcinoma for a 6 month period with no side effects (9). In addition, several thousand
individuals have been taking Immunocal (10-40 gr. a day) for months to several years. No
complaints have been reported to Immunotec which could be related to adverse reaction to the
treatment. The only provision was the exclusion of subjects with the rare form of milk protein
allergy or recipients of organ transplants. Immunocal contains less than 1% lactose well below
the threshold of lactose intolerance.
In conclusion, the delivery to the blood system of the crucial GSH precursor, cystine, from the
digestion-absorption of the undenatured whey proteins appear to represent a natural non toxic
way to obtain a sustained physiological level of cellular GSH.
REFERENCES
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1979; ii: 1298.
2. Vale JA, Wheeler DC. Anaphylactoid reactions to N-acetylcysteine. Lancet 1982; ii: 988.
3. Ho SW-C, Beilin LJ. Asthma associated with N-acetylcysteine infusion and paracetamol
poisoning. Report of two cases. Br Med J 1983: 287: 876-7.
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poisoning. Br Med J 1983; 187: 1223.
5. Herzenberg LA, DeRosa SC, Dubs JG, Roederer M, Anderson MT, Ela SW, Deresinski
SG, Herzenberg LA. Glutathione deficiency is associated with impaired survival in HIV
disease. Proc Natl Acad Sci 94/1967-72/1997.
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radicals in the self-sustained HIV-1 replication by N-acetyl-L-cysteine. J. Leucocyte Biol. 56:
702-707, 1994.
7. Cheney P. The Cheney Clinic, Charlotte N.C. USA, Personal communication May 1998.
8. Baruchel S, Viau G, Oliver P, Bounous G, Wainberg MA. Nutriceutrical modulation of
glutathione with a humanized native milk serum protein isolate, Immunocal. Application in
AIDS and cancer, in Oxidative stress in Cancer, AIDS, and neurodegenerative diseases. Ed
Montagnier L, Olivier R, Pasquier C, Publ. Dekker M. New York pp. 447-461, 1998.
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concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical
study. Anticancer Res. 15: 2663-50 1995.