Click Here for .pdf on: RAISING GLUTATHIONE USING CYSTEINE By Dr. Wulf Dröge & Dr. Jimmy Gutman
By Gustavo Bounous, MD
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 Fe3+ to Fe2+ thereby catalyzing •OH generation from H2O2 (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)
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.
1. Walton NG, Mann TAN, Shaw KM. Anaphylactoid reaction to N-acetylcysteine. Lancet 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.
4. Vale JA, Buckley BM. Asthma associated with N-acetylcysteine infusion and paracetamol 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.
6. Nottet HSLM, Asbeck Van, Graaf/L de vos NM de, Visser MR, Verhoff I. Role of oxygen 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.
9. Kennedy R.S, Konok GP, Bounous G, Baruchel S, Lee TD. The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical study. Anticancer Res. 15: 2663-50 1995.
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