Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients

Background HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxi dant. The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis. Therefore, different str ategies to supplement cysteine supply have been suggested to increase gluta thione levels in HIV-infected individuals. The aim of this study was to eva luate the effect of oral supplementation with two different cysteine-rich w hey protein formulas on plasma GSH levels and parameters of oxidative stres s and immune status in HIV-infected patients. Methods In a prospective double blind clinical trial, 30 patients (25 male, 5 female; mean age (+/- SD) 42 +/- 9.8 years) with stable HIV infection (2 21 +/- 102 CD4 + lymphocytes L-1) were randomized to a supplemental diet wi th a daily dose of 45 g whey proteins of either Protectamin (Fresenius Kabi , Bad Hamburg,Germany) or Immunocal (Immunotec, Vandreuil, Canada) for two weeks. Plasma concentrations of total, reduced and oxidized GSH, superoxide anion (O2-) release by blood mononuclear cells, plasma levels of TNF-alpha and interleukins 2 and 12 were quantified with standard methods at baselin e and after therapy. Results Pre-therapy, plasma GSH levels (Protectamin: 1.92 +/- 0.6 muM, Immu nocal: 1.98 + 0.9 muM) were less than normal (2.64 +/- 0.7 muM, P = 0.03). Following two weeks of oral supplementation with whey proteins, plasma GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.2 muM, P = 0.004) while the difference in the Immunocal group did not reach signif icance (+ 24.5 +/- 59%, 2.51 +/- 1.48 muM, P = 0.43). Spontaneous O2- relea se by blood mononuclear cells was stable (20.1 +/- 14.2 vs. 22.6 + 16.1 nmo l h(-1) 10(-6) cells, P = 0.52) whereas PMA-induced O2- release decreased i n the Protectamin group (53.7 +/- 19 vs. 39.8 +/- 18 nmol h(-1) 10(-6) cell s, P = 0.04). Plasma concentrations of TNF-alpha and interleukins 2 and 12 (P > 0.08, all comparisons) as well as routine clinical parameters remained unchanged. Therapy was well tolerated. Conclusion In glutathione-deficient patients with advanced HIV-infection, s hort-term oral supplementation with whey proteins increases plasma glutathi one levels. A long-term clinical trial is clearly warranted to see if this 'biochemical efficacy' of whey proteins translates into a more favourable c ourse of the disease.