|Treatment||Alternative treatments||Antioxidants supplementation||Glutamine/glutathione/cysteine/selenium|
|Dietary micronutrients intake and risk of progression to AIDS in HIV-1-infected homosexual men.|| ||Tang AM et al.
| ||In the MACS study, high levels of vitamin C, thiamin, or niacin intake were associated with a reduced risk of progression to AIDS|
| ||Am J Epidemiol 1993; 138: 937-951.||1993|
|Serum selenium concentration and disease progress in patients with HIV infection.|| ||Cirelli A et al.
| ||The selenium concentration in the serum of 67 patients with HIV infection was measured to determine whether selenium deficiency occurred in the different stages of the disease. In the first stage of the study, patients were divided into four groups: symptom-free subjects, PGL (persistent generalized lymphadenopathy), ARC (AIDS related complex), and AIDS (acquired immunodeficiency syndrome). Selenium concentrations were normal in HIV antibody positive symptom-free subjects (1.18 +/- 0.27 mumol/L) and lower than normal in the other three groups (p less than 0.001). There was a significant correlation (p less than 0.001) between selenium levels and values of hemoglobin and erythrocyte sedimentation rate. Selenium deficiency was in no case associated with a lack of zinc in serum (also determined in all patients). In the second stage of the study, 12 patients were treated for a period of two months with low doses of selenium to assess whether such supplementation was able to restore their impaired immunological and hematological functions. The therapy increased serum selenium concentrations (from 0.77 +/- 0.23 to 1.44 +/- 0.41 mumol/L) and symptomatic improvements were noted. However, no changes were observed in the immunological and hematological parameters.|
| ||Clin Biochem 1991; 24: 211-214.||1991|
|HIV-induced cysteine deficiency and T-cell dysfunction: a rationale for treatment with n-acetyl-cysteine|| ||Dorge W, Eck HL, Mihm S.
| ||No abstract / Pubmed|
| ||Immunol Today 1992; 13: 211||1992|
|Selenium deficiency in the acquired immuno-deficiency syndrome.|| ||Dworkin BM, Rosenthal W, Wormser G, Weiss L.
| ||Severe protein-calorie malnutrition is common in patients with AIDS (acquired immunodeficiency syndrome). These nutritional deficits are likely to further impair immune responses and other organ functions vital for recovery from serious infectious diseases. Since selenium deficiency is known to be associated with oral candidiasis and abnormal phagocytic function in animals and depressed helper T-cell numbers in man, we evaluated both selenium status and other nutritional parameters in 12 patients with AIDS compared to 27 healthy controls. Selenium was measured by a spectrofluorometric method. The mean (+/- SD) plasma selenium level in AIDS was 0.043 +/- 0.01 microgram/ml vs 0.095 +/- 0.016 microgram/ml in controls (p less than 0.001). Whole blood selenium and red blood cell selenium levels were also significantly reduced in AIDS (p less than 0.005). The mean weight loss in AIDS patients was 35.5 +/- 21.2 pounds. Serum albumin was significantly (p less than 0.01) lower in AIDS patients compared to controls. A good correlation between serum albumin and plasma selenium was noted (r = 0.77; p less than 0.001). We conclude that selenium deficiency is a common component of the malnutrition seen in AIDS patients. Therefore, aggressive nutritional support, including attention to selenium status, should be considered an integral part of the therapy of AIDS patients.|
| ||J Parenteral Enteral Nutr 1986; 10: 405.||1986|
|Selenium deficiency in HIV infection and the aquired immunodeficiency syndrome (AIDS).|| ||Dworkin BM.
| ||Selenium is required for activity of the enzyme glutathione peroxidase, and selenium deficiency may be associated with myopathy, cardiomyopathy and immune dysfunction including oral candidiasis, impaired phagocytic function and decreased CD4 T-cells. We assessed selenium status in 12 patients with AIDS compared to normals and found significantly low plasma and red blood cell levels. Plasma selenium in AIDS was 0.043 +/- 0.01 microgram/ml vs 0.095 +/- 0.016 in controls (P < 0.001). Selenium status correlated with serum albumin (r = 0.77; P < 0.001) and 60% had documented GI malabsorption as determined by abnormal D-Xylose tests. In a subsequent study blood selenium and glutathione peroxidase were diminished in 12 AIDS and 8 ARC patients compared with normals (all P < 0.001). For glutathione peroxidase the mean levels were decreased by 45% in AIDS and 27% in ARC versus controls (P < 0.001). Both plasma selenium and glutathione peroxidase significantly correlated with total lymphocyte counts (r = 0.65; P < 0.001; glutathione peroxidase and lymphocyte counts). This occurred in both homosexuals and drug users with AIDS and irrespective of the presence or absence of diarrhea or GI malabsorption. To determine if tissue levels of selenium were also depleted we studied cardiac selenium levels in autopsy AIDS hearts compared to age and sex matched controls. Cardiac selenium in AIDS was 0.327 +/- 0.082 micrograms/g dry weight versus 0.534 +/- 0.184 in controls (P < 0.01). Two cases had histologic cardiomyopathy pathologically consistent with the cardiomyopathy described in Keshan disease associated with low selenium blood levels. To further assess mechanisms of nutrient and selenium deficiency in AIDS we studied dietary intake in outpatients and inpatients with various stages of HIV infection. Inadequate selenium intake based on a computer (Nutritionist 3) analysis of 72 h diet records was present in only 17% of clinically stable HIV positive outpatients and 71% of inpatients with AIDS. Conclusions: Selenium deficiency is common in HIV positive patients as documented by low plasma and red blood cell levels of selenium, diminished activity of glutathione peroxidase, and low cardiac selenium levels in AIDS hearts. Patients with AIDS tend to have more severe deficits than those with earlier stages of HIV infection. The selenium deficit in blood does correlate with serum albumin levels and total lymphocyte counts. Poor dietary intake and malabsorption could lead to this condition which has important implications for both cardiac and immune functions in HIV positive patients.|
| ||Chemico-Biological Interactions 1994; 91: 181-186.||1994|
|Study on plasma polyunsaturated fatty acids and vitamin E, and on erythrocyte glutathion peroxidase in highrisk HIV infection categories and AIDS patients.|| ||Passi S et al.
| ||Clin Chem Enzym Comns 1993; 5: 169-177.||1993|
|Glutathione depletion in HIV-infected patients: role of cysteine deficiency and effect of oral n-acetyl-cysteine.|| ||Quey B et al.
| ||To determine whether a single oral dose of N-acetylcysteine corrects the deficiency of cysteine and glutathione in plasma and mononuclear cells of HIV-infected patients. Pharmacokinetic and pharmacodynamic study. Cysteine and glutathione were measured in plasma and peripheral blood mononuclear cells of patients at different stages of HIV infection before and after a single oral dose of N-acetylcysteine. At baseline, the plasma concentrations of glutathione and cysteine were significantly lower in HIV-infected patients than in healthy controls. The intracellular concentration of glutathione correlated with the absolute CD4 lymphocyte counts: the concentration of glutathione in mononuclear cells was significantly lower in patients with more advanced immunodeficiency. A single oral dose of N-acetylcysteine increased the concentration of cysteine in plasma and mononuclear cells of HIV-infected patients. Four hours after N-acetylcysteine administration, intracellular glutathione concentrations in the patients were moderately higher than at baseline and at 2 h. Oral N-acetylcysteine transiently increases the concentrations of cysteine and glutathione in mononuclear cells of patients with HIV infection. A sustained increase in intracellular cysteine may be necessary to normalize intracellular glutathione. This may be accomplished by repeat administration of N-acetylcysteine.|
| ||AIDS 1992; 5: 814.||1992|
|Selenium in the maintenance and therapy of HIV-infected patients.|| ||Schrauzer GN, Sacher J.
| ||Due to its antiviral effects and its importance for all immunological functions, the administration of selenium is suggested as a supportive measure in early as well as in advanced stages of HIV-induced disease. Initial observations on the effects of selenium supplementation in HIV-infected patients indicate that selenium causes symptomatic improvements and possibly slows the course of the disease. As selenium inhibits reverse transcriptase activity in RNA-virus-infected animals, supplemental selenium could also prevent the replication of HIV and retard the development of AIDS in newly HIV-infected subjects. An adequate supply of selenium and of antioxidant vitamins is also proposed as a measure to reduce the probability of the placental transmission of HIV in pregnancy.|
| ||Chem Biol Inter 1994; 91: 199.||1994|
|Intracellular glutathione levels in T-cells subsets decrease in the blood plasma of HIV-1 infected patients.|| ||Staal FJT et al.
| ||Biol Chem Hoppe Seyler 1989; 370: 101-108.||1989|
|Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns.|| ||Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C
| ||Current thinking attributes the balance between T helper 1 (Th1) and Th2 cytokine response patterns in immune responses to the nature of the antigen, the genetic composition of the host, and the cytokines involved in the early interaction between T cells and antigen-presenting cells. Here we introduce glutathione, a tripeptide that regulates intracellular redox and other aspects of cell physiology, as a key regulatory element in this process. By using three different methods to deplete glutathione from T cell receptor transgenic and conventional mice and studying in vivo and/or in vitro responses to three distinct antigens, we show that glutathione levels in antigen-presenting cells determine whether Th1 or Th2 response patterns predominate. These findings present new insights into immune response alterations in HIV and other diseases. Further, they potentially offer an explanation for the well known differences in immune responses in "Th1" and "Th2" mouse strains.|
| ||Proc Natl Acad Sci U S A 1998 Mar 17;95(6):3071-6||1998|
|No title|| ||No author
| ||A recent study in the Lancet reported that glutamine supplementation significantly decreased the incidence of pneumonia, and other life-threatening infections like bacteremia and septicemia, for patients with multiple traumas and who were being fed intravenously. In the study, only 17% of patients on glutamine got pneumonia, compared to 45% of the participants who were not on glutamine. 7% on glutamine contracted bacteremia, while 42% of the non-glutamine group did. Finally, 3% (one person!) of those in the glutamine group experienced sepsis, compared to 26% of the non-glutamine group.|
|Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1-infected patients.|| ||Eck HP, Gmunder H, Hartmann M, Petzoldt D, Daniel V, Droge W.
| ||Blood plasma samples from HIV-1 infected persons contain elevated glutamate concentrations up to 6-fold the normal level and relatively low concentrations of acid-soluble thiol (i.e. decreased cysteine concentrations). The intracellular glutathione concentration in peripheral blood-mononuclear cells (PBMC) and monocytes from HIV antibody-positive persons are also significantly decreased|
| ||Biol. Chem, 1989, Hoppe-Seyler 370:101-8.||1989|
|Oxidative stress in cancer,AIDS and neurogenerative diseases.|| ||Montagnier L, Olivier R, Pasquier C, eds.
| ||A book published with Luc Montagnier as principal editor further confirms the involvement of oxidative stress in AIDS. "We have shown that GSH depletion is associated with impaired survival; the greater the depletion, the worse the prospects for survival...By replenishing GSH, NAC or other agents we may be able to modulate such adverse effects of GSH depletion... HIV-infected individuals would be better served if we could identify the mechanism that underlines the GSH depletion and intervene, if possible, to prevent its occurrence... The best advice they can give in this regard is: "it may be prudent for those individuals to avoid excessive exposure to UV irradiation and unnecessary use of drugs that can deplete GSH - e.g., alcohol and prescription or over-the-counter formulations containing acetominophen [paracetamol]".|
| ||New York: Marcel Dekker Inc, 1998.||1998|
|The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus.|| ||Baruchel S, Wainberg MA
| ||This review describes the potential role of oxidative stress as a cofactor of disease progression from asymptomatic human immunodeficiency virus (HIV) infection to the acquired immunodeficiency syndrome (AIDS). Oxidative stress is a known activator of HIV replication in vitro through the activation of a factor that binds to a DNA-binding protein, NF-kappa B, which in turn stimulates HIV gene expression by acting on the promoter region of the viral long terminal repeat. Tumor necrosis factor alpha (TNF-alpha), an essential cytokine produced by activated macrophages, is also involved in the activation of HIV infection through similar mechanisms. TNF-mediated cytotoxicity of cells exposed to this substance is related to the generation of intracellular hydroxyl radicals. An indirect argument in favor of the role of oxidative stress in HIV-associated disease progression is the consumption of glutathione (GSH), a major intracellular antioxidant, during HIV infection and progression. GSH is known to play a major role in regulation of T cell immune functions. Oxidative stress may also play an important role in the genesis of cellular DNA damage and, in this context, may be related to HIV-associated malignancies and disease progression. Finally, the role of antioxidants as components of therapeutic strategies to combat HIV disease progression is discussed.|
| ||J Leukoc Biol 1992 Jul;52(1):111-4||1992|
|AIDS and the Selenium-CD4 T Cell Tailspin, the geography of a pandemic.|| ||Foster HD.
| ||“Declining host selenium levels...inhibit CD4 T cell production, which permits opportunistic infectious pathogens to proliferate. These pathogens in turn lead to further depression of serum selenium levels and associated decline in CD4 T cell count”|
| ||Townsend Letter. 2000 Dec;94-9.||2000|
|No title|| ||No author
| ||Glutathione and glutathione peroxidase levels are extremely crucial in AIDS/HIV. These important molecules guard against oxidative stress, and can help suppress the development of viruses (Hori K, Hatfield D, Maldarelli F, Lee BJ, Clouse KA. Selenium supplementation suppresses tumor necrosis factor alpha-induced human immunodeficiency virus type 1 replication in vitro. AIDS Res Hum Retroviruses 1997; 13(15):1325-1332). Studies show that glutathione and glutathione peroxidase are much lower in symptomatic AIDS patients than in HIV patients without symptoms or in healthy subjects (Akerlund B, Tynell E, Bratt G, Bielenstein M, Lidman C. N-acetylecysteine treatment and the risk of toxic reactions to trimethoprim-supamethoxazole in primary Pneumocytis carinii prophylaxis in HIV-infected patients. J Infect 1997;35(2):143-147, Look MP, Rockstroh JK, Rao GS, Kreuzer KA, Barton S, Lemoch H, et. al. Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase (GSH-Px)-levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1)-infection. Eur J Clin Nutr 1997;51(4):266 272). A recent study on AIDS wasting syndrome noted that decreasing oxidative stress is a crucial component of a therapeutic protocol for HIV-infected individuals (Kaminski M, Weil S, Bland J, Jan P. AIDS wasting syndrome as an entero-metabolic disorder: the gut hypothesis. Alt Med Rev 1998 (3): 40-53).|
|N-acetylcysteine replenishes glutathione in HIV infection|| ||De Rosa SC , Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, Mitra D, Watanabe N, Nakamura H, Tjioe I, Deresinski SC, Moore WA, Ela SW, Parks D, Herzenberg LA, Herzenberg LA
| ||Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks. HIV-infected, low GSH, CD4 T cells < 500 &mgr;L-1, no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors. Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and beta2-microglobulin levels, also increased in the NAC-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion. NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.|
| ||Eur J Clin Invest 2000 Oct;30(10):915-29||2000|
|The enzymatic antioxidant system in blood and glutathione status in HIV-infected patients: effects of supplementation with selenium or beta-carotene.|| ||Delmas-Beauvieux MC et al.
| ||Daily supplementation with selenium or beta-carotene for 1 year led to significant increases in glutathion peroxidase activity at 3 and 6 months among HIV-positive men and women in France|
| ||Am J Clin Nutr 1996; 64: 101-107.||1996|
|Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction.|| ||Droge W, Holm E
| ||The combination of abnormally low plasma cystine and glutamine levels, low natural killer (NK) cell activity, skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a complex of abnormalities that is tentatively called "low CG syndrome." These symptoms are found in patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic fatigue syndrome, and to some extent in overtrained athletes. The coincidence of these symptoms in diseases of different etiological origin suggests a causal relationship. The low NK cell activity in most cases is not life-threatening, but may be disastrous in HIV infection because it may compromise the initially stable balance between he immune system and virus, and trigger disease progression. This hypothesis is supported by the coincidence observed between the decrease of CD4+ T cells and a decrease in the plasma cystine level. In addition, recent studies revealed important clues about the role of cysteine and glutathione in the development of skeletal muscle wasting. Evidence suggests that 1) the cystine level is regulated primarily by the normal postabsorptive skeletal muscle protein catabolism, 2) the cystine level itself is as physiological regulator of nitrogen balance and body cell mass, 3) the cyst(e)ine-mediated regulatory circuit is compromised in various catabolic conditions, including old age, and 4) cysteine supplementation may be a useful therapy if combined with disease-specific treatments such as antiviral therapy in HIV infection.|
| ||FASEB J. 1997 Nov;11(13):1077-89. Review||1997|
|AIDS THE SELENO-ENZYME SOLUTION|| ||Foster Harold D.
| ||HIV/AIDS patients also display low plasma levels of cysteine at every stage of infection (Droge, W. and others, "Functions of glutathione and glutathione disulfide in immunology and immunopathology", FASEB J 1994; 8:1131-1138). Since this amino acid is one of the body's major sources of sulphur, they are very deficient in it (Breitkreutz, R. and others, "Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials", J Mol Med 2000; 78(1):55-62).|
| ||Nexus Magazine, Volume 11, Number 1 (December-January 2004)||2004|
|High risk of HIV-related mortality is associated with selenium deficiency.|| ||Baum MK et al.
| ||Several studies have documented declining plasma selenium levels in patients with HIV/AIDS. Probably the most convincing of these was conducted by Baum and co-workers in Florida. These researchers monitored 125 HIV-1–seropositive male and female drug users in Miami over a period of 3.5 years. This study collected data on CD4 T-cell count, antiretroviral treatment and plasma levels of vitamins A, E, B6 and B12 as well as selenium and zinc. A total of 21 of these patients died during the study. Only plasma selenium levels and CD4 T-cell counts could have been used to predict which of the 125 patients would die, with selenium levels being more accurate predictors than CD4 T-cell counts. The same research group also monitored 24 HIV-infected children over a five-year period, during which time half of them died of AIDS. As with adults, the lower their serum selenium levels, the faster that death occurred. One of the most significant symptoms of selenium deficiency is a reduction of CD4 T-lymphocytes, which occurs because this trace element is needed for their production.|
| ||J Acquir Immuno Defic Syndr Hum Retrovirol 1997; 15: 370-374.||1997|
|Contribution to characterization of oxidative stress in HIV/AIDS patients|| ||Gil, L. and others,
| ||There is strong evidence to show that HIV-seropositive individuals are deficient in glutathione peroxidase. Gil and colleagues for example, compared levels of it in the blood of 85 HIV/AIDS patients with those in 40 healthy controls, confirming the presence of a significant (p<0.05) reduction of the selenoenzyme in the infected group.|
| ||Pharmacol Res 2003; 47(3):217-224.||2003|
|Abnormal glutathione and sulfate levels after interleukin 6 treatment and in tumor-induced cachexia.|| ||Hack V, Gross A, Kinscherf R, Bockstette M, Fiers W, Berke G, Droge W.
| ||Excessive urea excretion associated with a negative nitrogen balance and massive loss of skeletal muscle mass (cachexia) is a frequent life threatening complication in malignancies and HIV infection. As these patients have often elevated interleukin-6 (IL-6) and abnormally low cystine levels, we have now determined the intracellular levels of glutathione and other cysteine derivatives in the liver and muscle tissue of IL-6-treated or tumor-bearing C57BL/6 mice. IL-6 treatment or inoculation of the MCA-105 fibrosarcoma caused a significant increase in hepatic gamma-glutamyl-cysteine synthetase activity and a decrease in the sulfate level, glutamine/urea ratio, and glutamine/glutamate ratio, suggesting that a decrease of the proton generating cysteine catabolism in the liver may increase carbamoyl-phosphate synthesis and urea formation at the expense of net glutamine synthesis. Treatment with cysteine, conversely, caused an increase in sulfate, glutamine/urea ratios, and glutamine/glutamate ratios and may thus be a useful therapeutic tool in clinical medicine. In contrast to the liver, muscle tissue of tumor-bearing mice showed decreased glutathione and increased sulfate levels, suggesting that the cysteine pool may be drained by an increased cysteine catabolism in this tissue. The findings indicate that tumor cachexia is triggered initially by IL-6 and is later sustained by processes driven by an abnormal cysteine metabolism in different organs.-|
| ||FASEB J. 1996 Aug;10(10):1219-26||1996|
|Cystine levels, cystine flux, and protein catabolism in cancer cachexia, HIV/SIV infection, and senescence.|| ||Hack V, Schmid D, Breitkreutz R, Stahl-Henning C, Drings P, Kinscherf R, Taut F, Holm E, Droge W.
| ||Patients with skeletal muscle catabolism (cachexia) fail to conserve the skeletal muscle protein and release large amounts of nitrogen as urea. Previous studies suggest that the threshold for the conversion of amino acids into other forms of chemical energy and the concomitant production of urea are regulated by the plasma cystine level and hepatic cysteine catabolism. Studies of plasma amino acid exchange rates in the lower extremities now show that healthy young subjects regulate their plasma cystine level in a process that may be described as controlled constructive catabolism. The term controlled describes the fact that the release of cystine and other amino acids from the peripheral tissue is negatively correlated with (certain) plasma amino acid levels. The term constructive describes the fact that the release of cystine is correlated with an increase of the plasma cystine level. The regulation of the plasma cystine level is disturbed in conditions with progressive skeletal muscle catabolism including cancer, HIV infection, and old age. These conditions show also a low plasma glutamine:cystine ratio indicative of an impaired hepatic cystine catabolism. In HIV+ patients and SIV-infected macaques, a decrease of the plasma cystine level was found to coincide with the decrease of CD4+ T cells.|
| ||FASEB J. 1997 Jan;11(1):84-92||1997|
|Glutathione deficiency is associated with impaired survival in HIV disease.|| ||Herzenberg LA, De Rosa SC, Dubs JG, Roederer M, Anderson MT, Ela SW, Deresinski SC, Herzenberg LA
| ||Glutathione (GSH), a cysteine-containing tripeptide, is essential for the viability and function of virtually all cells. In vitro studies showing that low GSH levels both promote HIV expression and impair T cell function suggested a link between GSH depletion and HIV disease progression. Clinical studies presented here directly demonstrate that low GSH levels predict poor survival in otherwise indistinguishable HIV-infected subjects. Specifically, we show that GSH deficiency in CD4 T cells from such subjects is associated with markedly decreased survival 2-3 years after baseline data collection (Kaplan-Meier and logistic regression analyses, P < 0.0001 for both analyses) [85% of those who started the study with high glutathione levels survived the three-year-long study while only 18% with low levels did]. This finding, supported by evidence demonstrating that oral administration of the GSH prodrug N-acetylcysteine replenishes GSH in these subjects and suggesting that N-acetylcysteine administration can improve their survival, establishes GSH deficiency as a key determinant of survival in HIV disease. Further, it argues strongly that the unnecessary or excessive use of acetaminophen, alcohol, or other drugs known to deplete GSH should be avoided by HIV-infected individuals.|
| ||Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1967-72||1997|
|A preliminary open label dose comparison using an antioxidant regimen to determine the effect on viral load and oxidative stress in men with HIV/AIDS|| ||Batterham, M. and others
| ||Batterham and co-workers showed that such depressed glutathione peroxidase levels in men with HIV/AIDS could be raised by supplementation with selenium and other antioxidants.|
| ||Eur J Clin Nutr 2001; 55(2):107-114.||2001|
|The possible role of glutamine in some cells of the immune system and the possible consequence for the whole animal.|| ||Newsholme EA.
| ||Glutamine is important for the function of lymphocytes and macrophages. A role for the high rate of glutamine utilisation by these cells is presented. Since muscle syntheses, stores and releases glutamine, this tissue may play a role in the immune response. Since the number of immune cells utilising glutamine may be large, the demand for glutamine from muscle, especially during trauma, sepsis or burns, may be very high. A speculative suggestion is put forward that this requirement for glutamine from muscle may play a role in cachexia under some of these conditions.|
| ||Experientia. 1996 May 15;52(5):455-9. Review||1996|
|A double-blind placebo-controlled pilot study of glutamine therapy for abnormal intestinal permeability in patients with AIDS|| ||Noyer, C.M. and others,
| ||Glutamine is a major requirement of cells which are rapidly proliferating. As a result there is a significant requirement for it in the digestive tract, where it is essential for intestinal cell proliferation, intestinal fluid/electrolyte absorption and mitogenic response to growth factors. Since glutamine deficiency is so characteristic of HIV/AIDS, it is not surprising that patients typically suffer badly from digestive malfunction and diarrhoea. It has been demonstrated by Noyer and co-workers, at the Albert Einstein College of Medicine, that glutamine therapy improves intestinal permeability in AIDS patients, although the amount required to enhance intestinal absorption may be as much as 20 grams per day.|
| ||Am J Gastroenterol 1998; 93(6):972-975.||1998|
|Glycyl-glutamine improves in vitro lymphocyte proliferation in AIDS patients|| ||Kohler, H. and others
| ||Kohler and co-workers have shown that glycyl-glutamine improves lymphocyte proliferation in AIDS patients.|
| ||Eur J Med Res 2000; 5(6):263-267.||2000|
|The keys of oxidative stress in acquired immune deficiency syndrome apoptosis.|| ||Romero-Alvira D, Roche E.
| ||"Apoptosis is the main cause of CD4+ T-lymphocyte depletion in acquired immune deficiency syndrome (AIDS). Various agents appear to be able to trigger apoptosis in CD4+ T cells... Since oxidative stress can also induce apoptosis, it can be hypothesized that such a mechanism could participate in CD4+ T-cell apoptosis observed in AIDS. This correlates strongly with the observation that AIDS patients present low levels of antioxidants (i.e. superoxide dismutase-Mn, vitamin E, selenium and glutathion) most likely due to ... drug consumption..."|
| ||Med Hypotheses 1998 Aug;51(2):169-73||1998|
|Investigation of the effect of selenium on T-lymphocyte proliferation and its mechanisms|| ||Wang, R.D. and others
| ||Wang and co-workers have demonstrated that selenium enhances lectin-stimulated T-lymphocyte proliferation and is an important modulator for immune response.|
| ||J Tongji Med Univ 1992; 12(1):33-38.||1992|
|2-Mercaptoethanol and n-acetylcysteine enhance T-cell colony formation in AIDS and ARC.|| ||Wu, J., Levy, E.M. & Black, P. H.
| ||One contributing factor to the loss of T cells in AIDS may be the impaired ability of T cell precursors to expand, as reflected in a decreased ability of patient cells to form T cell colonies in agar. We and others have noted such a defect in people with AIDS and ARC, and have found that suppressor cells and suppressive plasma contribute to decreased T-CFC formation. We report here that the reducing agents 2-mercaptoethanol (2-ME) and n-acetyl cysteine (NAC) can enhance colony formation in vitro. In part, 2-ME can reverse the defect in T cell colony-forming cells (T-CFC) formation by overcoming the effect of suppressor cells. In a group of 46 AIDS patients, T-CFC formation was initially 42 +/- 8% (mean +/- s.e.) that of control levels. 2-ME caused an increase of 401 +/- 76% in T-CFC formation which was significantly greater than the increase in control T-CFC formation; it also significantly enhanced T-CFC formation by cells from ARC patients. Suppressor cell activity from ten AIDS patients decreased from 58 +/- 21% to 12 +/- 10% when 2-ME was added. Similar data were obtained from 14 ARC patients. NAC, a related antioxidant with low toxicity, also enhanced T-CFC in cells of AIDS and ARC patients. Vitamin C generally did not increase T-CFC formation. The data suggest that certain antioxidants such as 2-ME and NAC may be useful in treatment protocols to enhance T cell numbers in patients with AIDS or ARC.|
| ||Clin. exp. Immunol., 1989, 77, 1-10.||1989|
|Uptake of selenium-75 by human lymphocytes in vitro|| ||Porter, E.K. and others
| ||Selenium is essential for lymphocytes—as shown by Porter and colleagues, who demonstrated that plasma proteins carry selenium to lymphocytes which absorb it.|
| ||J Nutr 1979; 109(11):1901-1908.||1979|
|Niacin as a potential AIDS preventative factor|| ||Murray, M.F,
| ||Med Hypotheses 1999; 53(5):375-379.||1999|
|Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials|| ||Breitkreutz, R.
| ||Cysteine is a significant source of sulphur and HIV/AIDS patients are very deficient in this element. A trial carried out in Germany by Breitkreutz and colleagues showed that N–acetylcysteine supplementation helped to correct this sulphur deficiency while simultaneously improving immunological functions in HIV/AIDS patients.|
| ||J Mol Med 2000; 78(1):55-62.||2000|
|NAC: First Controlled Trial, Positive Results|| ||James, J.S
| ||There have been numerous clinical trials to explore the impact of cysteine supplementation (usually given as N–acetylcysteine) on HIV/AIDS symptoms. De Rosa and co-workers at Stanford University, for example, have shown that the oral administration of N–acetylcysteine significantly replenished glutathione in HIV-infected individuals.|
| ||AIDS Treatment News 1996; 250:1-3, posted at http://www.aids.org/immunet/atn.nsf/ page/ZQX25002.html.||1996|
|Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast|| ||Peretz, A. and others
| ||There is a wealth of evidence that correcting one or more of the deficiencies of selenium, cysteine, glutamine and tryptophan, which are characteristic of HIV/AIDS, has significant health benefits. Selenium, for example, is a key immunological enhancement agent that has a strong impact on lymphocyte proliferation. This relationship was confirmed by Peretz and co-workers, who monitored enhanced lymphocyte response in elderly subjects given a daily 100-microgram selenium supplement over a six-month clinical trial.|
| ||Am J Clin Nutr 1991; 53(5):1323-1328.||1991|
|Systemic glutathione deficiency in symptom-free-HIV seropositive individuals.|| ||Buhl, R., Holroyd, K. J., Mastrangell, A. et al
| ||Buhl et al. determined the glutathione concentration (reduced, oxidised and total) in plasma and lung epithelial lining fluid of symptom-free HIV seropositive individuals: in both tissues, both the reduced and total GSH concentration was found to be significantly decreased.|
| ||Lancet, 1989, 11, 1294-1297.||1989|
|AIDS THE SELENO-ENZYME SOLUTION|| ||Foster Harold D.
| ||It is interesting to note that antiretroviral drug therapy, designed to prevent HIV-1 replication, slows the rate of tryptophan loss seen in seropositive individuals (Zangerle, R. and others, "Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection", Clin Immunol 2002; 104(3):242-247). Similarly, plasma tryptophan levels can be increased in HIV-infected patients by nicotinamide supplements (Murray, M.F. and others, "Increased plasma tryptophan in HIV-infected patients treated with pharmacologic doses of nicotinamide", Nutrition 2001; 17(7-8):654-656). This is perhaps not surprising, given the close chemical association between this nutrient and the tryptophan derivative, niacin.|
| ||Nexus Magazine, Volume 11, Number 1 (December-January 2004)||2004|
|The Healing Nutrients Within: Facts, Findings and New Research on Amino Acids|| ||Braverman, E.R. (with C.C. Pfeiffer)
| ||Cysteine deficiency, in and of itself, has been shown to be associated with depressed glutathione, poor wound and skin healing, psoriasis, abnormal immune function and greater susceptibility to secondary infections and cancers. All these characteristics of cysteine deficiency are seen in HIV/AIDS patients.|
| ||The Healing Nutrients Within: Facts, Findings and New Research on Amino Acids, Keats Publishing, New Canaan, 1987.||1987|
|Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial.|| ||Shabert JK, Winslow C, Lacey JM, Wilmore DW.
| ||Loss of body cell mass, the active functioning tissue of the body, commonly occurs in patients with human immunodeficiency virus (HIV) infection, and the extent of wasting is related to the length of survival. We evaluated the anabolic role of the amino acid L-glutamine (GLN) and antioxidants in a double-blind, placebo-controlled trial in 26 patients with > 5% weight loss since disease onset. Subjects received GLN-antioxidants (40 g/d) in divided doses or glycine (40 g/d) as the placebo for 12 wk. Throughout the study, the subjects were seen weekly by a nutritionist, and body weight, bioelectric impedance assessment, and nutritional counseling were performed. Twenty-one subjects completed the study, and the groups were well matched. The 5 patients excluded from analysis all met a priori exclusion criteria. Over 3 mo, the GLN-antioxidant group gained 2.2 kg in body weight (3.2%), whereas the control group gained 0.3 kg (0.4%, P = 0.04 for difference between groups). The GLN-antioxidant group gained 1.8 kg in body cell mass, whereas the control group gained 0.4 kg (P = 0.007). Intracellular water increased in the GLN-antioxidant group but not in the control group. In conclusion, GLN-antioxidant nutrient supplementation can increase body weight, body cell mass, and intracellular water when compared with placebo supplementation. GLN-antioxidant supplementation provides a highly cost-effective therapy for the rehabilitation of HIV+ patients with weight loss.|
| ||Nutrition. 1999 Nov-Dec;15(11-12):860-4||1999|
|Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methyl butyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study.|| ||Clark RH et al.
| ||“Supplementation of several amino acids has been suggested as a method for reducing weight loss among HIV-infected individuals. A combination of three amino acids known as HMB/Gln/Arg-beta-hydroxy-beta-methylbityrate (HMB), a metabolite of leucine, L-glutamine (Gln), and L-arginine (Arg), given for 8 weeks to patients with HIV-associated wasting, resulted in significant weight gain for patients in the treatment arm compared with those receiving placebo"|
| ||JPEN 2000; 24: 133-139.||2000|
|No title|| ||No author
| ||Glutamine is an amino acid involved in more metabolic processes than any other amino acid. Glutamine is converted to glucose when more glucose is required by the body as an energy source. It serves as a source of fuel for cells lining the intestines. Without it, these cells waste away. It is also used by white blood cells and is important for immune function. In animal research, glutamine has anti-inflammatory effects and evidence indicates that intravenous glutamine supplementation increases the survival rate of critically ill people (Griffiths RD. Outcome of critically ill patients after supplementation with glutamine. Nutrition 1997;13:752–4). Glutamine in combination with N-acetyl cysteine promotes the synthesis of glutathione, a naturally occurring antioxidant that is believed to be protective in people with HIV infection (Robinson MK, Hong RW, Wilmore DW. Glutathione deficiency and HIV infection. Lancet 1992;339:1603–4). Glutathione (L-gammaglutamyl-L-cysteinylglycine) is a tri-peptide of the amino acids cysteine, glycine, and glutamic acid, it takes up and gives off hydrogen and is important in cellular respiration. A deficiency of glutathione can cause hemolysis (destruction of red blood cells, leading to anemia) and oxidative stress. Glutathione is essential in intermediary metabolism as a donor of sulfhydryl groups which are essential for the detoxification of acetaminophen. [PDR Medical Dictionary. Spraycar. 1999] Selenium is a structural component of, and a co-factor for the antioxidant enzyme glutathione peroxidase. Glutathione participates directly in the neutralization of free radicals, reactive oxygen compounds, and maintains exogenous antioxidants such as vitamins C and E in their reduced (active) forms. It is known to play a critical role in the multiplication of lymphocytes (the cells that mediate specific immunity) which occurs in the development of an effective immune response. "The brain is particularly susceptible to free radical attack because it generates more oxidative-by-products per gram of tissue than any other organ. The brain's main antioxidant is glutathione- it's importance cannot be overstated. Oxidative stress and glutathione are important factors in such various disorders as brain injury, neurodegenerative disease, schizophrenia, Down syndrome and other pathologies." (Dr. Gutman M.D. Glutathione GSH.)|
|NUTRITIONAL THERAPY FOR THE TREATMENT AND PREVENTION OF AIDS, SCIENTIFIC BASES (Southern African Development Community (SADC), Health Ministers Meeting, Johannesburg, South Africa, January 20-21, 2003)|| ||Giraldo Roberto
| ||Selenium is necessary for the proper functioning of the enzyme glutathione peroxidase, which acts as an antioxidant. Selenium deficiency is associated with impaired phagocytosis, decresed CD4 T-lymphocytes, and the occurrence of opportunistic infections. Selenium supplementation as parenteral nutrition improved immune response in patients with chronic gut failure. (Rotruck JT et al. Selenium: biochemical role as a component of glutathione peroxides. Science 1973; 179: 588-590, Peretz A et al. Effects of selenium supplementation in immune parameters in gut failure patients on home potential nutrition. Nutrition 1991; 7: 215-221)|
| ||Roberto Giraldo website||2003|