-IBIS-1.7.0-
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AIDS/HIV Naturopathic Treatment
Anti-oxidant therapy to reduce oxidative stress
Integrative Therapies
definition
Treatment Principle 1:
Anti-oxidant therapy to reduce oxidative stress
Oxidative stress may contribute to several aspects of HIV disease pathogenesis and progression such as viral replication, inflammation, decreased immune cell proliferation, loss of immune function, apoptosis, weight loss, and increased drug toxicities. Since HIV-infected people are immunosuppressed, they are susceptible to inflammatory reponses induced by oxidative stress resulting from exposure to viral and opportunistic pathogens and drugs. Inflammation is associated with the formation of reactive oxygen intermediates (ROIs), cytokines such as IL-1, IL-2 and IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF- or ). Evidence for oxidative damage in HIV-infected patients is provided by the finding that malondialdehyde, a by-product of lipid peroxidation, is increased in HIV infection 3. HIV-infected patients have been demonstrated to have increased levels of TNF- and IL-6 in their serum 4. Even asymptomatic HIV+ patients show elevated sedimentation rates 5. The goal of anti-oxidant therapy is to quench free radicals or ROIs produced by inflammation.
B-carotene -- 150,000 IU twice daily
Found a significant depletion In HIV+ patients of plasma levels of all the carotenoids, including lutein, cryptoxanthin, lycopene, alpha-carotene and beta-carotene as well as vitamin C and cholesterol. 6
There is a dramatic serum beta-carotene deficiency in HIV-infected children. It is even more pronounced in children with AIDS. 7
Selenium and B-carotene improve the function of the enzymatic antioxidant system in blood and glutathione status in HIV-infected patients. 8
Greater than 5 times the RDA of B1; >5X RDA of B2; B3; >2X RDA of B6, and B-carotene all associated with increased survival in HIV-1-infected people. Any quantity of zinc was associated with poorer survival. 9
Serum vitamin A and B-carotene are decreased in HIV-1-infected pregnant women in the first trimester who have CD4 counts lower than 200. 10
Even asymptomatic patients present a severe B-carotene deficiency. Carotene deficit and associated increase in free radicals are potentially harmful, suppressing HIV latency in infected macrophages, stimulating viral replication and decreasing cellular immunity 11.
B-carotene 180 mg/day, increased CD4 counts by 17% in 4 wks in a randomized controlled trial in HIV+ patients. 12
Supplementation decreases fever, nocturnal sweating, diarrhea, weight loss and improved mean CD4 counts. 13
Low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed 14
Note: Recent data may indicate that synthetic B-carotenoids may increase risk of lung cancer in smokers 15. There is now controversy about the safety of B-carotene. Given these uncertainties, we use only natural carotenoids and inform our patients, particularly those who smoke, of the possible risks of taking B-carotene. For patients who have doubt about the safety of taking supplemental B-carotene, we recommend two glasses of freshly juiced carrot juice instead.
Co-enzyme Q10 (30-100 mg tid)
AIDS patients had a blood deficiency of co-Q 10 compared to non-HIV+ controls. This deficiency was greater than that seen in compared to ARC patients 16
Co-Q10 (100 mg/day) increased CD4+/CD8+ ratios in non-HIV subjects 17
Vitamin C -- 2000 mg three times daily between meals
Despite the fact that vitamin C is commonly taken in high doses by HIV+ individuals, no controlled studies have been done to date in humans. Some in vitro work suggests that ascorbate can suppress HIV replication in both chronically and acutely infected T-lymphocytes 18. Health care providers differ in recommendation regarding vitamin C dosing for HIV+ patients. Some recommend a slow increase in oral dosing until bowel tolerance (6-20 g/day) is attained. We have noticed that those patients with GI dysbiosis will experience diarrhea from even the lowest dose recommended. This may indicate a need to perform a complete digestive stool test to assess gastrointestinal candidiasis and/or inflammation.
Some of the antiviral protease inhibitors such as Indinavir can induce nephrolithiasis. Although there have been no specific studies addressing the question of whether vitamin C adds to the risk of kidney stones in patients taking Indinavir, there is some concern about adding excessive levels of ascorbic acid to the regime of a patient taking this particular protease inhibitor.
More information about vitamin C in its role as an antiviral may be found in the later section on naturopathic antiviral therapy.
Ascorbate saturation by lymphocytes has been linked to enhanced immunocompetence 19
Vitamin E -- 400 IU/day
Vitamin A, E, and B12 deficiency accelerated the development of AIDS 20
Supplementation at high levels can modulate cytokine production by thymocytes 21
Restores retrovirus-suppressed splenocyte proliferation and natural killer cell cytotoxicity 22
Partially reverses the myelosuppressive action of AZT in HIV-infected patients 23
The hazard of AIDS decreased as consumption increased for all 11 micronutrients; this relationship was statistically significant for iron, vitamin E, and riboflavin, in a sample of 296 HIV-seropositive men 24
Vitamin E has demonstrated immunoenhancing, and anti-oxidant properties 25
Reduced blood levels of vitamin E and polyunsaturated fatty acids of phospholipids (PUFA-PL) favor the onset and the development of AIDS 26
Selenium -- 200-600 mcg/day
Selenium deficiency common in HIV infection and AIDS 27
Selenium and beta carotene improve the function of the enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients 8
In vitro dose-dependent inhibition by selenium of NF-kappa B controlled gene expression in HIV-1 replication 28
Researchers at the University of Georgia have suggested that the latency period in HIV infection may be attributed to the period of time it takes to deplete the body of selenium storage 29
Stimulation of glutathione peroxidase activity with selenium decreases HIV-1 activation after oxidative stress 30
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 31
Measurements of plasma anti-oxidants and fatty acid (FA) composition of erythrocyte membranes and plasma anti-oxidants in HIV+ patients show that selenium is lower in patients with less than 400 CD4 cells/mm3, vitamin A is lower in the HIV+ regardless of the CD4 cell count, and that. saturated FA are higher and poly-unsaturated FA lower than in controls 32
N-acetyl cysteine -- 1000 mg twice daily
NAC (10 mmol/L) caused less than twofold inhibition of HIV, and conferred a synergistic effect (approximately eightfold inhibition) when tested simultaneously with Vit C (0.426 mmol/L) 33
Reduces HIV-1 replication in stimulated T cells 34
NAC oral administration reversed loss in CD4 count associated with change from optimal intracellular levels of glutathione and cysteine in HIV+ individuals 35.
A series of clinical studies and laboratory investigations suggests that the AIDS may be the consequence of a virus-induced cysteine deficiency36. The relationship between HIV-induced cysteine deficiency and T-cell dysfunction provides a rationale for treatment with N-acetylcysteine. 37
Treatment with N-acetyl-cysteine improved cysteine and glutathione deficiency in AIDS patients 36. Note that orally administered glutathione is hydrolyzed in stomach, and is thus not absorbable. Supplementing NAC and glutamine increases serum glutathione levels.
NAC is a potent suppresser of human immunodeficiency virus transcription in persistently infected cells 38
NAC reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated T cells. However, NAC and glutathione enhanced acute HIV-1 replication in monocyte-derived macrophages in vitro 34
NAC fully replenishes depleted GSH in vitro studies 39
The modulatory effects of NAC on the HIV-1 replication in both chronically and acutely infected lymphocytes that produce high virus levels independently from cytokine activation. In both cases, NAC doses of 0.12 and 0.25 mM decreased, whereas doses of 0.5-2 mM increased the infectious HIV-1 yield 40
Oral N-acetylcysteine increases serum glutathione. 41
Lipoic acid (lipoate, alpha-lipoic acid, dihydrolipoic acid, thioctic acid)
Alpha-lipoic acid was originally classified as a vitamin, but later was found to be synthesized by animals and human. Alpha-lipoic acid is unique in its ability to act as an anti-oxidant in fat- and water-soluble tissues in both its reduced and oxidized forms 42
Alpha-lipoic acid increases intracellular glutathione in human T-lymphocyte cells 43
Alpha-lipoic acid is a biological antioxidant, it prevents HIV activation, and reacts with reactive oxygen species 44
Lipoic acid prevents gene expression of HIV virus 45
Of all the compounds tested, thiamine disulfide, alpha-lipoic acid, and N-acetylcysteine significantly depressed HIV-1 Tat activity. 46
The inhibitory action of alpha-lipoic acid was found to be very potent as only 4 mM was needed for a complete inhibition, whereas 20 mM was required for N-acetylcysteine. These results indicate that alpha-lipoic acid may be effective in AIDS therapeutics47
Alpha-lipoic acid inhibits HIV replication. 48
Lipoate increased plasma ascorbate (9 of 10 patients) total glutathione (7 of 7 patients), total plasma thiol groups (8 of 9 patients), T helper lymphocytes and T helper/suppressor cell ratio (6 of 10 patients). 49
Increases antioxidant recycling and reduces activation of HIV virus by reducing the NF-kappa transcription factor. 50
footnotes
HIV/AIDS: Naturopathic Medical Principles and Practice. Standish, Leanna J., Ruhland, John F., DiDomenico, Beth, and Kjersten Gmeiner. Bastyr University AIDS Research Center. November, 1997.
Bastyr Footnotes:
2. Puro V, Petrosillo N, Ippolito G: Risk of hepatitis C seroconversion after occupational exposures in health care workers. Italian Study Group on Occupational Risk of HIV and Other Bloodborne Infections. Am J Infect Control 23:273-7, 1995
3. Sonnerborg A, Carlin G, Akerlund B, Jarstrand C: Increased production of malondialdehyde in patients with HIV infection. Scand J Infect Dis 20:287, 1988
4. Breen EC, Rezai AR, Nakajima K, Beall GN, Mitsuyasu RT, Hirano T, Kishimoto T, Martinez-Maza T: Infection with HIV is associated with elevated IL-6 levels and production. J Immunol 144:480, 1990
5. Standish LJ, et al.: One year open trial of naturopathic treatment of HIV infection class IV-A in men. J Natropath Med 3:42-64, 1992
6. Lacey CJ, Murphy ME, Sanderson MJ, Monteiro EF, Vail A, Schorah CJ: Antioxidant-micronutrients and HIV infection. Int J STD AIDS 7:485-9, 1996
7. Omene JA, et al.: Serum beta-carotene deficiency in HIV-infected children. J Natl Med Assoc 88:789, 1996
8. Delmas-Beauvieux MC, Peuchant E, Couchouron A, Constans J, Sergeant C, Simonoff M, Pellegrin JL, Leng B, Conri C, Clerc M: The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients: effects of supplementation with selenium or beta-carotene. Am J Clin Nutr 64:101-7, 1996
9. Tang AM, Graham NM, Saah AJ: Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. Am J Epidemiol 143:1244-56, 1996
10. Phuapradit W, et al.: Serum vitamin A and beta-carotene levels in pregnant women infected with human immunodeficiency virus-1. Obstet Gynecol 87:564, 1996
11. Sappey C, et al.: Vitamin, trace element and peroxide status in HIV seropositive patients: asymptomatic patients present a severe beta-carotene deficiency. Clin Chim Acta 230:35, 1994
12. Coodley GO, et al.: Beta-carotene in HIV infection. J AIDS 6:272-6, 1993
13. Bianchi-Santamaria A, et al.: Possible activity of beta-carotene in patients with the AIDS related complex. A Int Conf AIDS 9:496, 1993
14. Beach RS, Mantero-Atienza E, Shor-Posner G, Javier JJ, Szapocznik J, Morgan R, Sauberlich HE, Cornwell PE, Eisdorfer C, Baum MK: Specific nutrient abnormalities in asymptomatic HIV-1 infection. Aids 6:701-8, 1992
15. DeLuca LM, Ross SA: Beta-carotene increases lung cancer incidence in cigarette smokers. Nutr Rev 54:178-80, 1996
16. Folkers KF, Langsjoen P, Nara Y, Muratsu K, Komorowski J, Richardson PC, Smith TH: Biocehmical deficiencies of coenzyme Q10 in HIV-infection and exploratory treatment. Biochem and Biophysical Res Comm 153:886-896, 1988
17. Folkers KT, Hanioka T, Xia LJ, McRee J, Langsjoen P: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochem and Biophysical Res Comm 176:786-791, 1991
18. Harakeh, Jariwalla, Pauling: Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. Proc Natl Acad Sci USA 87:7245-9, 1990
19. Cameron E, Pauling L, Leibovitz B: Ascorbic acid and cancer: A review. Cancer Res 39, 1979
20. Liang B, Chung S, Araghiniknam M, Lane LC, Watson RR: Vitamins and immunomodulation in AIDS. Nutrition 12:1-7, 1996
21. Yuejian W, et al.: Vitamin E supplementation at various levels alters cytokine production by thymocytes during retrovirus infection causing murine AIDS. Thymus 22:153, 1994
22. Yuejian W, et al.: Modulation of immune function and cytokine production by various levels of vitamin E supplementation during murine AIDS. Immunopharm 29:225, 1995
23. Geissler RG, Ganser A, Ottmann OG, Gute P, Morawetz A, Guba P, Helm EB, Hoelzer D: In vitro improvement of bone marrow-derived hematopoietic colony formation in HIV-positive patients by alpha-D-tocopherol and erythropoietin. Eur J Haematol 53:201-6, 1994
24. Abrams B, Duncan D, Hertz-Picciotto I: A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. J Acquir Immune Defic Syndr 6:949-58, 1993
25. Wang Y, Watson RR: Is vitamin E supplementation a useful agent in AIDS therapy. Prog Food Nutr Sci 17:351, 1993
26. Passi S, De Luca C, Picardo M, Morrone A, Ippolito F: Blood deficiency values of polyunsaturated fatty acids of phospholipids, vitamin E and glutathione peroxidase as possible risk factors in the onset and development of acquired immunodeficiency syndrome. G Ital Dermatol Venereol 125:125-30, 1990
27. Dworkin BM: Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS). Chem Biol Interact 91:181-6, 1994
28. Makropoulos V, et al.: Selenium-mediated inhibition of transcription factor NF-kappa B and HIV-1 LTR promoter activity. Arch Toxicol 70:277, 1996
29. Cheung N: Looking at dietary effects on weight loss and diarrhea in HIV seropositive patients: a pilot project. Nutr Health 10:201, 1995
30. Sappey C, Legrand-Poels S, Best-Belpomme M, Favier A, Rentier B, Piette J: Stimulation of glutathione peroxidase activity decreases HIV type 1 activation after oxidative stress. AIDS Res Hum Retroviruses 10:1451-61, 1994
31. Schrauzer GN, Sacher J: Selenium in the maintenance and therapy of HIV-infected patients. Chem Biol Interact 91, 1994
32. Constans J, et al.: Membrane fatty acids and blood antioxidants in 77 patients with HIV infection. Rev Med Interne 14:1003, 1993
33. Harakeh S, Jariwalla RJ: Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells. Am J Clin Nutr 54:1231S-1235S, 1991
34. Nottet HS, van Asbeck BS, de Graaf L, de Vos NM, Visser MR, Verhoef J: Role for oxygen radicals in self-sustained HIV-1 replication in monocyte-derived macrophages: enhanced HIV-1 replication by N-acetyl-L-cysteine. J Leukoc Biol 56:702-7, 1994
35. Kinscherf R, Fischbach T, Mihm S, Roth S, Hohenhaus-Sievert E, Weiss C, Edler L, Bartsch P, Droge W: Effect of glutathione depletion and oral N-acetyl-cysteine treatment on CD4+ and CD8+ cells. Faseb J 8:448-51, 1994
36. Droge W: Cysteine and glutathione deficiency in AIDS patients: a rationale for the treatment with N-acetyl-cysteine. Pharmacology 46:61-5, 1993
37. Droge W, Eck HP, Mihm S: HIV-induced cysteine deficiency and T-cell dysfunction--a rationale for treatment with N-acetylcysteine. Immunol Today 13:211-4, 1992
38. Kinter AL, Poli G, Fauci AS: N-acetyl-cysteine is a potent suppressor of human immunodeficiency virus transcription in persistently infected cells. Trans Assoc Am Physicians 105:36-43, 1992
39. Raju PA, Herzenberg LA, Herzenberg LA, Roederer M: Glutathione precursor and antioxidant activities of N-acetylcysteine and oxothiazolidine carboxylate compared in in vitro studies of HIV replication. AIDS Res Hum Retroviruses 10:961-7, 1994
40. Pani A, et al.: Modulatory effect of N-acetyl-L-cysteine on the HIV-1 multiplication in chronically and acutely infected cell lines. Antiviral Res 22:31, 1993
41. de-Quay B, et al.: Glutathione depletion in HIV-infected patients: role of cysteine deficiency and effect of oral N-acetylcysteine. AIDS 6:815, 1992
42. Nichols TW: Alpha-lipoic acid: Biological Effects and clinical implications. Alt Med Rev 2:177-183, 1977
43. Han D, Tritschler HJ: Packer-L. Alpha-lipoic acid increases intracellular glutathione in a human T-lymphocyte Jurkat cell line. Biochem Biophys Res Commun 207:258, 1995
44. Packer L: alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med 19:227, 1995
45. Merin JP, et al.: Alpha-lipoic acid blocks HIV-1 LTR-dependent expression of hygromycin resistance in THP-1 stable transformants. FEBS Lett 394:9, 1996
46. Shoji S, et al.: Thiamine disulfide as a potent inhibitor of human immunodeficiency virus (type-1) production. Biochem Biophys Res Commun 205:967, 1994
47. Suzuki YJ, Aggarwal BB, Packer L: Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Biochem Biophys Res Commun 189:1709, 1992
48. Grieb G: Alpha-lipoic acid inhibits HIV replication. Med Monatsschr Pharm 15:243, 1992
49. Fuchs J, et al.: Studies on lipoate effects on blood redox state in human immunodeficiency virus infected patients. Arzneimittelforschung 43:1359, 1993
50. Packer L, Suzuki YJ: Vitamin E and alpha-lipoate: role in antioxidant recycling and activation of the NF-kappa B transcription factor. Mol Aspects Med 14:229, 1993
Special Thanks to Leanna Standish, N.D., Ph.D and the staff of the Bastyr University AIDS Research Center.
Reprinted with permission from Pizzorno J, Murray M, The Textbook of Natural Medicine. Revised Edition. London/New York: Churchill-Livingston, 1999.