-IBIS-1.7.0-
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AIDS/HIV Naturopathic Treatment
Immunomodulation
Integrative Therapies

definition

Treatment Principle #5
Immunomodulation

Adrenal glandular -- 2 caps twice daily (Use caution when using glandular products in the age of prions and cross-species viral contamination)

(see also Eleutherococcus below, and Glycyrrhiza. These herbs are purported to help in adrenal fatigue).


Astragalus
• Astragulus injections enhance antibody response to a T-dependent antigen 162


Co-enzyme Q10 -- 30-100 mg tid
• Increases blood levels of CD4-lymphocytes when administered at 100 mg/day 163
• Significantly increases levels of IgG in AIDS patients 164
• Shown to protect against tumor growth and enhance viral immunity in animals 165

Constitutional Acupuncture
(May help with depression, and other symptoms)
• Treating AIDS by acupuncture. 166

• See AIDS and Chinese Medicine by Shattuck and Ryan 167 for a comprehensive discussion of TCM in the treatment of HIV/AIDS.

• In a 12-week randomized, double-blind, placebo-controlled clinical trial, 30 adults with symptomatic HIV infection with CD4+ counts of 200-499 received a combination of 31 Chinese herbs or placebo. Outcome measures included quality of life, symptoms, weight and CD4+ count. No differences between treatment groups attained statistical significance, but there were trends toward greater improvement among herb-treated subjects on all symptom subscales except dermatologic. 168

• Moffett et al (1994) report in an uncontrolled outcomes study that 3 month treatment courses of acupuncture and Chinese herbal therapy in HIV+ patients statistically decreased symptom severity and improved quality of life. 169



• Goh (1991) in a study of 31 HIV+ patients with peripheral neuropathy, showed that acupuncture alleviated pain or tingling in 38% of the patients. 170



• Lu Weibo (1994) has treated 112 HIV/AIDS patients in Tanzania with a Chinese herbal formula called Glyke (60 mg twice daily, po) for 3-6 months. He reports improvements in CD4 counts and reduction in symptoms (Lu Weibo, 1994, personal communication).



Constitutional Homeopathy
• 34-case trial showed increase in CD4+ count in 23 cases, no change in 4 171
• Of 129 HIV-infected patients treated constitutionally, 12 have since seroconverted to negative using the ELISA 108


Constitutional Hydrotherapy
• The skin plays a significant role in immune function 172
• Alpha-2 macroglobulins and complement factor C3 were increased after hydrotherapy treatments 173
• Hydrotherapy helps maximize circulation of well oxygenated, nutrient rich, and toxin-low blood 174



DHEA -- if serum levels low, supplement with oral dosing 5-10 mg/day for women;
15-50 mg/day for men.

• The adrenal steroid hormone, dehydroepiandosterone (DHEA) is an intermediate compound in the synthesis of testosterone and other steroid reproductive hormones. Interest in DHEA accelerated with the publication of Jacobsen et als epidemiological data published in the Journal of Infectious Diseases in 1991175 showing the decreased levels of serum DHEA was a predictor for progression to AIDS in asymptomatic HIV infected men. Another study showed that both DHEA levels and CD4 counts were independent predictors of disease progression in HIV infected men (Mulder, 1992 #132). A correlational study of CD4 counts and serum cortisol and DHEA-sulfate showed a positive relationship between immune status as measured by CD4 count and DHEA, supporting an hypothesis that DHEA deficiency may worsen immune status in HIV infected patients 176



• The effects of oral administration of DHEA in 13 HIV+ patients with baseline CD4 counts of 250-600 cells/mm3 was evaluated in phase I study 177. Five patients treated with the highest of three doses (750 mg/day) had CD4+ cell increases at 8 weeks from a mean of 373/l pre-treatment to 463/l after 8 weeks. In another open label, uncontrolled study in 12 HIV+ patients, DHEA therapy (75 mg/day) increased CD4 and CD8 cell counts in the majority of patients 178.






• A subsequent study (Dyner et al, 1993) evaluated escalating oral doses of DHEA (750 mg/day up to 2,250 mg/day) for 16 weeks in 31 HIV+ patients with baseline CD4 counts between 250 and 600 cells/ul. Dose proportionality was not evidenced by serum DHEA nor by DHEA-sulfate. No sustained increases in CD4 counts nor decreases in serum p24 antigen or beta-2-microglobiulin levels were observed. However, serum neopterin levels decreased transiently by 23-40% at 8 weeks. Suzuki et al (1995) have suggested that low levels of DHEA may cause immunological deficits via deficient IL-2 production in lymphocytes. Abnormal levels of DHEA were associated with low levels of serum IL-2.

• Direct murine lymphocyte exposure to DHEA at low concentrations (10-10 - 10-7 M) enhanced secretion of IL-2 following immunological challenge. 179

• DHEA is a modest selective inhibitor of HIV-1 replication in human lymphocytes and macrophages. The antiviral mechanism does not appear to be mediated through reverse transcriptase inhibition since DHEA did not inhibit HIV-1 RT enzymatic activity when tested up to 100 uM. Acute infection of normal human lymphocytes was also inhibited by DHEA at 10-100uM 180. In another in vitro experiment, 50% inhibition of macrophage HIV p24 expression occurred at concentrations of 3-30 ug/ml 175.

• DHEA is frequently prescribed to, and self prescribed by, many HIV+ patients in the U.S. Caution may be appropriate given that high serum DHEA levels have also been implicated in the pathogenesis of Kaposis sarcoma in HIV/AIDS. DHEA levels were significantly higher, as were testosterone and androstenedione in 34 HIV+ patients with KS vs. 35 HIV+ controls without KS 181.

• In a small open-label trial with 20 HIV+ people, DHEA as monotherapy at fairly high doses of 600 mg twice a day was shown to reduce viral load by 0.6 log unit in HIV patients with baseline CD4 counts of 50-300 182.


Echinacea 1/2 tsp tincture qid for acute viral symptoms - not for chronic use
• Increases the number of polymorphonucleocytes and monocytes, induces C-reactive proteins and elevates ESR 183
• Stimulates macrophages in vivo 184
• Prophylactic treatment results in decreased number and severity of infections 185


Eleutherococcus -- Maxim-L (Omega) 10 gtt twice daily -- (helpful for adrenal fatigue)
• Increases T helper cells, as well as cytotoxic and natural killer cells in vitro or in vivo? 186
Lentinan (from Shiitake mushrooms (Lentinus edodes)) -- 3 caps tid
• Increase host resistance to various bacterial, viral and parasitic infections, including HIV 187

• Manifests marked antitumor and antimetastatic activity and prevents chemical and viral carcinogenesis 188

• With IL-2, Lentinan stimulates CD8+ cytotoxic T-lymphocyte anti-tumor activity in vitro 189

Maitake mushrooms -- 3 caps tid
• Polysaccharide fraction responsible for anti-tumor activity 190

• Activities of macrophage, killer cells and cytotoxic T cells increased in vitro. Significant immune stimulating activity confirmed even with oral administration, including increased Anti-tumor activity in vivo as well as anti-HIV activity in vitro 191


N-acetyl cysteine (see previous section)


Thymic fractions -- 2 caps twice daily (Use caution when using glandular products in the age of prions and cross-species viral contamination)
• Thymic hormone (of which zinc is essential cofactor) stimulation may be important in AIDS. 192
• Improves clinical symptoms and T-cell defects in early stages of HIV infection 193
• Thymostimulin increases CD4 lymphocytes 194
• Regulates differentiation of T-cell precursors, normalizing the ratio between helper and suppressor subsets 195
• Improves clinical symptoms and T-cell defects in early stages of HIV infection 193


Vitamin B6 (pyridoxine) -- up to 100 mg twice daily
• >5X RDA of B1; >5X RDA of B2; B3; >2X RDA of B6, and Beta-carotene all associated with increased survival in HIV-1-infected people. Any quantity of zinc was associated with poorer survival. 9
• Deficiency of pyridoxine induces atrophy of lymphoid organs, marked reduction in lymphocyte numbers, impairs antibody responses and IL-2 production. 196
• For HIV+ men, immunodeficiency was associated with consumption of vitamin B6 and zinc at the RDA level. 99
• 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
• Impaired immune responsiveness in HIV-1-infected patients with compromised vitamin B6 status. 197
• Vitamin B6 status in HIV-1-infected subjects was significantly associated with functional parameters of immunity. 198


Zinc -- Not generally recommended. Eat foods high in zinc instead of supplements. Pumpkin seeds, oysters, etc.
• 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
• Thymic hormone (of which zinc is essential cofactor) stimulation very important in AIDS. 192
• 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
• Serum copper levels were higher in HIV-1- seropositive progressors than the seropositive nonprogressors and the seronegatives. Conversely, serum zinc levels were lower in the seropositive progressors than the seropositive nonprogressors and the seronegatives. Furthermore, higher serum copper and lower serum zinc predicted progression to AIDS independently of baseline CD4+ lymphocyte level, age, and calorie-adjusted dietary intakes of both nutrients. 199
• Of a sample of 30 HIV-1 (+) subjects, some of whom were found to have below normal plasma concentrations include: zinc-30%, calcium-27%, magnesium-30%, carotenes-31%, total choline-50%, and ascorbate-27%. Percentages with above normal values include: folate-37% and carnitine-37%. Some subjects with above normal values for plasma vitamins reported self-supplementation, usually with large doses. 91

Promising substances to be further investigated:
Melatonin regulates not only neuroendocrine functions but also has immunoenhancing and antitumor effects. 200
Testosterone -- if levels low: 5-10 mg/day for women; 50-100 mg/day for men (see section 8)
Ganoderma lucidum mushrooms (Reishi)
Amino Acids: there may be reduced humoral antibody response with deficiency of cysteine, methionine, phenylalanine, threonine, tryptophan, tyrosine, or valine.


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:

162. Zhao KS, Mancini C, Doria G: Enhancement of the immune response in mice by Astragalus membranaceus extracts. Immunopharmacology 20:225-33, 1990
163. Folkers K, Morita M, McRee J, Jr.: The activities of coenzyme Q10 and vitamin B6 for immune responses. Biochem Biophys Res Commun 193:88-92, 1993
164. Folkers K, Brown R, Judy WV, Morita M: Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun 192:241-5, 1993
165. Tanner HA: Energy transformations in the biosynthesis of the immune system: their relevance to the progression and treatment of AIDS. Med Hypotheses 38:315-21, 1992
166. Dui J: Explore of treating AIDS by acupuncture. Chen Tzu Yen Chiu 15:250-1, 1990
167. Shattuck AD, Ryan, M.K.: Treatting AIDS with Chinese Medicine. Berkley, Pacific View Press, 1994
168. Burack JH, et al.: Pilot randomized controlled clinical trial of Chinese herbal treatment for HIV-associated symptoms. J AIDS Hum Retrovitrl 12:386-93, 1996
169. Moffett H, et al.: Using acupuncture and herbs for the treatment of HIV infection. AIDS Patient Care, 8, 1994
170. Goh M: Acupuncture treatment for neuropathy - patients with HIV infection. International Symposium on Viral Hepatitis and AIDS April, 1991
171. Wolffers I, et al.: Intl AIDS Conf , 1994
172. Edelson RL, Fink JM: The immunologic function of skin. Sci Am 252:46-53, 1985
173. Ring J, Teichmann W: Immunological changes during hydrotherapy. Dtsch Med Wochenschr 102:1625-30, 1977
174. Fisher E, et al.: Ther Heat and Cold Eliz Licht Publ , 1965
175. Jacobsen M, Fusaro R, Galmarini M, Lange W: Decreased serum dehydroepiandrosterone is associated with an increased progression of HIV virus infection in men with CD4 cell counts 200-499. J Infectious Dis 164:864-868, 1991
176. Wisniewski TL, Hilton CW, Morse EV, Svec F: The relationship of serum DHEA-S and cortisol levels to measures of immune function in human immunodeficiency virus-related illness. Am J Med Sci 305:79-83, 1993
177. Dyner TS, et al.: An open-label dose-escalation trial of oral dehydroepiandrosterone tolerance and pharmacokinetics in patients with HIV disease. J AIDS 6:459-465, 1993
178. Hasheeve D, Salvato P, Thompson C: DHEA: a potential treatment for HIV disease. Intl AIDS Conference Abstract no PB0322, 1994
179. Daynes R, Dudley DJ, Araneo BA: Regulation of murine lymphokine production in vivo II. DHEA is a natural enhancer of interleukin 2 synthesis by helper T cells. Eur J Immunol 20:793-802, 1990
180. Schinazi RF, Eriksson B, Arnold B, Lekas P, McGrath M: Effect of DHEA in lymphocytes and macrophages infected with HIV-1. Intr AIDS Conf Abstract # MCP 55, 1994
181. Christieff N, Gharakhanian C, Thobie N, et al.: Differences in androgens of HIV positive patients with and without Kaposis sarcoma. J Clin Pathology 48:513-518, 1995
182. Salvata ea: XI International Conference on AIDS Abstract We.B.3385, 1996
183. Roesler J, Emmendorffer A, Steinmuller C, Luettig B, Wagner H, Lohmann-Matthes ML: Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to test subjects mediates activation of the phagocyte system. Int J Immunopharmacol 13:931-41, 1991
184. Luettig B, Steinmuller C, Gifford GE, Wagner H, Lohmann-Matthes ML: Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J Natl Cancer Inst 81:669-75, 1989
185. Schoneberger D: Forum Immunologie 8:2, 1992
186. Bohn B, et al.: Flow-cytometric studies with eleutherococcus senticosus extract as an immunomodulatory agent. Arzneim Forsch/ Drug Research 37:1193, 1987
187. Chihara G: Recent progress in immunopharmacology and therapeutic effects of polysaccharides. Dev Biol Stand 77:191-7, 1992
188. Suzuki M, Takatsuki F, Maeda YY, Hamuro J, Chihara G: Antitumor and immunological activity of lentinan in comparison with LPS. Int J Immunopharmacol 16:463-8, 1994
189. Suzuki M, Kikuchi T, Takatsuki F, Hamuro J: Curative effects of combination therapy with lentinan and interleukin-2 against established murine tumors, and the role of CD8-positive T cells. Cancer Immunol Immunother 38:1-8, 1994
190. Yamada Y, et al.: Chemotherapy 38:790, 1990
191. Nanba H, et al.: Int Conf AIDS 8:30, 1992
192. Ripa S, Ripa R: Zinc and immune function. Minerva Med 86:315-8, 1995
193. Valesini G, Barnaba V, Benvenuto R, Balsano F, Mazzanti P, Cazzola P: A calf thymus acid lysate improves clinical symptoms and T-cell defects in the early stages of HIV infection: second report. Eur J Cancer Clin Oncol 23:1915-9, 1987
194. Carco F, Guazzotti G: Therapeutic use of thymostimulin in HIV-seropositive subjects and with lymphadenopathy syndrome. Recenti Prog Med 84:756-64, 1993
195. Trainin N: Prospects of AIDS therapy by thymic humoral factor, a thymic hormone. Nat Immun Cell Growth Regul 9:155-9, 1990
196. Harbige LS: Nutrition and immunity with emphasis on infection and autoimmune disease. Nutr Health 10:285-312, 1996
197. Vitamin B6 and immune function in the elderly and HIV-seropositive subjects. Nutr Rev 50:145-7, 1992
198. Baum MK, Mantero-Atienza E, Shor-Posner G, Fletcher MA, Morgan R, Eisdorfer C, Sauberlich HE, Cornwell PE, Beach RS: Association of vitamin B6 status with parameters of immune function in early HIV-1 infection. J Acquir Immune Defic Syndr 4:1122-32, 1991
199. Graham NM, Sorensen D, Odaka N, Brookmeyer R, Chan D, Willett WC, Morris JS, Saah AJ: Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. J Acquir Immune Defic Syndr 4:976-80, 1991
200. Kancheva RL, Zofkova I: Melatonin--the hormone of darkness. Cas Lek Cesk 135:231-5, 1996

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.