Astragalus as an Adjunctive Therapy in Immunocompromised Patients
November 1999; Volume 2: 125-128
By Teresa Klepser, PharmD and Nicole Nisly, MD
Many patients who are immunocompromised by diseases such as cancer, acquired immunodeficiency syndrome (AIDS), and lupus want to take an active role in controlling their disease. Herbs allow patients to take control without the advice of healthcare professionals. Self-administration of herbs such as astragalus, however, may be dangerous and may delay more useful help.
Historical Indications and Mechanisms
Astragalus (Astragalus membranaceus), also known as huang qi or huang chi, has been used in China for at least 2,000 years.1 Astragalus grows in northern China, Japan, and Korea; the most potent and expensive variety originates in China.2 The medicinal part of the plant is the yellowish-brown root which is sold in 15-20 cm slices.2 The yellowish-white marrow inside the root reportedly tastes like licorice.2
According to the Chinese materia medica, astragalus is recommended as an adaptogenic or tonic herb: It is "Qi tonifying." It is believed to increase the circulation of wei-chee (a protective energy) around the surface of the body.2 Astragalus is also believed to enhance immunity by protecting the body from the Six Evils of aberrant—wind, cold, heat, dampness, dryness, and fire.2 The Six Evils are believed to be the primary causes of disease. For example, wind evil is the carrier of aberrant energies associated with summer and autumn.2 Symptoms of wind injury would include fever and chills, coughs, and sinus congestion.2 Symptoms are also diagnosed in terms of yin and yang polarity.2 Fever would be considered a yang symptom, whereas chills would be considered a yin symptom.2
In traditional Chinese medicine, astragalus is prescribed for general debilities, chronic illnesses, and to increase overall vitality.3 Astragalus has also been recommended for "spleen-Qi deficiency" symptoms, general respiratory disorders (i.e., colds, flu, and shortness of breath), painful joints, numbness, edema, and for the promotion of healing of chronic sores, abscesses, and wounds.1,3,4 The spleen is believed to be the origin of Qi (vital energy) and blood. Therefore, if the spleen were not working properly, a person would be deficient in Qi and blood, and would become weak and tired.5 Spleen-Qi deficiency is believed to be the most common cause of chronic tiredness; symptoms include night sweating, fatigue, diarrhea, and loss of appetite.
Components
The root of the astragalus plant is considered to contain the medically important components. The biologically active compounds include a polysaccharide, saponins, coumarins, and flavonoids.6
Mechanism of Action
Little data exist regarding overall mechanism of action. The polysaccharide component possesses antirhinoviral activity and potentiates interferon activity, considered useful in treating the common cold and influenza.6 The saponins activate the peritoneal macrophages and enhance tissue necrotizing factor (TNF) activity, which may be helpful in the treatment of autoimmune disorders.6 Some data suggest astragalus may have antitumor activity mediated by interleukin-2.7 Other research has suggested that astragalus has an antioxidant effect, given the presence of isoflavones.8
Laboratory Studies
Much data regarding the immunostimulatory effects of astragalus have been generated using animal models. Unfortunately, most of the studies are published in Chinese medical journals9-12 and astragalus often is combined with other herbs such as ginseng, schisandra, angelica, codonopsis, echinacea, and/or licorice.2,4
Astragalus has been reported to reverse cyclophosphamide-induced immunosuppression in mice and rats.13-15 It has also been reported to exert antitumor effects in murine models of renal cell carcinoma via enhancement of phagocyte and lymphokine-activated killer cells.16 Sun et al evaluated the effect of astragalus and another traditional Chinese medicinal herb, Ligustrum lucidum, on mononuclear cells from 19 cancer patients and 15 normal healthy donors. Cancer patients’ mononuclear cells were incubated with either aqueous solutions of astragalus or ligustrum; healthy donor cells were incubated without an herbal solution. The number of mononuclear cells incubated with astragalus or ligustrum significantly increased compared to the mononuclear cells that were untreated.17
Chu et al evaluated the effect of astragalus on mononuclear cells isolated from healthy donors and 13 oncology patients.18 Among eight of the oncology patients, the number of mononuclear cells treated with fractionated astragalus increased compared to the untreated mononuclear cells and also to the healthy donor mononuclear cells.
Clinical Studies
A recent case report describes a 15-year-old male with Stage IIA nodular sclerosing Hodgkin’s disease who chose to treat his cancer with Matol Biomune OSF Plus instead of the traditional therapy of multiagent chemotherapy and low-dose irradiation. Matol Biomune OSF Plus contains astragalus, dairy colostrum, and whey. After the patient started taking Matol Biomune OSF Plus, the disease progressed into Stage IIB. Since the disease significantly progressed, the patient elected to discontinue Matol Biomune OSF Plus and start the traditional therapy of doxorubicin, etoposide, and bleomycin. The report does not state whether the pa-tient’s disease continued to progress.19
One Chinese study evaluated the effect of two concentrations of astragalus preparations in 115 cases of leukopenia. Patients received either 5 g or 15 g of astragalus twice daily. Both treatments had a significant increase in white blood cell count. However, the group that received the more concentrated astragalus preparation (15 g) had a significantly higher white blood cell count. There appears to be a dose-dependent relationship. Unfortunately, the abstract is the only description of this study in English.20
Another Chinese study compared the effect of astragalus administration among 28 patients with systemic lupus erythematosus to a group of normal controls also treated with the herb. It was reported that the astragalus-treated systemic lupus erythematous patients exhibited significantly decreased natural killer cell activity.21 Again, unfortunately, the abstract is the only description of this study in English.
Fifty-four cases of small cell lung cancer treated with chemotherapy, radiotherapy, immunotherapy, traditional Chinese medicine, and other adjuvants were evaluated in another Chinese study. Chemotherapy consisted of vincristine, cyclophosphamide, methotrexate, and carmustine. Traditional Chinese medicine included Asiatic ginseng leaf and Astragalus membranaceus root.
In this study, an overall treatment response of 98.1% was achieved. Treatment response was not defined in the abstract. Fifty-nine percent attained a complete response and 38.9% achieved partial response. Survival rates improved, especially with long-term (more than two years or 10 courses), short-interval, combined treatment. By using the combined therapies noted above, 10 of 12 patients reportedly gained from 3-17 years of survival.22 Again, unfortunately, the abstract is the only English description of this study.
For which of the following is astragalus touted to offer any benefit?
a. Impotence
b. Premenstrual syndrome
c. Nausea
d. Cancer
e. Kidney disease
Adverse Effects
No reports of astragalus-related adverse events could be identified in the published English literature in the following databases: MEDLINE, CINAHL, Current Contents, Cochrane, CancerLit, HealthStar, IBIDS, PubMed, National Center of Complementary and Alternative Medicine, and Alternative and Complementary Medicine Center HealthWorld Online. Astragalus may lower blood pressure and may cause diuresis.23 Overdosing may cause immunosuppression.23
Contraindications/Precautions
No contraindications or precautions are known.2 However, some Astragalus species appear to be toxic to livestock. Case reports of livestock grazing on Astragalus and Oxytropis species note irreversible neurologic toxicity because of the locoweed toxin, swainsonine. The toxins are only in the above-ground parts of the plants, not in the roots, which are the medicinal part of the plant.24,25
Drug Interactions
It is currently recommended that astragalus not be taken with opiates. It is unknown if astragalus will interact with any immunosuppressive medications such as cyclosporin. Herbalists caution against the use of astragalus in patients taking immunosuppressive medications.24
Formulation
Astragalus is available in a variety of preparations at varying dosages. Formulations include tinctures, tablets, capsules, powdered herb, and extracts. Astragalus is often included in combination herbal products that also frequently contain ginseng, schisandra, angelica, codonopsis, echinacea, and/or licorice.2,4 Fu Zheng is an herbal combination containing astragalus that some Chinese herbalists prescribe for patients undergoing chemotherapy and radiotherapy.
Dosage
In the practice of traditional Chinese medicine, astragalus tea is prepared using 9-15 g of the dried, sliced root simmered in water for several hours.4 A liquor may also be made by steeping 80-100 g of sliced root in one liter of spirits for two to three months. Patients are instructed to consume 1 oz of the liquor twice daily either straight or diluted with 1-2 oz of water.2 Some Chinese herbalists recommend adding the tongue-depressor shaped slices of astragalus root to medicinal soups, allowing them to flavor meals with their immunostimulating properties.
Capsules marketed in the United States generally contain 500 mg of dried herb. In this form, the recommended dose is 1,000 mg tid.4 Unfortunately, astragalus products are not standardized to a specific active ingredient.
Conclusion
Clinical evidence to support the use of astragalus for any clinical condition is scarce in the reported English-speaking literature.
Recommendation
Until more literature appears in the English language, Astragalus membranaceus should not be considered as an adjunct therapy for immunocompromised patients.
Dr. Klepser is Assistant Professor, Division of Clinical and Administrative Pharmacy, University of Iowa College of Pharmacy, and Dr. Nisly is Assistant Professor, Department of Internal Medicine, University of Iowa College of Medicine.
Which of the following drugs may interact with astragalus?
a. Bromocriptine
b. Haloperidol
c. Aspirin
d. Atenolol
e. Morphine
References
1. Leung AY. Better Health with (mostly) Chinese Herbs & Food. Glen Rock, NJ: AYSL Corporation; 1995.
2. Reid D. A Handbook of Chinese Healing Herbs. Boston, MA: Shambhala Publications; 1995.
3. Sinclair S. Chinese herbs: A clinical review of astragalus, ligusticum, and schizandrae. Altern Med Rev 1998;3:338-344.
4. Foster S. Astragalus. In: Herbs for Your Health. Loveland, CO: Interweave Press; 1996.
5. Maciocia G, ed. The Practice of Chinese Medicine: The Treatment of Diseases with Acupuncture and Chinese Herbs. New York: NY: Churchill Livingstone; 1994.
6. Huang KC, Williams WM, eds. The Pharmacology of Chinese Herbs. 2nd ed. Boca Raton, FL: CRC Press; 1999.
7. Chu DT, et al. Fractionated extract of Astragalus membranaceus, a Chinese medicinal herb, potentiates LAK cell cytotoxicity generated by a low dose of recombinant interleukin-2. J Clin Lab Immunol 1988;26:183-187.
8. Toda S, Shirataki Y. Inhibitory effects of isoflavones in roots of Astragalus membranaceus BUNGE (Astragali Radix) on lipid peroxidation by reactive oxygen species. Phytotherapy Res 1998;12:59-61.
9. Jin R, et al. Effects of shi-ka-ron and Chinese herbs in mice treated with anti-tumor agent mitomycin C [in Chinese]. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1995;15:101-103.
10. Li NQ. Clinical and experimental study on shen-qi injection with chemotherapy in the treatment of malignant tumor of digestive tract [in Chinese]. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1992;12:588-592.
11. Chu D, et al. F3, a fractionated extract of Astragalus membranaceus, potentiates lymphokine-activated killer cell cytotoxicity generated by low-dose recombinant interleukin-2 [in Chinese]. Chung Hsi I Chieh Ho Tsa Chih 1990;10:34-36.
12. Chu D, et al. Immune restoration of local xenogeneic graft-versus-host reaction in cancer patients in vitro and reversal of cyclophosphamide-induced immune suppression in the rat in vivo by fractionated Astragalus membranaceus [in Chinese]. Chung Hsi I Chieh Ho Tsa Chih 1989;9:351-354.
13. Zhao KS, et al. Enhancement of the immune response in mice by Astragalus membranaceus extracts. Immunopharmacology 1990;20:225-233.
14. Chu DT, et al. Immunotherapy with Chinese medicinal herbs. II. Reversal of cyclophosphamide-induced immune suppression by administration of fractionated Astragalus membranaceus in vivo. J Clin Lab Immunol 1988;25:125-129.
15. Rittenhouse JR, et al. Chinese medicinal herbs reverse macrophage suppression induced by urological tumors. J Urol 1991;146:486-490.
16. Lau BH, et al. Chinese medicinal herbs inhibit growth of murine renal cell carcinoma. Cancer Biother 1994:9:153-161.
17. Sun Y, et al. Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs. Cancer 1983;52:70-73.
18. Chu DT, et al. Immunotherapy with Chinese medicinal herbs. I. Immune restoration of local xenogeneic graft-versus-host reaction in cancer patients by fractionated Astragalus membranaceus in vitro. J Clin Lab Immunol 1988;25:119-123.
19. Coppes MJ, et al. Alternative therapies for the treatment of childhood cancer. N Engl J Med 1998;339: 846-847.
20. Weng XS. Treatment of leucopenia with pure Astragalus preparation—an analysis of 115 leucopenic cases [in Chinese]. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1995;15:462-464.
21. Zhao XZ. Effects of Astragalus membranaceus and Tripterygium hypoglancum on natural killer cell activity of peripheral blood mononuclear cells in systemic lupus erythematous [in Chinese]. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1992;12:669-671.
22. Cha RJ, et al. Non-surgical treatment of small cell lung cancer with chemo-radio-immunotherapy and traditional Chinese medicine [in Chinese]. Chung Hua Nei Ko Tsa Chih 1994;33:462-466.
23. Spaulding-Albright N. A review of some herbal and related products commonly used in cancer patients. J Am Diet Assoc 1997;97(10Suppl2):S208-215.
24. Weil A. Spontaneous Healing. New York, NY: Knopf; 1995:177.
25. Stegelmeier BL, et al. The pathogenesis and toxicokinetics of locoweed (Astragalus and Oxytropis spp.) poisoning in livestock. J Nat Toxins 1999;8:35-45.
November 1999; Volume 2: 125-128
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