Ginseng and Astragalus Combination (Bu Zhong Yi Qi Tang)
By Peter Townsend and Will Maclean

Ginseng and Astragalus Combination (GAC) is a very commonly used formula in traditional Oriental medicine. Its inclusion as an approved prescription in the Japanese Ministry of Health and Welfare's health insurance scheme also attests to its efficacy. Although it is mainly used for fatigue and various types of prolapse, its creator, Li Dong-Yuan, mainly designed it to treat febrile diseases. In this article I wish to re-examine Dong-Yuan's notes at the time he formulated GAC and compare them with modern usage and research.
Li Dong-Yuan lived from 1180 A.D. to 1251 - the period the Song dynasty fell to the invading Jin (Tartars) and Yuan (Mongols). The story goes that as the Jin army advanced South, an epidemic (febrile disease) broke out in the walled cities, - it is said that in one city alone between one thousand and two thousand bodies were taken out of its 12 gates every day.
In the treatment of this epidemic Dong-Yuan writes in the Nei Wai Shang Bian Huo Lun (Clarifying Doubts about Injury from Internal and External Causes):
"...use Sweet and Cold to purge Fire, but if there is tiredness (Qi deficiency) or injury it should be warmed, and I say again, warmth can expel strong Heat. Bitter Cold herbs should not be used, as they will purge the Stomach Earth. Sweet and warm should be used to tonify the Middle and cause Yang to rise, Sweet and Cold is used to purge fire (not to treat fever due to deficiency)."
The doctors of Dong-Yuan's time considered this illness to be Shang Han (Cold Injury), a type of infectious disease, and therefore treated their patients with diaphoretic, emetic and laxative methods (according to Shang Han Lun theory) to purge the pathogen from the body. However, after this type of treatment most patients took an acute turn for the worse and died. Dong-Yuan reasoned that this febrile disease was not due to Shang Han or other exogenous influences, but was due to malnutrition, fatigue, anxiety and other endogenous causes. In contrast to exogenous diseases like Shang Han, he called diseases that were endogenous Nei Shang (Internal Injury). Since Shang Han diseases are the reaction of the body to an invading pathogen and Nei Shang is an internal deficiency, Dong-Yuan goes on to say:
"Exogenous diseases should be purged, deficient Nei Shang should be tonified. If the doctor fails to recognize the difference between these two and attempts to purge an endogenous disease, the deficiency will become more deficient. If deficiency is made more deficient (by purging) or if excess is made more excessive (by tonifying), then the doctor will kill the patient."
To treat these types of deficiency he designed GAC. (See Minor Cinnamon & Paeonia, Steve Clavey, for more about Qi deficient fever.)
Indications and Pathology In modern TCM
GAC has three main uses:
" Collapse of Central Qi, Pure Yang Failing to Rise
" Spleen Not Governing Blood
" Qi Deficient Fever
The first usage, collapse of central Qi, is a condition which arises from chronic Spleen Qi deficiency where there is a lack of tone of the skeletal and smooth muscles, and supportive tissue. This in turn leads to gastric atony, floating kidney, hernia, rectal prolapse, uterine prolapse, and other forms of prolapse. Constipation may also occur due to loss of tone of the intestinal smooth muscles or, contrarily, diarrhea may occur due to a lack of fluid absorption. Loss of tone of the muscles of the urinary bladder may also cause trouble initiating urination. Muscular contraction, therefore, does not occur until a large volume of urine has accumulated. Urinary incontinence in the elderly, infants, postoperative, and postpartum patients can also occur due to atonicity of the sphincter muscles.
Pure Yang failing to rise is a condition characterized by dull headaches, dizziness upon standing, vague consciousness, sleepiness, fatigue and weak extremities. Although not necessarily part of this condition, many of these patients tend to have hypotension with especially low diastolic pressure. This is accompanied by reduced CNS excitement and loss of tone of the sweat glands, so the patient may sweat very easily (even upon only mild exertion). Spleen not governing Blood is characterized by persistent but scanty, intermittent hemorrhaging. This usually occurs in the lower body or subcutaneously. It is thought that this is due to loss of tone of the blood vessel walls or thrombocytopenia and may be compounded by reduced digestive function leading to an insufficient supply of protein and thus coagulants. The third usage, Qi deficient fever, was the disorder which Dong-Yuan was addressing when designing GAC. This type of fever may accompany an exogenous febrile disease, as was most likely the case in Dong-Yuan's time, or may be only due to general deficiency. In either case, however, the patient usually suffers from both mental and physical fatigue which may be accompanied by dull headaches, chills and sweating. The fever itself is low-grade and may only be subjective. In cases where the condition has come about due to an external pathogen, the patient is usually in the recovery stage from influenza or other similar illnesses but does not quite have the vitality to fully recover. Modern research has not yet been able to shed much light on the mechanism of this type of fever, but it is thought that a generally weakened metabolism and bodily functions with autonomic nervous system disorders may cause an imbalance in the body's thermostat. Habitual hyperthermia, a constitutional propensity to higher body temperature, may also be a factor.
Formula Ingredients
Astragalus tonifies Qi, helps Yang to rise and consolidates the Surface (skin), it stimulates the central nervous system, has cardiotonic and sex hormone-like actions, it strengthens muscle tone and promotes general metabolism. It has been found that in small quantities Astragalus raises blood pressure, but that in large quantities (over 30g/day) it lowers it. This, perhaps, partially justifies its use pharmacologically in Bu Yang Huan Wu Tang, a formula used for apoplexy which contains between 30g and 100g of Astragalus! Ginseng stimulates the CNS, increases digestive absorption, and strengthens general bodily functions. Atractylodes promotes the absorption of fluid from the digestive tract thus stimulating diuresis. Licorice strengthens general bodily functions and works with Astragalus to increase its efficacy. Ginseng, Astragalus and Atractylodes promote protein synthesis, and with Dang Gui also promote macrophage phagocytosis and antibody production. Bupleurum and Cimicifuga, when used in small quantities with Astragalus, help Qi to rise and strengthen muscle tone*. Dang Gui tonifies Blood and aids the action of the other herbs through nourishing the body and promoting circulation, it also prevents the parching herbs from over drying.
*Note that in larger quantities, Bupleurum and Cimicifuga are mainly used for their anti-inflammatory and antipyretic actions (Heat clearing). Their use in this context, however, is to aid the rising qualities of Astragalus. It has been reported that, experimentally, although a marked increase in muscle tone was reported when Astragalus, Bupleurum and Cimicifuga were used in combination; the action of only Bupleurum and Cimicifuga together was found to be quite weak.
Citrus (chen pi) and Ginger (sheng jiang) increase peristalsis and the secretion of stomach juices, aiding the absorption of the other ingredients, while Jujube harmonizes the ingredients and promotes digestion.
Formulation In modern TCM theory
GAC is considered to be a variation of Four Major Herb Combination (Si Jun Zi Tang), and although this is true from the point of view of GAC being a Qi tonic, historically Dong-Yuan based his formula on Minor Bupleurum Combination (xiao chai hu tang), a prescription from the Shang Han Lun used to treat Shao Yang Bing. He removed the Scute (huang qin) and Pinellia (ban xia) from MBC and then added Astragalus (huang qi), Cimicifuga (sheng ma), Atractylodes (bai zhu), Dang Gui and Citrus (chen pi).
As mentioned before, since Dong-Yuan reasoned that sweet-warming herbs should be used for Qi deficient conditions, he removed the pungent-warming Pinellia and bitter-cooling Scute. Scute is mainly used to clear excess Heat in MBC. Since the fever due to Nei Shang is due to deficiency, the inclusion of Scute would be inappropriate. The inclusion of Pinellia is also not necessary in GAC, as its anti-emetic, anti-tussive and expectorant actions are mainly used for Phlegm-Damp accumulation. Its parching effects may also be too strong for deficient conditions - especially when combined with the other herbs in GAC.
An elegant variation of GAC also designed by Dong-Yuan is Tiao Zhong Yi Qi Tang (Regulate the Middle and Invigorate Qi Decoction). This is for Collapse of central Qi accompanied by a heavy body sensation, loose to watery stools, abdominal distention, sticky sensation in the mouth and other middle Jiao Damp symptoms. From GAC, he took Atractylodes macrocephala (Bai Zhu) and replaced it with Atractylodes lancea (Cang Zhu) for its stronger Damp expelling properties, removed Dang Gui because of its "sticky" nature, and added Saussurea (mu xiang) to move Qi. The addition of Saussurea, Coix (yi ren), Atractylodes lancea and/or Hoelen (fu ling) to GAC would also achieve similar results. Dong-Yuan is primarily known as being the founder of the Earth Tonifying school, and therefore focused much attention on the tonification of Spleen Qi. The Pi Wei Lun (Treatise on the Spleen and Stomach) explains his Spleen tonification theories and treatment, while the Nei Wai Shang Bian Huo Lun is a treatise on the differentiation and treatment of exogenous and endogenous diseases. Although fever due to a deficiency of Yin was a well-recognized pattern before Dong-Yuan's time (Anemarrhena Phellodendron & Rehmannia Formula, [qi ju di huang wan] being an example of a formula used to treat this condition), this type of Qi or Yang-Qi deficient fever was not really fully understood. Even now, very few texts even mention this relatively common clinical phenomenon. That Dong-Yuan was able to recognize and formulate a treatment method for this condition says much about the depth of knowledge and innovative character of this man.
Pharmacology
Protection against Chemotherapy
GAC shows protective effects on the kidney and bone marrow in patients being treated with chemotherapy. When used in high doses (up to three times normal dose) pre and post chemotherapy, serum markers like BUN, serum creatinine were decreased relative to controls, and white blood cells and platelets were maintained significantly [1]. Adverse toxic effects induced by antitubercular medication (rifampicin, streptomycin and isoniazid), including fever, hepatic dysfunction, agranulocytosis and systemic eruption were significantly moderated in a 58 year old patient. Adjuvant therapy with GAC and Minor Bupleurum Combination (xiao chai hu tang) suppressed the hepatodermatological toxicosis moderately and the high fever completely [2].
Stress Regulating Action
GAC has a regulatory effect on the adrenal cortex and autonomic nervous function. Studies from Japan on patients with non-ulcer dyspepsia and psychovegetative syndrome demonstrated that when serum cortisol was high, administration of GAC decreased it, and when low and normal increased it. This modulatory effect is thought to be mediated by ACTH secretion [3].
Effect on Obstructive Sleep Apnea Syndrome (OSAS)
GAC has been used with some success on patients with OSAS. This disorder is characterized by recurrent obstruction of the upper airway leading to hypoxia and frequent arousal from sleep. Patients often present with daytime sleepiness, obesity, snoring, digestive system dysfunction, loss of appetite, impotence, weakness and poor muscle tone. These symptoms are consistent with the TCM diagnosis "Spleen failing to hold muscular structures in place" for which GAC is the indicated formula. The probable mechanism of OSAS is weakening of the structures which support the epiglottis with consequent airway blockage. This formula has been found to be effective in Japan [4] and by the author.
Effect on Immunity
In clinical tests with 35 patients suffering from rheumatoid arthritis, Sjoegren's syndrome, or bacterial infections, administration of GAC was shown to significantly increase natural killer cell (NK) activity. Eight of the patients had an improvement in clinical symptoms and it was noted that these patients also had the greatest rise in NK activity. Interestingly, it was found that patients who already had a high NK activity before administration of GAC demonstrated a slight decrease in NK activity.
These results were also supported with in vitro research. Human peripheral blood lymphocytes cultured with GAC demonstrated an augmentation of NK activity. However, NK activity in human peripheral blood lymphocytes with high activity prior to treatment was suppressed by GAC. The authors suggest that GAC has a biphasic (regulatory) action on human NK activity both in vivo and in vitro [5]. Oral and intraperitoneally administered GAC has been shown to enhance the phagocytic activity of peritoneal exudate cells (PEC) in mice as well as stimulating the phagocytosis of spleen cells and bone marrow cells [6].
Effect on Male Fertility
GAC can be used to treat male infertility. In order to demonstrate this pharmacologically, GAC was used on cultured hamster epididymal cells. A significant increase in 3H-leucine uptake was observed in the treated group suggesting that GAC has a stimulative effect on epididymal function [7]. Experiments with mice have also shown that in mice treated with adriamycin (ADR), GAC significantly inhibited a decrease of testis weight compared to mice treated only with ADR. The GAC treated group had a decrease of seminiferous tubules without germ cells, however at the same time there was a significant increase in the proportion of normal seminiferous tubules and the Sertoli cell ratio of spermatocytes as compared with the ADR-treated group [8].

References
1. Sugiyama K, Yokota M, Ichio Y, Ueda H (1993). Protective effects of Kampo medicine against cis-diaminedichloroplatinum induced nephrotoxicity and bone marrow toxicity in mice. Wakan Iyaku Gakkaishi 10(1):76-85.
2. Kasamatsu Y., et al (1993). A case of pulmonary tuberculosis complicated with drug toxicosis. Value of Shosaikoto and Hochuekkito as anti-allergic agents. Kekkaku 68(1):23-29
3. Oka T., et al (1993) Studies on the Effects of Rikkunshi-to and Hochu-ekki-to on Adrenal and Autonomic Nervous Function. Jap J Orient Med 43(3):439-446.
4. Sasaki M., et al (1994). The Effect of Hochu-ekki-to on Obstructive Sleep Apnea Syndrome. In: Proc 4th Int Con Trad Asian Med.
5. Tani T., et al. (1988). Jap. Journ. Allerg: 37 (2) 107-114.
6. Aburada M., et al. (1988). Jap. Journ. Inflammation: 8(1) 65-66.
7. Noda Y., et al. (1993). Jap. Journ. of Fertitlity & Sterility: 38(2)262-68
8. Sudo K., et al. (1988) Folia Pharmocol. Japonica: 92 (4) 251-261