Herbal Adaptogens For Asthma and Adrenal Function:
A Blend of Unique Herbs May Have Wide Clinical Application

In 2006 we reported a landmark study from the Mt. Sinai School of Medicine in New York, the Weifang Asthma Hospital and the Weifang School of Medicine in China, on a novel blend of Chinese herbs (named ASHMI) that proved statistically as effective as steroids in alleviating asthma symptoms. Now we report more fully on these unique adaptogenic herbs, which may have far wider application than asthma alone. There were preliminary indications that this formula may in fact restore adrenal function, and thus be useful in relationship to many chronic illnesses associated with adrenal fatigue. Highlights of the new information we include in this article:

• This formula is now the subject of a new, NIH-sponsored study at Mt. Sinai investigating whether steroid-dependent asthma sufferers can wean off their medications while taking these herbs. In the original study, this herbal formula not only significantly improved lung function and clinical symptoms, but increased cortisol production. In contrast, the study found that steroids suppressed cortisol levels.

• According to Dr. Stephen Feig, D.O., who utilizes these herbs in his practice, “In a subset of patients, these herbs seems to provide enhanced adrenal support that synergizes with more commonly used adrenal glandular products and with the use of cortisol.”

• “Since February of 2007,” writes clinical nutritionist and chiropractor Linda Li, DC, MS, CCN, who has been in practice for thirty years, “my family member, who suffered from severe, refractory asthma, has been off all medications, on twice daily doses of these herbs, and has had no asthma symptoms at all.” (see below)

• “My own experience is equally remarkable,” she continues, noting that these herbs have also improved her stamina, substantially decreased her need for sleep, helped her shed excess weight, and reduced her frequent nocturia. “This formula may be an important key to supporting the hypothalamus-pituitary-adrenal axis,” she suggests. (see below)

• A single, stunning herb in this formula, Sophora flavescens proved effective and potent in an open, recently published 3-year study of fourteen chronic, refractory asthmatics, by Ba Hoang, M.D., Ph.D., and colleagues, in Phytotherapy Research. All fourteen patients had improved lung function, clinical symptoms and quality of life, while reducing or even eliminating their use of inhaled steroids and beta-agonists without any significant adverse reactions.

Such a wide spectrum of clinical efficacy suggests that the synergistic power of this formula may help restore healthy adrenal function. As the Mt. Sinai researchers wrote of these herbs, “This is the first well-controlled study in which an anti-asthma Chinese herbal medicine has been found to be as effective as a corticosteroid drug. The mechanisms underlying the remarkable effects…are likely a result of synergistic or additive effects of the complex nature of its constituents.”

In this article, we review the entire scope of published work on this herbal formula and theorize as to how and why these herbs might restore adrenal function in a wide range of disorders in which adrenal function is compromised. In a companion article, one of the world experts on adrenal fatigue, James Wilson, N.D., Ph.D., distills a lifetime of experience diagnosing and treating hypoadrenia, which is, he says “monstrously underdiagnosed.” Finally, in a related article, we propose a completely novel theory on the pathogenesis of asthma—a theory which also has implications for the pathogenesis of cancer—and suggest that hyperexcitability of cellular membranes (due to ion channel activity) may be an important trigger of chronic disease. This novel theory gives us a remarkable new way of thinking about chronic illness, and may explain why at least one of the herbs in this formula, Sophora flavescens, is so powerful and well-tolerated.

Asthma Is a Model for Adrenal Dysfunction

The rate of asthma has tripled in the last quarter century. Twenty million Americans suffer from the condition, according to the CDC. Asthma is the third leading cause of hospitalization among those under 18, reports a 2006 article in the New England Journal of Medicine. Asthma accounts for $16 billion in annual health care costs, and there are 5,000 visits to the emergency room a day in the United States for asthma. At the same time, chronic use of asthma drugs may be harmful or even fatal. Steroids are well known to suppress cortisol and immune function. Other asthma drugs, such as Serevent and Advair, have “black box” warning labels because of the higher rate of deaths tied to exacerbations of asthma in patients taking them. And according to a 2004 article in the Annals of Internal Medicine, regular use of beta-agonist drugs for asthma not only causes tolerance to the drugs themselves, but increases airway inflammation compared to placebo use.

The entire picture of asthma, its soaring numbers, the dangers of drug treatment, and the efficacy of selected herbs for this condition, may serve as a model for a wide host of conditions marked by low cortisol, adrenal fatigue and chronic inflammation.

If we take a closer look at the Mt. Sinai research, it becomes apparent that it is remarkable for how thorough and robust its design has been all along.  Chinese herbs have a long tradition of use in asthma, but well-controlled clinical trials using herbs for the treatment of asthma are rare. That is one reason this Mt. Sinai research is so notable.

Of Mice and Men: The Remarkable Research Behind ASHMI

The Mt. Sinai study is remarkable because the researchers followed an unusually thorough and meticulous design over a period of many years. Their first study, published in 2000, tested a blend of fourteen herbal extracts commonly used in traditional Chinese herbal medicine for allergic asthma. This formula, dubbed MSSM-002, was based on a TCM formula used in the pediatric department of the China-Japan Friendship Hospital in Beijing to treat asthma and bronchitis in children. Unlike many asthma formulas, this one contained no Ma-Huang, a source of ephedrine that has been reported to cause central nervous system stimulatory activity, increased blood pressure, and heart palpitations.

The researchers first tested this blend of herbs in a mouse model of allergic asthma. Mice were sensitized to an egg-white protein and then challenged with it.  The mice reacted with allergic asthma including pulmonary eosinophilia, airway hyperreactivity (AHR), and increased antigen-specific IgE associated with inflammatory cytokines, including IL-4 and IL-5 in bronchial lavage fluids.

In the Journal of Allergy and Clinical Immunology, they report that treating mice with this formula “virtually eliminated airway hyperreactivity and markedly reduced the total number of cells and the percent eosinophils in bronchoalveolar fluid compared with the sham-treated group.” Inflammation and mucus were reduced in the lungs as well. Treatment with MSSM-002 twenty-four hours after intratracheal antigen challenge of sensitized mice virtually eliminated airway hyperreactivity and this effect was equivalent to dexamethasone. MSSM-002 down-regulated inflammatory cytokines including IL-4, IL-5 and IL-13, all involved in chronic asthma.

In comparison, “one of the most potent corticosteroids, dexamethasone, also suppressed antigen-induced airway hyperreactivity and eosinophilic inflammation in this model. However, unlike MSSM-002, dexamethasone suppressed Th1 responses.” The researchers concluded that the herbal formula was as effective as the potent corticosteroid, dexamethasone—without the harmful side effects.

The researchers then “used the concept of traditional Chinese medicine to reformulate several herbal blends into simplified formulas, and tested these new formulas,” says senior study researcher Xiu-Min Li, M.D., Associate Professor, Pediatrics and Assistant Professor, Center For Immunobiology, at the Mt. Sinai School of Medicine. The formula the researchers found most effective in mice contained three Chinese herbal extracts—Ling-Zhi (Ganoderma lucidum), Ku-Shen (Sophora flavescens) and Gan-Cao (Glycyrrhiza uralensis), also known as Reishi, Shrubby Sophora and Chinese Licorice—and was dubbed ASHMI (anti-asthma herbal medicine intervention). The ASHMI formula demonstrated the same broad spectrum of therapeutic effects on the major pathogenic mechanisms of asthma. “This formula was almost as effective as the original fourteen herbs, and was the simplest,” Li explains. All three herbs have a long history of human use in China and are considered to be safe when used according to TCM practice either alone or in formulas.

The next Mt. Sinai, NIH-sponsored study was on ASHMI in humans, and was published in the Journal of Allergy and Clinical Immunology in September of 2005. It reported the remarkable finding that ASHMI was as effective as steroids, without suppressing cortisol or immune function. This study included thirteen researchers—eleven of them physicians—from the Weifang Asthma Hospital, the Weifang School of Medicine, and the Mt. Sinai School of Medicine, and was remarkable for its methodical, careful design. Forty-five non-steroid dependent individuals received oral ASHMI capsules and prednisone placebo tablets, and forty-six non-steroid dependent individuals received oral prednisone tablets (20 milligrams) and ASHMI placebo capsules for four weeks. Serum cortisol, cytokine and IgE levels were evaluated before and after treatment, as well as symptom scores, side effects and spirometry measurements. Spirometry literally means “the measuring of breath” and is the most common pulmonary function test.

The study began with  a week-long “run-in period” before initiating treatment. Average daily symptom scores were evaluated during this period to establish a baseline. Beta-agonist inhalation was allowed as needed during the study, but all other medications, such as leukotriene modifiers, antihistamines, and either inhaled or intravenous steroids, were prohibited.

Symptom scores rated cough, chest tightness, wheezing, dyspnea, night awakening or early morning awakening caused by dyspnea, allergic rhinitis, and beta-agonist use. Lung function was evaluated with a spirometer, and serum levels of IgE, eosinophils, cortisol and cytokines including IL-5, IL-13 and IFN-gamma were measured. After four weeks both groups showed an equal, significant improvement in symptom scores, pulmonary function and eosinophil levels.

In both groups, pre-treatment cortisol levels were slightly below normal, as is common in asthma. However, after treatment, the corticosteroid group showed suppression of the hypothalamic-pituitary-adrenal axis, marked by even more depressed cortisol levels. In contrast, patients in the ASHMI formula group showed increased levels of serum cortisol into the normal range. After four weeks, the prednisone group had significant weight gain, while the ASHMI group did not. The difference between the two groups was statistically significant.

“The relationship between cytokine imbalance and the expression of both atopy and asthma is of considerable interest and importance,” the researchers note. “A Th1-Th2 imbalance has been hypothesized in asthma, with a shift in immune responses away from Th1 (IFN-gamma) toward Th2 (IL-4, IL-5 and IL-13). In a cohort study, patients with severe asthma exhibited significantly reduced IFN-gamma production in response to allergen compared with control subjects and subjects with resolved asthma. In addition, all patients with asthma…showed increased generation of IL-5." Numerous studies confirm that IL-4, IL-5 and IL-13 secretion is the major driving force behind persistent asthma.

ASHMI significantly reduced IL-3 and IL-5 levels. It also increased human interferon-gamma (IFN-gamma), a potent antiviral and immunomodulator, while cortisone suppressed IFN-gamma. These findings suggest strong immunotherapeutic effects of the Chinese herbal. Now, says Li, “we have an ongoing FDA-approved clinical trial using ASHMI as an investigational new drug. In the last study our patients were not steroid dependent. In this study our patients are steroid dependent, and we are trying to wean them off their steroids. They really don’t want to be on steroids anymore, and our results will be more significant if, with the use of ASHMI, we can reduce or replace steroids. We are almost finished with our Phase I trial, which included 18 patients, and we will begin our Phase II trial with 60 patients.”

How Do These Herbs Work?

Individually, these herbs all have a long history of use in asthma and other allergic, autoimmune and immune disorders, allergic rhinitis, hepatitis B, jaundice, adrenal insufficiency, peptic ulcers, and many other conditions. The researchers speculate that these herbs work both individually and synergistically. For instance, the increase in serum cortisol into the normal range could be in part due to the glycyrrhizin in Chinese licorice, “which affects the conversion of cortisol to cortisone by inhibition of 11-beta-hydroxysteroid dehydrogenase enzyme activity.” In addition, previous research has shown that Chinese licorice decreases IgE levels. Chinese licorice is a staple botanical in TCM for asthma and allergic rhinitis.

Ku-Shen, in turn, has been widely used for eczema, pruritus and asthma. Ku-Shen is particularly interesting. It is proving to have therapeutic value for a surprisingly wide range of conditions. The impact of Ku-Shen, which has excitatory modulator activity, was studied by Ba Hoang and colleagues. An open and selective 3-year follow-up of 14 chronic refractory asthmatics aged between 22 and 70 was used. Participants received an extract of Sophora flavescens. Medication use, a diary card of symptoms, and respiratory function were recorded. The study was retrospective and all patients gave written informed consent. The quality of life, clinical symptoms and respiratory function improved during all periods of measurement. The use of inhaled corticosteroid and beta-agonists were reduced or eliminated. There were no significant adverse reactions reported. It appears that the extract of S. flavescens as an excitatory modulator  may be safe and effective for chronic refractory asthma.

Within two weeks of starting therapy with Ku-Shen, the patients had reduced daytime and nighttime symptoms of asthma, and had begun to reduce their beta-agonist doses. By three years, all patients were off their corticosteroid medication, had almost entirely eliminated beta-agonist medications, and their symptoms of asthma were significantly reduced.

How does Ku-Shen work? Though the plant contains a rich cornucopia of chemicals, the focus has been on  two principle alkaloids, matrine and oxymatrine, which have been the subject of research for years. The toxicity of both alkaloids is very low, and Ku-Shen may contain about 2% of these two alkaloids. According to Dr. Ba Hoang’s theory, these alkaloids “act as modulators of membrane excitability…they can decrease body temperature, have a significant analgesic effect, have a tranquilizing effect, and an inhibitory action on glutamate-induced excitatory nerve impulses. They can also have an antiarrhythmic effect.” Glutamate receptors have been found in the lungs and airways, and the activation of glutamate receptors has led to increased airway submucosal glandular secretion. Activation of the glutamate receptor might be an important, unrecognized mechanism of airway inflammation and hyper-reactivity, and might explain one of the ways that Ku-Shen helps in asthma.

In fact, Dr. Ba and Dr. Levine propose a novel mechanism for asthma in a 2006 article in Medical Hypotheses entitled, “Bronchial epilepsy or broncho-pulmonary hyperexcitability as a model of asthma pathogenesis.” In this separate paper, Ba and Levine have hypothesized that membrane hyperexcitability may reflect a more generalized disease mechanism.

In sum, not only are the herbs in ASHMI remarkably effective in asthma, but the increase in cortisol levels and the shift away from inflammatory cytokines toward a balanced immune response, suggests that adrenal and immune function are being restored. This would argue for a far wider use of herbal formulas like ASHMI, in conditions associated with low cortisol, chronic inflammation and adrenal fatigue. Illnesses treated with corticosteroids would theoretically benefit from herbal formulas like that of ASHMI.

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