Chinese herbal medicine for the treatment of allergic diseases

INTRODUCTION — Traditional Chinese medicine (TCM) includes herbal therapy, acupuncture, massage, and dietary therapy. These practices originated in China and have been used in East Asia for centuries as a part of mainstream medical care. TCM is beginning to play a role in Western health care as a complementary and alternative medicine (CAM).

This topic will discuss Chinese herbal therapy for asthma, atopic dermatitis (AD), and food allergy. These therapies are considered experimental from the standpoint of conventional medicine. Overviews of herbal medicine and use of CAM in pediatrics are presented separately. Acupuncture for the treatment of asthma and allergic rhinitis is also discussed separately. (See "Complementary and alternative therapies for allergic rhinitis and conjunctivitis" and "Overview of herbal medicine and dietary supplements" and "Complementary and integrative health in pediatrics" and "Complementary, alternative, and integrative therapies for asthma", section on 'Acupuncture'.)

OVERVIEW — The prevalence of allergic disorders such as asthma, atopic dermatitis (AD), and food allergy has increased dramatically in industrialized countries over the past several decades. Atopic diseases are a serious public health problem, particularly in children. Conventional therapies, such as glucocorticoids, are widely used in controlling asthma and AD. However, these therapies are not completely effective in all patients, and there are concerns about side effects, especially in children. In addition, there is no curative treatment for food allergy, just rescue treatment of reactions. These and other issues have led patients and their parents/caregivers to seek complementary and alternative medicine (CAM) treatments.

Traditional Chinese medicine (TCM) has a long history of use in China and other Asian countries, such as Japan and Korea. TCM has several features that differ significantly from Western medicine:

●TCM practice does not focus only on the disease or a single organ. Rather, it also focuses on establishing and maintaining the balance of yin-yang (two opposite, but complementary forces), the homeostasis of organ systems in the body, and interactions with the environment [1]. The concepts and terminology of TCM cannot be easily translated to Western medicine.

●Treatment is customized for each patient. As an example, a Chinese herbal formulation is a mixture of many herbs. The practitioner starts with one or two main ingredients that target the illness. Additional ingredients are included depending upon the patient's particular yin-yang conditions and possible need for a catalyst that makes the other components effective or an antidote that cancels out negative effects of other ingredients. Thus, the formulation used to treat a particular disease varies from patient to patient and even for an individual patient depending upon their changing needs.

●TCM has not been rigorously evaluated in randomized clinical trials. Sham acupuncture is difficult to perform, for example. In addition, the content of herbal formulations is often not standardized, and, even if it is, the quality and pharmacologic activity of individual herbs in the formulation can vary.

Practitioners of Western medicine have tended to avoid recommending use of TCM, particularly herbal therapies, for a number of reasons:

●Western practitioners are unfamiliar with these therapeutic methods because they are not included in conventional medical training in Western countries.

●The mechanisms of action of TCM are largely unknown, despite extensive clinical experience with these modalities in Asia.

●Randomized trials of TCM are lacking. In addition, studies published in Chinese are usually not translated into English or other languages, with the possible exception of the abstract.

●Herbal therapies are not standardized, nor are the quality of the components consistent.

●Knowledge about side effects and drug-herb interactions is limited.

●Herbal therapies may contain undeclared conventional pharmaceuticals or heavy metal contaminants.

In the United States, the National Institutes of Health (NIH) National Center for Complementary and Integrative Health (NCCIH) supports clinical and basic research on CAM to help eliminate some of the gaps in knowledge about these therapies. In addition, the National Committee of Acupuncture and Oriental Medicine offers a certificate in Chinese Herbology to increase the quality of practice of Chinese herbal medicine.

Chinese herbal medicines are a major component in TCM practice and are prescribed in China both as monotherapy and in combination with conventional (Western) medicine. In the United States, Chinese herbs are categorized as dietary supplements by the Food and Drug Administration (FDA). As such, the efficacy, safety, and quality of these products do not need to be proven, nor do postmarketing adverse events need to be reported. (See "Overview of herbal medicine and dietary supplements".)

The US FDA has issued guidelines for investigation of botanical drug products, including complex formulas that contain several herbs, focusing on efficacy, safety, and consistency [2]. Thus, TCM products currently used as dietary supplements may be investigated as new botanical drugs. One of the major differences in US FDA requirements for investigation of synthetic versus botanical drugs is the Chemical, Manufacturing, and Control (CMC) Data requirement for new botanical drugs [2]. Quality and safety data must be supplied at three levels (raw herbs, extracts, and final product) for botanical drugs.

TCM views allergic disease as resulting from the loss of homeostasis in interactions between human organs, such as the lungs, skin, and gut, with the environment and foods. Asthma, allergic rhinitis, and AD are well documented in TCM literature. There are many widely used formulas for these disorders, although they have not been well studied [3,4]. Food allergy has not been reported in the TCM literature.

Research into the efficacy and safety of several herbal formulas for asthma and AD using standard methods is being actively pursued in some Western medical centers, and an herbal intervention for food allergy has been derived from TCM [5]. Standardization of these formulas is challenging because they contain many herbs and the active components are not clearly defined. Thus, the quality, potency, and consistency of formulas are standardized by using high-performance liquid chromatography (HPLC) fingerprinting of the molecular components. Chemical markers are also identified by liquid chromatography coupled with mass spectrometry.

Consistent quality of each individual raw herb is key for reproducibility of efficacy of herbal therapies. Factors that affect quality include authenticity, geographic location, harvest time, preprocessing methods, and storage, according to the Pharmacopoeia of the People's Republic of China [3]. Standard manufacturing procedure is important to further ensure the consistency and quality of the final product. Safety testing of the final product includes evaluation for contamination with heavy metals and pesticide and microbial limit testing. In addition, biologic analysis, including in vitro and in vivo models that represent asthma and food allergy, may be employed to ensure safety and efficacy prior to human clinical use. This combined approach has yielded satisfactory product quality control of antiasthma herbal medicine intervention (ASHMI) and food allergy herbal formula-2 (FAHF-2) [5-7].

THERAPY FOR ASTHMA — Chinese herbs have been used for centuries in Asia to treat asthma. There is increasing scientific evidence to support the use of Traditional Chinese medicine (TCM) herbal therapy for asthma [8]. Randomized trials of TCM herbal formulas for asthma have been published in the English-language literature [9], including modified Mai Men Dong Tang (mMMDT) [10], Ding Chuan Tang (DCT) [11], STA-1 [12], antiasthma herbal medicine intervention (ASHMI) [13,14], augmented Yu Ping Feng San (aYPFS) [15], Cordyceps sinensis [16], Bu Shen Fang Chuan (BSFC) [17], and Bu Shen Yi Qi (BSYQ) [17]. ASHMI has received investigational new drug approval in the United States. The last four herbal preparations were evaluated in single-center studies with a limited number of subjects. Although results from these studies suggested potential benefits on symptoms and quality of life, larger-scale studies are needed. Other formulas have only been studied in China.

A systematic review and meta-analysis of randomized controlled trials of herbal medicine as add-on therapy for adult asthma included 29 studies involving 30,001 participants published through May 2014 [18]. Positive effects on lung function, asthma control, rates of exacerbations and medication usage were noted, but the overall quality evidence was low, with high risk of bias in most studies.

A systematic review of studies of Chinese herbal medicine as adjunctive therapy for cough variant asthma identified 20 randomized, controlled trials including 1590 subjects published up until December 2014 [19]. Methodologic heterogeneity and low reporting quality were noted among the different studies. The meta-analysis showed that adjunctive use of Chinese herbal medicine appears to improve symptoms associated with cough variant asthma. Additional studies using rigorous study designs and larger samples sizes are needed to confirm these findings.

Antiasthma herbal medicine intervention (ASHMI) formula — ASHMI is a simplified formulation of the herbal formula MSSM-002 (original name MTSD) that contained 14 herbs. The modified formula contains only three herbs: Ling-Zhi (Ganoderma lucidum), Ku-Shen (Sophorae flavescentis), and Gan-Cao (Glycyrrhiza uralensis). Preliminary data suggest that ASHMI is safe and effective either as monotherapy or complementary therapy to standard treatment.

Indications for use — ASHMI has been studied in adults with moderate-to-severe persistent asthma [13] and in children with persistent asthma, with or without allergic rhinitis [14].

Clinical response — The first randomized trial of ASHMI investigated the efficacy and tolerability of the formula compared with oral prednisone therapy in 92 patients 18 to 60 years of age with moderate-to-severe asthma [13]. Patients in China were randomized 1:1 to receive ASHMI 3.6 g or prednisone 20 mg daily for four weeks. One patient (ASHMI group) withdrew from the study during the last week of treatment. This study found that ASHMI was nearly equivalent to prednisone in improving posttreatment lung function (forced expiratory volume in one second [FEV₁] and peak expiratory flow values) and reducing symptoms and inhaled beta-2 agonist use.

The second randomized trial of ASHMI performed in China examined the safety, tolerability, and immunologic effects of standard therapy alone versus standard therapy plus ASHMI in children 5 to 14 years of age with persistent asthma, with or without allergic rhinitis [14]. Subjects received an inhaled glucocorticoid (budesonide) plus ASHMI (complementary ASHMI group; n = 28) or inhaled glucocorticoid plus placebo (standard group; n = 28) for three months. Both standard and ASHMI plus standard treatment groups had significantly improved lung function (FEV₁) and clinical symptoms. The improvement in symptom scores, particularly nasal symptoms, was greater in the complementary ASHMI group than in the standard group.

Immunologic response — Both ASHMI and prednisone decreased peripheral blood eosinophils, serum immunoglobulin E (IgE), and T helper type 2 (Th2) cytokine (interleukin [IL] 5 and IL-13) levels [13]. Inhibition was greater in the prednisone group. However, ASHMI increased interferon (IFN) gamma secretion, unlike prednisone, which suppressed IFN-gamma secretion. Patients treated with both ASHMI and inhaled glucocorticoids showed significantly greater reduction of serum total IgE and serum eosinophil cationic protein and higher serum levels of IFN-gamma after three months of treatment compared with children treated with standard therapy alone [14]. In a mouse model, antigen-induced airway hyperresponsiveness and pulmonary eosinophilic inflammation were almost completely abrogated after treatment with ASHMI [20]. In this model, the effects were eliminated by the neutralization of IFN-gamma, but not transforming growth factor (TGF) beta, during therapy.

Enhanced adrenal function — Glucocorticoid-induced suppression of the hypothalamic-pituitary-adrenal axis, marked by depressed cortisol levels, is an adverse side effect of systemic glucocorticoid use [21]. In contrast, a beneficial effect of ASHMI treatment on adrenal function was found in one randomized trial [13]. Pretreatment cortisol levels were slightly below normal in both groups. After treatment, subjects in the prednisone treatment group showed a significant reduction in serum cortisol levels after treatment. Conversely, patients in the ASHMI treatment group showed increased levels of serum cortisol within the normal range. Thus, ASHMI restored adrenal homeostasis. This effect may be attributed to glycyrrhizin (a component of Gan-Cao), which affects the conversion of cortisol to cortisone by inhibition of 11-beta-hydroxysteroid dehydrogenase enzyme activity [2]. Gan-Cao has been used for treatment of adrenal insufficiency [22]. However, it is also possible that the increase in cortisol levels is due to the lack of suppression of adrenal function. Further research is required to understand the precise mechanisms.

Possible mechanisms of action — Potential mechanisms of action of ASHMI have been suggested by studies in murine models of asthma. ASHMI exhibits a broad spectrum of therapeutic effects on the major pathogenic mechanisms of asthma. ASHMI blocks the IgE-mediated early-phase airway response, airway hyperreactivity, pulmonary inflammation, and airway remodeling [7,23,24]. These changes are accompanied by downregulation of Th2 responses and reduced histamine and leukotriene release. ASHMI also appears to directly modulate airway smooth muscle contraction by a beta-2 adrenergic receptor-independent mechanism that is associated with increased prostaglandin I2, a potent muscle relaxer [7]. Flavonoids in Gan-Cao inhibit eotaxin production by human fetal lung fibroblasts [25]. Ku-Shen triterpenes suppress of IgE production [26] and airway smooth muscle contraction [27]. The possibility that several active compounds in ASHMI work synergistically in producing multiple actions relevant to asthma mechanisms requires further investigation.

Side effects and interactions — In the study of ASHMI used as monotherapy compared with prednisone, all hematologic, electrocardiogram, and liver and kidney function test results were normal in both groups [13]. ASHMI had no significant effect on body weight (0.8 kg increase) as compared with prednisone (2.8 kg increase). Gastric discomfort was experienced by 7 percent of patients in the ASHMI group compared with 20 percent in the prednisone group. In the pediatric study of ASHMI used in combination with an inhaled glucocorticoid versus glucocorticoid alone, no abnormalities in liver or kidney function were detected [14]. No drug interactions were observed.

The two studies discussed above were performed in China. A phase-I dose escalation study was subsequently conducted in the United States [6]. Twenty atopic subjects with asthma received placebo or one of three doses of ASHMI (600 mg, 1200 mg, or 1800 mg) twice daily for one week. Four active and two placebo subjects were treated at each dose level. Subjects continued to use their conventional asthma medications for the duration of the study. Eight subjects (four ASHMI and four placebo) reported mild gastrointestinal symptoms. Vital signs, laboratory studies, and electrocardiogram findings were all within normal limits at pre- and posttreatment visits. No serious adverse events were reported.

Modified Mai Men Dong Tang (mMMDT) formula — mMMDT contains five herbs: Ophiopogon japonicus, Panax quinquefolium (ginseng), Pinellia ternata, G. uralensis (licorice), and Tridax procumbens.

mMMDT was studied in 100 atopic children aged 5 to 18 years with mild-to-moderate persistent asthma [10]. Patients were randomized 2:2:1 to mMMDT 40 or 80 mg/kg/day or placebo capsules daily for four months. In addition, patients were treated as needed with a number of conventional asthma medications, including albuterol, theophylline, cromolyn, beclomethasone, and oral glucocorticoids. Approximately 20 percent of patients withdrew from the study, none due to adverse events. Intention-to-treat analysis was not used. There were significant improvements in FEV₁ and asthma symptom scores in the two treatment groups after four months of therapy relative to baseline measurements. No improvement in FEV₁ or symptom score was seen in the placebo group. No serious adverse events were reported, and all laboratory measurements, including complete blood count and liver and kidney function tests, were within normal limits.

Potential mechanisms of action of several of the herb components include effects on steroid metabolism (licorice) and immunomodulatory effects (ginseng) [10]. Further investigations are needed to confirm the findings of this study, determine which of the herbs are essential, and clarify the underlying mechanisms of action.

STA-1 formula — STA is a combination of two formulas, Mai Men Dong Tang (MMDT) and Lui Wei Di Huang Wan (LWDHW). MMDT contains O. japonicus, P. ternata, P. quinquefolium, and G. uralensis. LWDHW is comprised of Rehmannia glutinosa, Paeonia suffruticosa, Cornus officinalis, Poria cocos, Alisma orientalis, and Dioscorea opposita. STA-1 was made with crude drug powder of LWDHW and STAT-2 with a decoction (extraction by boiling of herbal material) of LWDHW.

STA-1 was studied in 120 atopic patients aged 5 to 20 years with mild-to-moderate asthma [12]. Patients were randomized to STA-1 or STA-2 (n = 50 each; both 80 g/kg/day) or placebo (n = 20) daily for six months. In addition, patients were treated as needed with a number of conventional asthma medications, including albuterol, theophylline, cromolyn, beclomethasone, and oral glucocorticoids. Twenty patients withdrew from the study. Intention-to-treat analysis was not used. Patients treated with STA-1 had improved symptoms scores, increased lung function (FEV₁), less systemic glucocorticoid treatment, and decreased total and dust mite-specific IgE compared with baseline. Improved symptom control was also seen in patients treated with STA-2, but no other significant changes were found in the STA-2 group or placebo group. No adverse events were reported.

LWDHW and a number of the individual components have been shown to have antiinflammatory and antiallergic properties. Further studies are needed to confirm the findings from this one study that had some methodologic issues and to determine the active components and their exact mechanisms of action.

Ding Chuan Tang (DCT) formula — DCT contains nine herbs: Ginkgo biloba, Ephedra sinica, Tussilago farfara, Morus alba, P. ternata, Perilla frutescens, Prunus armeniaca, Scutellaria baicalensis, and G. uralensis. DCT appears less promising than other formulas. In addition, it contains ephedra, which, in high doses, can interfere with the effects of glucocorticoids and has been linked to serious adverse effects including death.

DCT was studied in 58 atopic children aged 8 to 15 years with mild-to-moderate persistent asthma [11]. Patients were randomized 1:1 to 6 g of DCT or placebo daily for 12 weeks. In addition, patients continued their daily therapy of inhaled fluticasone and a beta-2 agonist as needed. Ten percent of patients withdrew from the study shortly after randomization. Intention-to-treat analysis was not used. Airway hyperresponsiveness to methacholine improved in the DCT group, but not the placebo group, compared with baseline. However, no improvement in FEV₁ was seen in either group. The combined symptom and medication use score was significantly better in the DCT group compared with the placebo group at the end of therapy, but there was no difference in the individual symptom and medication scores between the two groups. No hepatic, renal, or hematologic abnormalities were noted. One control patient was hospitalized for an acute asthma exacerbation. No other serious adverse events were reported.

THERAPY FOR ALLERGIC RHINITIS AND CONJUNCTIVITIS — There are several Traditional Chinese medicine (TCM) remedies for allergic rhinitis. They are discussed in detail separately. (See "Complementary and alternative therapies for allergic rhinitis and conjunctivitis", section on 'Traditional Chinese medicine'.)

THERAPY FOR FOOD ALLERGY — Herbal treatments for food allergy have not been reported in the Traditional Chinese medicine (TCM) literature. Thus, an herbal formula was developed for the treatment of food allergy using TCM principles.

Food allergy herbal formula-2 (FAHF-2) — The original food allergy herbal formula (FAHF-1) contained 11 herbs [28]. This formula was effective in blocking anaphylaxis in a murine model of peanut allergy. A modified formula, FAHF-2, containing nine herbs, was used in subsequent studies.

Indications for use — FAHF-2 has been studied in murine models of peanut allergy and multiple food allergies and in humans with peanut, tree nut, fish, and/or shellfish allergies.

Response — FAHF-2 completely prevents food-induced anaphylaxis in murine models of peanut allergy and multiple food allergies. However, a multicenter, randomized phase-II trial in humans did not demonstrate efficacy of FAHF-2 as monotherapy for the treatment of food allergy at the tested dose and duration (10 tablets [0.5 g per tablet] three times a day for six months) [29]. A phase-II study in humans assessing the efficacy as an adjunct to multiple allergen oral immunotherapy is underway in the United States.

Preclinical studies of efficacy and safety of FAHF-2 were performed using a well-established murine model of peanut allergy. FAHF-2 completely blocked peanut-induced anaphylaxis when administered intragastrically during the development of peanut hypersensitivity [30] or when administered after peanut hypersensitivity was fully established [31]. FAHF-2 provided persistent protection for almost a quarter of the mouse lifespan after a single course of treatment [32].

Having multiple food allergies, rather than a single food allergy, is becoming more common [33]. Thus, a multiple food allergy murine model (peanut, hen's egg, and fish allergies) was developed, and the effect of FAHF-2 was tested in this model. FAHF-2 provided complete protection from anaphylaxis to oral challenge with peanut, hen's egg, and fish allergens [34].

Mechanisms of action — FAHF-2 has direct inhibitory effects on mast cells and basophils and also has immunoregulatory effects on T helper type 1 (Th1)/T helper type 2 (Th2) responses. Berberine is the major compound responsible for suppression of IgE production [35].

In a murine model of peanut allergy, FAHF-2 reduced peripheral blood basophil and peritoneal mast cell numbers [36]. Expression of the high-affinity IgE receptor, FcEpsilonRI, was decreased both in vivo and in vitro. Fraction 2 from FAHF-2 also inhibited rat basophil leukemic cell and human mast cell degranulation in vivo. Dose-dependent responses were seen to three major compounds in fraction 2 (jatrorrhizine, palmatine, and berberine).

Enhancement of interferon (IFN) gamma production by CD8+ T cells may also be an important mechanism underlying the long-term protection produced by FAHF-2 [31,32]. In this same murine model of peanut allergy, FAHF-2 suppressed histamine release, reduced serum IgE, and increased immunoglobulin G2a (IgG2a) [31]. The protective effect was associated with upregulation of Th1 and downregulation of Th2 cytokines, including an increased the number of IFN-gamma producing CD8+ T. Depletion of CD8+ T cells during FAHF-2 treatment attenuated FAHF-2-mediated IFN-gamma production, suppression of peanut-specific IgE, and clinical protection [32]. Depletion of CD8+ T cells or neutralization of IFN-gamma significantly attenuated FAHF-2 suppression of IgE and Th2 cytokines. However, IFN-gamma neutralization did not significantly impact the ability of FAHF-2 to protect mice from symptoms of anaphylaxis immediately following treatment despite elevated IgE, although this protection was lost in a subsequent challenge four weeks later.

Side effects and interactions — FAHF-2 was tested for lethality in a murine model as a preliminary assessment of safety [30]. Mice were fed 12 or 24 times the effective murine daily dose. No mouse died within the two weeks after the dose, and all mice appeared healthy. Hepatic, renal, and hematologic tests were all within the normal range two weeks after feeding the test doses. In addition, all of the major organs analyzed appeared normal.

In a dose-escalation phase I safety study of FAHF-2, 18 patients 12 to 45 years of age who had a history of peanut, tree nut, fish, or shellfish allergy were randomized to receive placebo (n = 6) or FAHF-2 (n = 12) at a dose of 2.2, 3.3, or 6.6 g three times daily for seven days [37]. No significant differences were observed in vital signs, laboratory data, electrocardiographic findings, or pulmonary function tests after treatment compared with baseline. Two patients reported mild gastrointestinal symptoms (one FAHF-2 and one placebo) that resolved without intervention. Findings were similar in an extension of this phase I trial in which patients were treated with 3.3 g of FAHF-2 three times daily for six months [38]. The phase-II trial further demonstrated the safety and tolerability of FAHF-2 [29].

THERAPY FOR ATOPIC DERMATITIS — Oral and topical preparations of Chinese herbs have been used for centuries in Asia for the treatment of skin conditions, such as atopic dermatitis (AD; eczema). However, there have been only a few randomized trials, and these studies were methodologically flawed [39,40]. Further clinical trials are needed.

Several randomized, crossover trials of Zemaphyte, a 10-herb formula, were performed in the United Kingdom in children and adults with AD [41]. Erythema and surface damage were reduced and sleep improved in two studies, but not in another. Abnormalities in liver function tests that resolved with discontinuation of the formula were reported with longer-term use. No serious adverse events were reported. Intention-to-treat analysis was not used despite withdrawal rates of up to 22 percent. Zemaphyte is no longer manufactured.

A randomized trial of a five-herb formulation, PentaHerbs, was performed in China [42]. This formula contains P. suffruticosa, Phellodendron chinense, Lonicera japonica, Mentha haplocalyx, and Atractylodes lancea. Eighty-five children with chronic moderate-to-severe AD were randomized to PentaHerbs or placebo daily for 12 weeks. Only two children (placebo group) withdrew from the study. Intention-to-treat analysis was used. There were no significant differences in extent and severity of AD (SCORAD scores) between the treatment and placebo groups pre- and posttreatment, although there was greater improvement in quality of life and reduction in topical corticosteroid use in the PentaHerbs group. No serious adverse events were reported. PentaHerbs has been shown to have immunomodulatory effects [42,43].

Xiao-Feng-San (XFS), a 13-herb formula, was studied in a randomized trial in Taiwan [44]. Patients with severe intractable AD were treated for eight weeks with oral XFS (n = 47) or placebo (n = 24). There was a significantly greater improvement in the total lesion, erythema, surface damage, pruritus, and sleep scores in the treatment group compared with placebo. These differences, except for the erythema score, were still significant four weeks after the completion of treatment.

Preliminary observational studies suggest that the combination of Chinese herbal therapy and acupuncture may be more effective than herbal therapy alone [45,46]. Results of a review of three systemic reviews and two randomized, controlled trials up to June 2016 were inconclusive regarding the efficacy of Chinese herbal medication for improving symptoms of atopic dermatitis [47]. Additional controlled clinical studies are needed.

SUMMARY

●History – Chinese herbs have been used for centuries in Asia as a part of Traditional Chinese medicine (TCM). However, lack of standardization and controlled clinical trials, among other issues, have hampered their use as conventional therapies in Western medicine. (See 'Introduction' above and 'Overview' above.)

●Chinese herbal therapies hold promise – There is potential for developing novel therapies for atopic diseases from Chinese herbs. Several herbal formulas show early promise for the treatment of asthma, food allergies, and allergic rhinitis in randomized trials. Work remains to determine the active components of each herb, their mechanisms of action, and potential synergistic effects. In addition, issues with consistency of herb quality and standardization still need to be addressed. (See 'Therapy for asthma' above and 'Therapy for food allergy' above and 'Therapy for atopic dermatitis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Xiu-Min Li, MD, who contributed to earlier versions of this topic review.