Traditional Chinese medicine formula granules are granular preparations of TCM herbs that, guided by TCM theory, are produced by water extraction, concentration, drying, granulation, and quantitative packaging, enabling clinicians to directly formulate prescriptions. They are also referred to as non-decoction decoctions, convenient decoctions, or solid decoctions. These granules retain the medicinal properties and therapeutic effects of raw TCM herbs while eliminating the need for decoction, making them easy to dispense and use, with controllable quality, and well-suited to modern consumer and lifestyle needs. However, what is the actual efficacy and safety of these granules? This study analyzes the literature on clinical research utilizing TCM formula granules.

1. Basic Information on the Study

A total of 692 articles reporting clinical studies using traditional Chinese medicine formula granules were identified. Among these, 561 were randomized controlled trials, 36 were non-randomized controlled trials, 88 were uncontrolled case series, and 7 were case reports. The studies collectively involved 68,218 patients, with 38,335 of them receiving treatment with formula granules in the context of clinical research.

Clinical research has been conducted across 25 provinces, municipalities, and autonomous regions nationwide. Among the 692 studies included, Henan Province, which has the largest number of studies, accounted for 156, or 22.5% of the total. Together, Henan, Guangdong, Shandong, and Zhejiang Provinces contributed 372 studies, representing 53.8% of the overall total. Of the 105 cities in these four provinces, clinical research is predominantly concentrated in 11 major cities—Zhengzhou, Guangzhou, Beijing, Jinan, Shanghai, Wuhan, Ningbo, Changsha, Shenzhen, Changchun, and Chongqing—where a total of 363 studies were conducted, accounting for 52.5% of the overall total.

A total of 692 studies covered nearly all systemic diseases, with the largest number focusing on digestive system disorders—116 studies, accounting for 16.8% of the total—followed by circulatory system disorders (73 studies, 10.5%), urogenital system disorders (70 studies, 10.1%), and respiratory system disorders (62 studies, 9.0%). Among the 228 specific diseases and symptoms examined, the most frequently studied were depression (27 studies, 3.9%), chronic hepatitis B and hepatitis B virus carriers (26 studies, 3.8%), chronic gastritis (including chronic superficial gastritis, chronic atrophic gastritis, and reflux gastritis; 17 studies, 2.5%), asthma (17 studies, 2.5%), diarrhea (15 studies, 2.2%), hypertension (15 studies, 2.2%), cough (14 studies, 2.0%), migraine (12 studies, 1.7%), Parkinson’s disease (11 studies, 1.6%), insomnia (11 studies, 1.6%), and infertility (10 studies, 1.4%).

Among the 561 randomized controlled trials, 29 involved three treatment arms (25 of these included two comparisons related to the efficacy of granules, while 4 included three such comparisons), and 1 involved four treatment arms (all four comparisons were related to the efficacy of granules). Thus, a total of 597 comparison groups were included. Excluding the 35 comparisons whose study objectives were not to evaluate the efficacy of formula granules, the remaining 562 comparisons (94.1%) were specifically aimed at assessing the efficacy of traditional Chinese medicine formula granules. The most frequently studied comparison was between the use of formula granules alone and conventional Western medical treatment, followed by evaluations of whether formula granules could enhance the efficacy of standard therapy when used in addition to it.

A meta-analysis of randomized controlled trials on the efficacy and cure rates of traditional Chinese medicine granule formulations in clinical studies revealed that, across seven common comparison categories, these formulations demonstrated higher cure and effective response rates than conventional Western medical treatments in the included studies. When added to standard Western medical therapy, the granules further enhanced therapeutic outcomes; compared with proprietary Chinese patent medicines, they exhibited superior efficacy; when compared with decoctions, they showed a slight advantage, likely attributable to better patient compliance; when contrasted with placebo, their efficacy was approximately 1.5 times that of placebo; and even when compared with non-pharmacological therapies in traditional Chinese medicine, they still demonstrated a favorable therapeutic effect. In summary, traditional Chinese medicine granule formulations exhibit good clinical efficacy.

3. Safety of Traditional Chinese Medicine Formula Granules

The report on adverse events and the safety analysis of clinical studies on traditional Chinese medicine formula granules reveal that, among the 692 included clinical studies, 465 studies (enrolling a total of 46,613 cases) did not report any adverse events, while 227 studies (enrolling 21,605 cases) did report such events. Specifically, 119 studies reported no apparent adverse events, comprising 98 randomized controlled trials, 7 non-randomized controlled trials, and 14 case series; 93 studies reported the occurrence and number of adverse events, including 5 case series, 1 non-randomized controlled trial, and 87 randomized controlled trials; and 15 studies merely described which adverse events occurred without specifying their frequency. Among the studies that did describe adverse events, no serious adverse events were observed in the traditional Chinese medicine formula granules group. Transient adverse events included nausea, vomiting, constipation, abdominal pain, bloating, diarrhea, dizziness, headache, and rash, all of which resolved and returned to normal after discontinuation of the medication.

Among 561 randomized controlled trials, the herbal formula granule group included a total of 29,770 patients, while the control group comprised 27,877. Of these, 376 trials did not report the incidence of adverse events (19,514 in the granule group and 18,513 in the control group). Among the 185 trials that provided quantitative data on adverse events, 3,200 adverse events were reported among 10,256 patients in the granule group and 577 adverse events among 9,364 patients in the control group. The overall adverse event rate in the granule group (including studies that did not explicitly describe adverse events) was 1.1%, whereas the independent adverse event rate (based solely on the 185 studies with quantitative descriptions) was 3.1%; for the control group, these rates were 2.1% and 6.2%, respectively. Meta-analysis revealed that the relative risk (RR) of adverse events between the two groups, along with its 95% confidence interval, was 0.52 (95% CI: 0.45–0.59) for the granule group and 0.51 (95% CI: 0.44–0.58) for the control group. Therefore, it can be concluded that the herbal formula granule group exhibits a lower incidence of adverse events and a higher safety profile.

4. Advantages of Traditional Chinese Medicine Formula Granules

Among the 692 included studies, 25 reported outcome measures related to treatment duration, and all findings indicated that formula granules, whether used alone or in combination with conventional therapy, can shorten the treatment course, reduce the time to symptom resolution or hospital stay, and thereby benefit patients. Another 39 studies highlighted the convenience of using formula granules, primarily due to their application based on syndrome differentiation and individualized treatment, as well as advantages such as no need for decoction, portability, controllable dosage, and ease of administration. Furthermore, 21 studies noted good patient compliance, mainly attributable to the ease of dose control, portability and convenience of administration, and a low incidence of adverse events.