Unlocking the pharmaceutical potential of Kombucha: production, regulatory challenges and patents landscape

Abstract

Kombucha is a traditional fermented beverage known for its potential health benefits, including probiotic, antioxidant and energy-boosting properties. Its production involves the fermentation of sweetened tea with a symbiotic culture of bacteria and yeast (SCOBY). This article explores kombucha’s therapeutic potential in several health areas, such as metabolism regulation, anti-inflammatory and neurocognitive therapies, and dermatological applications. Although there are regulatory challenges in different countries, the lack of global standardization in production and safety of kombucha consumption is a bottleneck for developing new products. The investigation of compounds derived from kombucha for use in pharmaceutical applications is evidenced by several patents registered in recent years, which demonstrate the potential of kombucha for the pharmaceutical and functional food industries. This demonstrates the importance of conducting more robust clinical studies and research into the pharmaceutical potential of different biomolecules in this beverage.

Graphical abstract

Introduction

The search for a healthier lifestyle is growing worldwide. Consumers have become increasingly concerned about the types of food they consume, seeking tasty and sensorially attractive products and nutritious foods capable of bringing health benefits. The tendency is to add functionality to the foods people consume. As a result, health-conscious consumers are turning to healthy beverages such as kombucha and other functional drinks (de Oliveira et al., 2023).

Kombucha is a popular and traditional fermented drink characterized as refreshing, acidic and slightly sweet and consumed worldwide. The detoxifying and energizing properties of kombucha have been known since its origin in China in 220 BC. It is traditionally produced from the fermentation of black tea or green tea (Camellia sinensis), added sugar and SCOBY (Symbiotic Culture of Bacteria and Yeast) (de Oliveira et al., 2023). However, different research with other teas has been reported in the production of kombucha expanding the market possibilities of this beverage (Dufresne and Farnworth, 2000; Bueno-Rojas et al., 2025). The health benefits associated with kombucha consumption are linked to the presence of various bioactive compounds generated during fermentation, including organic acids, polyphenols, amino acids, ethanol, water-soluble vitamins, and antimicrobial substances. Its antioxidant and energizing effects are primarily attributed to the polyphenols present in tea (Amarasinghe et al., 2018). Additionally, the microorganisms present in kombucha contribute to its potential probiotic effects (Antolak et al., 2021).

Obtaining kombucha is a relatively simple process, so much so that many laboratory-scale and artisanal preparations are commonly found. Due to possible health impacts, production on an industrial scale has been developing, and the market has grown significantly. The Kombucha market size is estimated to be US$2.97 billion in 2024, and is expected to reach US$4.65 billion by 2029, growing at a Compound Annual Growth Rate (CAGR) of 9.48% during the forecast period (2024–2029) (Mordor Intelligence, 2024).

Although the composition and properties of kombucha are well documented, food legislation still needs to standardize its effects on health regarding consumption conditions and dosage and its artisanal preparation. This work aims to better understand kombucha production processes, its potential in biomolecules and its possible health benefits.

Variations in the cultivation medium and process conditions: differences in kombucha composition

Kombucha is traditionally made from green or black tea, with the latter being the most commonly used substrate (Abaci et al., 2022). In addition to tea, sugars or a mixture of sugars such as glucose, sucrose or fructose are used. However, alternative carbon sources such as lignocellulosic biomass, agro-industrial and agricultural by-products such as milk and agricultural waste are being evaluated (Su et al., 2023).

The type of substrate used for fermentation is extremely important as it affects the chemical composition of the product (Liu et al., 2022). One example is the use of substrates rich in anthocyanins, as described in the work of Bortolomedi et al. (2022), which studied the effect of adding anthocyanin-rich substrates, such as cherry, blackthorn, and red raspberry juices, in combination with green tea to check the effects on the composition and sensory characteristics of kombucha. According to the study, the use of anthocyanin-rich substrates in kombucha fermentation is beneficial due to the increase in total phenolic compounds during the process. Prior to fermentation, the highest levels of phenolic compounds were observed in concentrated black carrot juice and green tea, which were about twice as high as the other substrates. During storage, there was an increase in the content of total phenolic compounds in the kombuchas made with blackthorn, green tea, and black carrot. Thus, it can be concluded that substrates rich in anthocyanins are beneficial, since these compounds have properties against various clinical conditions, such as cardiovascular diseases, some types of cancer and neurodegenerative diseases, due to their antioxidant potential (Mattioli et al., 2020).

The main carbon source used in the production of kombucha is sucrose, both because of its ability to provide glucose and fructose for microbial metabolic pathways and its low cost and convenient availability (Abaci et al., 2022; Nyhan et al., 2022). The yeasts and bacteria utilize this substrate in complementary ways. Yeast cells break down sucrose into glucose and fructose, favoring fructose as a substrate while generating ethanol. Meanwhile, acetic acid bacteria metabolize glucose to form gluconic acid and convert ethanol into acetic acid (Malbaša et al., 2008). In his study, Reiss (1994), analyzed the influence of different sugars (sucrose, lactose, glucose and fructose), in addition to different sugars concentrations (50–150 g/L) on the final contents of ethanol, lactic, acetic, gluconic and glucuronic acids. Finally, in agreement with other researchers, such as Blanc (1996), Reiss considered 70 g/L sucrose to be the optimal concentration.

Other sugars can also be used as substrates, such as glucose, dextrose or fructose. For example, Treviño-Garza et al. (2020), compared the consumption rate of these four carbon sources for kombucha fermentation. A fluctuation in total sugar concentration was observed within the range of 825.74–1150.62 and 798.51–1276.24 mg/L. In addition, there was a significant decrease (p < 0.05) between days 0 and 6 of fermentation for all carbon sources. However, a significant increase (p < 0.05) in total sugar content was observed between days 6 and 12. Finally, by day 15, glucose and dextrose were almost completely consumed in the culture medium, followed by fructose and sucrose.

As mentioned before, the type of substrate used, and its concentration, affects directly the chemical composition of the final product. With that in mind, Cohen et al. (2023) illustrates its significant impact on the chemical composition of kombucha. Higher concentrations of sucrose facilitate a more vigorous fermentation, leading to increased production of organic acids, especially acetic acid, which directly affects the overall acidity and taste profile of the beverage. The study also notes that when higher sucrose concentrations (like 7.5% and 10%) are used, they can result in the production of a greater amount of titratable acidity. This increase in acidity correlates with a lower final pH, indicating more pronounced sourness and potential astringency in the beverage. Conversely, lower sucrose concentrations (e.g., 5%) lead to faster fermentation rates but may produce fewer acids, impacting the overall flavor balance and sweetness perception.

Other important nutrients in the production of kombucha are nitrogen (N), phosphorus (P) and potassium (K). These compounds usually come from green or black tea. According to Chen and Lin (2016), the leaves of these teas have a significant content of these nutrients, reaching concentrations between 4 and 6, 1.5–2.1 and 0.25 to 0.4% for N, P and K respectively. The combination and interaction between carbon and nitrogen sources is essential to maintain the chemical and nutritional balance for the microbiota present in the SCOBY (Lee et al., 2024). While the carbon source provides the energy for cell growth and metabolite production, nitrogen sources provide the essential nutrients for the synthesis of enzymes and proteins required by the microbiota. Alternative substrates, such as agro-industrial wastes, are currently being evaluated to reduce the production costs of fermented tea while maintaining the functional properties of the beverage (Bortolomedi et al., 2022).

In addition to macronutrients, kombucha production necessitates the presence of micronutrients and trace elements. These elements play a crucial role in the enzymatic cofactor and metabolic regulatory capacities of the bacteria and yeasts present within the SCOBY (Lee et al., 2024). Kombucha contains several microelements, including iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), P, and K. These microelements are also found in green and black teas, which are the main sources of micronutrients. For instance, Nath (2013), showed that the concentration of Mn, Fe, Cu, and Zn in the leaf samples was found to range from 224.4 to 568.6, 212.9 to 546.4, 14.3 to 29.8, and 24.8 to 58.3 mg/kg, respectively.

Kombucha fermentation occurs in bioreactors or static tanks, which facilitate gas exchange between the system and the external environment. This allows for the exit of CO₂ and the entry of oxygen. The working volume in kombucha fermentation is a variable that has not yet been optimized. However, it is within the range of 25 to 66% (Ali and Shivanna, 2017; Lee and Kim, 2000; Marsh et al., 2014; Sharma et al., 2021). For example, Lee and Kim (2000) made a kombucha using a mixture of black and green tea in a 500 mL container with a working volume of 200 mL. On the other hand, with Marsh et al. (2014) a larger working volume was employed, approximately two-thirds of the volume of the bioreactor.

In contrast, process conditions such as temperature and pH exhibit considerable variability between different studies. These parameters are significant, influencing microbial growth and the synthesis of metabolites in kombucha (Laavanya et al., 2021). The majority of kombucha production has been conducted under mesophilic conditions, defined as temperatures between 20 and 45 °C. However, there has been limited research on kombucha production under thermophilic conditions, defined as temperatures above 45 °C. According to Esam and Hassan (2014) temperature is a crucial factor in the production of kombucha, with some reactions inhibited and cellulose production ceasing at temperatures above 50 °C. Regarding pH, kombucha fermentation occurs when the hydrogen potential is within the range of 2.0–5.6 (Amarasinghe et al., 2018; Laavanya et al., 2021). At the outset of fermentation, the pH of the medium is approximately 5. As fermentation progresses, the pH decreases due to the accumulation of acids produced by the microbial pathway. In compliance with Laavanya et al. (2021) acetic acid bacteria, including Acetobacter, have been identified in kombuchas with a pH between 4 and 6.0.

The fermentation of kombucha occurs over a period between 15 and 22 days. During the initial stages, ethanol production is the primary metabolic process, reaching its maximum concentration (approximately 10 g/L) between the sixth and tenth day. Between days 10 and 22, the formation of organic acids by the bacteria becomes the dominant metabolic process (Laureys et al., 2020). Table 1 provides a summary of the process conditions for producing kombucha. Some studies have reported longer fermentation times, for example Dima et al. (2017) and Amarasinghe et al. (2018), reported that kombuchas ferment for 30 and 56 days, respectively. However, there are potential disadvantages to such lengthy fermentation times. These include an increased likelihood of contamination of the fermented beverage and the consumption of the biometabolites produced in the fermented broth as alternative carbon sources.

Table 1.

Process conditions for producing Kombucha

Substrate	Sources	Inoculum	Process Conditions	Working Volume	Metabolites	References
Green tea Carbon: 20 g/L Nitrogen: 0,18 g/L Phosphorus: 0,017 g/L Potassium: 0,0648 g/L	Carbon: Glucose Nitrogen: Green tea Phosphorus: Green tea Potassium: Green tea	Starter solution 10% (V/V)	15 days 25 ± 2 °C pH: 2,94 – 3,03	34%	Acetic acid Lactic acid Citric acid Malic acid	Treviño-Garza et al. (2020)
Black tea residues Carbon: 42 g/L Nitrogen: 0,15 g/L Phosphorus: 0,009 g/L Potassium: 0,054 g/L	Carbon: Sucrose Nitrogen: Black tea Phosphorus: Black tea Potassium: Black tea	Starter solution 10% (V/V)	14 days 25 °C pH: 2,5 – 4,5	60%	Gallic Acid—47 mg/L Caffeine—100 mg/L Epicatechin—240 mg/L Galocatechin gallate—20 mg/L Ellagic Acid—6.5 mg/L	Zhou et al. (2022)
Black tea Carbon: 29,4 g/L Nitrogen: 0,5 g/L Phosphorus: 0,033 g/L Potassium: 0,18 g/L	Carbon: Sucrose Nitrogen: Black tea Phosphorus: Black tea Potassium: Black tea	Starter solution 4% (V/V) SCOBY – 23 g/L	21 days 25 ± 2 °C pH: ± 6,4	95%	Acetic acid Glycuronic acid Vitamins C, B1, B2, B12 Phenolic compounds—36.0 to 221.6 mg	Villarreal-Soto et al. (2019)
Black tea Carbon: 42 g/L Nitrogen: 0,50 g/L Phosphorus: 0,033 g/L Potassium: 0,18 g/L	Carbon: Sucrose Nitrogen: Black tea Phosphorus: Black tea Potassium: Black tea	Starter solution 10% (V/V)	21 days 25 ± 2 °C pH: 2,58	50%	Acetic acid Glycuronic acid—27.2 mg/L	Ansari et al. (2019)
Clitoria Ternatea Carbon: 9,9 g/L Nitrogen: 0,114 g/L Phosphorus: 0,0174 g/L Potassium: 0,04 g/L	Carbon: Coconut sugar Nitrogen: Clitoria ternatea Phosphorus: Clitoria ternatea Potassium: Clitoria ternatea	SCOBY and Starter solution	10 days 23 ± 2 °C pH: 3,5	25%	Ethanol—1.6 g/L Acetic acid—1.654 g/L Anthocyanins—0.027 g/L Phenolic compounds—1.29 g/L	Kushargina et al. (2024)
Black tea Carbon: 42 g/L Nitrogen: 0,225 g/L Phosphorus: 0,014 g/L Potassium: 0,081 g/L	Carbon: Sucrose Nitrogen: Black tea Phosphorus: Black tea Potassium: Black tea	SCOBY – 2,5% (W/V)	18 days 28 ± 3 °C aseptic conditions	40%	Acetic acid—8 g/L Malic acid Vitamins B1, B2, B6, C Ethanol—5.5 g/L Glycuronic acid—39 g/L Lactic acid Catechins	Srihari and Satyanarayana, (2012)

As illustrated in Table 1, variations in the process conditions and substrate concentrations influence directly the metabolites produced during kombucha fermentation. For example, green tea with lower carbon (20 g/L) and nitrogen content (0.18 g/L), fermented for 15 days at a pH range of 2.94–3.03, predominantly generates organic acids such as acetic, lactic, citric, and malic acids. Meanwhile, black tea residues with a higher carbon content (42 g/L) result in the production of diverse secondary metabolites, such as gallic acid, caffeine, and catechins, emphasizing the substrate's nutrient density's role in metabolite diversity.

It is also shown that physical conditions such as pH and fermentation time also affect the metabolites produced. This is consistent with the findings of Lonǎr et al. (2006), in which temperature was identified as a more influential factor in fermentation kinetics compared to the quantity of added inoculum. When fermentation temperatures of 22 °C and 30 °C were compared, it was observed that sugar consumption and acidification occurred more rapidly at 30 °C within the first 10 days for inoculum levels of 10% and 15%. This led to the conclusion that higher temperatures accelerate fermentation kinetics. However, these findings contrast with the results of Neffe-Skocińska et al. (2017), who determined that an optimal temperature of 25 °C is preferable. Their study suggested that 25 °C supports yeast activity, which is critical since the metabolites produced by yeasts, such as monosaccharides and ethanol, serve as the primary substrates for acetic acid bacteria at the initial stages of fermentation.

Microorganisms and metabolic pathways

The production process for the fermented beverage is batch and is carried out in static bioreactors without any agitation. In addition to the production of the fermented broth that is kombucha tea (containing organic acids, vitamins, alcohol, antioxidants, among other compounds), microbial cellulose is also produced in the form of a floating zoogleal, containing bacterial and yeast cells also known as SCOBY (Laureys et al., 2020; Laavanya et al., 2021). However, Sharma et al. (2021) concluded that the static fed system yielded a higher quantity of fermented products than the traditional batch process.

Yeasts are of paramount importance in the production of kombucha, as they are the microorganisms that initiate the fermentation process. The SCOBY contains significant amounts of yeast, but most of it is suspended in the fermented broth or at the bottom of the fermenter (Laavanya et al., 2021). A variety of yeast types have been identified in kombuchas, as reported by Teoh et al. (2004) The diversity of yeast species and the proportion in which they are found vary considerably from one beverage to another. However, common yeast genera have been identified among the different kombuchas, including Schizosaccharomyces, Brettanomyces, Candida, Torulaspora, Saccharomyces, Torulospora, Pichia, and others. Among the most abundant genera found were Zygosaccharomyces and Pichia, with a relative abundance of up to 95% (Chakravorty et al., 2016; Chen and Liu, 2000; Marsh et al., 2014). Other yeast genera related to kombucha fermentation and found in smaller proportions include Lachancea, Torulopsis, Rhodotorula, Brettanomyces, Dekkera, Kluyveromyces, and Eremothecium (Coton et al., 2017; St-pierre, 2019).

Another type of microorganism of great importance in the fermentation of kombucha are bacteria, which are mainly responsible for the synthesis of organic acids and cellulose. According to Laavanya et al. (2021) and Marsh et al. (2014), in kombucha, a considerable number of bacteria are present in the fermented broth and in the SCOBY. However, the latter is particularly notable for its high concentration of bacteria, both in terms of the number of species present and their relative abundance. The bacteria most closely associated with kombucha are those responsible for producing acetic acid, including Gluconacetobacter (reclassified as Komagataeibacter), which represent a minimum of 85% of the bacterial population. In fact, Kushargina et al. (2024) reported a relative abundance of the genus Komagataeibacter ≥ 99% in a kombucha made with Clitoria ternatea flowers. Other bacterial genera with significant abundance in kombuchas are Lactobacillus and Lactococcus, which can reach relative abundances of between 3.3% and 39.4% (Marsh et al., 2014; Podolich et al., 2017). Additionally, the genera Acetobacter and Oenococcus have been identified, although their relative abundances are below 2% (Kushargina et al., 2024; Marsh et al., 2014).

The fermentation process for kombucha production is complex due to the large number of reactions that take place, and the vast number of microorganisms involved in fermentation. To produce kombucha, SCOBY is generally used as an inoculum, but fermentation broth can also be used as an inoculum. The primary advantage of the former is that it has the highest microbial load with respect to the fermented broth. However, the primary disadvantage is that it lacks control over the amount of inoculum used in each fermentation, which makes it difficult to standardize and control the quality of the process and the product (Kilmanoglu et al., 2024; Su et al., 2023).

The process of fermentation initiates with the hydrolysis of sucrose present in the medium into its monomers, namely glucose and fructose. This is accomplished by the enzyme invertase, which is produced extracellularly by both yeasts and bacteria (Manoochehri et al., 2020). Ethanol is then synthesized by yeasts via the Embden-Meyerhof-Parna’s pathway (Sarris and Papanikolaou, 2016). Thees processes can be seen in Fig. 1. Furthermore, carbohydrate monomers serve as substrates for bacteria, which utilize them to synthesize organic acids, including acetic, gluconic, and glucuronic acid, among others (Laavanya et al., 2021), by the action of the enzyme glucose oxidase, which catalyzes the oxidation of the β-d-glucose molecule into gluconic acid using molecular oxygen as an electron acceptor and with the simultaneous production of H₂O₂ (Bankar et al., 2009). The organic acids produced induce stress in the yeast, which not only increases ethanol production but also acetic acid production. This is due to the fact that alcohol can be oxidized initially to aldehyde and subsequently to acetic acid by the alcohol dehydrogenase and aldehyde dehydrogenase enzyme, respectively (Edenberg and Bosron, 2010; Laavanya et al., 2021).

Fig. 1.

Metabolic pathways and enzymes involved in the production of Kombucha. Adapted: (Laavanya et al., 2021; Schneider et al., 2016). (source: created with Biorender.com)

Another metabolite generated during the production of kombucha is extracellular cellulose, which plays an essential role in the fermentation process. This metabolite is synthesized specifically by acetic acid bacteria following various reactions mediated by specific enzymes. In the process, all the oxygen dissolved in the medium is consumed by the microorganisms, which is why layers of cellulose are formed at the air–liquid interface (Laavanya et al., 2021), at this point, the microorganisms utilize atmospheric oxygen during the fermentation process, thereby increasing the thickness of the cellulose film (Esa et al., 2014). In the process of cellulose synthesis, glucose is initially converted into glucose-6-phosphate, then into glucose-1-phosphate, and finally catalyzed by uridine diphosphate (UDP) to form UDP glucose, which serves as the precursor of the cellulose biopolymer. The UDP glucose units are then linked together by the enzyme cellulose synthase (Laavanya et al., 2021; Schneider et al., 2016).

Potentials in drugs

An important area of study in Kombucha research is its capacity to impact the gut microbiome. Kombucha contains bacteria and yeast, particularly including probiotic strains from the Lactobacillus and Acetobacter genera (Antolak et al., 2021). Living bacteria have the ability to improve gut microbiota, which is crucial for digestion, immunity, and drug metabolism. An appropriate gut microbiota can impact the body's metabolism and response to medication (Vina et al., 2014; Taupiqurrohman et al., 2024).

Kombucha is not just a functional beverage; new scientific research suggests that it possesses medicinal properties that could be effective for medication discovery and formulation (Kapp and Sumner, 2019). Researchers are currently studying the potential health benefits of kombucha and its potential for pharmaceutical industry applications (Vargas et al., 2021).

Several clinical trials are currently being conducted to investigate these possibilities. An example is a clinical trial (NCT04107207) examining the potential of kombucha to enhance cognitive performance and mood in older adults. Researchers will analyze alterations in cognitive functions, emotional state, and gut microbiota composition to explore a possible connection between consuming kombucha and brain health (ClinicalTrials, 2024a). A distinct research trial (NCT04051294) investigates how drinking kombucha affects the gut flora and metabolic health in overweight or obese individuals. The study focuses on gut flora composition alterations, metabolic health indicators, and body composition to see if kombucha can enhance metabolic health (ClinicalTrials, 2024b). Furthermore, other trials are investigating the influence of kombucha on gut health. One trial (NCT03873350) (ClinicalTrials, 2024c) is examining its impact on healthy adults, while others are concentrating on patients with Irritable Bowel Syndrome (IBS) (NCT05164861) (ClinicalTrials, 2024d) and Inflammatory Bowel Disease (IBD) (NCT05717972) (ClinicalTrials, 2024e).

Kombucha's therapeutic potential goes beyond its impact on the microbiome. Its natural composition and potential benefits open possibilities for addressing common health concerns. Acne is one such concern where the search for natural alternatives to synthetic treatments highlights a gap that turmeric-infused kombucha could potentially fill (Muhsinin et al., 2023).The acidic nature of a substance could improve the absorption of specific pharmaceuticals, potentially boosting their effectiveness, especially for drugs that have low solubility or are prone to breakdown in the digestive system (Ghandehari et al., 2023). Furthermore, kombucha's antioxidant and anti-inflammatory qualities show the potential to reduce the negative effects caused by medication. Researchers are investigating if kombucha can help mitigate the negative effects linked to some drugs, therefore enhancing patient tolerance and treatment results (Mousavi et al., 2020). The distinct SCOBY created during kombucha fermentation results in a biocompatible, biodegradable, and permeable cellulose-based biofilm (Charoenrak et al., 2023). It is a promising option for controlled drug delivery systems, allowing targeted release in specific body areas or gradual release over a period of time (Balistreri et al., 2024).

The composition of kombucha might vary based on the ingredients and the brewing methods used (Tran et al., 2020). Standardization will guarantee consistency and reliability in drug research and formulation. Although generally safe, individuals with pre-existing health conditions or compromised immune systems should be cautious.

The outcomes of these and other clinical trials will be essential in validating the safety, efficacy, and mechanisms behind kombucha's therapeutic promise. This ancient beverage has the potential to significantly contribute to the development of novel pharmaceutical treatments by combining traditional knowledge with modern scientific advancements, resulting in improved and patient-centered medication therapy.

Kombucha regulatory standards

There has been an explosion of interest in kombucha products among consumers in recent years. As a result, regulation and standardization are more than necessary to guarantee the quality and safety of these products for end consumers. Because kombucha is a product that is often made by hand, there are many risks involved in the production chain until it reaches the consumer (de Oliveira et al., 2023).

Kombucha is regulated in Brazil by Normative Instruction No. 41 of September 17, 2019, instituted by the Ministry of Agriculture, Livestock and Supply (MAPA), contains definitions, classifications, labeling rules, prohibitions related to production and trade, and analytical quality parameters. These parameters include properties such as pH, which should be in the 2.5–4.2 range, the alcohol concentration of kombucha without alcohol (up to 0.5%) and with alcohol (0.6–0.8%), volatile acidity (30–130 mEq/L) and CO₂ pressure (1.1 to 3.9 atm) in kombucha (de Miranda et al., 2022).

As a result, the lack of standardization in the regulation of these products, coupled with a lack of information on the safety and quality of this drink, has a detrimental effect on the kombucha producer and consumer markets (Batista et al., 2022).

The year 2014 saw the creation of an international trade association called Kombucha Brewers International (KBI). Through debate, education, and research, modern legislation would be developed that would cater to all sectors of this emerging market, through communication between producers, consumers, and legislators from different countries (Kim and Adhikari, 2020). Thus, KBI has developed and provided a kombucha production code, aimed at ensuring product safety and quality, as well as greater transparency for consumers. The company even offers a quality seal and certification program for drinks that meet KBI's manufacturing standards (Kombucha Brewers International Code of Practice, 2024).

In the United States, a major producer and consumer of kombucha, the Food and Drug Administration (FDA) determines food and drink regulations. The FDA keeps fermented beverages exempt from regulation, and they are only subject to a hazard analysis and critical control points (HACCP) plan (Coelho et al., 2020). In 2017, the KBI, in partnership with the US Senate, attempted to draft and implement the "Kombucha Act". According to this proposal, kombucha would be fermented only by bacteria and yeasts, could not contain alcohol concentrations over 1.25%, and would be derived from sugar, malt or malt substitute, tea, or coffee. However, to date, no such regulatory law has been passed (de Miranda et al., 2022). In parallel, at the same time, the Pennsylvania Department of Agriculture published a document, which followed analytical standards very similar to Brazilian legislation and also instituted prohibitions such as false claims of health benefits, as well as informing about contraindications for immunocompromised individuals, consumption limits (which should not exceed 120 mL/day) and the presence or absence of alcohol (Dutta and Paul, 2019).

Further north, neighboring Canada, more precisely at the British Columbia Centre for Disease Control (BCCDC), there is a document with recommendations for the production and marketing of kombucha. The document contains information on biological and chemical risks and hazards during the production process of kombucha. The plan states that the pH should not be below 2.5 and the alcohol concentration should not exceed 1% and should not increase as the product ages (de Miranda et al., 2022).

On the Asian continent, where kombucha originated, countries such as Japan, China, and India are leaders in the production and consumption of probiotic-fermented foods and beverages such as kombucha. Both countries have regulatory authorities and systems that set the standards for inoculum, packaging, labeling, cold storage, taste, and the fermentation process of production (Batista et al., 2022).

Japan has a regulatory system called “Foods for Specific Health Uses” (FOSHU) was created in 1991 to standardize and control the quality of foods with functional properties, including probiotics. Probiotics, such as kombucha, are widely marketed and distributed as foods with health claims (FHCs). In the Japanese system, FHCs can be classified as “foods with nutritional function claims” (FNFC), FOSHU, or “foods with functional claims” (FFC). The manufacture and distribution of such products requires a special permit from the Ministry of Health and Welfare (MHLW), which decides whether the product qualifies as FOSHU. The FOSHU registration thus acts as a seal of quality, indicating that the product has met the analysis, safety, and processing parameters (Arora and Baldi, 2015).

In China, the regulations are a little more liberal. In 1995, the Food Hygiene Law was enacted, which provides for licensing for the sale of food supplements. The Chinese government has created a system in which these foods are divided into three categories: "dietary supplements", "new resource food products" and "functional foods". Kombucha falls into the "new resource foods" category, for which no scientific evidence is required under the legislation if there is published literature indicating efficacy and health benefits. The China Food and Drug Administration (CFDA) is the government agency responsible for regulating functional foods. Its standardization includes a list of microorganisms approved for use in functional foods. The number of health claims on product labels is not limited and there are also no specific regulations governing the production and marketing of kombucha, so it is only classified as a simple probiotic (Yang, 2016).

India has a slightly different situation. The Indian Council of Medical Research (ICMR) was established to fill the gaps in the lack of regulatory guidelines for the sale of probiotic products. The ICMR is therefore tasked with evaluating product strains, the potential toxicity of strains, the efficacy of effect in animal models, food safety for human consumption, and labeling requirements. To assist in this regulatory process, the Prevention of Food Alteration (PFA), the FDA, and the Food Safety Standards Act (FSSA) also regulate probiotics. These institutions help establish ICMR guidelines. However, despite all this progress, there is still a lack of categorization and minimum safety standards to produce probiotics such as kombucha (Sharma et al., 2013).

On the old European continent, probiotics are regulated by the Food Directive and Regulation (regulation 178/2002/EC; directive 2000/13/EU). The regulation is supported by the European Food Safety Authority (EFSA), which carries out the safety assessment of all foods, and by Functional Food Science in Europe (FUFOSE), which regulates and categorizes functional foods. There is also Regulation 1924/2006, which stipulates that a product to be marketed must be supported by scientific literature and must not have unknown benefits. A further requirement is that the probiotic passes the qualified presumption of safety (QPS) test by EFSA's scientific panels, whose task it is to assess the toxicity of the strains. However, the level of control and standardization of the production process is still insufficient, which requires an update of the regulatory standards (Leuschner et al., 2010).

In an attempt to keep up with the regulations, Africa has published a document with requirements and tests to ensure the quality and safety of beverages such as kombucha was promulgated in Uganda in 2018. The analytical quality parameters concern maximum values for biological and chemical impurities (heavy metals and pesticides), pH, alcohol content, total sugar content, acidity in acetic and lactic acid, etc. All these parameters are similar to those used by Brazilian legislation and the FDA in the United States (de Miranda et al., 2022).

Comparing legislation around the world, it is clear that there are still gaps that need to be filled, such as the lack of general standardization of what is already regulated and parameters that still need to be added. Parameters such as inoculum and its toxicity, the quality and type of packaging and distribution container, proper storage, the assessment of the presence of toxic fermentation residues and by-products, the amount and allowable concentration of additives, the need for pasteurization and the ideal fermentation production process deserve more attention and general standardization.

Patents and Products

In order to gain a comprehensive understanding of the technological evolution of the products and by-products derived from the preparation of kombucha, a patent search was conducted in the Derwent Innovations Index database. This search identified a multitude of potential applications, either as a standalone raw material or as an integral component of another developed product.

To retrieve documents related to applications in the pharmaceutical area, the International Patent Classification (IPC) code group A61K was selected. This code group encompasses section A, which covers "Ordinary necessities of life" class A61 (medical or veterinary sciences), subclass A61K (preparations for medical, dental or hygienic purposes). The search was conducted over the past five years (2019–2024) to gain a deeper understanding of current developments and trends. The final search algorithm combined the keywords kombucha, "fermented tea," or "probiotic tea" with the IPC code A61K*.

This initial search yielded a total of 121 patents, which were then filtered based on the criteria of exclusive use of kombucha in pharmaceutical applications or exclusive use of kombucha-derived products in pharmaceutical applications. Furthermore, it was assumed that kombucha is a fermented product derived from a submerged culture of tea plants (Camellia sinensis), either through spontaneous fermentation or inoculation with probiotic microorganisms known as "SCOBY".

After a rigorous selection process, 43 patent documents from the previous five years were chosen for their diverse applications within the pharmaceutical field. The selected patent documents evidenced a diverse range of therapeutic applications, which is why they have been grouped into the following categories: dermatological therapies, metabolism regulation therapy, anti-inflammatory therapy, cognitive therapy, neurological therapy, immunotherapy, oncological therapy, antimicrobial therapy, cardiovascular therapy, respiratory disease therapies, and gastrointestinal diseases therapies. The first two categories, dermatological and metabolism regulation therapy, gathered the largest numbers of patent documents, with 18 patents each. Figure 2 presents the patent network map where each patent document number is associated to one or more of the subject categories mentioned above.

Fig. 2.

Patent network analysis of products and by-products derived from kombucha preparation and application as pharmacotherapies. This network representation illustrates the distribution of patents related to pharmacotherapies based on kombucha-derived products and by-products. Large nodes indicate pharmacological therapy categories with the highest number of associated patents, while edges represent the relationships between patents linked to one or more therapy types. Smaller nodes surrounding each large node correspond to individual patents, which are color-coded according to their respective therapeutic category. The network analysis was performed using Gephi software. Abbreviations: UPenn, University of Pennsylvania; UBC, University of British Columbia; app, application

With regard to the applications of kombucha compounds in dermatological therapies, Xuan et al. (2023) describe a product derived from tea fermentation that improves skin microcirculation by increasing vascular permeability in document CN116650380A. Similarly, it can enhance the synthesis of type I collagen and hyaluronic acid from skin cells and inhibit the secretion of inflammatory factors by regulating and controlling transient signaling pathways of Transient Receptor Potential Vanilloid 3 (TRPV3) and Transient Receptor Potential Melastatin 8 (TRPM8), thereby achieving the effect of resisting cellular aging.

This technology is developed from a fermentation process that involves tea leaves that have been pre-treated by a sterilization process, a 0.7 mmol/L solution of pipecolic acid, and an inoculum of a probiotic strain of Bacillus subtilis. After a suitable culture time, the ferment is sterilized and the extract is recovered by filtration, thus obtaining the final product.

In the field of metabolism regulation therapy, Jiang et al. (2024) describe, in document CN117838740A, the application of Penicillium jiangxi and kombucha for the preparation of a drug that reduces blood fat and/or reduces liver injury. The invention entails inoculating a suitable volume of the Penicillium jiangxi fungus strain, previously isolated through spontaneous fermentation of tea, in a culture medium based on leaves, stems, or powder of black, green, or other similar tea. The fermented product, following the incubation process, was reported to have beneficial effects on cholesterol, triglycerides, and low-density lipoprotein levels in the blood. Pyruvic transaminase and glutamic oxaloacetic transaminase were also found to reduce lipotoxic liver injury, protect liver cells, and have positive effects on blood fat and liver injury.

Additionally, innovative technologies such as anti-inflammatory therapy products were identified. Ji (2019) in the patent document CN110279774A describes the preparation of a beverage to relieve pain and dissolve nodules in the mammary gland, composed of kombucha and a combination of tangerine seeds and fibers. The patent describes the preparation of a beverage comprising the following ingredients, expressed in parts by weight: 30–60 parts of kombucha and 15–30 parts of the combination of tangerine seeds and fibers. The anti-inflammatory potential of the beverage is supported by the presence of various components in the organic matter of tea and tangerine seeds, including proteins, amino acids, alkaloids, polyphenols, carbohydrates, organic acids, lipids, pigments, fragrance components, vitamins, and soap. Additionally, the agents, sterols, as well as the products generated after tea fermentation, such as theaflavin and thearubigin, possess anti-inflammatory properties and can facilitate gastrointestinal digestion, promote appetite, diuresis, edema elimination, and robust cardiac function. Finally, the product was subjected to a clinical evaluation in a sample of 70 individuals, with recovery rates between 80 and 100% observed in alleviating symptoms of inflammation and pain in the breast.

In the field of cognitive therapies, Wang et al. (2023), in the document CN117337980A, describe an oral liquid for improving sleep disorders and the method of preparation thereof. The product is composed of 100 to 200 parts of cereal soup, which is a precooked solution of millet material, wild jujube powder, and grape seed powder. Additionally, it contains 0.05 to 0.07 parts of probiotic strain Lactobacillus plantarum. Additionally, the product contains 0.03–0.05 parts of kombucha liquid, 0.03–0.05 parts of acetic bacteria culture, 0.02–0.04 parts of angel yeast SY, and 5–10 parts of white sugar. Similarly, the authors describe the significant potential of the innovation as a product that can regulate the intestinal microbiota, enhance neurotransmitters, and enhance probiotic products to improve disorders related to sleep and wakefulness. These benefits are due to the presence of certain components such as gamma-aminobutyric acid (GABA) produced by L. plantarum strain, that also produces a variety of compounds, including organic acids, phenolic compounds, trace elements, vitamin C, vitamin B complex, theanine, and others. These compounds exhibit antimicrobial, antioxidant, antiproliferative, and anticancer properties. Additionally, they facilitate the growth of beneficial bacteria in the gut, thereby restoring the dynamic balance of the intestinal tract.

Some patent documents have also described compounds derived from tea as having potential therapeutic applications in the improvement of brain functions. For instance, the patent WO2022085212A1 Atsuko et al. (2020) describes the invention of a higher brain function enhancing agent related to motor control and body balance function. This compound, designated as phototrienol, is responsible for the beneficial characteristics observed in human health and can be found as a compound derived from the fermentation of tea (Camellia sinensis) or Kombucha. The brain function-enhancing agent of this invention alleviates peripheral symptoms, such as psychological symptoms (anxiety/depressive symptoms) and behavioral symptoms (sleep disorder symptoms), in upper brain dysfunction associated with brain dysfunction due to aging. Furthermore, it alleviates central symptoms (memory disorder, judgment disorder, problem-solving ability disorder, performance dysfunction, sensitive disorder, aphasia/agnosia/aphasia, etc.). It is important to note that, according to the patent description, the method for producing this compound in a natural manner involves distillation processes of the tea fermentation liquid, either by vacuum or steam distillation, rectification, and adsorption of the component in an adsorbent material such as black tea itself.

In contrast, innovations that utilize the diverse characteristics of kombucha products with multiple applications have been developed. For instance, Chen (2020) describes the development of a mask liquid in the document CN112294687A. This mask liquid exhibits remarkable effects on skin care, including high moisturizing capacity, anti-inflammatory, antibacterial, and antiallergic properties. Additionally, it has been shown to favor tissue regeneration and cellular repair. The following product is composed of the following proportions by weight: 8–15 parts of fermented kombucha liquid, 1–2 parts of natto extract, 1–2 parts of cherry leaf extract, 0.5–1.5 parts of natural Epilobium extract, 1–2 parts of young barley juice. The composition of the product in question is as follows: juice, 2–3 parts of topinambur soluble protein, 0.5–1.5 parts of hawthorn fermented liquid, 2–3 parts of Chinese herb extract, 0.3–0.8 parts of hydrophilic modified castor oil, and 50–60 parts of deionized water. Similarly, clinical trials involving a sample of 220 individuals demonstrated efficacy in reducing the effects of skin ailments, with results ranging from 3.8 to 5 on a scale of 1 to 5. This evidence supports the utility of this treatment in dermatological, anti-inflammatory, and immunotherapeutic therapies.

Similarly, other patents were retrieved, albeit in smaller quantities, which covered areas of application such as oncological or antimicrobial therapy. Document IN201931007429A, developed by Subrata et al. (2019), provides an example of this. It describes the development of a synergistic herbal composition of fermented tea made from black tea, sucrose, cultured yeast, Saccharomyces cerevisiae yeast, acetic acid bacteria, and water.

This product has the potential to provide antimicrobial activity and enhance immunity in humans, while also reducing the generation of reactive oxygen species (ROS) in living organisms when exposed to radiation. It can also protect against radiation-induced DNA damage, offering protection against chromosomal alterations produced by radiation exposure. Furthermore, it can minimize the side effects produced during radiotherapy for cancer patients. Additionally, it functions as an antipyretic, antibacterial, antifungal, analgesic, uricosuric, antiarthritic, anti-inflammatory, antituberculosis, and antitumor agent. In an in vitro test to evaluate antioxidant activity by ferric reducing antioxidant power assay (FRAP), the fermented tea composition exhibited an absorbance of 0.78–0.83, while the positive control (normal black tea) exhibited an absorbance of 0.39–0.42. This indicates that the fermented tea composition has excellent antioxidant power. A summary of other patents is presented in Table 2.

Table 2.

Patent documents describing technologies employed to produce pharmaceutical products derived from kombucha or its derivatives

Code	Title of patent	Year	Country	Application Field
CN118319998A	Blood lipid-lowering fermented tea and preparation method thereof	2024	China	Metabolism regulation therapy
CN118185784-A	Lactobacillus plantarum (Lactiplantibacillus plantarum) L123 with selenium enrichment and purine reduction functions and application thereof	2024	China	Metabolism regulation therapy
CN117838740-A	Application of Penicillium jiangcha and fermented tea in preparation of drugs for reducing blood lipid and/or reducing liver injury	2024	China	Metabolism regulation therapy
CN117731574-A	Camellia seed fermented facial cleanser and preparation method thereof	2024	China	Dermatological therapy
CN117337980-A	Oral liquid for improving sleep disorder and preparation method thereof	2024	China	Cognitive therapy; Neurological therapy
CN116650380-A	Anti-aging tea fermentation product for improving skin microcirculation and preparation method and application thereof	2023	China	Dermatological therapy
CN116831960-A	Fermented tea extract and preparation method and application thereof	2023	China	Dermatological therapy
CN116966120-A	Preparation method and application of tea dreg bioconversion extract	2023	China	Dermatological therapy; Anti-inflammatory therapy
TW202337478-A	Fermented tea preparation and preparation method for preventing and improving gout and hyperuricemia	2023	Taiwan	Metabolism regulation therapy
TW202337486-A	Fermented tea preparation and preparation method for improving renal filtration function and reducing serum creatinine to prevent renal injury to protect renal function	2023	Taiwan	Metabolism regulation therapy
WO2023067509-A1	Compositions for supplementing kombucha products with therapeutic agents and methods of making and use thereof	2023	United States	Neurological therapy
FR3130515-A1	Method for producing a fermented grape marc, resulting fermented grape marc and use thereof in dietary supplements or in cosmeceuticals	2023	France	Metabolism regulation therapy; Dermatological therapy
CN114391594-A	Avocado peel fermented tea and extract thereof, and preparation method and application thereof	2022	China	Dermatological therapy
CN115192614-A	Sea cucumber preparation for improving immunocompromised condition and preparation method and application thereof	2022	China	Immunotherapy
DE202022100395-U1	Fermented Kombucha powder encapsulated with fibers and containing ingredients that regulate physiological functions and maintain efficacy	2022	Germany	Metabolism regulation therapy
CA3122201-A1	Kombucha natural health products	2022	Canada	Metabolism regulation therapy; Anti-inflammatory therapy; Gastrointestinal diseases therapies
CN114600986-A	Preparation of black tea fungus by direct-vat-set starter and blood sugar reducing effect of black tea fungus	2022	China	Metabolism regulation therapy
JP2022067866-A	Brain function improving agent	2022	Japan	Neurological therapy
CN113546107-A	Fermentation extraction method process and preparation method of gentian flower and black tea fungus	2021	China	Dermatological therapy; Respiratory disease therapies; Metabolism regulation therapy
CN112842968-A	Skin care liquid composition and preparation method thereof	2021	China	Dermatological therapy
CN112294687-A	Black tea fungus fermentation mask liquid and preparation method thereof	2021	China	Dermatological therapy; Anti-inflammatory therapy; Immunotherapy
JP2021180619-A	Fermented tea composition for controlling intestinal function and method of producing the same; Tea fermentation composition for regulating intestinal tract and its preparation method	2021	Japan	Gastrointestinal diseases therapies; Metabolism regulation therapy
CN111329929-A	Dietotherapy formula for treating tumor and cancer and tibia and preparation method thereof	2020	China	Oncological therapy
JP2020080820-A	Post-fermented tea-containing trans fatty acid selective absorption inhibitor and use thereof	2020	Japan	Metabolism regulation therapy
JP2020083857-A	Selective absorption inhibitor of trans fatty acid containing semi-fermented tea and use thereof	2020	Japan	Metabolism regulation therapy
CN109833267-A	A kind of pot marigold makes composition against age essence	2019	China	Dermatological therapy
CN109745278-A	A kind of skin activity water and preparation method thereof	2019	China	Dermatological therapy
CN110051617-A	A kind of sunscreen and preparation method thereof of high SPF	2019	China	Dermatological therapy
CN109568181-A	A kind of tea oil hand lotion	2019	China	Dermatological therapy; Anti-inflammatory therapy
CN110279774-A	The mammary gland analgesic dissipating bind tea and preparation method thereof combined by fermented tea with tangerine seed tangerine pith	2019	China	Anti-inflammatory therapy

Similarly, Fig. 3 shows an overview of the countries of origin of the published patent documents, with China being the country with the highest number of innovation patents. This is justified by the fact that it is the country of origin of Kombucha, as well as one of the main regions where the tea plant (Camellia sinensis) grows, as well as other similar plants that are part of an ancient culture in the study of Chinese natural medicine. On the other hand, it is observed that the evolution of patent publications in the last 5 years has been progressively increasing with a slight drop in the year 2020, which could be attributed to the world pandemic crisis due to COVID-19 and the limitations for research, which also reflects that this type of technology was not related as a possible alternative for treatments related to the viral infection caused by SARS-CoV-2. After this year, it is evident that the growth of published patents has been increasing, being 2022 the year when the largest number of publications was found (10 patent documents). Finally, in 2024, there are 6 patent publication to the date of this analysis was identified but considering the secrecy period of usually 18 months between a patent filing and its publication, this number will probably increase in the next months.

Fig. 3.

a The map displays the number of patent documents registered in the last five years by country of origin, highlighting China as the country with the highest number of patents. b The graph represents the number of patents published per year in the Derwent Innovations Index database related to kombucha-derived products for pharmaceutical applications. The increased color intensity indicates that 2022 was the year with the highest number of registered patents (source: created in mapchart.net;

© 2024 GraphPad Software)

In this way it is observed that numerous patents have been developed and interest from both consumers and the scientific community has grown. However, the lack of standardization in production and global regulation represents a challenge to be overcome.

Due to the presence of several bioactive compounds already found in its composition and in the organisms involved, this drink has potential uses in the pharmaceutical industry. New studies with the use of different teas and variations in the culture medium have expanded the possibilities of the drink market.

In addition, the interest in conducting clinical studies that effectively prove the effectiveness and safety of the use of kombucha in health treatments has also increased in recent years. Thus, according to what has been observed in the recent literature, kombucha presents itself as a beverage with potential for further research on the mechanisms of action of the bioactive compounds present in the production control and use in the pharmaceutical industry.

Declarations

Conflict of interest

The authors declare no conflicts of interest.