catequinas

Catechins

1. Identity: Chemical Nature, Botanical Sources, and Common Preparations

1.1 Chemical Classification and Nomenclature

Catechin, the name of which is derived from catechu of the extract of Acacia catechu L., is 3,3′,4′,5,7-pentahydroxyflavan with two steric forms of (+)-catechin and its enantiomer. In a broad sense, catechin represents the chemical family name of the compounds derived from catechin. They are condensation-type tannins with a ring and the basic structure of flavan-3-ol. They have many chemical structural features, such as hydroxyl groups (−OH), that combine easily with other materials.

Catechin chemically consists of two benzene rings (A- and B-rings) and a dihydropyran heterocycle (the C-ring). The antioxidant properties of catechins are largely dependent on the structure of molecules, and the number and location of hydroxyl groups or their substituents.

Catechins belong to the broader class of flavonoids — specifically the flavanol (flavan-3-ol) subclass — and are members of the larger polyphenol family of plant secondary metabolites. The abbreviations and full names of various catechins are as follows: C, catechin; CG, catechin gallate; EC, epicatechin; ECG, epicatechin gallate; EGC, epigallocatechin; EGCG, epigallocatechin gallate; GC, gallocatechin; GCG, gallocatechin gallate. Among all these forms, epigallocatechin-3-gallate (EGCG) has attracted the greatest research attention.

1.2 Principal Botanical Sources

The major sources of catechins are Camellia sinensis (C. sinensis) and C. assamica. Tea is one of the world's most widely consumed non-alcoholic beverages and is a rich source of bioactive compounds. The synthesis and accumulation of catechins, central flavonols in the secondary metabolism of the tea plant, not only define the bitterness and astringency of the tea infusion but also form the chemical cornerstone of its remarkable antioxidant activity.

Catechins account for more than 75% of the polyphenol compounds in tea leaves. According to the data currently available, these chemicals may account for as much as 30–35% of green tea's dry matter. EGCG accounts for about two-thirds of the catechins in green tea and thus has attracted the most attention in the scientific community.

Beyond tea, catechins are present in a wide range of plant foods. Catechins are distributed in a variety of foods and herbs including tea, apples, persimmons, cacaos, grapes, and berries. High concentrations of catechin can be found in fresh tea leaves, rock-rose leaves, broad beans, red wine, black grapes, strawberries, and apricots. Apples, blackberries, broad beans, cherries, black grapes, pears, raspberries, and chocolate are rich in epicatechin. Catechin, epicatechin, and gallate epicatechin are present in red wine where reacting with tannins they are responsible for wine flavor. Cocoa-based products such as chocolate also contain catechin and epicatechin in high amounts.

1.3 Tea Type and Catechin Content

EGC, ECG, and EGCG are found in high concentrations in oolong, black, and green teas, but particularly in green tea because the leaves are dried and steamed instead of fermented — fermentation converts some of the catechins into more complex theaflavins and other flavonoids. EGCG accounts for about two-thirds of the catechins in green tea. Green tea is grown mainly in Japan, China, and Taiwan.

Recently, the monograph of green tea was included in the European Pharmacopoeia, where green tea is standardized for caffeine content (min 1.5%) and for total content of catechins, expressed as (−)-epigallocatechin-3-O-gallate (min 8%).

1.4 Common Preparations and Dosage Forms

Catechins are available in several forms. The most traditional is as a water infusion — brewed tea. As dietary supplements, they are commercially available as standardized green tea extracts (GTE) in capsule or tablet form, often standardized to a defined EGCG percentage. The average daily intake of EGCG from green tea infusions ranges from 90 to 300 mg/day, whereas the exposure of high consumers is estimated to reach 866 mg EGCG/day in the adult EU population.

Research preparations have ranged significantly. In one major double-blind trial, subjects ingested green tea containing 583 mg of catechins (catechin group) or 96 mg of catechins (control group) per day over 12 weeks. Among studies utilizing beverage or food-based dosage forms, one of the highest reported intakes involved a green tea extract delivering 1519.7 mg/day of total catechins and 704 mg/day of EGCG, administered in three divided doses before meals.

The bioavailability of catechins can be improved by nanostructure-based drug delivery systems, molecular modification, and co-administration with other bioactive ingredients. Encapsulation of tea catechins on protein-based, carbohydrate-based, and lipid-based nanoparticles improved stability, sustainable release, and cell membrane permeation of catechins, resulting in increased bioavailability.

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2. Traditional and Historical Use

2.1 China

Its use dates back to around 3000 BC in ancient China. Historical records, including the ancient medical text Shen Nong's Herbal Classic, demonstrate that the Chinese population was aware of tea's health-promoting and disease-preventative properties. Lu Yu (733–803) published a book that describes the history of tea, the techniques and utensils used for manufacturing, the method of preparation, and drinking of tea in the People's Republic of China. In traditional Chinese medicine (TCM), tea prepared from Camellia sinensis leaves was used for a range of purposes including improving digestion, alertness, and general vitality. In modern China, green tea remains a component of TCM herbal formulations and is recommended by some practitioners for specific conditions.

2.2 Japan

The Japanese tea ceremony (chanoyu) incorporated mindfulness, aesthetics, and social harmony alongside the health benefits of the tea itself. Today, Japan's approach to green tea reflects this holistic perspective: tea is consumed daily not as medicine per se, but as a foundational element of a healthy lifestyle. In Japan, green tea is not classified as medicine but is recognized as a functional health food.

Processing methods in Japan have historically influenced catechin preservation. Japanese green teas hold one crucial advantage over Chinese and other green teas: steam processing. This method (sencha style) immediately halts the oxidation of the leaves and preserves the maximum amount of catechins. In China, tea leaves are traditionally pan-fired, which is gentler on flavour but less effective at preserving catechins.

2.3 General East Asian Traditional Use

Tea has been applied as a cure for many ailments and features prominently in traditional Chinese medicine. Preparations traditionally consisted primarily of hot-water infusions of dried, minimally processed green tea leaves. The beverage was associated in traditional literature with benefits spanning digestion, mental acuity, fever reduction, and wound healing, though these claims long preceded any modern clinical verification. Both China and Japan view daily green tea consumption as a foundational health practice, similar to how Western cultures view exercise or a balanced diet.

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3. Key Constituents and Active Compounds

3.1 The Major Catechins

The four main catechins that occur in green tea are (−)-epicatechin (EC), (−)-epicatechin-3-gallate (ECG), (−)-epigallocatechin (EGC), and (−)-epigallocatechin-3-gallate (EGCG). Of these catechins, EGCG and EGC are found in the highest amounts in green tea and have been the subject of most studies.

Epigallocatechin-3-gallate (EGCG), a flavon-3-ol polyphenolic compound, is the most active. Tea contains, as the major catechin, (−)-epigallocatechin-3-gallate (EGCG), which has many beneficial properties for human health such as anticancer, anti-obesity, antidiabetic, anticardiovascular, anti-infectious, hepatoprotective, and neuroprotective effects.

3.2 Structural Basis of Activity

The structure of catechin is the key determinant of its free-radical scavenging and metal chelating activities. Their antioxidant activity largely depends on the number and location of hydroxyl and other chemical groups. These allow catechins to act as metal ion chelators, providing them with the ability to reduce the level of lipid peroxidation biomarkers and improve lipid metabolism disorder caused by oxidative stress.

Catechins are well-known powerful antioxidants, have metal-chelating properties, and show cell-protective effects, but they can also play pro-oxidant and cytotoxic roles in some cellular contexts. They can interact directly with molecular targets such as proteins and phospholipids, regulate signal transduction pathways, and modulate enzymes, and they have a strong affinity with lipid bilayers, which may facilitate their entry into cancer cells.

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4. Mechanisms of Action

4.1 Antioxidant Activity

As an exogenous antioxidant, catechins can effectively eliminate lipid peroxidation products. They can also play an antioxidant role indirectly by activating the endogenous antioxidant system by regulating enzyme activity and signaling pathways.

Some studies have demonstrated that catechins could significantly inhibit the excessive oxidative stress through direct or indirect antioxidant effects and promote the activation of the antioxidative substances such as glutathione peroxidases (GPO) and glutathione (GSH), reducing the oxidative damages to the colon.

The bulk of evidence has shown that the cardio-protective activity of green tea is mainly attributed to the antioxidant properties of its catechins, which act by inducing antioxidant enzymes, inhibiting pro-oxidant enzymes, and scavenging free radicals.

4.2 Anti-inflammatory Signaling

Catechins can exert their significant anti-inflammatory properties by regulating the activation or deactivation of inflammation-related oxidative stress-related cell signaling pathways, such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), signal transducer and the activator of transcription 1/3 (STAT1/3) pathways.

Usually, Nrf2 remains in an inactive state in the cytosol, binding to the protein kelch-like ECH-associated protein 1 (Keap1), forming a complex. After stimulated by various oxidative stresses, like ROS, this complex would be disrupted to form active Nrf2, leading Nrf2 to translocate to the nucleus and bind to antioxidant response element (ARE) genes, which can encode proteins with cytoprotective functions, like NADPH regenerating enzymes.

One mechanism is the inhibition of a key oxidative stress-sensitive transcription factor — nuclear factor-κB (NF-κB). After exposure to oxidative and inflammatory stimuli, IκB kinase (IKK) is activated, leading to IKK signalsome phosphorylation, which are subsequently degraded by the proteasome. Then NF-κB translocates to the nucleus, where it binds to specific promoter regions and initiates transcription.

Catechin inhibited the gene expression of pro-inflammatory cytokines including IL-1α, IL-1β, IL-6, IL-12p35, and inflammatory enzymes including iNOS and COX-2.

4.3 Modulation of Cell Survival Pathways

EGCG has demonstrated considerable therapeutic potential through a multifaceted mechanism of action, chiefly by modulating key signaling pathways such as JAK/STAT, NF-κB, AKT, and Notch. This regulatory capacity underscores its pivotal role in governing essential cellular processes, including apoptosis, proliferation, and survival.

In addition to the known antioxidant activity of catechins, other mechanisms such as modulation of signal transduction pathways, cell survival/death genes, and mitochondrial function contribute significantly to the induction of cell viability.

4.4 Metal Chelation

Many lines of evidence suggest that oxidative stress resulting in reactive oxygen species (ROS) generation and inflammation play a pivotal role in the age-associated cognitive decline and neuronal loss in neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's diseases. One cardinal chemical pathology observed in these disorders is the accumulation of iron at sites where the neurons die. The buildup of an iron gradient in conjunction with ROS are thought to constitute a major trigger in neuronal toxicity and demise in all these diseases. Catechins, particularly EGCG, address this through their iron-chelating properties.

4.5 Gut Microbiota Interaction

Growing evidence highlights the gut microbiota as a key modulator of EGCG's biotransformation and biological activity. The interaction between catechins and gut microbiota is pivotal in elucidating the mechanisms through which these compounds can exert substantial health effects despite their limited bioavailability. Variations in microbiota composition can influence catechin metabolism and may partially explain the heterogeneity observed in individual treatment responses.

4.6 Gut and Mucosal Effects

Catechins can also stabilize the structure of the gastrointestinal micro-ecological environment via promoting the proliferation of beneficial intestinal bacteria and regulating the balance of intestinal flora, so as to relieve inflammatory bowel conditions. Furthermore, catechins may regulate the tight junctions (TJ) in the epithelium.

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5. Scientific Evidence by Area of Health Use

5.1 Cardiovascular Health

Randomized controlled trials (RCTs) of green tea and cardiovascular risk factors suggest that green tea may reduce low-density lipoproteins and total cholesterol, although studies are of short duration. There is no robust evidence to support a reduction in coronary artery disease risk in green tea drinkers.

In line with animal studies where green tea catechins had lowering effects on cholesterol, the administration of green tea catechins has been reported to reduce total cholesterol (TC) and low-density lipoprotein (LDL) in human clinical trial studies. An umbrella review and meta-analysis showed that regular consumption of green tea significantly decreases systolic blood pressure (SBP) and diastolic blood pressure (DBP).

One pivotal clinical trial illustrates these findings specifically: the body fat reducing effect and reduction of risks for cardiovascular disease by a green tea extract (GTE) high in catechins was investigated in humans with typical lifestyles. Japanese women and men with visceral fat-type obesity were recruited for the trial. After a 2-week diet run-in period, a 12-week double-blind parallel multicenter trial was performed, in which the subjects ingested green tea containing 583 mg of catechins (catechin group) or 96 mg of catechins (control group) per day. Randomization was stratified by gender and body mass index at each medical institution. The subjects were instructed to maintain their usual dietary intake and normal physical activity. Data were analyzed using per-protocol samples of 240 subjects. A greater decrease in systolic blood pressure (SBP) was found in the catechin group compared with the control group for subjects whose initial SBP was 130 mm Hg or higher. LDL cholesterol was also decreased to a greater extent in the catechin group. The continuous ingestion of a GTE high in catechins led to a reduction in body fat, SBP, and LDL cholesterol, suggesting that the ingestion of such an extract contributes to a decrease in obesity and cardiovascular disease risks.

Evidence strength: Several epidemiological studies have shown beneficial effects of green tea in cancer, cardiovascular, and neurological diseases. The health benefits associated with green tea consumption have also been corroborated in animal studies of cancer chemoprevention, hypercholesterolemia, and atherosclerosis. However, most human RCTs are of short duration, and mechanistic pathways are not fully established in humans. Evidence for LDL reduction and blood pressure lowering is supported by multiple RCTs and meta-analyses; evidence for reduction of hard endpoints such as myocardial infarction remains observational and indirect.

5.2 Body Weight and Metabolic Health

There are a considerable number of RCTs to suggest that green tea does reduce body weight in the short term, but this is not likely to be of clinical relevance.

A systematic review and meta-analysis of RCTs examining whether green tea catechins enhance the weight-loss effect of exercise training found: of 1,015 retrieved studies, 24 were identified for full-text review, out of which 10 randomized trials met the inclusion criteria. Exercise plus green tea versus exercise alone had a small and consistent effect on weight [Standardized mean difference (SMD) = −0.30, CI: −0.53 to −0.07], BMI [SMD = −0.33, CI: −0.64 to −0.02] and fat reduction [SMD = −0.29, CI: −0.57 to −0.01], and there was no evidence of heterogeneity across the trials.

Although the exact mechanism of action of green tea to reduce cholesterol is not fully understood, an increase in thermogenesis, enhancement of gene expression of enzymes involved in bile acid production, and appetite suppression have been proposed as potential mechanisms.

Evidence strength: Multiple RCTs and meta-analyses document modest, statistically significant reductions in body weight, BMI, and fat mass, particularly when combined with exercise. Effect sizes are small and likely of limited clinical significance for most populations.

5.3 Cancer Chemoprotection

The evidence for green tea and cancer risk is inadequate and inconclusive. However, there is some positive evidence for risk reduction of breast, prostate, ovarian, and endometrial cancers with green tea.

At the mechanistic level, it was shown that green tea catechins significantly inhibited cancer development, increased survival rates, and induced apoptosis in an animal model that spontaneously develops metastatic prostate cancer. EGCG has been shown to induce apoptosis by binding to Fas in cultured human leukemia cells. This binding activates the caspase 8 protease, which in turn activates a caspase-dependent deoxyribonuclease that degrades DNA, thereby leading to cell death.

The use of green tea as a cancer chemopreventive or for other health benefits has been confounded by the low oral bioavailability of its active polyphenolic catechins, particularly epigallocatechin-3-gallate (EGCG), the most active catechin.

Evidence strength: Mechanistic and animal data are substantial. Epidemiological findings suggest possible associations with reduced risk of certain cancers, but clinical trial evidence in humans is not yet conclusive. The low bioavailability of EGCG when taken orally complicates translation from preclinical to clinical settings.

5.4 Neuroprotection and Cognitive Function

In numerous studies, catechins have been demonstrated to scavenge free oxygen radicals, enhance cellular antioxidant defense, and suppress inflammation processes. Oxidative stress, neuroinflammation, insufficient neurotrophic factor support, and mitochondrial dysfunction have been implicated in cognitive decline and progression of neurodegenerative diseases.

Catechins, especially EGCG, possess antioxidant, anti-inflammatory, anti-apoptotic and neuritogenic, and metal chelation characteristics, along with the ability to trigger diverse molecular mechanisms, such as lipid peroxidation inhibition, induce metal-chelating effects on amyloid-β, and α-synuclein fibrillation, inhibiting amyloid-β fibrillation. They produce anti-inflammatory effects by regulating the levels of inflammatory markers, including TNF-α, NF-κB, IL-6, IL-1, NFB, and NO, increasing antioxidants, such as GSH, SOD, and CAT, and decreasing lipid peroxidation by increasing Nrf2 protein expression. Moreover, catechins have the ability to cross the blood–brain barrier, which makes them feasible neuroprotective candidates against neurodegenerative diseases.

For Alzheimer's disease specifically: numerous studies have demonstrated the potential of tea consumption to mitigate cognitive decline in older adults; however, experimental evidence supporting its efficacy in AD is lacking. Controlled studies examining AD cases have not yielded significant findings regarding tea consumption, thus limiting the inference of beneficial effects of green tea catechins solely based on AD pathogenesis and in vitro studies. Despite this, the observed efficacy of green tea in AD surpasses initial expectations, warranting further investigation.

For cognitive function in older adults, one clinical study found: consumption of matcha green tea powder, which contains bioactive compounds such as catechins, theanine, and caffeine, has beneficial effects on emotional perception and sleep quality in older adults with mild cognitive decline. This observation suggests the potential for a daily routine to enhance cognitive function and prevent dementia.

More research, particularly clinical trials in humans, is required to understand catechins' involvement in various biochemical pathways associated with neurological diseases.

Evidence strength: Preclinical (cell and animal) evidence for neuroprotection is strong. Human observational data support associations with cognitive preservation. Controlled clinical trial data in defined neurodegenerative diseases remain limited and preliminary. Evidence strength for Alzheimer's and Parkinson's disease specifically is currently insufficient for therapeutic recommendations.

5.5 Antimicrobial and Antiviral Activity

The important components in green tea that show antimicrobial properties are the catechins. The four main catechins that occur in green tea are (−)-epicatechin (EC), (−)-epicatechin-3-gallate (ECG), (−)-epigallocatechin (EGC), and (−)-epigallocatechin-3-gallate (EGCG). Of these, EGCG and EGC are found in the highest amounts in green tea and have been the subject of most studies. These catechins have been shown to demonstrate a variety of antimicrobial properties, both to organisms affected and in mechanisms used.

The antibacterial activity of catechins was observed in many different species, both gram-negative and gram-positive. In recent years, interest in these antibacterial properties has increased as resistance to traditional antibiotics continues to expand. Increasing evidence from in vitro studies demonstrated antimicrobial effects of catechins on both gram-positive and gram-negative bacteria, and proposed direct and indirect therapeutic mechanisms. Additionally, catechins were reported to be effective anti-virulence agents. Furthermore, a number of studies presented evidence that catechins display synergistic effects with certain antibiotics, thus potentiating the activity of antibiotics in resistant bacteria.

Catechins have been shown to reduce infectivity and replication of RNA and DNA viruses. In terms of their antifungal activity, catechins enhance the antifungal effects of amphotericin B and fluconazole against Candida albicans.

One clinical RCT in upper respiratory tract infections (URTIs): a placebo-controlled, single-blind, randomized control trial evaluated the clinical effectiveness of consumption of a catechins-containing beverage for preventing acute upper respiratory tract infections. Two hundred and seventy healthcare workers were randomly allocated to high-catechin (three daily doses of 57 mg catechins and 100 mg xanthan gum), low-catechin (one daily dose of 57 mg catechins and 100 mg xanthan gum), or placebo (0 mg catechins) groups. Subjects consumed a beverage with or without catechins for 12 weeks. The primary endpoint was incidence of URTIs compared among groups using a time-to-event analysis.

Catechins, phytochemicals contained mainly in green tea, exhibit antiviral activity against various acute infectious diseases experimentally. Clinical evidence supporting these effects, however, is not conclusive.

Evidence strength: In vitro antimicrobial and antiviral data are extensive. Human clinical trial evidence remains limited and inconclusive. No catechin preparation has been approved as an antimicrobial or antiviral agent.

5.6 Skin Health

Green tea catechins (GTCs) are a group of bioactive polyphenolic compounds found in fresh tea leaves. They have garnered significant attention due to their diverse health benefits and potential therapeutic applications, including as antioxidant and sunscreen agents.

Research has demonstrated that GTCs possess potent antioxidant properties that help neutralize free radicals generated by oxidative stress. This action not only mitigates cellular damage but also supports the repair mechanisms inherent in human skin. Furthermore, GTCs exhibit anti-carcinogenic effects by inhibiting pathways involved in tumor promotion and progression. GTCs have been shown to exert anti-inflammatory effects through modulation of inflammatory signaling pathways.

A promising alternative therapy is the catechin family, a group of flavonoids with a unique structure that has anti-inflammatory, antimicrobial, antioxidant, and skin barrier modulating properties.

Evidence strength: Mechanistic and preclinical data on photoprotection and anti-inflammatory skin effects are robust. Human clinical evidence for specific dermatological conditions (such as atopic dermatitis) remains preliminary, with small-scale studies and no established clinical guidelines recommending catechins as a primary treatment.

5.7 Inflammatory Bowel Disease (IBD)

Catechins can regulate the infiltration and proliferation of immune-related cells, such as neutrophils, colonic epithelial cells, macrophages, and T lymphocytes, helping reduce inflammatory reactions and providing benefits to IBD. Catechins can further inhibit the deterioration of intestinal lesions through regulating the cell gap junctions.

Evidence strength: Current data on catechins and IBD are largely from animal models and in vitro experiments. Human clinical trial evidence in IBD is limited and preliminary.

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6. Bioavailability

The use of green tea as a cancer chemopreventive or for other health benefits has been confounded by the low oral bioavailability of its active polyphenolic catechins, particularly EGCG, the most active catechin.

Human data show that administration of green tea extract under fasting conditions, and as a bolus, leads to a significant increase in the area under the plasma concentration–time curve of EGCG compared to administration with food and in split doses.

Green tea catechins are known to bind to dietary components such as proteins leading to a possible decrease in bioavailability of both catechins and dietary components, such as proteins.

Molecular modification such as synthesizing peracetylated EGCG (AcEGCG) protects hydroxyl groups on EGCG from oxidative degradation until it is deacetylated into its parent EGCG by esterases in cells, which decreases biotransformation and efflux of EGCG.

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7. Safety Considerations

7.1 Hepatotoxicity

Although green tea has shown promise as an adjunctive therapy for numerous chronic health conditions, fears of hepatotoxicity have prevented its widespread clinical use. The first studies on EGCG toxicity, particularly hepatotoxicity, date back to the early 2000s. More recently, the EFSA's Panel on Food Additives and Nutrient Sources considered the possible association between EGCG (from dietary sources) and hepatotoxicity.

Based on the available data on the potential adverse effects of green tea catechins on the liver, the Panel concluded that there is evidence from interventional clinical trials that intake of doses equal to or above 800 mg EGCG/day taken as a food supplement has been shown to induce a statistically significant increase of serum transaminases in treated subjects compared to control.

A systematic review identified transaminase and cholestasis parameter increases with daily intake of at least 800 mg EGCG in 9 of 38 intervention studies. Although traditional green tea infusion was considered harmless, a possible causal relationship for the observed liver damage was considered possible for food supplements with EGCG doses of cumulatively >800 mg/day. A safe dose could not be named.

The Panel concluded that catechins from green tea infusions or reconstituted beverages are generally regarded as safe, provided that intakes are consistent with reported intakes in European Member States. However, rare cases of liver injury have been reported following the consumption of green tea infusions.

The close association of liver injury from green tea with the HLA allele B*35:01 suggests an immunologic etiology. This HLA association, the lack of clear cut dose dependency, and the recurrence of injury on reexposure (with a shorter latency) indicates that the injury is idiosyncratic and not due to direct toxicity of the catechins.

Fasting was demonstrated to result in increased toxicity, presumably due to increased bioavailability of green tea catechins and reduced hepatic glycogen levels. Furthermore, fasting is known to reduce liver glutathione (GSH) levels, which is important to consider when considering human case studies as hepatotoxicity may also deplete GSH levels.

Across all dosage forms, none of the studies reviewed by Hu et al. reported adverse hepatic effects at EGCG doses equivalent to or below 676 mg/day.

7.2 Dose Thresholds and Observed Safe Levels

The review demonstrated that the dosing method was critical, and that a large bolus dose caused an increased frequency of adverse events compared to ingestion through food and drink. Therefore, an observed safe level (OSL) of 704 mg EGCG/day was proposed for human consumption when taken as a supplement.

In a safety assessment of green tea supplements, Dekant et al. (2017) proposed a tolerable upper level (TUL) of EGCG of 300 mg/person, based on clinical trials not reporting any liver effects (using a two-fold safety margin), and NOAELs from animal studies of dietary administration of green tea catechins (using a safety factor of 100).

The liver effects were more pronounced in subjects with high body mass index (BMI), which is an important finding as green tea extracts are used in food supplements for weight control.

7.3 Drug–Catechin Interactions

Patients are likely to consume green tea while taking their medications, unaware of its potential to interact with drugs and influence drug efficacy and safety. Catechins are the abundant polyphenolic compounds in green tea which are reported to influence determinants of drug pharmacokinetics, such as drug solubility and the activity of drug transporters and drug-metabolizing enzymes.

The majority of analyses (72%) reported significant decreases (by 18–99%) in systemic drug exposure with green tea consumption — affecting atorvastatin, celiprolol, digoxin, fexofenadine, folic acid, lisinopril, nadolol, nintedanib, raloxifene, and rosuvastatin.

The interaction between nintedanib and green tea extract is hypothesized to be based on the induction of the efflux transporter ABCB1, which is responsible for drug excretion. This effect was predominant in patients with the wild-type ABCB1 transporter compared to those with the heterozygous single-nucleotide variant.

7.4 Gastrointestinal Effects and General Tolerability

EGCG carries risk of gastrointestinal upset and rare liver toxicity. The literature supports a potential relationship between high-dose green tea extract consumption and transient changes in serum liver enzymes. Rare (<5%) and transient liver transaminase elevations have been documented. Hepatotoxicity tended to show a temporal relationship between green tea extract consumption and effect onset, mainly manifesting after roughly 3–4 months of consumption. Daily intake of 1315 mg of green tea catechins containing 843 mg EGCG poses mainly mild, transient hepatic adverse effects.

Various contributing risk factors to hepatotoxicity were studied, and the previously suggested risk factors, such as COMT genotype, use of non-steroidal anti-inflammatory drugs, paracetamol, statins, or weekly alcohol consumption, did not increase the liver effect of green tea catechins.

There is great variability in the concentration of green tea extract, EGCG, and other components among marketed products, which may explain why some products have been implicated in hepatotoxicity.

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8. Regulatory Status

The monograph of green tea was included in the European Pharmacopoeia, where green tea is standardized for caffeine content (min 1.5%) and for total content of catechins, expressed as (−)-epigallocatechin-3-O-gallate (min 8%). Concerns have been raised concerning possible harmful effects associated with the use of green tea extracts and infusions, including reported cases of liver toxicity possibly associated with the intake of green tea catechins. A risk assessment of green tea catechins was carried out in the framework of Regulation (EC) No 1925/2006 on the addition of vitamins and minerals and of certain other substances to foods.

The EFSA Panel concluded that catechins from green tea infusion, prepared in a traditional way, and reconstituted drinks with an equivalent composition to traditional green tea infusions, are in general considered to be safe according to the presumption of safety approach, provided the intake corresponds to reported intakes in European Member States.

The NIH's LiverTox database has assigned green tea extract a likelihood score of A (well established cause of clinically apparent liver injury).

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9. Summary of Evidence Strength

• Cardiovascular risk factors (LDL, blood pressure): Moderate evidence from multiple RCTs and meta-analyses; reductions are statistically significant but often modest. Hard clinical endpoints are not established.
• Body weight and fat mass: Modest but consistent evidence from RCTs and meta-analyses; effect sizes are small and likely of limited clinical relevance in isolation.
• Cancer chemoprotection: Evidence is preliminary and inconclusive in humans. Epidemiological signals for some cancer types exist; human trial data are insufficient for therapeutic recommendations.
• Neuroprotection / Cognitive function: Mechanistic and animal data are strong; human clinical evidence is limited and mostly observational. Definitive clinical trial evidence in neurodegenerative disease is lacking.
• Antimicrobial / Antiviral: Substantial in vitro evidence; human clinical evidence is not conclusive.
• Skin health: Mechanistic evidence is robust; clinical trial evidence in humans remains preliminary.

References

• Activity of catechins and their applications — PMC, NIH
• Catechin in Human Health and Disease — PMC, NIH
• The Role of Catechins in Cellular Responses to Oxidative Stress — PMC, NIH
• Catechins and Human Health: Breakthroughs from Clinical Trials — PMC, NIH (2025)
• Green Tea: Current Knowledge and Issues — PMC, NIH
• Beneficial Properties of Green Tea Catechins — PMC, NIH
• Catechins and Their Therapeutic Benefits to Inflammatory Bowel Disease — PMC, NIH
• Catechins: Protective mechanism of antioxidant stress in atherosclerosis — PMC, NIH
• Catechin attenuates TNF-α induced inflammatory response via AMPK-SIRT1 pathway — PMC, NIH
• Green tea and green tea catechin extracts: an overview of the clinical evidence — PubMed
• A green tea extract high in catechins reduces body fat and cardiovascular risks in humans — PubMed
• Does green tea catechin enhance weight-loss effect of exercise training — PMC, NIH (2024)
• The effects of green tea supplementation on cardiovascular risk factors: A systematic review and meta-analysis — Frontiers in Nutrition
• Green Tea Catechins Attenuate Neurodegenerative Diseases and Cognitive Deficits — PMC, NIH
• Multifunctional activities of green tea catechins in neuroprotection — PubMed
• Neurodegenerative diseases and catechins: EGCG as a modulator of chronic neuroinflammation — Frontiers in Nutrition (2024)
• Scientific opinion on the safety of green tea catechins — EFSA Journal (2018)
• Scientific opinion on the safety of green tea catechins — PMC, NIH
• Green Tea — LiverTox®, NCBI Bookshelf, NIH
• Green Tea Extract–Associated Acute Liver Injury: Case Report and Review — PMC, NIH
• Hepatotoxicity of High Oral Dose (−)-Epigallocatechin-3-Gallate in Mice — PMC, NIH
• The safety of green tea catechins — UK Committee on Toxicity (COT)
• Green Tea Catechins as Perpetrators of Drug Pharmacokinetic Interactions — PubMed (2025)
• Bioavailability of Tea Catechins and Its Improvement — PMC, NIH
• Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases — PMC, NIH
• Applications of Catechins in the Treatment of Bacterial Infections — PMC, NIH
• Prevention of Acute Upper Respiratory Infections by Consumption of Catechins in Healthcare Workers: A Randomized, Placebo-Controlled Trial — PMC, NIH
• Green Tea Catechins and Skin Health — PMC, NIH (2024)
• A review of catechins and their use in atopic dermatitis — PMC, NIH (2024)
• Anti-infective potential of catechins and their derivatives against viral hepatitis — PMC, NIH
• Biosynthesis and Application of Catechins and Their Derivatives in Camellia sinensis — PubMed (2025)
• Green Tea Catechins: Nature's Way of Preventing and Treating Cancer — PMC, NIH