1 Introduction

Antioxidants play a crucial role in the prevention of chronic diseases by neutralizing reactive oxygen species (ROS) and reducing oxidative stress, which is a key factor in the pathogenesis of various chronic conditions. Oxidative stress can lead to cellular damage, inflammation, and apoptosis, contributing to the development of diseases such as cardiovascular diseases, neurodegenerative disorders, diabetes, and cancer (Di Meo et al., 2020; Rudrapal et al., 2022a; 2022b). The consumption of antioxidants through diet, particularly polyphenols, has been shown to mitigate these effects and promote overall health (Yan et al., 2020; Rudrapal et al., 2022a).

Tea, one of the most widely consumed beverages globally, is rich in polyphenols, which are potent antioxidants. The primary polyphenols in tea include catechins, flavonoids, and tannins, which have been extensively studied for their health benefits (Yan et al., 2020; Hong et al., 2022). These compounds exhibit strong antioxidant properties, helping to reduce oxidative stress and inflammation, and have been linked to the prevention of various chronic diseases. Tea polyphenols have been shown to regulate gut flora, protect the intestinal mucosa, and prevent neurodegenerative diseases, among other health benefits (Ru et al., 2019; Hong et al., 2022; Wang et al., 2022).

This study summarizes the current understanding of the mechanisms by which tea polyphenols exert their antioxidant effects. It emphasizes the specific chronic diseases that can be prevented or mitigated by the consumption of tea polyphenols and identifies gaps in existing research to propose future directions for studies on tea polyphenols and chronic disease prevention. By synthesizing findings from multiple studies, this study provides a comprehensive overview of the potential health benefits of tea polyphenols and their role as powerful antioxidants in chronic disease prevention. The study delves into the biochemical pathways through which tea polyphenols act, explores their interactions with cellular components, and examines their impact on various physiological processes. This study underscores the importance of tea polyphenols in promoting health and preventing chronic diseases, offering valuable insights for both scientific exploration and practical application.

2 Chemical Properties of Tea Polyphenols

2.1 Structure and types of polyphenols in tea

Tea polyphenols are a diverse group of naturally occurring compounds found in tea leaves, primarily consisting of catechins, theaflavins, thearubigins, flavonols, and phenolic acids (Figure 1) (Yan et al., 2020; Truong and Jeong, 2021). The most abundant and well-studied catechin in green tea is (-)-epigallocatechin-3-gallate (EGCG), which has been shown to possess a wide range of biological activities (Mokra et al., 2022b). Other significant catechins include epicatechin, epicatechin gallate, and epigallocatechin (Diao et al., 2019). The chemical structure of these polyphenols is characterized by multiple hydroxyl groups attached to aromatic rings, which contribute to their potent antioxidant properties (Truong and Jeong, 2021).

2.2 Mechanisms of antioxidant action

Tea polyphenols exhibit their antioxidant action through several mechanisms. They act as direct antioxidants by scavenging reactive oxygen and nitrogen species, chelating transition metals, and inhibiting lipid, protein, and DNA oxidation (Truong and Jeong, 2021). Additionally, tea polyphenols can suppress pro-oxidant enzymes and induce endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) (Diao et al., 2019; Wang et al., 2019). These compounds also modulate cellular signaling pathways, including the nuclear factor erythroid 2-related factor 2 (NFE2L2) pathway, which plays a crucial role in the cellular defense against oxidative stress (Ma et al., 2022).

2.3 Stability and bioavailability of tea polyphenols

The stability and bioavailability of tea polyphenols are critical factors that influence their effectiveness as antioxidants. Polyphenols in tea are relatively stable under acidic conditions but can degrade under alkaline conditions, which can occur during intestinal digestion (Baeza et al., 2018). The bioavailability of these compounds is influenced by their chemical structure, with galloylated catechins like EGCG being less bioavailable compared to non-galloylated catechins (Mokra et al., 2022b). Despite these challenges, regular consumption of tea provides a significant amount of polyphenols that can exert beneficial effects on health by preventing oxidative stress-related disorders (Baeza et al., 2018).

3 Epidemiological Evidence

3.1 Population studies on tea consumption and disease prevention

Numerous population studies have investigated the relationship between tea consumption and the prevention of chronic diseases. For instance, long-term consumption of diets rich in polyphenols, including tea, has been associated with a reduced risk of developing various chronic diseases such as cardiovascular diseases (CVDs), cancer, diabetes, and neurodegenerative diseases (Rudrapal et al., 2022a; 2022b). Specifically, green tea has been highlighted for its chemopreventive effects against lung cancer induced by cigarette smoke (Rudrapal et al., 2022b). Additionally, tea polyphenols have been shown to regulate gut flora, which plays a crucial role in maintaining overall health and preventing chronic diseases (Wang et al., 2022).

3.2 Statistical correlations between tea polyphenols and chronic diseases

Statistical analyses from various studies have demonstrated significant correlations between tea polyphenol intake and reduced incidence of chronic diseases. For example, polyphenols from green tea have been shown to reduce the oxidation of low-density lipoprotein cholesterol (LDL-C), which is a key factor in the development of atherosclerosis and cardiovascular diseases (Cicero and Colletti, 2018; Tung et al., 2020). The antioxidant properties of tea polyphenols have been linked to their ability to protect against oxidative stress-related disorders, including cancer and neurodegenerative diseases (Figure 2) (Zhao et al., 2019; Yan et al., 2020; Rudrapal et al., 2022a). Studies have also shown that regular consumption of tea can lead to significant improvements in antioxidant capacity, which is crucial for preventing oxidative damage and associated chronic conditions (Baeza et al., 2018; Zhang et al., 2018).

Yan et al. (2020) illustrates the significant impact of tea polyphenols on reducing oxidative stress and inflammation through the regulation of key cellular signaling pathways. By modulating pathways such as Pi3-K/AKT, AMPK, ERK, JNK, and NF-κB, tea polyphenols enhance antioxidant enzyme activity and reduce reactive oxygen species (ROS) levels. This regulatory action helps protect cells from oxidative damage and inflammation, contributing to the prevention of diseases like cancer, cardiovascular issues, and obesity. The overall insight emphasizes the therapeutic potential of tea polyphenols in managing oxidative stress and supporting cellular health, highlighting their broad protective effects against various chronic conditions.

3.3 Limitations of current studies

Despite the promising findings, there are several limitations in the current body of research on tea polyphenols and chronic disease prevention. One major limitation is the variability in study designs, including differences in population demographics, tea types, and consumption patterns, which can affect the generalizability of the results (Zhang et al., 2018; Yan et al., 2020). Additionally, many studies rely on self-reported dietary intake, which can be prone to recall bias and inaccuracies (Cicero and Colletti, 2018). Another limitation is the lack of long-term randomized controlled trials (RCTs) that can provide more definitive evidence of causality (Cicero and Colletti, 2018). Furthermore, the bioavailability and metabolism of tea polyphenols can vary significantly among individuals, which can influence their effectiveness in disease prevention (Baeza et al., 2018; Tung et al., 2020). More research is needed to address these limitations and to better understand the mechanisms by which tea polyphenols exert their protective effects.

4 Biochemical Mechanisms

4.1 Interaction of tea polyphenols with cellular pathways

Tea polyphenols, including catechins, theaflavins, and flavonols, interact with various cellular pathways to exert their beneficial effects. One significant pathway is the ERK1/2-NFE2L2-HMOX1 pathway, which is activated by green tea polyphenols (GTP) to alleviate oxidative stress and inflammation in bovine mammary epithelial cells (Ma et al., 2022). Additionally, tea polyphenols regulate the TGF-β1/p38/JNK pathway, enhancing antioxidant capacity and reducing inflammation in mammary glands (Xu et al., 2022). The Mst/Nrf2 axis and the Keap1/Nrf2/HO-1 pathway are also crucial, as tea polyphenols modulate these pathways to protect cells from oxidative damage (Li et al., 2021).

4.2 Effects on inflammation and oxidative stress

Tea polyphenols exhibit potent anti-inflammatory and antioxidant properties. They reduce oxidative stress by scavenging reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) (Li et al., 2021; Ma et al., 2022; Xu et al., 2022). These polyphenols also inhibit pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α, thereby mitigating inflammation (Xu et al., 2022). Furthermore, they modulate the NF-κB pathway and other signaling pathways involved in inflammation, contributing to their anti-inflammatory effects (Yahfoufi et al., 2018).

4.3 Modulation of gene expression and enzyme activity

Tea polyphenols influence gene expression and enzyme activity, which are critical for their protective effects. They upregulate genes involved in antioxidant defense, such as those encoding SOD, CAT, and GSH-Px, while downregulating genes associated with oxidative stress and inflammation (Li et al., 2021; Ma et al., 2022; Xu et al., 2022). The modulation of gene expression is partly mediated through the activation of transcription factors like Nrf2, which enhances the expression of antioxidant response elements (Li et al., 2021). Additionally, tea polyphenols inhibit enzymes involved in ROS production, such as xanthine oxidase and NADPH oxidase, further reducing oxidative stress (Yahfoufi et al., 2018).

5 Case Studies

5.1 Case studies on the role of tea polyphenols in diabetes prevention

Tea polyphenols have been extensively studied for their potential role in diabetes prevention, with several case studies highlighting their efficacy. Olcha et al. (2022) emphasizes the antidiabetic properties of tea polyphenols, suggesting that regular tea consumption can aid in diabetes prevention due to its antioxidative and anti-inflammatory effects. Similarly, Rudrapal et al. (2022a) discusses the protective effects of dietary polyphenols, including those found in tea, against oxidative stress-related diseases such as diabetes, highlighting the importance of antioxidant activity in mitigating oxidative damage, a significant factor in diabetes development. Furthermore, Xing et al. (2019) underscores the antihyperglycemic properties of green tea polyphenols, particularly EGCG, which have been shown to reduce blood glucose levels and improve insulin sensitivity, thereby aiding in diabetes prevention. 

5.2 Case Studies on cardiovascular health

Tea polyphenols have shown significant benefits in cardiovascular health through various mechanisms. Giglio et al. (2018) discusses the cardioprotective functions of polyphenols, including those from tea, which help in lowering blood pressure, improving endothelial function, and reducing inflammation, thereby preventing cardiovascular diseases. Cicero and Colletti (2018) focuses on the lipid-lowering and atheroprotective effects of polyphenols from tea, which help in reducing the risk of cardiovascular diseases by lowering LDL cholesterol and preventing its oxidation. Moreover, Zhou et al. (2021) highlights the beneficial effects of green tea polyphenols on the cardiovascular system, including reducing blood pressure and improving lipid profiles, which are crucial for cardiovascular health. 

5.3 Case studies on cancer prevention

Tea polyphenols have been investigated for their potential in cancer prevention, with several case studies providing evidence. Olcha et al. (2022) highlights the anticancer properties of tea polyphenols, particularly in the context of endometrial cancer, suggesting that regular tea consumption can aid in cancer prevention (Figure 3). Similarly, Rudrapal et al. (2022a) discusses the chemopreventive effects of dietary polyphenols, including those found in tea, against various cancers by reducing oxidative stress and inflammation. Moreover, Yan et al. (2020) reviews the anticancer effects of tea polyphenols, which are attributed to their antioxidant and anti-inflammatory properties, helping in the prevention of cancer. 

Olcha et al. (2022) illustrates the interplay between genetic factors, lifestyle, and diet in influencing endometrial cancer (EC) risk. It emphasizes obesity and associated conditions like type 2 diabetes and metabolic syndrome as significant risk enhancers due to their role in promoting oxidative stress and chronic inflammation. The figure also highlights the potential benefits of tea polyphenols in reducing EC risk by interfering with inflammatory processes, regulating immune responses, and influencing gene expression. These polyphenols can mitigate factors like insulin resistance and oxidative stress, contributing to cancer prevention. The overall message underscores the importance of healthy lifestyle choices and dietary interventions, particularly the consumption of tea, in reducing the risk of endometrial cancer.

6 Clinical Trials

6.1 Overview of clinical trials involving tea polyphenols

Tea polyphenols (TP) have been extensively studied for their potential health benefits, particularly in the prevention and treatment of chronic diseases. Clinical trials have explored various aspects of TP, including their antioxidant, anti-inflammatory, and lipid-lowering properties, involving different types of tea such as green tea, black tea, and specific varieties like Anji white tea and small-leaved Kuding tea. 

6.2 Insights from recent clinical findings

Recent clinical findings have provided valuable insights into the efficacy of TP in chronic disease prevention. For example, clinical trials have shown that TP can positively impact cardiovascular health by reducing the oxidation of LDL cholesterol and improving lipid profiles, with polyphenols from green tea, cocoa, and berries demonstrating significant effects in reducing cardiovascular disease risk factors (Cicero and Colletti, 2018; Giglio et al., 2018). Studies involving green tea polyphenols (GTP) and Anji white tea polyphenols (AJWTP) have shown promising results in preventing liver injury by enhancing antioxidant enzyme activities and reducing oxidative stress markers, thereby protecting liver cells from damage (Diao et al., 2019; Wang et al., 2019).

Furthermore, TP have been found to protect neuronal cells from oxidative stress and DNA damage induced by harmful substances like methamphetamine. This neuroprotective effect is attributed to the enhancement of DNA repair mechanisms and the reduction of oxidative stress (Ru et al., 2019). Small-leaved Kuding tea polyphenols (PSLKDT) have demonstrated significant anti-aging effects by improving antioxidant enzyme activities and reducing oxidative damage in various tissues. This suggests that TP can be effective in preventing age-related oxidative stress and associated diseases (Liu et al., 2019). TP also have shown potential in modulating gut flora and protecting the intestinal mucosa. Clinical trials have indicated that TP can alleviate intestinal inflammation and oxidative stress, thereby improving gut health and preventing related chronic diseases (Zhang et al., 2020; Wang et al., 2022).

6.3 Challenges in clinical research of tea polyphenols

Clinical research on tea polyphenols (TP) has yielded many promising findings, but several challenges remain. The bioavailability of TP varies significantly depending on the type of tea and the individual's metabolism, and this variability can affect the consistency of clinical outcomes (Giglio et al., 2018). Determining the optimal dosage and standardizing TP extracts for clinical use also presents a challenge, as different studies use varying doses and forms of TP, making it difficult to compare results and establish clear guidelines (Cicero and Colletti, 2018). Many clinical trials are short-term, necessitating long-term studies to fully understand the chronic effects of TP consumption. Further investigation is required to assess the long-term adherence to TP supplementation and its sustained effects on chronic disease prevention (Giglio et al., 2018). Additionally, lifestyle factors, dietary habits, and genetic differences among study participants can confound the results of clinical trials. Therefore, controlling these variables is crucial for obtaining accurate and reliable data (Rudrapal et al., 2022a). While the antioxidant and anti-inflammatory properties of TP are well-documented, the precise mechanisms through which they exert their effects are not yet fully understood. Further research is needed to elucidate these mechanisms and their implications for chronic disease prevention (Yan et al., 2020). 

Clinical trials have highlighted the potential of tea polyphenols in preventing and managing chronic diseases. However, addressing challenges related to bioavailability, dosage standardization, long-term effects, and mechanistic understanding is essential for advancing the clinical application of TP.

7 Applications and Practical Recommendations

7.1 Dietary guidelines involving tea polyphenols

Tea polyphenols, including catechins, flavonoids, and tannins, have been extensively studied for their antioxidant properties and potential health benefits. Incorporating tea polyphenols into dietary guidelines can help in the prevention and management of various chronic diseases. It is recommended to include a variety of teas such as green, black, and oolong tea in daily diets to maximize the intake of these beneficial compounds. Studies have shown that tea polyphenols can regulate gut flora, protect the intestinal mucosa, and prevent chronic diseases (Yan et al., 2020; Wang et al., 2022). Additionally, they have been found to improve lipid metabolism, reduce inflammation, and provide antioxidative benefits, which are crucial for cardiovascular health (Cicero and Colletti, 2018; Giglio et al., 2018; Yan et al., 2020).

7.2 Recommendations for daily consumption

For optimal health benefits, it is recommended to consume 3~5 cups of tea daily. This amount has been associated with significant improvements in antioxidant status and reductions in oxidative stress markers (Yan et al., 2020; Rudrapal et al., 2022a). Green tea, in particular, is rich in epigallocatechin-3-gallate (EGCG), a potent antioxidant that has been shown to reduce the risk of cardiovascular diseases, cancer, and neurodegenerative disorders (Rudrapal et al., 2022a; 2022b). It is important to note that the bioavailability of polyphenols can vary, so consuming tea with meals that contain healthy fats may enhance their absorption (Zhang et al., 2020). Additionally, individuals with specific health conditions or those taking certain medications should consult with healthcare providers before significantly increasing their tea consumption.

7.3 Future potential of tea polyphenols in functional foods

The future potential of tea polyphenols in functional foods is promising. As natural antioxidants, tea polyphenols can be incorporated into a variety of food products to enhance their health benefits. Research suggests that tea polyphenols can be used to develop functional foods aimed at preventing and managing chronic diseases such as cardiovascular diseases, diabetes, and inflammatory disorders (Giglio et al., 2018; Yan et al., 2020; Olcha et al., 2022). For instance, incorporating tea polyphenols into snacks, beverages, and dietary supplements could provide an easy and effective way to increase daily polyphenol intake. Moreover, ongoing research into the mechanisms of action of tea polyphenols will likely lead to the development of more targeted and effective functional foods (Yan et al., 2020; Zhang et al., 2020).

Tea polyphenols offer significant health benefits and should be considered in dietary guidelines and daily consumption recommendations. Their potential in functional foods also presents an exciting avenue for future research and development, aiming to improve public health outcomes through natural dietary interventions.

8 Future Research Directions

8.1 Emerging areas of research in tea polyphenols

The field of tea polyphenols is rapidly evolving, with several emerging areas of research that hold promise for future discoveries. One such area is the role of tea polyphenols in modulating gut microbiota. Recent studies have shown that tea polyphenols can significantly alter the composition of intestinal flora, which in turn can impact overall health and disease prevention (Wang et al., 2022). Another emerging area is the potential of tea polyphenols in respiratory diseases. Research has indicated that (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, could be beneficial in treating various respiratory conditions, including COVID-19, asthma, and chronic obstructive pulmonary disease (COPD) (Mokra et al., 2022a). Additionally, the anti-cancer properties of tea polyphenols, particularly in endometrial cancer, are gaining attention. These compounds have shown antioxidative, anti-inflammatory, and antidiabetic properties, making them suitable for long-term consumption and potential prophylactic use (Olcha et al., 2022).

8.2 Technological advancements in polyphenol research

Technological advancements are playing a crucial role in advancing our understanding of tea polyphenols. High-throughput screening methods and advanced analytical techniques such as mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy are being used to identify and quantify polyphenols in various tea types (Truong and Jeong, 2021). These technologies have enabled researchers to explore the structure-activity relationships of tea polyphenols, providing insights into their antioxidant and anti-inflammatory properties (Truong and Jeong, 2021). Furthermore, advancements in molecular biology techniques, including CRISPR and RNA interference, are being utilized to study the molecular pathways influenced by tea polyphenols. For instance, the ERK1/2-NFE2L2-HMOX1 pathway has been identified as a key mechanism through which green tea polyphenols alleviate oxidative stress and inflammation in bovine mammary epithelial cells (Ma et al., 2022).

8.3 Integration of genomics and metabolomics

The integration of genomics and metabolomics is a promising approach to understanding the complex interactions between tea polyphenols and human health. Genomic studies have identified several genes involved in the hereditary incidence of diseases like endometrial cancer, which can be modulated by tea polyphenols (Olcha et al., 2022). Metabolomic analyses are being used to profile the metabolites produced in response to tea polyphenol consumption, providing a comprehensive understanding of their biological effects. For example, the modulation of non-coding RNAs (ncRNAs) by dietary polyphenols, including tea polyphenols, has been shown to play a significant role in cancer chemoprevention (Shah et al., 2021). This integrative approach can help identify novel biomarkers and therapeutic targets, enhancing the efficacy of tea polyphenols in disease prevention and treatment.

9 Concluding Remarks

Tea polyphenols, a group of naturally occurring compounds found in tea, have demonstrated significant potential in the prevention and management of various chronic diseases. These compounds exhibit strong antioxidant properties, which play a crucial role in mitigating oxidative stress and inflammation, thereby contributing to the prevention of diseases such as cancer, cardiovascular diseases, diabetes, and neurodegenerative disorders. The antioxidant capacity of tea polyphenols is influenced by factors such as geographical location, plantation elevation, and leaf grade, which affect the polyphenol content and overall health benefits of different tea types. Additionally, tea polyphenols have been shown to regulate gut flora, enhancing intestinal health and providing protective effects against chronic diseases.

For the tea industry, it is recommended to focus on optimizing cultivation practices to enhance the polyphenol content in tea leaves. This includes selecting appropriate geographical locations and plantation elevations, as well as harvesting smaller leaves which have been shown to contain higher levels of polyphenols. Additionally, the industry should invest in research and development to create tea products with maximized health benefits, potentially through the development of functional foods and nutraceuticals enriched with tea polyphenols.

From a public health perspective, promoting the regular consumption of tea, particularly green tea, could be an effective strategy to reduce the incidence of chronic diseases. Public health campaigns should emphasize the antioxidant and anti-inflammatory benefits of tea polyphenols and encourage the inclusion of tea in daily diets. Furthermore, educating the public on the proper preparation and consumption of tea to preserve its polyphenol content is essential for maximizing its health benefits.

Future research on tea polyphenols should aim to further elucidate their specific mechanisms of action at the molecular level, particularly in relation to their antioxidant and anti-inflammatory properties. There is also a need for more clinical studies to confirm the health benefits observed in pre-clinical models and to establish effective dosages for disease prevention and management.

One of the challenges in tea polyphenol research is the variability in polyphenol content due to factors such as tea type, cultivation conditions, and processing methods. Standardizing these variables will be crucial for conducting reliable and reproducible studies. Additionally, understanding the bioavailability and bioaccessibility of tea polyphenols, as well as their interactions with gut microbiota, will be important for developing effective dietary recommendations and therapeutic applications.

In conclusion, tea polyphenols hold great promise as natural antioxidants with significant potential in chronic disease prevention. Continued research and collaboration between the tea industry and public health sectors will be essential to fully harness their benefits and address the challenges in this field.

Acknowledgments

The authors extend sincere thanks to two anonymous peer reviewers for their invaluable feedback on the manuscript of this study.

Conflict of Interest Disclosure

The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

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