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Effects of green tea supplementation on antioxidant status and inflammatory markers in adults: a grade-assessed systematic review and dose-response meta-analysis of randomised controlled trials

Published online by Cambridge University Press:  14 March 2025

Mohammad Jafar Dehzad
Affiliation:
Student Research Committee, Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Shiraz University of Medical Sciences, Shiraz, Iran
Hamid Ghalandari
Affiliation:
Student Research Committee, Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Shiraz University of Medical Sciences, Shiraz, Iran
Mehran Nouri
Affiliation:
Student Research Committee, Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Shiraz University of Medical Sciences, Shiraz, Iran Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
Maede Makhtoomi
Affiliation:
Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
Moein Askarpour*
Affiliation:
Student Research Committee, Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Shiraz University of Medical Sciences, Shiraz, Iran
*
Corresponding author: Moein Askarpour; Email: [email protected]

Abstract

Green tea, a plant rich in bioactive compounds, has been highlighted for its beneficial effects. In the present systematic review and meta-analysis of randomised controlled trials (RCTs), the impact of green tea on inflammatory and oxidative markers is investigated. Using pre-defined keywords, online databases (PubMed, Scopus, Web of Science Core Collection, and Google Scholar) were searched for relevant articles, published from inception up to February 2024. The outcomes included C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX). Analyses of subgroups, linear, and non-linear associations were also carried out. Out of 1264 records initially retrieved, 38 RCTs were included. Supplementation with green tea improved the following indicators: IL-1β (weighted mean difference (WMD): −0.10 pg/mL; 95% CI: −0.15, -0.06), MDA (WMD: −0.40 mcmol/L; 95 % CI: −0.63, −0.18), TAC (WMD: 0.09 mmol/L; 95% CI: 0.05, 0.13), SOD (WMD: 17.21 u/L; 95% CI: 3.24, 31.19), and GPX (WMD: 3.90 u/L; 95% CI: 1.85, 5.95); but failed to improve others, including CRP (WMD: 0.01 mg/L; 95% CI: −0.14, 0.15), IL-6 (WMD: −0.34 pg/mL; 95% CI:−0.94, 0.26), and TNF-α (WMD: −0.07 pg/mL; 95% CI: −0.42, 0.28). Supplementation with green tea can improve the body’s oxidative status. However, the results showed no significant effect of green tea on inflammatory markers, except for IL-1β. Further studies are needed to determine the effectiveness of green tea, particularly on inflammatory status.

Type
Review
Creative Commons
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Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society

Introduction

Inflammation is known as the underlying factor contributing to the pathology of multiple diseases.(Reference Furman, Campisi and Verdin1) Specifically, the footsteps of inflammatory processes are apparent in the pathophysiology of most metabolic disorders.(Reference Saltiel and Olefsky2) By nature, inflammatory pathways are designed to take part in the human defence system, against potential foreign dangers. However, owing to various reasons, sometimes these secreted agents (interleukin (IL)-1, IL-6, tumour necrosis factor-α (TNF-α) are among the most studied) involuntarily cause harm to the individual; hence, many disorders are followed as the inevitable ramifications(Reference Chen, Deng and Cui3); including autoimmune diseases (such as rheumatoid arthritis, systematic lupus erythematosus), cardiovascular diseases, diabetes, and so forth.(Reference Xiang, Zhang, Jiang, Su and Shi4Reference Tsalamandris, Antonopoulos and Oikonomou6) Oxidative processes are among the most significant triggers in deriving an inflammatory response from the body(Reference Lauridsen7); they are also the means used by immune cells to eradicate unwanted cells/microbes.(Reference Yang, Min and Yu8) Reactive oxygen species (ROSs) and reactive nitrogen species, mainly by-products of vital oxidative processes, have been highlighted in their role of provoking inflammatory cascades.(Reference Forrester, Kikuchi, Hernandes, Xu and Griendling9,Reference Weidinger and Kozlov10)

Nonetheless, there exist built-in mechanisms to keep the imperative oxidative/inflammatory response and the indiscriminate response causing chronic diseases in consonance.(Reference Barnig, Bezema and Calder11) These include antioxidant proteins, such as glutathione peroxidase (GPX) and superoxide dismutase (SOD); as well as anti-inflammatory eicosanoids.(Reference Pei, Pan, Wei and Hua12Reference Yamaguchi, Botta and Holinstat14) Dietary factors have been found integral in the aforementioned balance; these encompass a range from wholistic dietary patterns to individual foodstuff.(Reference Minihane, Vinoy and Russell15) Green tea, by the scientific name of Camellia sinensis, is amongst the most studied for its beneficial health effects.(Reference Musial, Kuban-Jankowska and Gorska-Ponikowska16) Abundant in chemicals with antioxidant properties (mostly polyphenols, such as flavonoids and phenolic acids), green tea is hypothetically capable of repressing destructive oxidative/inflammatory environment in the body.(Reference Haghighatdoost and Hariri17) Nevertheless, these claims are still controversial, both in matters of long-term effectiveness and dosages needed to evoke them.

Therefore, the present systematic review, meta-analysis, and dose-response analysis of the existing literature in the form of randomised controlled trials (RCTs) were designed to conclusively answer the question of whether green tea supplementation/consumption could ameliorate the oxidative/inflammatory environment (indicated by clinically relevant factors, including C-reactive protein (CRP), IL-6, IL-1β, TNF-α, total antioxidant capacity (TAC), malondialdehyde (MDA), GPX, and SOD).

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used to perform the present systematic review and meta-analysis.(Reference Page, McKenzie and Bossuyt18) The protocol is registered in the international prospective register of systematic reviews (PROSPERO) under the number CRD42024506734. It is worthy to note that additional analyses, such as sensitivity and non-linear dose-response, were conducted beyond the predefined analyses in PROSPERO registration, due to their significance in strengthening the findings.

Search strategy

The inclusion criteria of eligible studies were determined using the population, intervention, comparison, outcome, study design (PICOS) model, which stands for participants (aged ≥ 18 years old), intervention (green tea supplementation), comparison (studies with control group), outcome (C-reactive protein (CRP), tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX)), and study (randomised controlled trials). We conducted a thorough search of the online databases of PubMed, Scopus, Web of Science Core Collection, and Google Scholar from inception up to February 2024, regardless of language or time limitations. Search terms are listed in Supplementary Table 1. To ensure that all qualified publications were identified, we manually searched the reference lists of all relevant studies and previous reviews.

Study selection and eligibility criteria

We included eligible studies in the current meta-analysis if they met the following criteria: randomised controlled trials; adult population (aged more than 18 years); reported CRP, IL-6, TNF-α, IL-1β, TAC, MDA, SOD, or GPX in both the intervention and placebo groups; and had an intervention period of more than 2 weeks. We excluded the studies that had the following conditions: had duplicated data, lacked the placebo group, had a non-RCT design, and were carried out on animals, children, pregnant or breastfeeding women, and those with inadequate information for the outcomes of interest.

Data extraction

Two independent reviewers performed the data extraction and study selection. The following data were extracted from the included studies: the first author’s last name, the duration and location of the study, the year of publication, the age and gender of participants, the research design, the type and dose of green tea, the number of participants in each group, and results (means and standard deviations (SDs) for the outcomes of interest before and after the intervention).

Risk of bias assessment

A comprehensive evaluation of the bias risk in the included studies is presented in Table 1. The risk of bias in the included studies was assessed using the updated version of the Cochrane risk-of-bias instrument (RoB-2).(Reference Sterne, Savovic and Page19) This tool assesses potential sources of bias with regard to the following methodological domains: the randomisation procedure; deviations from intended interventions; missing outcome data; selective reporting of results; outcome measurement; and the final assessment. The included studies were assessed as low risk (L), some concerns (S), or high risk (H) of bias with regard to each potential source of bias, based on the recommendations for risk of bias assessment published in the Cochrane Handbook.

Table 1. Results of risk of bias assessment for randomised clinical trials included in the current meta-analysis by the revised Cochrane risk-of-bias tool (RoB-2)

H: high risk, L: low risk, S: some concerns.

Certainty assessment

To assess certainty of evidence across the included studies, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines were used. This tool includes five domains to examine the quality of evidence including risk of bias, inconsistency, imprecision, indirectness, and publication bias. With respect to the quality of evidence, studies were categorised into four groups: high, moderate, low, and very low.(Reference Falck-Ytter, Guyatt, Vist and Kunz20)

Statistical analysis

The mean changes and standard deviations (SDs) of the outcome of interest for the intervention and placebo groups were used to estimate the effect sizes. The results of effect sizes were displayed as weighted mean differences (WMDs) and 95% confidence intervals (CIs).(Reference Andrade21) Mean changes were estimated by calculating changes in the outcomes during the trial, if mean changes were not reported. The Hozo et al. method was also applied to convert standard errors, 95% CIs, and interquartile ranges to SDs.(Reference Hozo, Djulbegovic and Hozo22) Using the following formula, missing SDs for changes were estimated: SDchange=square root [(SDbaseline 2 + SDfinal 2) − (2×R×SDbaseline×SDfinal)]. The R-value of the mentioned formula was considered to be 0.9.(Reference Borenstein, Hedges, Higgins and Rothstein23) We calculated the overall effect size using a random effect model that takes into account study differences (the DerSimonian-Laird method).(Reference DerSimonian and Kacker24) Furthermore, between-study heterogeneity was measured using the I2 statistic and Cochrane’s Q test. Significant between-study heterogeneity was identified with an I2 value >50% or a p-value <0.05 for the Q-test.(Reference Brondani, Assmann, de Souza, Boucas, Canani and Crispim25,Reference Zahedi, Djalalinia and Sadeghi26) We conducted subgroup analyses, to identify potential sources of heterogeneity considering some important variables including baseline body mass index (BMI (kg/m2)), health condition of participants, type of green tea, study location, green tea dosage (mg/ day), duration of intervention (weeks), and gender. Sensitivity analysis was used to show how each study affected the overall effect size using the leave-one-out method.(Reference Tobias27) We used the Elbourne et al. method to handle the cross-over design study.(Reference Elbourne, Altman, Higgins, Curtin, Worthington and Vail28) Publication bias was assessed using visual inspection of the funnel plots and a Begg rank correlation test. The study utilised the trim-and-fill method to examine the impact of publication bias on the study’s outcomes and adjust the overall effect size.(Reference Shi and Lin29) Meta-regression and non-linear dose-response (using fractional polynomial modelling) were performed to observe the association between the green tea dosage (mg/day) and the intervention duration (weeks) with the outcomes of interest.(Reference Foster30) The meta-analysis was done using the Stata Software, version 14 (StataCorp). p-values <0.05 were considered as statistically significant.

Results

Study selection

We obtained 1264 records from the initial search. Following that, we eliminated 35 duplicate papers. After evaluating the remaining 1229 records, we excluded 820 irrelevant articles based on title and abstract assessment. Among the 409 papers retained for more comprehensive full-text evaluation, 253 RCTs were excluded due to reporting irrelevant outcomes. Furthermore, additional 34 articles were excluded due to their intervention duration being insufficient (specifically, less than two weeks). Additionally, 72 RCTs were removed from the analysis due to administering green tea in combination with other compounds exclusively within the intervention group. Twelve RCTs were also excluded because they were conducted on children. Finally, 38 eligible RCTs were used in the current systematic review and meta-analysis,(Reference Ahmad Merza Mohammad31Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) among which 19 articles assessed the impact of green tea on CRP,(Reference Rondanelli, Gasparri and Perna32,Reference Hadi, Alipour and Aghamohammadi37Reference Azizbeigi, Stannard and Atashak40,Reference Shin, Lee and Seo42,Reference Nogueira, Nogueira Neto, Klein and Sanjuliani46Reference Hussain, Habib Ur and Akhtar48,Reference Lee, Charng, Tseng and Lai50,Reference Borges, Papadimitriou, Duarte, Lopes de Faria and Lopes de Faria51,Reference Mielgo-Ayuso, Barrenechea, Alcorta, Larrarte, Margareto and Labayen54,Reference Liu, Huang, Huang, Chen, Chiu and Hsu55,Reference Bogdanski, Suliburska, Szulinska, Stepien, Pupek-Musialik and Jablecka60Reference Mohammadi, Hosseinzadeh Attar and Karimi63,Reference Fukino, Ikeda, Maruyama, Aoki, Okubo and Iso65,Reference De Maat, Pijl, Kluft and Princen67) 13 articles on TAC,(Reference Bazyar, Hosseini and Saradar36,Reference Azizbeigi, Stannard and Atashak40,Reference Venkatakrishnan, Chiu and Cheng41,Reference Tabatabaee, Alavian and Ghalichi44,Reference Soeizi, Rafraf, Asghari-Jafarabadi, Ghaffari, Rezamand and Doostan45,Reference Hadi, Pourmasoumi, Kafeshani, Karimian, Maracy and Entezari49,Reference Kuo, Lin, Bernard and Liao52,Reference Spadiene, Savickiene and Ivanauskas53,Reference Lasaite, Spadiene, Savickiene, Skesters and Silova56,Reference Mousavi, Vafa, Neyestani, Khamseh and Hoseini57,Reference Suliburska, Bogdanski, Szulinska, Stepien, Pupek-Musialik and Jablecka59,Reference Bogdanski, Suliburska, Szulinska, Stepien, Pupek-Musialik and Jablecka60,Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) 11 articles on MDA,(Reference Naderifar, Gangeh, Mehri and Kazemi33,Reference Azizbeigi, Stannard and Atashak40,Reference Tabatabaee, Alavian and Ghalichi44,Reference Soeizi, Rafraf, Asghari-Jafarabadi, Ghaffari, Rezamand and Doostan45,Reference Hadi, Pourmasoumi, Kafeshani, Karimian, Maracy and Entezari49,Reference Kuo, Lin, Bernard and Liao52,Reference Spadiene, Savickiene and Ivanauskas53,Reference Mousavi, Vafa, Neyestani, Khamseh and Hoseini57,Reference Li, Chen and Aldini64,Reference Erba, Riso, Bordoni, Foti, Biagi and Testolin66,Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) 10 articles on IL-6,(Reference Ahmad Merza Mohammad31,Reference El-Elimat, Qasem and Al-Sawalha34Reference Bazyar, Hosseini and Saradar36,Reference Bagheri, Rashidlamir and Ashtary-Larky39,Reference Azizbeigi, Stannard and Atashak40,Reference Nogueira, Nogueira Neto, Klein and Sanjuliani46,Reference Mombaini, Jafarirad, Husain, Haghighizadeh and Padfar47,Reference Basu, Du and Sanchez62,Reference De Maat, Pijl, Kluft and Princen67) 8 articles on TNFα,(Reference Ahmad Merza Mohammad31,Reference Kondori, Ghaleh and Hosseini35,Reference Bagheri, Rashidlamir and Ashtary-Larky39,Reference Azizbeigi, Stannard and Atashak40,Reference Nogueira, Nogueira Neto, Klein and Sanjuliani46,Reference Mombaini, Jafarirad, Husain, Haghighizadeh and Padfar47,Reference Bogdanski, Suliburska, Szulinska, Stepien, Pupek-Musialik and Jablecka60,Reference De Maat, Pijl, Kluft and Princen67) 7 articles on GPX,(Reference Naderifar, Gangeh, Mehri and Kazemi33,Reference El-Elimat, Qasem and Al-Sawalha34,Reference Venkatakrishnan, Chiu and Cheng41,Reference Spadiene, Savickiene and Ivanauskas53,Reference Basu, Betts, Mulugeta, Tong, Newman and Lyons58,Reference Erba, Riso, Bordoni, Foti, Biagi and Testolin66,Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) 5 articles on SOD,(Reference El-Elimat, Qasem and Al-Sawalha34,Reference Venkatakrishnan, Chiu and Cheng41,Reference Maeda-Yamamoto, Nishimura and Kitaichi43,Reference Spadiene, Savickiene and Ivanauskas53,Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) and two articles on IL-1β.(Reference Basu, Du and Sanchez62,Reference De Maat, Pijl, Kluft and Princen67) Figure 1 illustrates the flow diagram representing the process of study selection.

Fig. 1. Flow diagram of study selection.

Characteristics of the included studies

Table 2 provides an overview of the characteristics of the 38 RCTs included in the present systematic review and meta-analysis. These RCTs were conducted in Iran,(Reference Naderifar, Gangeh, Mehri and Kazemi33,Reference Kondori, Ghaleh and Hosseini35Reference Hadi, Alipour and Aghamohammadi37,Reference Bagheri, Rashidlamir and Ashtary-Larky39,Reference Azizbeigi, Stannard and Atashak40,Reference Tabatabaee, Alavian and Ghalichi44,Reference Soeizi, Rafraf, Asghari-Jafarabadi, Ghaffari, Rezamand and Doostan45,Reference Mombaini, Jafarirad, Husain, Haghighizadeh and Padfar47,Reference Hadi, Pourmasoumi, Kafeshani, Karimian, Maracy and Entezari49,Reference Mousavi, Vafa, Neyestani, Khamseh and Hoseini57,Reference Mohammadi, Hosseinzadeh Attar and Karimi63) Taiwan,(Reference Venkatakrishnan, Chiu and Cheng41,Reference Lee, Charng, Tseng and Lai50,Reference Kuo, Lin, Bernard and Liao52,Reference Liu, Huang, Huang, Chen, Chiu and Hsu55) the United States,(Reference Basu, Betts, Mulugeta, Tong, Newman and Lyons58,Reference Basu, Du and Sanchez62,Reference Li, Chen and Aldini64) Japan,(Reference Maeda-Yamamoto, Nishimura and Kitaichi43,Reference Sone, Kuriyama and Nakaya61,Reference Fukino, Ikeda, Maruyama, Aoki, Okubo and Iso65) Poland,(Reference Suliburska, Bogdanski, Szulinska, Stepien, Pupek-Musialik and Jablecka59,Reference Bogdanski, Suliburska, Szulinska, Stepien, Pupek-Musialik and Jablecka60) Lithuania,(Reference Spadiene, Savickiene and Ivanauskas53,Reference Lasaite, Spadiene, Savickiene, Skesters and Silova56) Netherlands,(Reference De Maat, Pijl, Kluft and Princen67,Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) Spain,(Reference Benlloch, Cuerda Ballester and Drehmer38,Reference Mielgo-Ayuso, Barrenechea, Alcorta, Larrarte, Margareto and Labayen54) Italy,(Reference Rondanelli, Gasparri and Perna32,Reference Erba, Riso, Bordoni, Foti, Biagi and Testolin66) South Korea,(Reference Shin, Lee and Seo42) Jordan,(Reference El-Elimat, Qasem and Al-Sawalha34) and Iraq,(Reference Ahmad Merza Mohammad31) and were published between years 1997 and 2023. Six studies were exclusively performed on male subjects,(Reference Kondori, Ghaleh and Hosseini35,Reference Benlloch, Cuerda Ballester and Drehmer38Reference Azizbeigi, Stannard and Atashak40,Reference Tabatabaee, Alavian and Ghalichi44,Reference Kuo, Lin, Bernard and Liao52) 4 studies on female subjects,(Reference Naderifar, Gangeh, Mehri and Kazemi33,Reference Nogueira, Nogueira Neto, Klein and Sanjuliani46,Reference Mombaini, Jafarirad, Husain, Haghighizadeh and Padfar47,Reference Mielgo-Ayuso, Barrenechea, Alcorta, Larrarte, Margareto and Labayen54) and others on both genders. The number of participants in the included RCT samples ranged from 20 to 143, yielding a total sample size of 1985 individuals. The mean age of participants was between 19 and 63 years. The dosage of green tea supplementation varied between 200 mg/day (green tea extract) and 9 g/day (green tea leaves), and the duration of intervention ranged from 4 to 48 weeks across selected RCTs. Except for three studies that had cross-over design,(Reference Nogueira, Nogueira Neto, Klein and Sanjuliani46,Reference Sone, Kuriyama and Nakaya61,Reference Fukino, Ikeda, Maruyama, Aoki, Okubo and Iso65) the majority of studies took advantage of a parallel design. Regarding the vectors of green tea supplements used in the intervention, 12 studies used green tea extract,(Reference Rondanelli, Gasparri and Perna32,Reference Kondori, Ghaleh and Hosseini35,Reference Shin, Lee and Seo42,Reference Hussain, Habib Ur and Akhtar48,Reference Hadi, Pourmasoumi, Kafeshani, Karimian, Maracy and Entezari49,Reference Kuo, Lin, Bernard and Liao52,Reference Spadiene, Savickiene and Ivanauskas53,Reference Liu, Huang, Huang, Chen, Chiu and Hsu55,Reference Lasaite, Spadiene, Savickiene, Skesters and Silova56,Reference Bogdanski, Suliburska, Szulinska, Stepien, Pupek-Musialik and Jablecka60,Reference Mohammadi, Hosseinzadeh Attar and Karimi63,Reference Li, Chen and Aldini64) 9 studies used epigallocatechin-3-gallate (EGCG),(Reference Bazyar, Hosseini and Saradar36Reference Benlloch, Cuerda Ballester and Drehmer38,Reference Maeda-Yamamoto, Nishimura and Kitaichi43,Reference Borges, Papadimitriou, Duarte, Lopes de Faria and Lopes de Faria51,Reference Mielgo-Ayuso, Barrenechea, Alcorta, Larrarte, Margareto and Labayen54,Reference Basu, Betts, Mulugeta, Tong, Newman and Lyons58,Reference Suliburska, Bogdanski, Szulinska, Stepien, Pupek-Musialik and Jablecka59,Reference Basu, Du and Sanchez62) 5 studies used green tea catechins,(Reference Ahmad Merza Mohammad31,Reference Venkatakrishnan, Chiu and Cheng41,Reference Sone, Kuriyama and Nakaya61,Reference Fukino, Ikeda, Maruyama, Aoki, Okubo and Iso65,Reference Erba, Riso, Bordoni, Foti, Biagi and Testolin66) and other studies used green tea leaves. Also, four RCTs examined post-exercise impact of green tea.(Reference Naderifar, Gangeh, Mehri and Kazemi33,Reference Kondori, Ghaleh and Hosseini35,Reference Bagheri, Rashidlamir and Ashtary-Larky39,Reference Azizbeigi, Stannard and Atashak40) It should be noted that we made sure that in case of combined intervention, the control group received the same accompanied treatment. The included studies were conducted on healthy individuals,(Reference Naderifar, Gangeh, Mehri and Kazemi33,Reference Venkatakrishnan, Chiu and Cheng41,Reference Maeda-Yamamoto, Nishimura and Kitaichi43,Reference Kuo, Lin, Bernard and Liao52,Reference Sone, Kuriyama and Nakaya61,Reference Erba, Riso, Bordoni, Foti, Biagi and Testolin66Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) patients with type 2 diabetes (T2D) and prediabetes,(Reference Bazyar, Hosseini and Saradar36,Reference Hadi, Alipour and Aghamohammadi37,Reference Spadiene, Savickiene and Ivanauskas53,Reference Liu, Huang, Huang, Chen, Chiu and Hsu55Reference Mousavi, Vafa, Neyestani, Khamseh and Hoseini57,Reference Mohammadi, Hosseinzadeh Attar and Karimi63,Reference Fukino, Ikeda, Maruyama, Aoki, Okubo and Iso65) obese and overweight individuals,(Reference Rondanelli, Gasparri and Perna32,Reference El-Elimat, Qasem and Al-Sawalha34,Reference Bagheri, Rashidlamir and Ashtary-Larky39,Reference Azizbeigi, Stannard and Atashak40,Reference Nogueira, Nogueira Neto, Klein and Sanjuliani46,Reference Suliburska, Bogdanski, Szulinska, Stepien, Pupek-Musialik and Jablecka59,Reference Bogdanski, Suliburska, Szulinska, Stepien, Pupek-Musialik and Jablecka60) athletes,(Reference Kondori, Ghaleh and Hosseini35,Reference Hadi, Pourmasoumi, Kafeshani, Karimian, Maracy and Entezari49) patients with metabolic syndrome,(Reference Basu, Betts, Mulugeta, Tong, Newman and Lyons58,Reference Basu, Du and Sanchez62)  non-alcoholic fatty liver disease (NAFLD),(Reference Tabatabaee, Alavian and Ghalichi44,Reference Hussain, Habib Ur and Akhtar48) diabetic nephropathy,(Reference Borges, Papadimitriou, Duarte, Lopes de Faria and Lopes de Faria51) chronic stable angina,(Reference Lee, Charng, Tseng and Lai50) β–thalassaemia major,(Reference Soeizi, Rafraf, Asghari-Jafarabadi, Ghaffari, Rezamand and Doostan45) polycystic ovary syndrome,(Reference Mombaini, Jafarirad, Husain, Haghighizadeh and Padfar47) multiple sclerosis,(Reference Benlloch, Cuerda Ballester and Drehmer38) COVID-19,(Reference Ahmad Merza Mohammad31) and older adults.(Reference Li, Chen and Aldini64)

Table 2. Characteristics of included studies

DB: Double-blind/NR: Not reported/T2DM: Type 2 diabetes mellitus/MetS: Metabolic syndrome/ PCOS: Polycystic ovary syndrome/NAFLD: Non-alcoholic fatty liver disease/MS: Multiple Sclerosis/M: male/F: female/CRP: C-reactive protein/TNF-a: Tumour necrosis factor-a/IL: Interleukin/TAC: Total antioxidant capacity/MDA: Malondialdehyde/GPx: Glutathione peroxidase/SOD: Superoxide dismutase.

Data presented in order of year.

Results from quality assessment

Risk of bias was assessed using the Cochrane Risk of Bias Tool version 2 (RoB2) for the following domains: randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. All but five studies were considered at overall low risk for bias.(Reference Shin, Lee and Seo42,Reference Soeizi, Rafraf, Asghari-Jafarabadi, Ghaffari, Rezamand and Doostan45,Reference Fukino, Ikeda, Maruyama, Aoki, Okubo and Iso65,Reference De Maat, Pijl, Kluft and Princen67,Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) Two assessors conducted the assessment independently. Any disagreements were resolved either through discussion or with the involvement of a third reviewer. None of the studies demonstrated a high risk of bias in any areas (Table 1).

Meta-analysis

The pooled effect size of the included studies indicated that green tea supplementation could decrease levels of IL-1β (WMD: −0.10 pg/mL; 95% CI: −0.15, −0.06; I2 = 39.3 %; Fig. 2), and MDA (WMD: −0.40 mcmol/L; 95 % CI: −0.63, −0.18; I2 = 99.2 %; Fig. 3). Also, the supplementation increased levels of TAC (WMD: 0.09 mmol/L; 95% CI: 0.05, 0.13; I2 = 84.9 %; Fig. 3), SOD (WMD: 17.21 u/L; 95% CI: 3.24, 31.19; I2 = 92.1 %; Fig. 3), and GPX (WMD: 3.90 u/L; 95% CI: 1.85, 5.95; I2 = 93.1 %; Fig. 3). However, green tea intake did not show a beneficial impact on CRP (WMD: 0.01 mg/L; 95% CI: −0.14, 0.15; I2 = 94.0%; Fig. 2), IL-6 (WMD: −0.34 pg/mL; 95% CI: −0.94, 0.26; I2 = 84.2 %; Fig. 2), or TNF-α (WMD: −0.07 pg/mL; 95% CI: −0.42, 0.28; I2 = 90.3 %; Fig. 2).

Fig. 2. Forest plots for the effect of green tea supplementation on inflammatory markers. Horizontal lines represent 95% CIs. Diamonds represent pooled estimates from random-effects analysis. WMD: weighted mean difference, CI: confidence interval.

Fig. 3. Forest plots for the effect of green tea supplementation on antioxidant status. Horizontal lines represent 95% CIs. Diamonds represent pooled estimates from random-effects analysis. WMD: weighted mean difference, CI: confidence interval.

Subgroup analysis

The findings of subgroup analyses are shown in Table 3. To find sources of heterogeneity and explore the effect sizes, we carried out subgroup analyses based on some confounding factors. The results showed that green tea consumption is unable to improve CRP levels in any of the subgroups. The supplementation decreased IL-6 levels in participants who consumed less than 500 mg of green tea per day. The green tea intake could improve TNF-α in those studies which included participants with a BMI equal to or more than 30 kg/m2, carried out in non-Asian countries, and lasted more than 8 weeks.

Table 3. Subgroup analysis to assess the effect of green tea supplementation on inflammatory markers and antioxidant status

Abbreviation: WMD: Weighted Mean Difference, CI: Confidence Interval, CRP: C-reactive protein, IL-6: Interleukin-6, TNF-a: Tumour Necrosis Factor Alpha, TAC: Total Antioxidant Capacity, MDA: Malondialdehyde, GPX: Glutathione Peroxidase, SOD: Superoxide Dismutase, BMI; Body Mass Index.

aRefers to the mean (95% CI).

bInconsistency, percentage of variation across studies due to heterogeneity.

cObtained from the Q-test.

dObtained from the fixed-effects model.

The beneficial effect of the green tea on TAC was not observed in some subgroups (male participants, non-Asian countries, duration greater than 8 weeks, and supplementation dosage less than 500 mg/day). In addition, we observed that green tea intake could not decrease MDA levels in studies enrolling participants with BMIs equal to or more than 30 kg/m2, participants who had a daily intake of green tea less than 500 mg, studies carried out in non-Asian countries, studies with a duration more than 8 weeks, and studies that included only male participants. Moreover, the beneficial impact of the supplementation on GPX was not found in studies that included unhealthy individuals, lasted more than 8 weeks, administered a daily dose of less than 500 mg, and had participants with a BMIs equal to or more than 30 kg/m2. Furthermore, green tea consumption increased SOD in those studies performed on healthy individuals, studies that administered brewed green tea to the subjects, studies with a period of intervention equal to or less than 8 weeks, and studies with a supplementation dosage equal to or more than 500 mg/day. Subgroup analysis with regard to IL-1β was rendered impossible due to lack of sufficient arms in each subgroup.

Sensitivity analysis and publication bias

The sensitivity analyses indicated that the elimination of none of the studies could alter the overall effect sizes of CRP (95% CI: -0.22, 0.27), TNF-α (95% CI: -0.55, 0.44), IL-1β (95% CI: −0.22, −0.02), TAC (95% CI: 0.04, 0.14), MDA (95% CI: −0.77, −0.09), and GPX (95% CI: 1.09, 7.46). However, the results showed that the overall effect size depended on some studies with respect to IL-6(Reference Kondori, Ghaleh and Hosseini35) and SOD(Reference El-Elimat, Qasem and Al-Sawalha34,Reference Venkatakrishnan, Chiu and Cheng41,Reference Maeda-Yamamoto, Nishimura and Kitaichi43,Reference van het Hof, de Boer, Wiseman, Lien, Westrate and Tijburg68) ; such that by removing the studies, the non-significant effect for IL-6 converted to a decreasing statistically significant effect, and the significant impact of SOD became non-significant.

We utilised Begg’s weighted regression test and examined funnel plots to detect publication bias in the papers that were included. Based on visual assessment, the funnel plots showed asymmetries regarding all the outcomes of interest (Supplementary Fig. 1). However, the findings of Begg’s test showed no publication bias for TAC (p = 0.692), MDA (p = 0.956), IL-6 (p = 0.945), or SOD (p = 0.462). The Begg’s test showed that there was publication bias for both CRP (p = 0.021) and GPX (p = 0.032). To further investigate the results, we used the trim-and-fill method. The overall effect size for CRP changed from not significant to significant (WMD: −0.22 mg/l; 95% CI: −0.38, −0.07), but there was no significant change for GPX after the trim-and-fill analysis. The Begg’s test was not conducted for TNF-α and IL-1β due to the lack of robustness of the Begg’s test in studies with less than 10 effect sizes.

Non-linear dose-response between duration and dose of green tea supplementation and the outcomes of interest

Non-linear dose-response analysis showed that supplementation dosage had no association with the outcomes of interest, except for IL-1β (P-non-linearity = 0.016) (Fig. 4). Moreover, we did not find any non-linear associations between the duration of the studies and the outcomes of interest (Fig. 5).

Fig. 4. Dose-response relations between green tea dosage (mg/day) and absolute (unstandardised) mean differences of the outcomes in non-linear fashion.

Fig. 5. Dose-response relationships between duration of intervention (week) and absolute (unstandardised) mean differences of the outcomes in non-linear fashion.

Meta-regression analysis

We performed a meta-regression analysis to assess the linear effect of dose and duration on the outcomes of interest. The results showed that the effect of green tea intake was not related to the dose of supplementation. In addition, the impact of green tea consumption on the outcomes of interest was independent of study duration, except for TAC (coefficient = − 0.004, p = 0.019).

Grading of evidence

At the outcome level, the GRADE guidelines were utilised to evaluate the quality of evidence across all included studies. As presented in Supplementary Table 2, the evidence quality was moderate for IL-1β, low for TAC and TNF-a, and very low for CRP, IL-6, MDA, GPX, and SOD.

Discussion

The findings of the present investigation can be summed up in the following statements: (1) supplementation with green tea seems to be unable to ameliorate pro-inflammatory indicators/agents of CRP, IL-6, and TNF-α; contrary to IL-1β which appears to be improved by the intervention; (2) supplementation with green tea improves measurements/indices of oxidative stress, including TAC, MDA, GPX, and SOD; (3) analyses of the subgroups show factors such as dosage, duration, and vectors of intervention; health status and biological gender of participants; and the location of the study all might contribute to the heterogeneity of the findings; and (4) linear regression and the examination of possible non-linear associations revealed that study duration influences the impact of green tea supplementation on TAC and that there is a non-linear association between the dosage of intervention and changes in IL-1β.

The impact of green tea on indicators of oxidative balance, owing to its abundance of antioxidant agents, could be considered self-explanatory. As aforementioned, green tea contains multiple compounds with antioxidant properties, the most important of which are catechins, or tea flavonoids; these include (−)-epigallocatechin (EGC), (−)-epicatechin (EC), (−)-epigallocatechin-3-gallate (EGCG), and (−)-epicatechin-3-gallate (ECG).(Reference Musial, Kuban-Jankowska and Gorska-Ponikowska16) In fact, the impact of Camellia sinensis on scavenging free radicals and enhancing the performance of antioxidant enzymes (such as GPX and SOD) have been previously examined.(Reference Lei, Zhu and Cheng69) The tea flavonoids are hypothesised to also suppress oxidative stress through induction of several pathways, such as protein kinase Cδ/acidic sphingomyelinase (PKCδ/ASM) and protein kinase B/endothelial nitric oxide synthase (Akt/eNOS).(Reference Mao, Gu, Chen, Yu and He70) Furthermore, down-regulation of other enzymes, such as matrix metalloproteinase-12 (MMP-12), extracellular signal-regulated kinase, nuclear factor-kappa B (NF-κB), phosphoinositide-3 kinase (PI3K), and haem oxygenase-1 (OH-1), have been hypothesised as possible mechanisms through which green tea polyphenols might equilibrise the production of ROSs and their eradication.(Reference Chen, Mo and Zhao71)

The findings of the present study support the potent antioxidant influences of acute consumption of green tea. Nonetheless, there are some notes that need to be accounted. For instance, the effect of intervention, on direct measurements of indices of antioxidant balance (i.e., TAC, MDA, GPX, and SOD), seem to be diluted when the duration of intake exceeds eight weeks, which undermines the effectiveness of such a dietary intervention in the long-term. However, these observations are in sharp contrast to what Rojano-Ortega(Reference Rojano-Ortega72) concluded in a systematic review of its impact on exercise-induced oxidative stress. The author suggests that ‘regular’ intake of green tea, rather than an acute portion, might be more relevant in reducing the exercise-induced oxidative stress. Nevertheless, in a clinical setting which dictates a comprehensive outlook regarding the preventive potency of green tea (in the context of various oxidative-related pathologies, such as cancer), the findings of the present study seem more pertinent. In spite of that, comprehensive reviews of observational studies still suggest that green tea consumption might be associated with lower risk of diseases with long periods of latency, such as cancer.(Reference Kim, Jeong and Yang73) With respect to this discrepancy, we suggest that mechanisms, other than that of long-term modification of detoxification enzymes, should be further investigated.

With respect to inflammatory markers (including IL-6, TNF-α, and CRP), our analyses suggest no beneficial impact of green tea supplementation. The only marker which seemed to be affected by the intervention was IL-1β. Not too much merit can, and should be given to the latter, since it is backed by merely two studies; further investigations are needed to clarify whether the observed discrepancy is meaningful or not. Nonetheless, there seems to be a sharp disparity between the findings of the present study and what the existing literature demonstrates, since most studies suggest that consumption/supplementation with green tea ameliorates the inflammatory flare caused by various conditions. For instance, in a review of clinical and epidemiological studies, Ohisi et al(Reference Ohishi, Goto, Monira, Isemura and Nakamura74) concluded that green tea/EGCG consumption is capable of improving the inflammatory balance. They even proposed that green tea catechins do so by their ROS-scavenging properties, repressing the expression of NF-κB which is responsible for production of various pro-inflammatory cytokines/enzymes, such as IL-1β, TNF-α, MMP-9, and cyclooxygenase-2 (COX-2) (which mediates the production of some pro-inflammatory eicosanoids). Likewise, Oz(Reference Oz75) investigated the role of green tea/its polyphenols in chronic inflammatory diseases. The author suggested that green tea polyphenols can be indeed regarded as potential therapeutic agents to treat diseases with chronic inflammation at their epicentre, such as inflammatory bowel diseases, gastrointestinal malignancies, and neurodegenerative disorders. Nonetheless, two important interwoven deductions can be made regarding the findings of the present study: (1) even though supplementation with green tea is potent in modifying the oxidative environment, this does not necessarily conclude in a reduced inflammation (in spite of most of the proposed mechanisms); and (2) this might be due to the fact that, as observed in our subgroup analyses, the impact of green tea supplementation seems to be disputable in the long-term; thus, partially explaining the lack of effectiveness in altering the inflammatory equilibrium which evidently must go through delayed processes of signalling pathways and transcription.

The present systematic review is unprecedented in its comprehensiveness and findings which contravene the previous presumptions. However, these findings must be interpreted in light of some limitations. Firstly, significant heterogeneities were observed with regard to most of the, accepted only for the sake of inclusion of more studies. We attempted to investigate these heterogeneities via extensive subgroup analyses. Secondly, the assessment of the evidence showed us that the quality of the included studies with regard to most of the outcomes was low and very low. Therefore, it can be recommended that the following investigations be conducted whenever fresh/high-quality evidence emerges on the same issue.

Conclusion

Our findings suggest that supplementation with green tea can ameliorate indices of oxidative stress. However, there is no solid evidence that inflammatory markers are influenced by green tea consumption/supplementation. Therefore, supplementation should only be aimed at reduced oxidative stress. The answer to whether the intervention would lead to a long-term modification of inflammatory status warrants further uniform investigations.

Supplementary material

The supplementary material for this article can be found at https://doi.org/10.1017/jns.2025.13

Acknowledgements

Not applicable.

Author contributions

The authors’ contribution was as follows: MA contributed to the design and statistical analysis. HG and MJD conducted the systematic search, screening and data extraction. MA, MM, MN, and HG interpreted data and wrote the manuscript. All authors read and approved the final manuscript.

Financial support

None.

Competing interests

The authors declared no conflicts of interest.

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Figure 0

Table 1. Results of risk of bias assessment for randomised clinical trials included in the current meta-analysis by the revised Cochrane risk-of-bias tool (RoB-2)

Figure 1

Fig. 1. Flow diagram of study selection.

Figure 2

Table 2. Characteristics of included studies

Figure 3

Fig. 2. Forest plots for the effect of green tea supplementation on inflammatory markers. Horizontal lines represent 95% CIs. Diamonds represent pooled estimates from random-effects analysis. WMD: weighted mean difference, CI: confidence interval.

Figure 4

Fig. 3. Forest plots for the effect of green tea supplementation on antioxidant status. Horizontal lines represent 95% CIs. Diamonds represent pooled estimates from random-effects analysis. WMD: weighted mean difference, CI: confidence interval.

Figure 5

Table 3. Subgroup analysis to assess the effect of green tea supplementation on inflammatory markers and antioxidant status

Figure 6

Fig. 4. Dose-response relations between green tea dosage (mg/day) and absolute (unstandardised) mean differences of the outcomes in non-linear fashion.

Figure 7

Fig. 5. Dose-response relationships between duration of intervention (week) and absolute (unstandardised) mean differences of the outcomes in non-linear fashion.

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