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Research Article
Open Access Peer-reviewed

Green Tea Intake Effect on Lipoprotein, Liver Enzymes, Body Mass Index, and Liver Cancer: A Meta-analysis

Mingzhen Li, Yunjie Duan, Ying Wang, Lei Chen, Mohamed EA Abdelrahim, Jun Yan
Journal of Food and Nutrition Research. 2021, 9(7), 321-328. DOI: 10.12691/jfnr-9-7-1
Received May 17, 2021; Revised June 21, 2021; Accepted July 01, 2021

Abstract

Introduction: Green tea is related to the reduction of liver enzymes, lipoprotein, and body mass index. However, some reports related green tea to the risk of developing liver cancer, but their outcomes were conflicting. Hence, the present study aimed to determine the relationship between green tea intake and lipoprotein, liver enzymes, body mass index, and liver cancer. Methods: A systematic literature search up to January 2020 was performed and 22 studies included 169599 subjects with 97316 of them use green tea intake. Odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CIs) was calculated to evaluate the relationship between green tea intake and lipoprotein, liver enzymes, body mass index, and liver cancer using the dichotomous or the contentious method with a fixed effect or a random effect models. Results: Green tea intake significantly lowered the risk of developing liver cancer, and body mass index compared to no green tea intake. Also, there was a significant lowering effect of green tea intake on liver enzymes, lipoprotein compared to no green tea intake. However, no significant different was found between green tea intake and no green tea intake on high-density lipoprotein. Conclusions: Based on this meta-analysis, green tea intake had a significant lowering effect on the risk of developing liver cancer and had a significantly improving effect on body mass index, liver enzymes, and lipoprotein compared to no green tea intake. These results suggest that green tea may be added to the daily dietary program to improve cardiovascular status with no possible risk of liver cancer. It even may have a protecting effect against liver cancer in the usual daily number of cups.

1. What is already Known about This Topic?

Green tea is related to the reduction of liver enzymes, lipoprotein, and body mass index. However, some reports related green tea to the risk of developing liver cancer, but their outcomes were conflicting. Hence, the present study aimed to determine the relationship between green tea intake and lipoprotein, liver enzymes, body mass index, and liver cancer.

2. What does This Article Add?

Based on this meta-analysis, green tea intake had a significant lowering effect on the risk of developing liver cancer and had a significantly improving effect on body mass index, liver enzymes, and lipoprotein compared to no green tea intake. These results suggest that green tea may be added to the daily dietary program to improve cardiovascular status with no possible risk of liver cancer. It even may have a protecting effect against liver cancer in the usual daily number of cups.

3. Introduction

Cardiovascular disease is a leading cause of morbidity, mortality, and disability worldwide. 1 Hyperlipidemia, which results from abnormalities in lipid metabolism, leads to the development of atherosclerosis and is one of the key risk factors of cardiovascular disease. 2 The Risk of heart attack is higher in subjects with hyperlipidemia than in subjects with normal lipid. 3 It was found that a one percent decrease in serum cholesterol has been shown to reduce the risk of cardiovascular disease by three percent. 1 With the increasing frequency of hyperlipidemia, more and more subjects are aware of the influence of what they eat and drink on their lipid profiles.

Green tea is a widely consumed drink worldwide and is conventionally used in Asian countries as a medication. Green tea is produced from fresh leaves of Camellia sinensis and is not conventionally fermented. Green tea contains antioxidants and other beneficial nutrients such as protein, carbohydrates, minerals, vitamins, and flavonoids. 4 Epidemiologic studies have shown an inverse relation between green tea intake and risk of cardiovascular disease. Subjects who drink two cups of green tea per day had lower plasma total cholesterol concentrations and have been shown to reduce their risk of death from cardiovascular disease by about 33%. 5, 6 Previous studies have shown that green tea exerts a cardio-protective effect via multiple mechanisms including the inhibition of oxidation, vascular inflammation, thrombogenesis, and improvement in lipoproteins concentrations. 7 Recent studies have revealed that green tea could inhibit enzymes involved in lipid biosynthesis and reduce the intestinal absorption of total cholesterol, thereby improving lipoproteins and makes it effective for weight loss 8.

Unfortunately, some reports of adverse effects, mainly hepatitis, and possibly liver cancer, were associated with the intake of green tea as herbal supplements for control of body weight, however, the results were conflicting. 9, 10 Since then, much attention has been paid to the possible hepatotoxic effects of green tea. Hence, whether green tea intakes increase or decrease liver cancer prevalence, remains a question with uncertain answers.

Therefore, we performed this meta-analysis to investigate the effects of green tea intake on liver enzymes, lipoprotein, and body mass index; additionally, we extended the study to investigate the effect of green tea on the development of liver cancer.

4. Methods

The study performed here followed the meta-analysis of observational studies in the epidemiology statement, 11 which was conducted following an established protocol.

4.1. Study Selection

Studies included were those reported statistical measures of relationship and randomized controlled trials evaluating the relationship between green tea intake and lipoprotein, liver enzymes, body mass index, and liver cancer. The study included healthy subjects using green tea as a supplement compared to non-user and followed up for any possible outcome e.g. liver cancer, body mass index (BMI), liver enzymes including Alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and lipoprotein including triglycerides (TG), total cholesterol (TC), Law-density lipoprotein (LDL), and High-density lipoprotein (HDL).

Only human studies in any language were considered. Inclusion was not limited by study size or publication type. Figure 1 shows a schematic diagram of the study procedure. The articles were integrated into the meta-analysis when the following inclusion criteria were met:

1. The study was randomized controlled trials or retrospective studies

2. The target population was healthy subjects

3. The intervention program was based on the effect of green tea intake on lipoprotein, liver enzymes, body mass index, and liver cancer

4. The study included a comparison between healthy subjects using green tea as a supplement and non-user and followed up for any possible outcome.

4.2. Identification

A protocol of search strategies was prepared according to the PICOS principle, 12 and we defined it as follow: P (population): healthy subjects; I (intervention/exposure): the effect of green tea intake on lipoprotein, liver enzymes, body mass index, and liver cancer; C (comparison): healthy subjects using green tea as a supplement compared to non-user and followed up for any possible outcome; O (outcome): any possible effect on lipoprotein, liver enzymes, body mass index, and liver cancer; and S (study design): no restriction. 13

First, we conducted a systematic search of Chinese databases (China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu (VIP) databases), OVID, Embase, Cochrane Library, PubMed, and Google scholar from January 1990 till January 2020, using a combination of keywords and similar words for green tea, liver cancer, body mass index, liver enzymes, and lipoprotein as shown in Table 1. All identified studies were combined in an EndNote file, duplicates were discarded, and the title and abstracts were reviewed to eliminate studies that did not report data on the effect of green tea intake on lipoprotein, liver enzymes, body mass index, and liver cancer, based on pre-specified inclusion and exclusion criteria. The remaining articles were inspected for related information.

4.3. Screening

Data were summarized on the following bases; study-related and patient-related features onto a consistent form; last name of the primary author, period of study, year of publication, country, region of the studies, and study design; population type, the total number of subjects, demographic data, clinical and treatment characteristics, categories, qualitative and quantitative method of evaluation, information source, outcome evaluation, and statistical analysis. 14 When there were separate data from 1 study based on any variable, we extracted them separately. The risk of bias in these studies; individual studies were evaluated using the quality in prognosis studies tool, which evaluates validity and bias in studies of prognostic factors across 6 domains: participation, attrition, prognostic factor measurement, puzzling measurement and account, outcome measurement, and analysis and reporting. 15 Any inconsistencies were addressed by a reevaluation of the original article.

4.4. Eligibility

The primary outcome focused on the effect of green tea intake on lipoprotein, liver enzymes, body mass index, and liver cancer. Similarly, a comparison between green tea intake and no green tea intake effect on lipoprotein, liver enzymes, body mass index, and liver cancer were extracted to form a summary.

4.5. Inclusion

Sensitivity analyses were limited only to studies evaluating the effect of green tea intake on lipoprotein, liver enzymes, body mass index, and liver cancer. For subgroup and sensitivity analysis, we used comparisons between green tea intake and no green tea intake as reference.

4.6. Statistical Analysis

The dichotomous or continuous method with random-effect or fixed-effect models was used to calculate the odds ratio (OR) or mean difference (MD) and 95% CI. We used the Chi-square test to perform biological heterogeneity analyses between different studies. We calculated the I2 index; the I2 index is from 0% to 100%. Values of about 0%, 25%, 50%, and 75% indicate no, low, moderate, and high heterogeneity, respectively. 16 When I2 was higher than 50%, we chose the random effect model; when it was lower than 50%, we used the fixed-effect model. A subgroup analysis was performed by stratifying the original evaluation per liver cancer and chemotherapy different outcomes as described before. In this analysis, a p-value for differences between subgroups of <0.05 was considered statistically significant. Publication bias was evaluated quantitatively using the Egger regression test (publication bias considered present if p≥0.05), and qualitatively, by visual examination of funnel plots of the logarithm of ORs or MDs versus their standard errors (SE). 14 All p-values were 2 tailed. All calculations and graphs were performed using Reviewer manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).

5. Results

A total of 1100 unique studies were identified, of which 22 studies satisfied the inclusion criteria and were included in the study. 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38

The 22 studies included 169599 subjects; of them, 97316 were green tea intake. 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 All studies were cohort by design. For developing liver cancer in healthy subjects in relation to green tea intake; all studies were large cohorts of cancer-free subjects at inception and followed them for the development of liver cancer. For the liver enzymes, lipoprotein, and body mass index related outcomes in association with green tea intake; all studies were healthy subjects. There was no limitation to the size of the study.

Study size ranged from 20 to 4378 subjects at the baseline of the study. The risk of developing liver cancer in the healthy subject was detected in 4 studies, with evaluation performed at least 5 years before liver cancer diagnosis. 17, 18, 19, 20 Liver enzymes, lipoprotein, and body mass index related outcomes and green tea intake outcomes were detected in 18 studies, with 3 weeks to 3 months follow up period. 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 One of the studies had two types of methods of green tea administration within the same study with a separate result for each administration method; 22 one using green tea as a drink and the other using green tea as a supplemental capsule. So we extracted them separately. 22

Green tea intake significantly lowered the risk of developing liver cancer (OR, 0.85; 95% CI, 0.74-0.97, p=0.02) with no heterogeneity (I2 = 5%), and BMI (MD, -0.69; 95% CI, -0.95- -0.42, p<0.001) with low heterogeneity (I2 = 36%) compared to no green tea intake as shown in Figure 2. Also, there was a significant lowering effect of green tea intake on liver enzymes; ALT (MD, -0.65; 95% CI, -0.92- -0.38, p<0.001) with low heterogeneity (I2 = 45%), and AST (MD, -0.77; 95% CI, -1.40- -0.14, p=0.02) with high heterogeneity (I2 = 80%) compared to no green tea intake as shown in Figure 3. Also, there was a significant lowering effect of green tea intake on lipoprotein; TG (MD, -0.70; 95% CI, -1.35- -0.04, p=0.04) with high heterogeneity (I2 = 78%), TC (MD, -0.39; 95% CI, -0.74- -0.04, p=0.03) with high heterogeneity (I2 = 88%), and LDL (MD, -0.44; 95% CI, -0.69- -0.19, p<0.001) with moderate heterogeneity (I2 = 72%) compared to no green tea intake as shown in Figure 4. However, no significant different was found on HDL between green tea user and non-user (MD, 0.16; 95% CI, -0.11-0.44, p=0.24) with high heterogeneity (I2 = 79%) compared to no green tea intake as shown in Figure 4.

Stratified analysis of studies that did and did not adjust for cirrhosis, liver cancer stage, underlying etiology, treatment modality, or performance status was not performed because no studies reported or adjusted for those factors.

Based on the visual inspection of the funnel plot as well as on quantitative measurement using the Egger regression test, there was no evidence of publication bias (p = 0.89).

6. Discussion

This meta-analysis study based on 22 studies included 169599 subjects; of them, 97316 were green tea intake. 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 Green tea intake had a significant lowering effect on the risk of developing liver cancer and a significantly improving effect on body mass index, liver enzymes, and lipoprotein compared to no green tea intake and this was found in all populations studied. 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 However, no significant difference was found on HDL between green tea intake and no green tea intake.

As mentioned above, some reports of adverse effects, mainly hepatitis and possibly liver cancer, were associated with the intake of green tea as a herbal supplement for control of body weight. 9, 10 Since then, attention has been paid to the possible hepatotoxic effects of green tea. However, the dose of epigallocatechin gallate as a main chemical constituent of green tea, which could cause hepatotoxicity in humans, is approximately 10-32 cups of green tea per day. This is way above the maximum number of cups in the present study <5 cups. In mice, the hepatotoxic effects of high dose green tea could attribute to increased markers of oxidative stress, including hepatic lipid peroxidation and plasma 8-isoprostane. 30

In the present meta-analysis, we could not divide data according to the number of cups consumed per day since some studies compared 0-1, 2-4 and <5 cups, some compare 0-1, 1-2, 3-4, and <4 cups and some compared 0-1, 1-3, 3-5, and <5 cups. So we just compared green tea non-consumer to consumer as a whole. This might affect our results since the intake of 2-3 cups of green tea per day by healthy subjects was proven to have the best outcome on reducing liver cancer. 17, 18, 19, 20

Also, our meta-analysis showed that green tea intake significantly reduced blood lipoprotein concentrations but did not affect HDL concentrations. A large population-based study, that involved forty thousand middle-aged Japanese, revealed that green tea intake was related to a lower risk of mortality from cardiovascular disease compared to no green tea intake. 6 The advantageous effects of green tea on the cardiovascular system may be due to the high concentration of green tea catechins, which have been confirmed to favorably control the plasma lipoprotein. The catechins exert different physiologic actions and, thus, affect lipid metabolism. Animal trials showed that the inhibition of cholesterol absorption may be the mechanism of cholesterol reducing effects of green tea. Green tea was shown to interfere with the biliary micelle system in the lumen of the intestine by creating insoluble precipitates of cholesterol. 39 This reduction in cholesterol absorption and decrease in lipoprotein concentrations leads to an elevation of -receptor activity. 8 These receptors exist on the outer surface of liver cells; they can eliminate cholesterol-with from the circulation. Trials in animals have provided evidence that green tea can decrease lipoprotein and increase hepatic receptors, and also significantly improved receptors' binding capacity. 8, 40 Also, catechins have direct inhibitory effects on cholesterol synthesis. A previous study has shown that green tea was an effective and selective inhibitor of squalene epoxidase, which is a rate-limiting enzyme of cholesterol biosynthesis. 41 These effects of green tea are related to hypocholesterolemic drugs like statins, which decrease cholesterol synthesis and increase the receptor activity. 42

In summary, the results indicated that green tea intake had a significant lowering effect on the risk of developing liver cancer and had a significantly improving effect on body mass index, liver enzymes, and lipoprotein compared to no green tea intake. These results suggest that green tea could be added to the daily dietary program to improve cardiovascular status with no possible risk of liver cancer. It even may have a protecting effect against liver cancer in the usual daily number of cups (up to 5 a day).

7. Limitations

In part of the study evaluating the risk of the development of liver cancer only observational studies were included, which are very sensitive to have biases and suboptimal controls of variables. Most studies in the risk of developing liver cancer in healthy subjects were large cohort studies, which enrolled cancer-free subjects at baseline and followed them for the development of many different outcomes one of them were liver cancer; these studies did not adjust for challenging risk such as, etiology and severity of cirrhosis, and liver cancer stage and treatment.

The studies included in the liver enzymes and the lipoprotein outcomes were short in their durations (from 3 weeks to 3 months). Therefore, more long-term (over years) randomized studies are needed in the future. The included studies had also another limitation since evaluation time in studies was variable.

There may be selection bias in this study since so many of the studies found were excluded from the meta-analysis. However, the studies excluded did not satisfy the inclusion criteria of our meta-analysis. Also, we could not answer whether the results were associated with ethnicity and gender or not. The study designed to assess the evaluation of the effect of green tea intake on lipoprotein, liver enzymes, body mass index, and liver cancer was based on data from previous studies, which might cause bias induced by incomplete details. Variables including ethnicity, gender, and nutritional status of subjects were also the possible bias-inducing factors. Some unpublished articles and missing data might lead to a bias in the pooled effect.

8. Conclusions

Based on this meta-analysis, green tea intake had a significant lowering effect on the risk of developing liver cancer and had a significantly improving effect on body mass index, liver enzymes, and lipoprotein compared to no green tea intake. These results suggest that green tea could be added the daily dietary program to improve cardiovascular status with no possible risk of liver cancer. It even may have a protecting effect against liver cancer in the usual daily number of cups.

Ethics Approval and Consent to Participate

Not applicable

Consent for Publication

Not applicable.

Availability of Data and Materials

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Competing Interests

The authors declare that they have no competing interests

Funding

There was no external funding for this study itself. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Data Availability Statement

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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[42]  Endo A., The discovery and development of HMG-CoA reductase inhibitors. Journal of lipid research, 1992. 33(11): p. 1569-1582.
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Published with license by Science and Education Publishing, Copyright © 2021 Mingzhen Li, Yunjie Duan, Ying Wang, Lei Chen, Mohamed EA Abdelrahim and Jun Yan

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Normal Style
Mingzhen Li, Yunjie Duan, Ying Wang, Lei Chen, Mohamed EA Abdelrahim, Jun Yan. Green Tea Intake Effect on Lipoprotein, Liver Enzymes, Body Mass Index, and Liver Cancer: A Meta-analysis. Journal of Food and Nutrition Research. Vol. 9, No. 7, 2021, pp 321-328. http://pubs.sciepub.com/jfnr/9/7/1
MLA Style
Li, Mingzhen, et al. "Green Tea Intake Effect on Lipoprotein, Liver Enzymes, Body Mass Index, and Liver Cancer: A Meta-analysis." Journal of Food and Nutrition Research 9.7 (2021): 321-328.
APA Style
Li, M. , Duan, Y. , Wang, Y. , Chen, L. , Abdelrahim, M. E. , & Yan, J. (2021). Green Tea Intake Effect on Lipoprotein, Liver Enzymes, Body Mass Index, and Liver Cancer: A Meta-analysis. Journal of Food and Nutrition Research, 9(7), 321-328.
Chicago Style
Li, Mingzhen, Yunjie Duan, Ying Wang, Lei Chen, Mohamed EA Abdelrahim, and Jun Yan. "Green Tea Intake Effect on Lipoprotein, Liver Enzymes, Body Mass Index, and Liver Cancer: A Meta-analysis." Journal of Food and Nutrition Research 9, no. 7 (2021): 321-328.
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  • Figure 2. Forest plot of green tea intake vs no green tea intake effect on a) the risk of developing liver cancer in healthy subjects and b) BMI
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