Effect of coffee and coffee extract on liver function test in non-alcoholic fatty liver disease ‎patients, a systematic review and meta-analysis

Abstract

Aim:

This study aimed to investigate the effect of coffee or coffee extract on serum ALT and AST levels in patients with non-alcoholic fatty liver disease (NAFLD), by compiling data from randomized controlled trials up to November 2024.

Background:

NAFLD represents the most prevalent hepatic disorder, characterized by the accumulation of lipids within hepatocytes in the absence of substantial alcohol consumption or viral infections. Effective management relies on lifestyle changes, such as diet and exercise. Recent studies have suggested that coffee consumption may offer liver-protective benefits, potentially helping to reduce serum levels of liver enzymes.

Methods:

Two researchers conducted an independent search across PubMed, Web of Science, and Scopus, including clinical trials that assessed the effects of coffee or coffee extract on liver function tests (LFTs) in individuals diagnosed with NAFLD. Meta-analysis was carried out using STATA software.

Results:

After screening titles, abstracts, and full texts, four studies comprising five placebo-treatment pairs were included in the meta-analysis. Coffee or coffee extract did not significantly affect serum ALT (p= 0.45) and AST (p= 0.54) levels.

Conclusion:

There is insufficient evidence to support the effectiveness of coffee or coffee extract on serum ALT and AST levels. Due to the limited number of studies, small sample sizes, and short follow-up durations, further randomized controlled trials with adequate sample sizes and more extended follow-up periods are recommended.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease (1). It is defined as fat accumulation of more than 5% in liver cells, without viral infection, any cause of liver disease, or excessive alcohol consumption (2).

Elevated serum concentrations of aspartate transaminase (AST) and alanine transaminase (ALT) can aid in differentiating steatohepatitis from simple fatty liver disease (3). Furthermore, the pattern of abnormal liver enzymes may distinguish different forms of liver damage, with ALT and AST typically increased in hepatocellular injury (4). Given that the management of NAFLD remains a significant concern, recent studies have shown growing interest in the impact of nutrients on this condition (5).

Numerous studies have suggested that coffee consumption may confer a hepatoprotective effect (6). As one of the most commonly consumed beverages worldwide, coffee is abundant in various bioactive phytochemicals that exhibit antioxidant and anti-inflammatory properties (7).

Several studies have identified potential benefits of coffee consumption in patients with NAFLD (8-12). A study found that daily caffeine intake of more than 123 mg was associated with decreased liver fibrosis (13). However, in some intervention studies, questionable or inconclusive results have been reported (10, 14). This study aimed to address these doubts by integrating the existing clinical trials that have examined the impact of coffee or coffee extract on serum ALT and AST levels in patients with NAFLD.

Methods

Search strategy

According to the PRISMA-2009, two investigators (M S, Z Ch) independently searched online databases (Web of Science, PubMed, and Scopus), up to November 2024, to find clinical trials assessing the impact of coffee or coffee extract on liver function tests (LFTs), including ALT and AST in NAFLD patients, without language and publication time limits.

The search queries included the following terms in all parts of the papers

PubMed: (("Liver Function Tests"[Mesh]) OR ("Alanine Transaminase"[Mesh]) OR ("Aspartate Aminotransferases"[Mesh])) AND (("Non-alcoholic Fatty Liver Disease"[Mesh]) OR fatty liver OR Steatohepatitis) AND (("Coffee"[Mesh]) OR coffee).

Scopus: ((Liver Function Tests) OR (Alanine Transaminase) OR (Aspartate Aminotransferases) OR ALT OR AST OR GOT OR GPT OR SPOT OR SGPT) AND ((Non-alcoholic Fatty Liver Disease) OR (fatty liver) OR Steatohepatitis) AND (Coffee).

Web of Science: ("Non-alcoholic Fatty Liver Disease" OR "Fatty Liver" OR NAFLD) AND (ALT OR AST OR GOT OR GPT OR Alanine Transaminase OR Aspartate Aminotransferases) AND ("Caffeine" OR coffee).

We also examined trial registries for unpublished studies and reviewed the reference lists of eligible studies to identify additional relevant research.

Inclusion and exclusion criteria

Clinical trial studies examining the impact of coffee or coffee extract on LFTs in NAFLD patients were included. Studies with unclear eligibility criteria for inclusion and exclusion, or insufficient information, were excluded.

Data extraction

The subsequent data was extracted from the selected studies, including the title and DOI, the name of the first author, the date of publication, the country in which the study was carried out, the sample sizes, the quantity of coffee or dosage of coffee extract administered, the duration of the intervention, as well as the mean and standard deviation of lean body mass (LBM) for both groups. Additionally, the necessary details for calculating the Jadad scale were collected, encompassing information on randomization, blinding, and the reporting of outcomes for all participants.

When the standard error (SE) or 95% confidence interval (95% CI) was provided instead of the standard deviation (SD), the conversion methods outlined in the Cochrane Handbook (15) were used to derive the SD. Furthermore, the estimation techniques recommended by Wan et al. (16) were utilized to estimate the mean and SD when only the median, along with the interquartile range (IQR) or the minimum and maximum values, were available.

Quality assessment

The Jadad scale (17) was employed to evaluate the quality of the eligible studies. This scale assesses the methodological quality of clinical trials and assigns a score ranging from 0 (indicating inferior quality) to 5 (indicating rigorous quality).

Statistical analysis

The meta-analysis (using a random-effects model) and the graph were generated with Stata (StataCorp).

Results

Sixty-one studies were found in the initial search from the three online sources. Following a screening of the titles and abstracts and a thorough review of the full texts of the remaining studies, four studies comprising five independent intervention groups met all the inclusion criteria (Figure 1). A summary of the four included studies is presented in Table 1.

Figure 1.

PRISMA flow chart of the study.

Table 1.

Characteristics and findings of the included studies.

First author	country	date	Sample size		Total prescribed caffeine	duration (weeks)	ALT		AST
			treatment	placebo			Mean ± SD (treatment)	Mean ± SD (placebo)	Mean ± SD (treatment)	Mean ± SD (placebo)
Asieh Mansour	Iran	2020	7	6	16800	12	18.14± 7.43	20.17± 16.58	24.97± 6.36	18.97± 7.35
Hedayat Allah Shahmohammdi	Iran	2017	22	22	56000	8	26.04±3.3	34.04±4.81	36±11.13	36.77±9.96
Valentina Cossiga	Italy	2019	26	23		26	28.8±12	28±12	25.2±12	24±8
Samaneh Hosseinabadi	Iran	2019	23	21	22400	8	44.52±30.08	37.04±19.99	32.66±16.74	32.13±11.14
Asieh Mansour	Iran	2020	7	6	16800	12	21.13 ± 19.23	20.17 ± 16.58	23.8± 6.22	18.97± 7.35

Eligible studies

In the study conducted by Shahmohammadi et al., the effects of green coffee bean extract (GCBE) supplementation on serum liver enzymes in overweight and obese patients with NAFLD in Iran were investigated (8). Forty-four NAFLD men and women aged 20 to 70 with BMI between 24.9 and 35 kg/m2 were randomly assigned to two groups. The intervention group consumed two capsules daily (each capsule containing 500mg GCBE), and the placebo group consumed two capsules daily, which were similar in appearance to GCBE capsules and included the same amount of edible starch for eight weeks.

At the end of the study, the mean serum ALT level was significantly lower in the treatment group than in the placebo group (P < 0.001). However, changes in serum AST were not statistically different between the two groups.

Table 2.

Quality of the selected studies, based on the JADAD scale.

First author	randomized	Researcher blind	Patient blind	Account for all patients	JADAD score
Asieh Mansour	2	1	1	1	5
Hedayat Allah Shahmohammdi	2	1	1	1	5
Valentina Cossiga	2	0	1	1	4
Samaneh Hosseinabadi	2	1	1	0	4
Asieh Mansour	2	1	1	1	5

Cassiga et al. (9) investigated the effects of a mixture of plant extracts comprising Berberis Aristata, Elaeis guineensis, and decaffeinated green coffee on glycemic profile in NAFLD patients. Pregnant or lactating women, or those with excessive alcohol consumption, BMI≥35 kg/m2, or taking lipid-lowering medications, vitamin E, as well as any drug that affects liver function, and those with hepatitis, coronary artery, kidney, lung, and thyroid diseases were not included. Forty-nine patients were randomly assigned to two groups (Plant Extracts or placebo). The treatment group took one capsule containing plant extracts daily for six months (26 weeks). Consuming this supplement resulted in a significant decrease in ALT and AST levels.

In the study by Hosseinabadi et al. (14), 48 patients with NAFLD, aged 20 to 60 years and with a body mass index of 25 to 35 kg/m², were randomly assigned to two groups. Participants were provided with recommendations for a healthy lifestyle and received their supplements biweekly for the next two weeks. The treatment group was administered a daily dosage of 400 mg of green coffee extract (GCE) (2 x 300 mg; n = 24) or a placebo (n = 24), which was identical in capsule form regarding dosage, size, color, and starch content, for eight weeks. Compliance was monitored through weekly telephone interviews, and returned capsules were counted biweekly. Three individuals in the intervention group withdrew from the study for non-compliance with the supplement regimen, while one participant in the control group withdrew due to relocation. No significant differences in serum ALT and AST levels were observed between the two groups compared with baseline values.

Asieh Mansour et al. (10) conducted an RCT involving 26 patients with diabetes and NAFLD aged 30-65 years. The participants were randomly assigned to one of four groups: one group received 200 mg of caffeine combined with 200 mg of chlorogenic acid (CFCA), another group received 200 mg of caffeine along with 200 mg of placebo (CFPL), a third group was given 200 mg of chlorogenic acid plus 200 mg of placebo (CAPL), and the fourth group received two 200 mg placebo tablets (PLPL) for 12 weeks. After the three-month intervention, the CFCA group exhibited a significant reduction in serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Meta-analysis

Four studies, each with five placebo-treatment pairs (a total of 95 patients in the treatment group and 78 in the placebo group), provided the required data. Publication bias was not evaluated because fewer than 10 studies were included (18). A random effects model was used for the meta-analysis.

Figures 2 and 3 show that coffee or coffee extract did not affect serum ALT (p= 0.45) and AST (p= 0.54) levels.

Figure 2.

Forest plot for the impact of coffee or coffee extract on the serum ALT in NAFLD patients.

Figure 3.

Forest plot for the impact of coffee or coffee extract on the serum AST in NAFLD patients.

Discussion

In this systematic review and meta-analysis, which investigated the effects of coffee and coffee extract on liver enzymes (ALT and AST) in patients with non-alcoholic fatty liver disease (NAFLD), it was found that coffee does not significantly affect serum levels of liver enzymes in NAFLD patients.

Coffee contains many biological compounds, the most well-known being caffeine. In addition, chlorogenic acids, lactones, and diterpenes, such as cafestol and kahweol, are other compounds found in coffee (19). Caffeine was extracted from cocoa in the early nineteenth century. Caffeine is present in more than sixty plants, including coffee. Its amount in coffee ranges from 65 to 120 mg per cup (20).

Some studies have suggested a positive effect of coffee on liver health (20). A meta-analysis of observational studies revealed that consuming more than 2 cups of coffee per day in individuals with pre-existing liver disease was associated with reduced incidence of liver fibrosis and cirrhosis, decreased rates of hepatocellular carcinoma and other cancers, and lower mortality (21). Additionally, the NHANES study reported that consuming coffee is associated with a lower risk of developing this liver disease and reduces the risk of increasing ALT levels by 44% (22, 23). Similar results were reported in another cohort study (24). Other meta-analyses have suggested that coffee consumption is associated with a lower incidence of NAFLD or a lower risk of liver fibrosis in patients with NAFLD (25, 26). On the other hand, a meta-analysis found no association between coffee consumption and NAFLD incidence. However, the protective effect of coffee consumption on liver fibrosis in patients with NAFLD was emphasized (27).

Although coffee consumption is correlated with a reduced incidence of liver disease and other chronic diseases, it is unclear whether this effect is due to caffeine or other components (20). Additionally, these associations may be influenced by potential confounding factors, such as the simultaneous consumption of different foods or increased physical activity. Therefore, experimental studies or clinical trials will have more reliable results.

Experimental studies have suggested that coffee with or without caffeine has beneficial effects on liver health (28, 29). Moreover, several experimental studies have demonstrated the positive effect of coffee supplementation on serum liver enzyme levels in patients with NAFLD (8, 9). However, an RCT study has not confirmed such an effect (14). Similarly, the current meta-analysis did not demonstrate a statistically significant effect. However, the limited sample sizes and short follow-up durations in the included studies underscore the need for further clinical trials with larger samples and extended follow-up periods. Moreover, the small number of eligible studies precluded subgroup or sensitivity analyses, thereby limiting the analytical depth and generalizability of the findings. Moreover, due to the limited number of studies, assessing publication bias was not feasible, which remains a methodological limitation and should be considered when interpreting the findings.

Conflict of interests

There is no conflict of interest for authors of this article.