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Page 4 of 9 Calabrò et al. Hepatoma Res 2020;6:69 I http://dx.doi.org/10.20517/2394-5079.2020.63

four groups and treated for 16 weeks as follows: control group; HFD Group; HFD group and 20 mg of
caffeine; HFD group and 30 mg of caffeine. HFD-induced liver injury was determined by evaluating the
alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, bilirubin, triglycerides and
cholesterol. Results indicated that caffeine treatment reduced elevated serum levels of ALT, AST, bilirubin
and hepatic mRNA expression of fatty acid synthase and acetyl CoA carboxylase.

Chlorogenic acid (CGA) is a phenolic compound that is obtained from the combination of caffeic acid
and (L)-quinic acid. It belongs to the family of polyphenols, substances with powerful antioxidant actions.
It is well known that the polyphenols present in coffee as chlorogenic acid increase the production of
[34]
antioxidants agents . Moreover, caffeine increases peroxiredoxin-1 which has positive effects on ROS,
[34]
reducing oxidative stress at the level of hepatocytes .
The synergistic effect of polyphenols and caffeine on hepatocytes also decreases insulin resistance, while
polyphenols contained in caffeine exerts an antifibrotic effect on the liver, an action that has been widely
[35]
highlighted in studies carried out on obese rats . It is present in high concentrations in green coffee and
in other typical foods of the Mediterranean diet [36,37] . Coffee roasting produces a compound that takes the
name of hydroxy-hydroquinone, which however reduces its bioavailability. It is estimated that one liter of
coffee provides between 500 and 800 mg of CGA .
[38]

Ferulic acid (FA) is a phenolic acid found in coffee, in some cereals such as oats, wheat and rice, in
artichokes and in some types of fruit. FA is a derivative of trans-cinnamic acid and is able to interfere
with the expression and activity of cytotoxic enzymes such as nitric oxide synthase, caspases and the
cyclooxygenase-2. Ferulic acid has been proposed as treatment for neurodegenerative, cardiovascular and
diabetic disorders.

Furthermore, it must be emphasized that the interest in this compound has increased due to its potential
therapeutic effects to reduce the deposition of triglycerides and cholesterol inhepatocytes, anti-microbial,
anti-inflammatory, and anti-tumor properties [39,40] .

COFFEE AND NAFLD
Among the several studies that analyzed the activities of coffee in NAFLD, Hosseinabadi et al. evaluated
[41]
the effects of green coffee extract (GCE) on the lipid profile and adiponectin levels in patients with NAFLD.
The randomized double-blind study was conducted on 48 patients aged between 20 and 60 years with a
2
body mass index (BMI) between 25-35 kg/m . In this study the patients were divided into two groups, one
group has been treated with 400 mg/die GCE and the other with placebo. The liver enzymes, lipid profile,
adiponectin concentration, and degree of hepatic steatosis were analyzed at the beginning and at the end
of the trial. The results showed that GCE supplementation significantly reduced BMI (MD: -0.57; 95%CI:
-0.84 to -0.29; P < 0.001). Moreover the study also showed an increase in HDL levels (MD: 7.06; 95%CI: 0.25
to 13.87; P < 0.05) and a reduction in serum blood triglyceride levels (MD: -37.91; 95%CI: -72.03 to -3.80; P
= 0.03) and total cholesterol (MD: -13.33; 95%CI: -26.04 to -0.61; P < 0.05) compared to the control group
[Table 1].

[42]
Graeter et al. have assessed the impact of caffeine consumption on liver fat concentration and ALT values
in a total population sample of 1,452 subjects, including 789 women, and 663 men with an average age of
42.3 years. After completing an informative questionnaire on personal data and lifestylewith particular
focus on coffee consumption, the liver health of all patients were examined using ultrasound. Univariate
logistic regression was used to evaluate the association between caffeine consumption and hepatic steatosis.
From the results, a significant association emerged between hepatic steatosis and the male gender (P <
0.0001), the same significance was also detected for advanced age subjects (P < 0.0001) and the high body-