Potential mechanisms

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As per the above studies, there is some epidemiological evidence for an inverse association between coffee consumption and liver cancer. The same may be the case for liver fibrosis and alcoholic cirrhosis. Clearly, a plausible biological mechanism is required to explain and confirm these associations.

The role of caffeine

Caffeine has been suggested as a key component in the observed associations between coffee consumption and a reduced risk of liver conditions9,25,28,30,48. The precise mechanisms behind this effect are unclear, however a number of potential mechanisms have been proposed.

A number of papers have suggested that caffeine, and in particular its main primary metabolite, paraxanthine, can suppress the synthesis of CTGF (connective tissue growth factor) via a cascade of control cycles, thereby slowing down the growth of this type of tissue, which in turn slows down the progression of liver fibrosis, alcoholic cirrhosis and liver cancer10,26,30,48. However, some of the epidemiological studies did not find an association with tea48, which suggests that the mechanism of action might be not dependent solely on caffeine (via paraxanthine)30,48.

It has also been suggested that caffeine may act via by blocking adenosine receptors, since the structure of caffeine mimics that of adenosine48, in turn inhibiting activation of liver cells.

However, caffeine may not be the most important component, as other caffeinated drinks such as tea do not appear to provide similar protection against liver disease19.

Other coffee constituents

A 2010 paper also mentions the potential role of the coffee components kahweol and cafestol in lowering the risk of liver cancer27. There is some evidence that they may have anti-carcinogenic properties27.

It has also been proposed that the polyphenols found in coffee, such as chlorogenic acid, may reduce oxidative stress in the liver, in turn reducing the risk of fibrosis and development of cancers28-30.

A 2019 literature review suggests that caffeine, trigonelline and chlorogenic acid may be important in the association between coffee consumption and a reduced risk of liver cancer, by modulating common molecular targets directly implicated in key cancer hallmarks28. A further 2019 review on liver cancer also suggested that the potential mechanisms include a role for compounds such as caffeine, chlorogenic acids, phenolic compounds and diterpenes, as well as potentially an improvement in insulin sensitivity and prevention of metabolic syndrome and diabetes29.

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