Coffee and Non-alcoholic Fatty Liver Disease: Brewing Evidence for Hepatoprotection?

Shaohua Chen; Narci C Teoh; Shiv Chitturi; Geoffrey C Farrell

J Gastroenterol Hepatol. 2014;29(3):435-441.

Conclusions and Future Perspectives

Taken together, these studies provide reasonably strong evidence for a protective effect of coffee consumption on development of NAFLD, and on reducing its severity in NASH. Since the most convincing effect of coffee consumption on other forms of liver disease is its association with a substantially reduced rate of HCC, future studies on HCC in NAFLD examining coffee consumption with other potential environmental factors (fructose, vegetables, smoking, vitamin D, and selenium, etc.) are keenly awaited. Meanwhile, it does appear that possible hepatoprotective effects of coffee are related more to polyphenols not caffeine. The possible protective effects of coffee bean polyphenols may be related to a diverse range of mechanisms, including anti-oxidant, anti-inflammatory, anti-fibrotic pathways as well as modulation in energy metabolism, reduced insulin resistance, and reduced severity of diabetes (Fig. 2). However, studies to date have been exploratory and confined to a limited range of experimental systems, only a small subset of which have utilized clinically relevant experimental models of NASH. It is clear that some components of coffee other than caffeine may be involved, and specific identification of these compounds require more rigorous study to elucidate the mechanisms underlying coffee's hepatoprotective effects in patients with NAFLD.

(Enlarge Image)

Figure 2.

Schematic diagram illustrating the mechanisms underlying coffee's potential hepatoprotective effects in non-alcoholic fatty liver disease. CTGF, connective tissue growth factor; GSSG, oxidized glutathione; IFN-γ, interferon-γ; IL-10, interleukin-10; IL-1β, interleukin-1β; IL-4, interleukin-4; MCP-1, monocyte chemoattractant protein-1; NASH, non-alcoholic steatohepatitis; PPAR-α, peroxisome proliferator-activated receptor α; ROS, reactive oxygen species; Smad2, Mothers against decapentaplegic homolog 2, SMAD family member 2; SREBP-1C, sterol regulatory element-binding protein-1C; TGF-β, transforming growth factor β; TNF-α, tumor necrosis factor α.

1 2 3 4 5

Next Section

Abstract and Introduction
Sources of Information
Relationship Between Coffee Consumption and NAFLD in Community Studies
Mechanisms by Which Coffee may Reduce Severity of NAFLD
Conclusions and Future Perspectives
References

Table 1. Relationship between coffee consumption and non-alcoholic fatty liver disease (NAFLD) in community studies
Authors (Reference)	Subjects	Design	Results	Comments
Birerdinc A et al.²⁴ 2012; USA	1 782 NAFLD; 16 768 controls from 4 continuous cycles of NHANES	NAFLD defined by ALT/AST exclusive of other liver disease	Caffeine intake in NAFLD 165 ± 6.55 mg, controls 188 ± 4.90 mg (P = 0.0006). MVA showed caffeine intake an independent predictor of NAFLD (OR = 0.999, 95% CI: 0.999–1.00, P = 0.0003)	Minor effect in lowering prevalence of NAFLD
Catalano D et al.²⁵ 2010; Italy	137 NAFLD; 108 controls.	Assessed by ultrasound BLS, with exclusion criteria	BLS less in coffee drinkers than in non-coffee drinkers. Coffee consumption as cups/day (0/< 3/≥ 3) per groups by BLS: severe: 9/7/0; moderate: 12/37/33; light: 9/21/29 (P < 0.0001)	Inverse association between coffee intake and degree of BLS
Gutierrez-Grobe, Y et al.²⁶ 2012; Mexico	57 NAFLD 73 controls.	Case control study Assessed by ultrasonography Dietary history questionnaire.	Coffee intake(log caffeine) between different severity of NAFLD: severe steatosis: 0.15 ± 0.05; moderate steatosis: 1.58 ± 0.72; mild steatosis: 1.61 ± 0.79; no steatosis: 1.75 ± 0.70(P ≤ 0.05)	High coffee intake associated with lower grade NAFLD
Molloy JW et al.²⁷ 2012; USA	36 NASH stage 2–4; 61 NASH stage 0–1; 83 bland steatosis; 126 controls	Biopsied NAFLD cases. Validated caffeine questionnaire	Coffee caffeine intake (mg/day): NASH stage 2–4: 153; NASH stage 0–1: 256; bland steatosis: 160; controls: 228. (r = −0.215, P = 0.035).	Negative correlation between caffeine intake and stage of fibrosis

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BLS, bright liver score; MVA, multivariate analysis; NASH, non-alcoholic steatohepatitis; NHANES, National Health and Nutrition Examination Surveys.

Table 2. List of chemical composition of coffee proposed biological effects
Constituents	Effects	References
Carbohydrates and fiber Sucrose Reducing sugars	Most non-digestible, the digestible carbohydrate fraction is negligible.	²⁸
Nitrogenous compounds Protein/peptides Free amino acids Caffeine Trigonelline	Caffeine: stimulation of hepatic lipid metabolism, induction of thermogenesis, anti-oxidative stress, anti-fibrosis	^24,27,28
Lipids Coffee oil Diterpenes (Cafestol and Kahweol)	Cafestol and Kahweol: cholesterol raising, anti-carcinogenesis	^29,30
Minerals	Potassium: reducing hypertension but in minimal amount	²⁸
Acids and esters/polyphenol Chlorogenic acids Aliphatic acids Quinic acid	CPP: enhancing energy metabolism, reducing lipogenesis, downregulating SREBP-1c Chlorogenic acids: the predominant antioxidant in coffee; reducing hepatic glucose output, lowering cholesterol, attenuating fatty liver and upregulating PPAR-α	^28,31–33
Melanoidins	Anti-oxidation, anti-inflammation, and increase expression of adiponectin receptor and PPAR-α	^34,35