Coffee and NAFLD: Brewing Evidence for Hepatoprotection?

Relationship Between Coffee Consumption and NAFLD in Community Studies

Four continuous cycles of the National Health and Nutrition Examination Surveys (NHANES, USA 2001–2008) were used to investigate the effects of dietary behavior in NAFLD patients. Dietary intake was evaluated by questionnaires that included nutrition components. Multivariate analyses were conducted of variables that included demographics, clinical parameters, and nutritional components in relation to presence of NAFLD (defined in this study by elevated aminotransferase, without ultrasonography). Five factors were independently associated with NAFLD: African American race, male gender, obesity, caffeine intake, as well as plain water consumption. These findings show a strong association between coffee consumption and protection against the development of NAFLD^[24] (see Table 1). The limitation of the NHANES data analysis is the restricted define of NAFLD; cases with cirrhosis may not have shown elevated ALT.

In an Italian study, 137 NAFLD cases and 108 controls were enrolled, and coffee intake determined by the absolute number of cups of coffee consumed. This was graded as 1 (0 cups of coffee/day), 2 (1–2 cups of coffee/day), and 3 (≥ 3 cups of coffee/day). Insulin resistance was analyzed by homoeostasis model assessment-insulin resistance (HOMA-IR) index. When compared with non-coffee drinkers, those who consumed coffee had less severe fatty liver evaluated by ultrasound "bright liver score" (BLS). Further, obesity, insulin resistance, lower high-density lipoprotein (HDL) cholesterol, older age, and arterial hypertension were associated with a greater risk of more severe grades of BLS, while coffee intake was associated with a lower risk of severe BLS. By multiple regression analysis, coffee use was inversely associated with the degree of "bright liver," while insulin resistance and obesity were directly associated with increased likelihood and severity of BLS on ultrasound.^[25] A case–control study from Mexico also found similar protective effects of coffee consumption against NAFLD as assessed by ultrasonography^[26] (Table 1). The limitations of these studies are the insensitivity of ultrasound for minor grade of steatosis and possibly for established cirrhosis when steatosis may be resolved.

The association of caffeine consumption with both the prevalence and severity of NAFLD was further established in another study where a validated questionnaire of caffeine consumption was utilized to determine if there was a relationship between caffeine intake and NAFLD severity, this time established by histological examination of liver biopsies. In this study, the authors reported a strong inverse relationship between caffeine consumption and hepatic fibrosis^[27] (Table 1).

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