Oily fish, coffee and walnuts: Dietary treatment for nonalcoholic fatty liver disease

Table 1 Mechanisms of action and potential health benefits of foods

Food	Active components	Metabolic benefits	Hepatic benefits
Oily fish/fish oil	Omega-3 PUFAs (EPA, DHA)	↑ Insulin sensitivity	↓ LFTs
		↑ Adiponectin/PPARγ	↑ Fatty acid oxidation
		↓ Inflammation	↓ Hepatic steatosis
		↓ Serum lipids
		↓ Blood pressure
Coffee	Caffeine	↓ BMI	↓ LFTs
	Diterpenes	↑ Insulin sensitivity	↓ Development of NAFLD
	Polyphenols (chlorogenic acid)	↓ Development of T2DM	↓ Development of HCC
		↓ Development of CVD	↓ Severity of NASH
Nuts	MUFAs and PUFAs	↓ Serum lipids	↓ LFTs
	Vitamin E	↓ Blood pressure	↓ Development of NAFLD
	Phytochemicals (phenolic acid)	↓ Development of T2DM	↓ Oxidative stress
		↓ Cardiovascular mortality
		↓ All cause mortality
Tea	Polyphenols (catechins such as ECGC), Caffeine	↓ BMI	↓ LFTs
	Flavonol glycosides	↑ Insulin sensitivity	↓ Hepatic steatosis
Red wine	Phenols (resveratrol)	↓ Serum lipids	↓ Oxidative stress
		↑ Insulin sensitivity
		↓ Cardiovascular mortality
Avocado	MUFAs and PUFAs	↑ Adiponectin/PPARγ	↓ LFTs
	Phytosterols (β-sitosterol)	↑ Satiety and ↓ Body weight	↓ Oxidative stress
	Phytochemicals (carotene, lutein, phenolics)	↓ Inflammation	↓ Hepatic steatosis
	Fiber	↓ Blood glucose
		↓ Serum lipids
Olive oil	MUFAs (oleic acid)	↓ BMI	↓ LFTs
		↑ Insulin sensitivity	↓ Oxidative stress
		↓ Serum lipids	↓ Hepatic steatosis

BMI: Body mass index; CVD: Cardiovascular disease; DHA: Docosahexaenoic acids; ECGC: Epigallocatechin-3-gallate; EPA: Eicosapentaenoic acid; HCC: Hepatocellular carcinoma; LFT: Liver function test; MUFA: Monounsaturated fatty acid; n-3: Omega-3; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; PPARγ: Peroxisome proliferator-activated receptor gamma; PUFA: Polyunsaturated fatty acid; T2DM: Type 2 diabetes mellitus.

Table 2 Important human studies assessing effect of foods on non-alcoholic fatty liver disease

Food	Ref.	Sample (n)	Study type	Intervention	Duration	Outcomes
Oily Fish/ Fish oil (n-3 PUFAs)	Parker et al[14]	355	Meta-analysis	4 g/d (median); range 0.83-13.7 g/d	6 mo (median); range 8 wk-12 mo	Improvement in liver fat (P < 0.001); AST (P = 0.02)
						Sub-analyses of RCTs only: Significant reduction in liver fat (P < 0.001); No significant improvement in ALT (P = 0.74) or AST (P = 0.28)
Coffee	Molloy et al[50]	306	Cross-sectional	Validated questionnaire for coffee caffeine and total caffeine consumption	Recall	Coffee caffeine intake (but not total caffeine intake) demonstrated negative correlation with fibrosis stage (r = -0.215, P = 0.035) and associated with reduced incidence advanced NASH (F2-4).
				NAFLD cases - liver biopsy
Nuts	Barrera et al[3]	106 17	Longitudinal	Walnut and other nut intake assessed	6 mo	Walnut intake correlated with reduced GGT (r = -0.26), ALT (r = -0.31) and AST (r = -0.21, P < 0.05 for all) at 3 months. At 6 months intake of other nuts was associated with reduced GGT (r = -0.23, P = 0.03), while both walnuts and other nut intake correlated to reduced AST (r = -0.22, P < 0.05)
Tea	Sakata et al[85]		Pilot RCT	Green tea; High catechin (1080 mg) vs standard catechin (200 mg) vs placebo	12 wk	Significant reductions in ALT, body fat percentage and hepatic fat based on CT in high catechin green tea group alone
Avocado	Pahua-Ramos et al[120]	35		Group 1: Control	7 wk	Addition of avocado paste to high cholesterol/fructose diet (HFF) was associated with decreased total cholesterol, LDL, TG, ALT and AST (43.1%, 45.4%, 32.8%, 39.8% and 35.1% respectively; P ≤ 0.05) and improved insulin sensitivity compared to HFF diet alone
				Group 2: ↑ cholesterol diet + 60% Fructose (HHF)
				Group 3: HHF + Avocado
				Group 4: HHF + reduced-calorie avocado paste (P)
				Group 5: HHF + P + fiber		HHF + avocado paste and fiber vs HHF associated with reduced hepatic steatosis and inflammation, reduced total cholesterol, AST, ALT,LDL and glucose levels (P ≤ 0.05 for all)
Olive oil	Nigam et al[133]	93	Randomised controlled parallel study	Olive oil vs canola oil vs control (< 20 g/d) with normal diet and 40-45 min morning walk advised for all groups	6 mo	Weight loss: -6% (olive oil, P < 0.05) 2% (control, NS)
						Histology: significant reduction in steatosis grading (P < 0.05)
						Other: significant reduction in BMI (P < 0.05) and insulin resistance (P < 0.05)

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; CT: Computed tomography; GGT: Gamma-glutamyl transferase; LFT: Liver function test; MUFA: Monounsaturated fatty acid; n-3: Omega-3; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; PUFA: Polyunsaturated fatty acid; RCT: Randomised control trial; TG: Triglycerides.

Table 3 Recommendations

Food	Evidence level (good, moderate, poor)	Dose
Oily fish/fish oil (Omega-3 PUFAs)	Moderate (NAFLD)	≥ 0.83 g/d n-3 or 2 servings of oily fish/wk (3.5 oz/serve)1
	Good (Metabolic disease)	Coronary artery disease (CAD): 1 g/d
		Hypertriglyceridemia: 2-4 g/d
Coffee	Moderate (NAFLD)	≥ 3 cups per day1
	Moderate (Metabolic disease)
Nuts	Moderate (NAFLD)	100 g (handful)/d1
	Good (Metabolic disease)
Tea	Poor (NAFLD)	≥ 5-10 cups per day1
	Poor (Metabolic disease)
Red wine	Poor (NAFLD)	100-200 mL/d1
	Moderate (Metabolic disease)
Avocado	Poor (NAFLD)	1/2 avocado (68 g)/per day1
	Moderate (Metabolic disease)
Olive oil	Poor (NAFLD)	Consumption as part of Mediterranean diet < 20 g/d1
	Moderate (Metabolic disease)

¹Optimal dose not yet defined. NAFLD: Non-alcoholic fatty liver disease; PUFA: Polyunsaturated fatty acid.