TABLE 2.

Proposed mechanisms for nutrients, foods and dietary patterns in NAFLD¹

Dietary components	Association with NAFLD risk	Mechanism of dietary characteristic	Mechanism in NAFLD
Traditional Mediterranean dietary pattern2	⇓ Possibly reduces risk and/or disease severity (9, 26–28, 40)	Plant-based diet, mainly vegetables, fruit, and legumes, which are high in antioxidants and anti-inflammatory (58). Legumes have been specifically identified as the most predictive dietary component for longevity (59).	Carotenoids, folic acid, and fiber, may play a fundamental role in the prevention of oxidative stress (60). Vegetables provide an important source of phytosterols, which have been associated with reductions in serum cholesterol concentrations and cardiovascular risk (61).
Dietary fiber	⇓ Possibly reduces risk and/or disease severity (35, 49, 50)	Foods which are unrefined, naturally high fiber may stimulate gut microbiota, leading to increased production of SCFAs, phytochemical composition (vitamins, phenolic acids, betaine) (62).	Increased whole grain, vegetable, legume, and fruit consumption has been shown to reduce the risk of type 2 diabetes mellitus, CVD, and all-cause mortality, and significantly lower concentrations of fasting glucose and total and LDL cholesterol (51, 53). Reduced coronary heart disease rates are associated with increased legume consumption, specifically high plant-based diets providing high antioxidants; vegetables and fruits are the main source of phenolic compounds, and whole grains are an important source of cereal fiber, vitamins, minerals, lignans, and other phytochemicals (54). Animal models demonstrate a possible protective effect of prebiotic fibers, which may modulate the human microbiome to improve health outcomes in individuals with NAFLD (63).
Long-chain ω-3 FAs	⇓ Possibly reduces risk and/or disease severity (35–37, 46, 47)	ω-3 Foods, especially from marine sources, have vascular and anti-inflammatory properties that likely attenuate the oxidative stress that leads to liver apoptosis (64).	Increased ω-6 FAs may increase production of proinflammatory arachidonic acid-derived eicosanoids, impairing the regulation of hepatic and adipose function, which leads to an increased risk of NAFLD (64, 65).
Monounsaturated fats, e.g., olive oil	⇓ Possibly reduces risk and/or disease severity (27, 48)	Olive oil, especially extra virgin olive oil which contains higher amounts of oleic acid, is high in antioxidant phytochemicals. These are likely to attenuate the oxidative stress that leads to liver apoptosis (66).	MUFAs decrease blood triglycerides by increasing fatty acid oxidation through activation of PPARα or by reducing the activation of SREBP and inhibiting lipogenesis (67). Dietary MUFAs activate PPARα and PPARγ, which increase lipid oxidation and decrease insulin resistance, leading to a reduction in hepatic steatosis (67).
			Oleic acid has been shown to elicit a reduction in LDL cholesterol and TG concentrations without associated reductions in HDL (66, 68).
Saturated fat	⇑ Possibly increases risk and/or disease severity (69–71)	Fatty and processed meats, butter, and commercial bakery goods are high in saturated FAs and pose inflammatory and insulin-antagonizing effects, which contribute to the development of MetS.	SFAs induce endoplasmic reticulum stress and cell death in liver cells (72). Mechanisms responsible include: accumulation of diacylglycerol and ceramide; activation of NF-κB, protein kinase C-θ, and mitogen-activated protein kinases, and thus induction of inflammatory genes in white adipose tissue, immune cells, and myotubes; decreased activation of PPARγ coactivator-1 α/β and production of adiponectin, leading to decreased oxidation of glucose and FAs; and accumulation of immune cells such as macrophages, neutrophils, and bone marrow-derived dendritic cells to white adipose tissue and muscle (73).
Fructose	⇑ Possibly increases risk and/or disease severity (30, 32–34, 45)	Processed foods, especially soft drinks, promote liver fat accumulation through de-novo lipogenesis of fructose in the liver (74).	Liver fat accumulation may be attributed in part to excess dietary sugar consumption, especially from fructose, which increases the levels of enzymes involved in hepatic de-novo lipogenesis, which is already enhanced in individuals with NAFLD (75, 76).

¹CVD, cardiovascular disease; MetS, metabolic syndrome; NAFLD, nonalcoholic fatty liver disease; SREBP, sterol regulatory element binding protein.

²Mechanisms listed for all other dietary components are also applicable to the Mediterranean dietary pattern which encompasses these components.