Over the past 40 years, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. The incidence rate of NAFLD ranges from 13.5% (Africa) to 31.8% (Middle East), with a world average incidence rate of 20%. Obesity, type 2 diabetes mellitus (T2DM) and hyperlipidemia are the major risk factors for NAFLD. Notably, the incidence of NAFLD in obese patients has reached a staggering 80%. In terms of the dangers of NAFLD, although less than 10% of patients will develop liver fibrosis or hepatocellular carcinoma within 10–20 years (1–3), the dangers cannot be ignored given the large number of patients. Moreover, based on the increasing obesity rate in the population and the extremely high incidence rate of NAFLD in the obese population, the economic burden of people on NAFLD increases year by year.

Inflammation, as a response of the body to tissue damage, involves massive recruitment of inflammatory factors and inflammation-associated cells. The pro-inflammatory mediators tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and interleukin-1β (IL-1β) contribute to the recruitment and activation of Kupffer cells, whilst the massive activation of Kupffer cells eventually leads to NAFLD (3). Besides, several studies have shown that specific dietary components are associated with inflammation. A recently published meta-analysis suggested that the Mediterranean diet (MD), as a dietary pattern with low inflammatory potential, significantly reduces the risk of NAFLD compared to other dietary patterns (4). Generally speaking, the MD is characterized by a diet rich in plant foods (vegetables, grains, legumes, fruits, and nuts), moderate amounts of fish and poultry, small amounts of red meat, and foods with a low degree of processing (5, 6). Additionally, high-sugar and high-fat dietary patterns have been shown to cause the body to produce high levels of inflammatory factors which can increase the risk of NAFLD or even exacerbate a patient’s pre-existing liver disease (7, 8).

The dietary inflammation index (DII), a tool to assess the ability of diet to influence inflammatory processes, was first proposed by researchers at the University of South Carolina in 2009 and has been continuously updated and refined since then (9). The revised version of the DII currently in common use is based on literature on inflammation and diet published up to 2010. The DII categorizes an individual’s inflammatory potential from maximally anti-inflammatory to maximally pro-inflammatory based on the potential of the diet. A higher DII indicates higher pro-inflammatory potential and a lower DII indicates higher anti-inflammatory potential. The DII consists of 45 food parameters, including 36 anti-inflammatory foods (fiber, alcohol, monounsaturated fatty acids, polyunsaturated fatty acids, omega 3, omega 6, niacin, thiamin, riboflavin, vitamin B6, zinc, magnesium, selenium, vitamin A, vitamin C, vitamin D, vitamin E, folic acid, beta carotene, anthocyanidins, flavan3ols, flavonols, flavanones, flavones, isoflavones, garlic, ginger, onions, thyme, oregano, saffron, turmeric, rosemary, eugenol, caffeine, and tea) and 9 pro-inflammatory foods (energy, carbohydrates, proteins, total fat, trans fat, cholesterol, vitamin B12, saturated fatty acids and iron) (9, 10). This meta-analysis is based on the results of published studies that aims at investigating the association between the DII and the risk of NAFLD.

The study complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (11) and is registered on PROSPERO (CRD42023455013).

To our knowledge, there has been no previous meta-analysis of the relationship between DII and NAFLD been published so far. Our meta-analysis found a possible correlation between the risk of DII and NAFLD based on relevant cohort studies. The results suggested that people exposed to higher levels of DII may have a higher risk of NAFLD (OR = 1.26, 95%CI 1.12 to 1.40, p < 0.001). Correspondingly, the lower the exposure to DII, the lower the risk of NAFLD in the population.

Previous studies have shown that diet could affect NAFLD indirectly or directly by causing changes in inflammation in the body in various ways.

Pro-inflammatory diets, such as high-fat diets, can lead to the accumulation of ectopic lipids that cause the recruitment of macrophages (M1) and pro-inflammatory cytokines. It also activates inflammatory pathways in the brain by activating M1 macrophages and upregulating circulating pro-inflammatory cytokines (28). In conclusion, high-fat diets can cause oxidative stress in the body by activating a large number of signaling pathways. The level of inflammatory response in the body can have a direct impact on liver health. Pro-inflammatory diets may genetically interfere with hepatic β-oxidation, resulting in a massive upregulation of pro-inflammatory molecules (e.g., IL-1β, IL-17, and IL-18) and oxygen-responsive substances, which in turn increases the production of endogenous lipids and increases the risk of NAFLD, as well as exacerbating the damage related to chronic disease (1, 29, 30).

Anti-inflammatory diets, such as those rich in vegetables and fruits, are thought to be effective in preventing and ameliorating NAFLD (31). It contains flavonoids, α-tocopherol (vitamin E) and vitamin C which act as antioxidants to reduce oxidative stress in the body (32). The results of a randomized double-blind placebo-controlled trial showed that α-tocopherol (vitamin E) and vitamin C are excellent and potent antioxidants with anti-inflammatory properties (33). In addition, flavonoids have been reported extensively to be potent antioxidants in the prevention of NAFLD (34, 35). Their protective nature is attributed to their ability to accelerate the oxidation of fatty acids in the liver, enhance the antioxidant capacity of the cells and inhibit the production of nuclear factor-κ B, which in turn attenuates the release of inflammatory cytokines (36). As a result, it can reduce the risk of NAFLD through the mechanisms described above.

In addition, diet plays a crucial role in the regulation of inflammation levels in the body by influencing the maintenance of a balance of gut flora in the gut (37). Plant-based dietary patterns that have a lower potential to stimulate inflammation have been associated with the production of short-chain fatty acids (SCFA), a byproduct of gut flora, which have anti-inflammatory capacity. SCFA can affect energy metabolism and immunity by mediated via binding to G-protein coupled receptors expressed in the immune system and endocrine cells of the gut. In this way, SCFA can reduce the level of inflammation in the body (1, 38). Conversely pathogen-associated molecular proteins (PAMPs), products of intestinal microbes, also can increase inflammation levels in the liver. Recent studies in mice have shown that PAMPs, as a danger-associated molecular pattern (DAMPs), activate the hepatocyte inflammasome (a multiprotein cytoplasmic complex) in hepatocytes. Activation of inflammasomes in hepatocytes may be important for hepatocytes to cause initial stress, which subsequently leads to hepatocyte death and fibrosis (39–41).

Diets can also modulate inflammation levels through metabolic syndrome (MetS), including obesity and diabetes (42), which can lead to further development of NAFLD. A cross-sectional study of middle-aged and older adults found that higher DII was associated with a higher risk of MetS (43). Therefore, we guess that a high DII dietary pattern may indirectly increase the risk of NAFLD by increasing the risk of MetS.

In the case of obesity, for example, the state of obesity is often considered to be a causative factor of inflammation in the body (44), but there is growing evidence that inflammation can also contribute to the development of obesity (45). A longitudinal study of the MD showed that the higher the DII score in the exposed population, the progressively higher the incidence rate of overweight and obesity (46). Thus, pro-inflammatory diets trigger obesity by raising inflammation levels in the body. Obesity is an important risk factor for NAFLD. Hepatocytes in obese patients are exposed to high lipid and carbohydrate levels, leading to hepatic dysfunction and liver injury through dual processes of lipotoxicity and glucotoxicity (7, 30, 47).

Other MetS (including hypertension, hyperuric acid, and hyperlipidemia) have a bi-directional relationship with NAFLD, and these disorders can not only increase the risk of NAFLD but also increase some features and complications of these disorders (29, 48).

The genetic and environmental factors are known to influence the onset and development of NAFLD in individuals (49). A meta-analysis showed that the risk of NAFLD was lower in the black population and higher in the Hispanic population (50). In this regard, we analyzed subgroups of the population from different regions. However, our results were not statistically significant (Europe: OR = 2.37, 95%CI 0.47 to 11.94; Iran: OR = 2.25, 95%CI 0.92 to 5.49; US: OR = 1.19, 95%CI 0.94 to 1.49). This may be due to insufficient data on the subgroups in the included studies and the possibility that the same area contains multiple races.

Data from previous studies have shown that men have a significantly higher risk of developing NAFLD than women (51), and our results of subgroup analysis are consistent with these results (OR = 1.11, 95%CI 1.00 to 1.24). It suggests that gender is also an influential factor in NAFLD development. Estrogen may be a major contributor to the above phenomenon. A prospective study in Italy included 5,408 women with hysterectomies who were randomly assigned to tamoxifen (an estrogen inhibitor) or placebo. The results showed that tamoxifen was associated with an increased risk of NAFLD, especially in obese women (52). Additionally, we found that a pro-inflammatory diet increased the risk of NAFLD in the female population (OR = 1.26, 95%CI 1.08 to 1.47). This may be related to the fact that pro-inflammatory diets are associated with the modulation of inflammation levels in the body. A cross-sectional study of adult women in the United States found that a pro-inflammatory diet led to a decrease in sex hormone binding globulin (SHBG) (53). It has also been suggested that pro-inflammatory diets may be associated with decreased testosterone and estradiol levels in adolescent males (54). However, our findings were not statistically significant in the male population (OR = 2.64, 95%CI 0.66 to 10.56), which may be related to the paucity of relevant studies. More well-designed clinical trials are still needed to validate this aspect.

Our subgroup results suggest that pro-inflammatory diets increase the risk of NAFLD in chronic smokers (OR = 1.20, 95%CI 1.05 to 1.37). During smoking, nicotine accumulates in large quantities in gastric juices and saliva, producing pathogenic effects (55). On the one hand, cytotoxic chemicals produced by smoking may accelerate the growth and proliferation of fibroblasts, leading to the formation of scar tissue (56). On the other hand, smoking may also induce a massive recruitment of pro-inflammatory factors (IL-1, IL-6, and TNF-α) involved in hepatocyte injury (57). In addition, nicotine strongly stimulates hepatic injury and hepatic fibrosis by activating the nicotinic acetylcholine receptor (nAChR) in the liver (58). Smoking can increase the risk of NAFLD through multiple pathways along with pro-inflammatory diets.

Because of the high degree of heterogeneity among the included studies, for this, we performed subgroup analyses. Based on the results of the subgroups, we speculate that the different percentages of smoking, hypertension, and female characteristics in the included study populations may contribute to the potential heterogeneity. In addition, the different ethnicity and dietary habits of the sources of the included study population are also an important cause of heterogeneity. Finally, the differences in study design could also be an objective reason for the high degree of heterogeneity.

This study systematically explored the relationship between DII and NAFLD with some subgroup analysis. Meanwhile, our meta-analysis proves that the inflammatory potential of the diet might positively correlate with the risk of NAFLD. Additionally, the results of this meta-analysis can be used in clinical practice and public health interventions that aim to reduce the risk of NAFLD. Finally, our review may provide some reference for future clinical and basic trials on the relevant topics. There are also some limitations in this study. Due to the small sample size, more subgroup analysis could not be performed or the results were inaccurate. At the same time, the small number of studies included and the presence of a high degree of heterogeneity in this meta-analysis may affect the credibility of the results. Well-designed, larger clinical trials are required to prove this point.

In conclusion, the results of our meta-analysis suggest an association between DII and the risk of NAFLD. The more pro-inflammatory the diet, the higher the risk of NAFLD; conversely, the more anti-inflammatory the diet, the lower the risk of NAFLD. Therefore, promoting foods low in DII could help reduce the risk of NAFLD in the population. In addition, more and further well-designed, large, multicenter clinical studies are needed to confirm the correlation between DII and NAFLD.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

XZ: Conceptualization, Data curation, Formal analysis, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. JR: Data curation, Formal analysis, Resources, Software, Supervision, Validation, Writing – original draft, Writing – review & editing. YH: Data curation, Formal analysis, Resources, Software, Writing – original draft, Writing – review & editing. AX: Resources, Software, Supervision, Writing – original draft, Writing – review & editing. YF: Data curation, Supervision, Writing – original draft, Writing – review & editing. QZ: Conceptualization, Data curation, Writing – original draft, Writing – review & editing. LG: Formal analysis, Investigation, Writing – original draft, Writing – review & editing. XL: Formal analysis, Investigation, Methodology, Project administration, Resources, Writing – original draft, Writing – review & editing.