# Can Walnut Serve as a Magic Bullet for the Management of Non-Alcoholic Fatty Liver Disease?
## 4 Conclusions and Future Perspectives  
Walnut is one of the most popular nuts globally. It is a common dietary ingredient that is an important component of the Mediterranean diet and Asian diets. Over the past few decades, the health effects of walnut consumption have been extensively investigated as walnut contains a variety of nutrients and bioactive components. Due to the global increase in obesity, hyperlipidemia, T2 DM, and metabolic syndrome, NAFLD has attracted more attention because it is a hepatic manifestation of these unhealthy conditions. Furthermore, because NAFLD can progress to NASH and subsequently result in the development of hepatic fibrosis and hepatocellular carcinoma, the incidence of NAFLD-associated hepatocellular carcinoma is expected to increase, whereas the incidence of hepatitis B and C viruses associate hepatocellular carcinoma is declining after the introduction of antiviral agents effective against these two viruses. However, because there is no specific medicine available for NAFLD, metabolic correction with nutritional intervention could be a major strategy to enable treatment for this condition. Over recent decades, accumulating evidence from a series of clinical and experimental studies has demonstrated that walnut phenolic and lipid extracts, walnut hydrolysate, walnut oil and walnut-enriched diet have consistently demonstrated the health effects on aberrant lipid and/or glucose metabolisms as well as metabolic disorders including NAFLD. We have described here that consumption of walnuts, which are rich in a range of nutrients and bioactive components, can ameliorate aspects of NAFLD pathophysiology such as steatosis, lipotoxicity, steatohepatitis, insulin resistance, down-regulated immunity and gut microbiota dysbiosis, thereby alleviating NAFLD and hopefully preventing its progression towards NASH and fibrosis. Future studies should focus on the molecular mechanisms by which walnuts exert protective effect against NAFLD development, progression to NASH and fibrosis, and ultimately hepatocarcinogens. More evidence is needed to understand the effects of walnut on hepatic stem cells and on the gut microbiota. The effects of walnut on alcoholic liver disease, which is similar in some respects to NAFLD, will also be an interesting subject. NAFLD development is also associated with genetic makeup such as the Patatin-like phospholipase domain-containing 3 (_PNPLA3_) polymorphism [93]; therefore, investigating the interactions between walnut and genes would be helpful to understand the individually different effects of walnut on NAFLD. \begin{table}
\begin{tabular}{c c c} \hline \hline
**NAFLD-Associated Mechanisms** & **Walnut Constituents** \\ \hline Lipid metabolism & Essential fatty acids (\(\alpha\)-linolenic acid and linoleic acid), phytosterols, vegetable protein, fiber \\ \hline One-carbon metabolism & Folate, vitamin B-6, methionine, serine, glycine, glucose, choline \\ \hline Insulin resistance and glucose metabolism & Walnut oil, fiber, magnesium \\ \hline Oxidative stress with lipotoxicity & Polyphenols, \(\gamma\)-tocopherol, melatonin, selenium \\ \hline Inflammation & Walnut phenolic extracts, fiber, \(\alpha\)-linolenic acid, \(\gamma\)-tocopherol \\ \hline Immune function & Walnut oligopeptide, walnut protein \\  & hydrolysate, walnut phenolic extract, \\  & \(\gamma\)-tocopherol, vitamin B-6, copper, zinc, selenium \\ \hline Stemness & Phenolic compounds, walnut lipid extracts, \\  & walnut oil \\ \hline Gut microbiota & Fiber, polyphenol, polysaccharide, \\  & \(\alpha\)-linolenic acid \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Walnut constituents that target the NAFLD-associated pathophysiologic mechanisms.