# Can Walnut Serve as a Magic Bullet for the Management of Non-Alcoholic Fatty Liver Disease?
## 3 Results and Discussion
### Mechanisms by Which Walnut Contributes to the Management of NAFLD  
#### 3.2.1 Effects of Walnut on Metabolism  
Lipid Metabolism  
Walnut has a unique fatty acid composition; it is rich in linoleic acid as well as other compounds such as phytosterols, vegetable protein, and fiber, thereby having a positive effect on dyslipidemia (Table 2). A meta-analysis demonstrated that walnut-enriched diets can significantly reduce the blood levels of total cholesterol, low-density lipoprotein cholesterol, triglyceride, and apolipoprotein B compared with those of the control groups. More significant reductions in blood lipids were found upon comparing American and Western diet groups. Furthermore, adding walnut--which has 654.4 calories per 100 g--to diet did not induce body weight gain [58]. An early animal study using Zucker rats demonstrated that dietary lipids from walnut oil can reduce hepatic steatosis by decreasing the hepatic triglyceride level [59]. Another animal study using C57 BL/6] mice demonstrated that walnut protected the liver from high-fat diet-induced hepatic triglyceride accumulation by modulating the levels of sirutin 1 (Sirtl), 5\({}^{\prime}\) adenosine monophosphate-activated protein kinase (AMPK), and FAS cell surface death receptor (FAS). This resulted in hepatic lipid homeostasis, suppression of adipose tissue inflammation and macrophage migration, and prevention of adipocyte apoptosis via a reduction in the levels of phosphorylated c-JNK (p-JNK) and phosphorylated p38 mitogen-activated protein kinases (p-p38K) [60]. A large prospective study combined with the Nurses' Health Study and the Health Professionals Follow-up Study showed that individuals consuming one serving of nuts at least five times per week had a 14% lower risk of cardiovascular disease and a 20% lower coronary artery disease compared with those of individuals with lowest nut consumption. Interestingly, walnut consumption (one or more times/week) was more strongly associated with a lower risk of total cardiovascular disease and coronary artery disease compared with the risk associated with consumption of other nuts [61]. Evidence also indicated that walnuts are also useful for the prevention of T2 DM. A Nurses' Health Study revealed a protective effect of walnut consumption on the development of T2 DM [62]. The National Health and Nutrition Examination Survey data demonstrated that walnut consumers were at a lower risk of developing T2 DM than non-nut consumers and also had lower levels of fasting blood glucose and hemoglobin A1c (HbA1c), which reflects the average blood glucose levels for the last two to three months [63]. In a randomized, double-blind, placebo-controlled clinical trial, the addition of walnut oil into the daily diet of T2 DM patients improved the lipid profiles. Consumption of walnut oil significantly decreased the blood levels of total cholesterol, low-density lipoprotein, and triglyceride compared with their levels in the control group [64]. Collectively, walnut helps maintaining healthy cholesterol and triglyceride levels. Currently, there is no direct evidence from human studies regarding the effect of walnut on the lipid profile of NAFLD patients, and only animal study data are available (Table 3). However, walnut, which can improve the lipid profile--in human--and reduce the risk of cardiovascular disease and correct dyslipidemia in diabetes mellitus, may provide beneficial effects for NAFLD patients by correcting dyslipidemia and thereby reducing steatosis. One-carbon metabolism is interrelated metabolic pathways that produce purines and thymidylate through the nucleotide synthesis pathway, S-adenosylmethionine through the transmethylation pathway and demethylation pathway, and glutathione and taurine through the transsulfuration pathway. One-carbon metabolism also metabolizes toxic homocysteine through demethylation pathway and transsulfuration pathway.