To the best of our knowledge, this is the first study to comprehensively examine the links between OBS and all-cause mortality risk among NAFLD patients, utilizing nationally representative data. Our findings demonstrated that higher total/dietary OBS were associated with a lower risk of all-cause mortality in NAFLD patients. Furthermore, subgroup analysis indicated that this negative correlation was stronger in individuals who were obese, physically inactive, and had high levels of alcohol consumption and smoking.
NAFLD is emerging as a significant global health concern, paralleling the rise in obesity and metabolic syndrome[30]. The pathogenesis of NAFLD is multifaceted, involving insulin resistance, lipid metabolism dysregulation, inflammation, and others. Among these, oxidative stress is recognized as a pivotal mechanism, exacerbating liver damage and disease progression. Oxidative stress arises from an imbalance between reactive oxygen species production and antioxidant defense mechanism[31]. Excess ROS can lead to peroxidation of macromolecules, such as lipids and proteins, which are essential components of cell membranes and cellular function. These oxidative modifications may initiate and worsen liver injury, leading to the development of the disease from steatosis to steatohepatitis and potentially to hepatocellular carcinoma[32]. Additionally, a growing body of evidence emphasizes the pivotal role of oxidative stress in progressing from hepatic steatosis to steatohepatitis and ultimately to the more severe condition of hepatocellular carcinoma[33]. Therefore, recognizing the state of oxidative stress throughout the body is important for the prognosis of NAFLD.
Most previous studies have explored the potential relationship between exposure to single or multiple antioxidants (i.e., vitamin E) and the improvement in NAFLD disease, while scant attention paid to the relationship between overall oxidative homeostasis and the prognosis of NAFLD. However, our findings largely align with those of previous research. For example, a preliminary study has found that vitamin C and E therapy can diminish the levels of inflammatory markers (C-reactive protein, CRP), and improve liver histology in NASH patients[34]. Additionally, vitamin E supplementation has been shown to significantly improve histological outcomes for these patients[11]. Research also indicates a stable link between carotenoid intake and NAFLD. In a study that examined the correlation between NAFLD and serum carotenoid levels, it was found that serum β-carotene levels decreased in parallel with increased hepatic fat accumulation[35]. Moreover, prior randomized controlled trials have reported that a diet high in protein and low in calories, when enhanced with β-cryptoxanthin, is more effective at reducing biomarkers associated with oxidative stress in patients with NAFLD than a conventional low-calorie diet[36]. Research also has identified that micronutrients may contribute to the progression of NAFLD. Research has shown that elevated iron stores are linked to increased insulin resistance and a higher risk of NAFLD[37]. Moreover, supplementation with selenium and zinc has been shown to contribute to the amelioration of oxidative stress in individuals with NAFLD[38, 39].
The development of NAFLD may also influenced by lifestyle factors. Previous studies have found that physical activity emerges as a crucial protective measure, enhancing liver function and insulin sensitivity independent of weight change[40]. Similarly, studies have reported that moderate exercise causes a significant increase in blood antioxidant enzyme activity[41], such as superoxide dismutase, which can reduce the level of oxidative stress. Furthermore, clinical guidelines by the American Gastroenterological Association also recommend that enhanced physical activity, a hypocaloric diet, and body weight management might be effective strategies for reducing hepatic steatosis[42].
The OBS is a method for evaluating the overall oxidative status of the body by measuring various dietary and lifestyle pro-oxidants and antioxidants[43]. Although the OBS was limited to exogenous exposures, some studies have shown statistically significant correlations between the OBS and oxidative stress and inflammatory biomarkers (e.g., F2-isoprostanes, FIP) [44]. Similarly, several studies have reported that certain components of the OBS (e.g., beta-carotene intake) can influence the oxidative stress states[45]. These findings demonstrate the validity of the OBS in assessing oxidative homeostasis.
It is plausible that an anti-oxidant diet and lifestyle may improve oxidative stress in NAFLD by scavenging ROS from the body. Several previous literatures have reported that antioxidant vitamins, such as vitamins C and carotenoids, can scavenge ROS in the body and prevent lipid peroxidation[46]. Nevertheless, additional studies found that the oxidative stress level is influenced not just by the balance between antioxidants and pro-oxidants, but also affected by gender differences. Studies have found that, typically, women exhibit lower levels of oxidative stress and reactive oxygen species production compared to men, which could be linked to the roles of specific hormones and enzymes [47, 48]. It has also been shown that estrogen levels affect oxidative stress states[49]. For our study, we found that OBS was associated with mortality from any causes in female NAFLD patients not found in males. The mechanism of this remains unclear. Consequently, the implications of oxidative stress on the prognosis of NAFLD should be further investigated based on gender differences.
Strengths
Our study has the following strengths. First, the NHANES database provides detailed individual health, dietary, lifestyle, and biomarker data. In evaluating OBS, we used comprehensive and detailed dietary intake data for precise calculations. Second, as an interannual national survey program, NHANES includes individuals of different races, ages, genders, and socioeconomic statuses. This diversity ensures that the findings can be generalized to a broader population. Third, this study incorporates information on multiple aspects of participants' health status, lifestyle, and dietary habits, and conducts a multidimensional research analysis that contributes to a deeper understanding of the factors associated with health and disease.
Limitations
The current study also presents certain constraints. First, the calculation of OBS was based on data from two dietary interviews that could not reflect the long-term status of oxidative stress. Second, much of the data in NHANES, including dietary and lifestyle factors, are based on participants' self-reports, this may introduce recall bias and social desirability bias. Third, we used non-invasive parameters to diagnose NAFLD, this may be different from that of traditional liver biopsy or magnetic resonance imaging (MRI). In addition, the influence of medication intake on the results for patients with NAFLD was not eliminated, the use of anti-inflammatory drugs, antipsychotic drugs, and other factors may affect these indicators that were not available and were not taken into account.