Oxidative stress (OS) is a condition that occurs when there is an imbalance between the production of free radicals and defense of antioxidants, resulting in excessive accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) (Niki, 2018). It is reported that OS plays an important role in initiating and mediating chronic non-communicable pathophysiology diseases, such as cardiovascular disease (CVD), hypertension, and type 2 diabetes (Stanner et al., 2004). The presence of OS can alter protein structure and hinder enzymes such as the endothelial nitric oxide synthase (eNOs), thereby resulting in dysfunction and inability of the endothelium to release and respond to vasodilators (Cathcart, 2004; Yokoyama, 2004; Antelava et al., 2005). Although the pathophysiology of CVD is extremely complex and multifactorial, local injury to, or dysfunction of, endothelial cells appear to be an important factor in the initiation of atherosclerosis (Dokken, 2008). Besides, the mitochondrial respiratory chain, NADPH oxidase, an uncoupled endothelial nitric oxide (NO) synthase, and xanthine oxidase also produce ROS that causes elevated levels of OS in the vascular system of people with high risk factors (Griendling et al., 2021). An increased formation of ROS from all layers of the vascular wall may alter the vascular function and contribute to the development and progression of CVD (Cersosimo and DeFronzo, 2006). OS may be the earliest biological event in chronic CVD pathological cascade and is responsible for triggering all other pathologies, indicating that reducing OS may be a viable approach in disease treatment.

OS process is affected by environment, lifestyle, and diet. Cigarettes, ionizing radiation, environment pollution, medicine, iron, saturated fatty acid, and other prooxidants all boost the OS process. Fitting exercise and antioxidants, which include vitamin C, vitamin E, vitamin A, carotenoids, and selenium, all reduce the OS degree (Valko et al., 2007). Notably, although lab work has demonstrated that antioxidants can slowdown the progression of hypertension, further clinical evidence is still required (Pietta, 2000; Padayatty et al., 2003; Stahl and Sies, 2003), and clinical trials have failed to find any benefit of antioxidant supplements in hypertension treatment (Heart Protection Study Collaborative Group, 2002; Rodrigo et al., 2013) or cardiovascular disease prevention (Yusuf et al., 2000; Cortés-Jofré et al., 2020). Such an inconsistency between lab and clinical research implies that the impact of the body’s oxidative status on the cardiovascular system is complex and not exclusively determined by antioxidant factors. In fact, the body’s oxidative status is the result of interactions among multiple pro-/antioxidant factors. Therefore, studies on OS-related pathophysiology should combine information of both pro- and antioxidant factors, rather than a single factor. The oxidative balance score (OBS) is an approach that evaluates the overall oxidative status in the body via the combined status of pro- and antioxidants (Van Hoydonck et al., 2002). Previous studies have used 12–14 pro- and antioxidant factors related to nutrients, lifestyle, body composition, and medical history for OBS calculation, with antioxidants contributing positively to the value and prooxidants contributing negatively to the value (Kong et al., 2015; Noruzi et al., 2021). The higher OBS has been associated with a lower risk of various non-communicable diseases and adverse outcomes, such as hypertension (Annor et al., 2015), colorectal adenoma (Dash et al., 2013), prostate cancer (Lakkur et al., 2014), chronic kidney disease, and all-cause mortality (Ilori et al., 2015; Kong et al., 2015). In the development of these disease conditions, OS-induced endothelial dysfunction, which is usually estimated by flow-mediated dilation (FMD) of the brachial artery (Thijssen et al., 2019; Lv et al., 2020), is one of the earliest signs. Such endothelial dysfunction might be affected by serum 8-iso-prostaglandin F2α (FIP), a specific sensitive indicator of OS that is involved in the pathophysiological changes of atherosclerosis (Mueller et al., 2004; Lepara et al., 2020). FMD of the brachial artery is a widely used parameter in evaluating the vascular endothelial function (Thijssen et al., 2011) and independently predicting the risk of cardiovascular diseases (Donato et al., 2018). Notably, although pro- and antioxidant factors are associated with endothelial dysfunction risk, the relationship between the holistic effect of these factors (evaluated by the OBS) and vascular endothelial function has not been reported. Additionally, associations between the OBS subgroups (such as the lifestyle- and diet-related OBS) and vascular endothelial functions are also informative in understanding how our living habits are associated with vascular endothelial conditions from the OS aspect.

Therefore, the present study calculated the OBS based on lifestyle- and diet-related pro- and antioxidant factors to investigate the OBS association with vascular endothelial function. Moreover, associations between the OBS components and endothelial function were analyzed to identify potential factors for vascular endothelial dysfunction prevention.

The current study calculated the OBS based on 16 pro- and antioxidant factors to evaluate the influence of the ROS on the oxidative status in Chinese community dwellers. FIP was measured to estimate the OS level, and FMD was measured to evaluate the endothelial function. Our analyses showed that lower overall OBS and dietary OBS were associated with higher OS levels (i.e., a higher FIP value) and worse endothelial functions (i.e., a lower FMD value). Analyses on the OBS components showed that dietary and lifestyle pro- and antioxidant factors were associated with OS. Meanwhile, four dietary antioxidants (α-carotene, zeaxanthin, α-tocopherol, and γ-Toc) were associated with the endothelial function.

Recent studies have indicated that endothelial dysfunction may predict long-term atherosclerotic disease progression and cardiovascular event occurrence (El Assar et al., 2013). Although the mechanisms underlying endothelial dysfunction are multifactorial, cumulative evidence suggest that OS can directly affect the vascular function and tone by oxidative modification of proteins or nucleic acids. A major mechanism for the impact of OS on vascular tone is the decrease of NO bioavailability and/or signaling, leading to endothelial dysfunction. Additionally, excessive ROS may also promote vascular cell proliferation and migration, inflammation, and apoptosis, as well as extracellular matrix alterations (Schulz et al., 2011). Therefore, OS is a major cause of endothelial dysfunction (Incalza et al., 2018). The OBS has become a popular tool in evaluating the global OS status with diseases. Lower OBSs are associated with higher OS status and increased risk of hypertension (Annor et al., 2015), prostate cancer, and colon cancer (Kong et al., 2014). The current study extended the association between the OBS and OS by showing that the OBS was reversely associated with the OS status (reflected by serum FIP) in Chinese community dwellers. FIP is commonly used to evaluate lipid oxidative damage (Gào et al., 2018). FIP is a member of the F2-isoprostane family, which includes prostaglandin-like compounds produced by non-enzymatic peroxidation of arachidonic acid (Nourooz-Zadeh, 2008). Multiple studies have shown that FIP is a reliable marker of oxidative stress in vivo (Morrow, 2005; Milne et al., 2007). Considering the convenience of collecting data for the OBS, this parameter might be a potential surrogate of FIP for evaluating the OS status.

The OBS components are mainly derived from diet and lifestyle, where the former are nutrients while the latter are lifestyle-related factors, such as smoking, alcohol consumption, physical activity, and the use of medicine. To explore the impact of diet and lifestyle on endothelial function, the corresponding OBS was analyzed separately. The results have shown that the dietary OBS, rather than the lifestyle OBS, is significantly associated with endothelial function, indicating that nutrients might play a more important role than lifestyle in regulating endothelial function. Notably, four dietary antioxidants (α-carotene, zeaxanthin, α-tocopherol, and γ-Toc) have shown significant differences between high and low endothelial function groups. Such results are consistent with previous research on the supplementation of antioxidants and diseases (Ehara et al., 2001; Van Beelen et al., 2006) in which some pro- or antioxidants alone have no direct relationship with the occurrence and development of diseases. Meanwhile, a previous study found that the lifestyle OBS was more significantly associated with adenoma incidence than the dietary OBS, and the physical activity level in lifestyle was more important for colorectal adenoma than components in dietary (Kong et al., 2014). Such inconsistent findings of the dietary OBS and lifestyle OBS in previous disease studies have indicated that the importance of diet- and lifestyle-related OS might vary with diseases.

In this cross-sectional study, we examined the associations between FIP and the different types of OBSs and found that the dietary OBS had a strong, statistically significant inverse association with FIP, but the lifestyle OBS had no such association with FIP. In the analysis of the associations between the FIP and OBS components, we observed that all components showed significant differences between low FIP and high FIP groups except BMI and low physical activity. Such results are within our expectation since antioxidants can lower the body’s oxidative status and prooxidants exert the opposite effect. We also found a discrepant result that the proportions of aspirin use in the high FIP group were significantly higher than those in the low FIP group despite that the use of these medicines should have been in favor of lowering FIP. A possible explanation might be the bias of medicinal usage among participants. Specifically, people begin taking aspirin only after the onset of hypertension, hyperlipidemia, and other cardiovascular and cerebrovascular diseases that are closely related to the oxidative status. Consequently, people with comparatively high oxidative status tend to use aspirin, while others with a lower oxidative status do not take these medicines actively.

One of the strengths of this study is that the micronutrient levels were measured from samples instead of being estimated by food frequency questionnaire. Therefore, our OBS calculation on diet-related pro- and antioxidants is quite accurate. Separate analyses of the dietary OBS and lifestyle OBS is another novelty, which helped clarify the aspect of OBS that contributes more to endothelial function. Furthermore, the analyses of their associations with OS and vascular endothelial function helped explore the main factors influencing the vascular endothelial function to identify and propose preventive measures. The limitation of this study is that it is a cross-sectional and of limited sample size. Therefore, the current research conclusion should be treated with caution. In addition, the study population is limited to Chinese community dwellers, and some aspects of their lifestyle are less diverse, therefore it is unclear if these findings can be generalized to other populations. The OBS was limited to dietary/lifestyle exposures and failed to include endogenous enzymatic mechanisms (e.g., superoxide dismutase, glutathione peroxidase, and catalase), which might also affect the oxidative balance by clearing free radicals and reducing OS (Valko et al., 2016; Kattoor et al., 2017).

In conclusion, this study analyzed the association between the oxidative balance score and vascular endothelial function. The overall oxidative balance score reflects the body’s oxidative stress status and was found negatively associated with endothelial function. The dietary-related oxidative balance score was more closely associated with vascular endothelial function when compared with the lifestyle-related one.