Sarcopenia, a disorder related to the progressive loss of muscle mass and function, has adverse effects on falls, functional decline, frailty, and mortality (1). Recently, sarcopenia has been found in the younger population, despite its general association with advanced aging (2, 3). Globally, the number of patients with sarcopenia is expected to increase from 50 to 200 million over the next 40 years (4). Among the population aged < 60 years, the incidence of sarcopenia ranges between 8% and 36% (5). Healthcare costs can be substantially increased due to sarcopenia (6). For sarcopenia patients aged < 65 years, hospitalization costs increase even further than they do for those aged >65 years (7).

Sarcopenia can be classified into two types: primary and secondary. With aging, the aggravation of muscle fiber loss, neurodegeneration, and dysfunctional proteins in the skeletal muscles contribute to primary sarcopenia (8). Several factors can contribute to secondary sarcopenia—including insulin resistance, inactivity, poor nutrition, neuromuscular diseases, and hormonal imbalances (9). The histopathological characteristics of the two types of sarcopenia are similar, such as muscle fiber replacement by adipose tissue, increased fibrosis, oxidative stress, altered muscle metabolism, and neuromuscular junction degeneration (10). Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS), also known as free radicals, and the antioxidant defense system (11). ROS accumulation in sarcopenia occurs as a result of mitochondrial dysfunction. This accumulation can affect the function of myofibrils, motor neurons, and the sarcoplasmic reticulum—thus hindering muscle regeneration (12, 13). Therefore, a potential therapy for sarcopenia patients is to reduce ROS levels via antioxidant treatment. This treatment can include increasing dietary antioxidant intake, increasing physical activity, avoiding obesity, and avoiding tobacco smoking.

However, a single factor is unlikely to have a significant impact on the overall antioxidant/oxidative system. To evaluate the roles of multiple diets and lifestyles on the overall oxidative/antioxidant system, the Oxidative Balance Score (OBS) has been developed to measure one's general exposure to oxidants and antioxidants (14). Studies have demonstrated that a higher OBS reflects increased protection against a range of diseases—including kidney disease (15), diabetes (16), non-alcoholic fatty liver disease (17), and even depression (18). However, few studies in the literature have reviewed the correlation between sarcopenia and OBS. Therefore, this study aimed to assess the association between OBS and sarcopenia among young and middle-aged adults in the United States, using National Health and Nutrition Examination Survey (NHANES) data, for aiding the development of new preventive interventions for the condition.

Using data from NHANES 2011–2018, we conducted a cross-sectional study to clarify the negative association between OBS and the risk of sarcopenia, demonstrating that a higher OBS may be associated with a lower risk of sarcopenia. Despite adjusting for possible confounders, this association remained significant for both dietary and lifestyle OBS.

Sarcopenia-associated skeletal muscle loss generally begins at the age of 35 years and progresses at a rate of 1%−2% per year (22). Recent studies have revealed that pre-sarcopenia was identified in 33%−66% of healthy young women in Japan (23, 24). Therefore, it is imperative to initiate preventive measures against frailty at a young age to circumvent potential future mobility challenges or conditions such as sarcopenia.

The multifactorial and intricate pathogenesis of sarcopenia can be caused by a range of factors including genetics, aging, diet, and physical inactivity (25). Skeletal muscle loss has been linked to oxidative stress, inflammation, insulin resistance, mitochondrial dysfunction, and telomere shortening, among other factors (12, 26–30). The skeletal muscle becomes more vulnerable to oxidative stress with increase in metabolic activity, resulting in ROS production (31). Oxidative stress is increased in sarcopenia, leading to an increased risk of CVD in sarcopenic obesity and chronic obstructive pulmonary disease (32, 33). Bernabeu-Wittel et al. reported that oxidative stress markers, including lower total antioxidant capacity for ROS (TAC-ROS) and higher superoxide dismutase (SOD) levels, were increased in sarcopenia patients (34). Oxidants in tobacco smoke and obesity can cause oxidative stress by producing ROS or reducing the defensive mechanisms of the antioxidant system, including several dietary components (35). Individuals with antioxidant deficiency coupled with poor nutrition are more likely to experience adverse health reactions as a result of oxidative stress (36). Therefore, it is a feasible strategy for individuals at high risk of sarcopenia to reduce free radical generation through antioxidant treatments. ROS can be produced either by endogenous antioxidant defense systems or by exogenous systems (i.e., dietary intake) (37). The OBS is a synthetic metric used to assess the overall exposure balance of dietary and lifestyle oxidants and antioxidants (14). The results of our study support the current understanding of the role of OS in the pathogenesis of sarcopenia, as a higher OBS level protects against sarcopenia.

Although no direct evidence has been reported linking OBS with sarcopenia, several studies have demonstrated an association between dietary intake and sarcopenia. A higher intake of fiber may result in a greater abundance of specific gut bacteria, which slows the development of sarcopenia (38). Vitamins C and E are antioxidant vitamins, as they can scavenge ROS and promote cellular antioxidant activity (39). A study by Lewis et al. reported a positive association between dietary and circulating vitamin C levels and skeletal muscle mass in middle-aged and older individuals (40). Vitamin E plays a significant role in the recovery of myogenic cell membranes and is beneficial for treating muscle cells (41). One cross-sectional study showed that dietary and plasma vitamin E concentrations can reduce the risk of both hip and total fractures (42). Intake of a wide range of B vitamins can also reduce the risk of sarcopenia. Niacin, also known as vitamin B3, plays a vital role in preventing sarcopenia (43). Moreover, consumption of B6 may be beneficial in combating sarcopenia, frailty, and all-cause mortality (44). During B6 deficiency, the modulation of PLP-dependent enzymes results in several pathophysiological states that can impair skeletal muscle function (44). Sufficient evidence indicates that low micronutrient intake can result in a higher risk of sarcopenia. Magnesium is an important cofactor in many enzymatic reactions essential for the preservation of muscle mass and the protection of muscle tissue from oxidative damage (45, 46). In a cross-sectional study, oral intake of magnesium was observed to potentially prevent sarcopenia (47). One systematic review reported that sarcopenia could be prevented and treated by increasing intake of micronutrients such as calcium, iron, magnesium, phosphorus, potassium, selenium, sodium, and zinc (48). The benefits of dietary antioxidants, including the reduction of oxidative stress in skeletal muscles, are well known (49). The Composite Dietary Antioxidant Index (CDAI), which includes vitamins A, C, and E; carotenoids; zinc; and selenium, was examined in a recent study (49). The CDAI is related to hand grip strength, which indirectly supports the evidence that dietary factors contribute to sarcopenia (49).

The preservation, loss, and restoration of muscle mass rely on the balance between two concurrent yet opposing processes: protein degradation (PD) and protein synthesis (PS), collectively referred to as protein turnover. (50). The mTOR kinase serves as a central regulator of muscle protein synthesis, and its activity is significantly influenced by the availability of nutrients—particularly amino acids and growth factors (50). Whey proteins may further enhance antioxidant capacity by providing cysteine-rich proteins, which work in the synthesis of glutathione, a crucial intracellular antioxidant (51).

A correlation between a healthy lifestyle and sarcopenia has been confirmed. To date, physical activity has been proven to help maintain muscle health and delay sarcopenia (52), and resistance exercise, in particular, is a potent stimulus for PS (53). In the absence of exercise, muscle atrophy occurs because of reduced production of myocytokines, an imbalance between anti-inflammatory and pro-inflammatory mediators, and altered protein synthesis (54). However, consistent research has demonstrated that exercise generates ROS, which can be both beneficial or harmful depending on several factors, including the concentration of ROS, the duration of exposure, and the individual's training status (55).For example, ROS triggers the mitochondrial biogenesis cascade in response to endurance exercise (56). Additionally, within physiological concentrations, ROS regulates antioxidant systems by boosting the content and activities of SOD1 and SOD2 in muscle cells, thereby reducing ROS concentration (57).Given the current findings regarding oxidative balance and sarcopenia, it could be hypothesized that the impact of exercise on sarcopenia is multifaceted and may involve the regulation of oxidative balance. Further research is needed to prove this hypothesis.

Tobacco smoking and alcohol consumption represent two other primary factors that can affect muscle health. The effects of smoking include inactivity, lack of energy, and systemic inflammation—all of which interfere with muscle protein synthesis (58). A longitudinal cohort study investigating the correlation between smoking and the prevalence of sarcopenia observed that smokers had a 2.36-fold higher risk of developing sarcopenia than non-smokers (59). The prevalence of sarcopenia was aggravated by excessive alcohol consumption, possibly because skeletal muscle protein synthesis is restricted by excessive alcohol consumption (58, 60). BMI was used to assess body fat and thickness in this study. A previous study discovered an association between abdominal obesity and muscle mass and strength decline (61). Some individuals have both obesity and sarcopenia, sometimes referred to as sarcopenic obesity. The systemic energy burden associated with obesity accelerates disease onset by driving muscle loss (62).

These results further demonstrate the importance of antioxidant capacity in patients with sarcopenia or those at risk of developing it. Thus, we measured the oxidative balance in our participants and assessed its role in sarcopenia using OBS—a comprehensive indicator. Our study indicated that OBS was significantly higher in the non-sarcopenia group than in the sarcopenia one. Furthermore, observation of continuous OBS showed that lifestyle OBS had a more positive influence on sarcopenia than dietary OBS. After stratification by age, sex, ethnicity, educational level, family income, hypertension, diabetes, and CVD, no substantial alterations were observed in the association between OBS and sarcopenia.

Our study had several notable strengths. First, we used data from a nationally representative population-based study to generate our results, making them more generalizable. Furthermore, OBS, as a comprehensive measurement method, provides an assessment of multiple aspects of oxidant–antioxidant exposure. Finally, as opposed to older adults, our study surveyed the relationship between OBS and sarcopenia in young and middle-aged adults. However, this study also had several key limitations. Owing to its cross-sectional design, we were unable to establish a causal relationship between OBS and sarcopenia. Second, sarcopenia is defined as a decline in skeletal muscle mass with functional deterioration. In this study, sarcopenia was assessed based on low muscle mass. In the NHANES datasets, inadequate information regarding muscle function was found. Thus, future studies for determining the correlation between muscle function and OBS should be conducted. In addition, collecting 24-h dietary data may induce recall bias and fail to reflect long-term dietary patterns. Therefore, further clinical randomized controlled trials are warranted to confirm our findings.

This study showed that higher antioxidant and lower oxidant exposure may decrease the risk of developing sarcopenia. A higher OBS may indicate higher protection against sarcopenia. Therefore, individuals may be able to reduce the loss of muscle mass and delay the development of sarcopenia by maintaining healthy lifestyles and taking dietary antioxidant supplements. However, further clinical studies are warranted to confirm these findings.

Publicly available datasets were analyzed in this study. This data can be found here: https://wwwn.cdc.gov/nchs/nhanes.

The studies involving humans were approved by the National Center for Health Statistics' Ethics Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

ZC: Formal analysis, Methodology, Supervision, Writing – original draft, Writing – review & editing. DD: Formal analysis, Writing – review & editing.