The Impact of Physical Exercise on Oxidative and Nitrosative Stress: Balancing the Benefits and Risks

This review comprehensively evaluates the effects of physical exercise on oxidative and nitrosative stress, mainly focusing on the role of antioxidants. Using a narrative synthesis approach, data from empirical studies, reviews, systematic reviews, and meta-analyses published between 2004 and 2024 were collated from databases like PubMed, EBSCO (EDS), and Google Scholar, culminating in the inclusion of 41 studies. The quality of these studies was rigorously assessed to ensure the clarity of objectives, coherence in arguments, comprehensive literature coverage, and depth of critical analysis. Findings revealed that moderate exercise enhances antioxidant defenses through hormesis, while excessive exercise may exacerbate oxidative stress. The review also highlights that while natural dietary antioxidants are beneficial, high-dose supplements could impede the positive adaptations to exercise. In conclusion, the review calls for more focused research on tailored exercise and nutrition plans to further understand these complex interactions and optimize the health outcomes for athletes and the general population.


Introduction
Physical activity is intimately connected to the body's management of oxidative and nitrosative stress, crucial processes that involve the production and build-up of reactive oxygen species (ROS) and reactive nitrogen species (RNS).These processes are fundamental for cellular signaling, regulation, and maintaining balance [1,2].The impact of exercise-induced oxidative stress on the body can vary, producing positive or negative outcomes depending on exercise intensity, duration, and an individual's health status [3,4].Regular exercise enhances the body's antioxidant capabilities and overall redox balance, contributing to numerous health benefits.However, excessive or poorly tailored exercise can increase oxidative damage and impair muscle function.
The relationship between exercise and oxidative stress is complex, influenced by factors such as the exercise's type, intensity, and duration.Supplementing antioxidants may be beneficial in situations characterized by high oxidative stress or inadequate dietary antioxidant intake.There is a pressing need for further research to fully understand how various exercise protocols affect the management of oxidative and nitrosative stress across different populations.This necessity is driven by the growing understanding of how exercise-induced biochemical responses play pivotal roles in health outcomes.While generally advantageous, physical activity can also provoke oxidative and nitrosative stress, leading to beneficial adaptations or potential cellular damage, contingent on the exercise's intensity and duration.This study explores the intricate relationship between exerciseinduced stress and antioxidant responses, aiming to inform targeted interventions that maximize health benefits across diverse populations.

Importance of Understanding Oxidative and Nitrosative Stress
The role of oxidative and nitrosative stress in the development of diseases such as cardiovascular diseases, neurodegenerative disorders, diabetes, and cancer cannot be overstated.These stresses have a dual nature, with the potential to be damaging at high levels and regulatory at low levels.Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can impact health and disease in complex ways, modulating inflammation, apoptosis, and mitochondrial function.High levels of ROS resulting from oxidative stress have been linked to the pathology of many diseases including metabolic syndrome, atherosclerosis, Alzheimer's disease, and rheumatoid arthritis [5].Oxidative stress is also related to various chronic diseases such as cardiovascular diseases, neurodegenerative diseases, infections, and cancer [6].Excessive ROS production can alter cellular structure and function, leading to aging and chronic degenerative pathologies [7].However, antioxidant interventions can help mitigate oxidative stress and its effects on cardiovascular health [8].Antioxidants have been shown to reduce the harmful effects of oxidative stress on the body, helping to promote better health and reduce the risk of disease [9].

Brief Overview of Mechanisms behind Exercise-Induced Stress Responses
Physical exercise profoundly impacts metabolism by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS).During aerobic activities, the enhanced oxygen consumption of muscles leads to electron leakage from the mitochondrial electron transport chain, elevating the ROS levels [10].While potentially compromising cellular integrity, these elevated ROS and RNS levels also serve crucial signaling roles that activate antioxidant defenses and other protective mechanisms [11].In cases where oxidation products exceed the body's antioxidant defense capabilities, oxidative stress detrimentally affects the muscles' molecular, structural, and functional integrity [12].Regular exercise beneficially activates pathways such as erythroid-related nuclear factor 2 (NRF2) and antioxidant-responsive elements (ARE), which enhance cellular antioxidant defenses and help maintain cellular homeostasis and proper mitochondrial function [13].
Incorporating sociodemographic factors like age, gender, ethnicity, and socioeconomic status is essential for understanding the variability in responses to exercise-induced oxidative and nitrosative stress.Age affects the recovery dynamics and ROS production, with younger individuals often having more efficient antioxidant responses than older adults.Gender differences such as the antioxidant effects of estrogen in women influence oxidative stress levels.Genetic predispositions associated with ethnicity can modify how reactive species are metabolized, impacting an individual's susceptibility or resilience to oxidative stress.Additionally, socioeconomic status plays a role in access to antioxidant-rich diets and safe exercise environments, which are essential for effectively managing oxidative stress.
Engagement in routine physical activities leads to the production of ROS and RNS in the skeletal muscle, resulting in cellular adaptations that include an increase in the production of endogenous antioxidant enzymes.These enzymes enhance the muscle's capacity to neutralize ROS and RNS, contributing to several health benefits such as improved cardiovascular health, increased insulin sensitivity, and better muscle function [14,15].Furthermore, exercise induces the production of nitric oxide (NO) via endothelial nitric oxide synthase (eNOS).NO is crucial for vasodilation, regulating blood flow, and delivering nutrients to active muscles.However, excessive NO can react with superoxide to form peroxynitrite, a potent oxidant that induces nitrosative stress, thus necessitating a balance to mitigate health risks [16][17][18].
These insights into the interplay between exercise, oxidative and nitrosative stress, and sociodemographic factors are vital for crafting personalized exercise and dietary interventions.Such tailored recommendations aim to optimize health benefits and minimize oxidative damage, accommodating individual differences in physiology and life circumstances.

Methodology 2.1. Research Design
This general review was formulated to evaluate the effects of physical exercise on oxidative and nitrosative stress, with a particular emphasis on the role of antioxidants.A comprehensive narrative synthesis methodology was employed to integrate and analyze the findings from diverse studies.This section delineates our systematic approach to the literature selection.We concentrated on empirical research, encompassing both quantitative and qualitative studies, to thoroughly investigate the impacts of physical exercise on oxidative and nitrosative stress.Furthermore, our analysis included a review of the existing reviews, systematic reviews, and meta-analyses to provide a holistic examination of the subject matter.

Search Strategy Description
The literature search was confined to studies published within the last two decades  to incorporate the most recent data to reflect contemporary insights, practices, and findings regarding the impact of physical exercise on oxidative and nitrosative stress as well as the mitigative effects of antioxidants.Search terms such as "physical exercise", "oxidative stress", "nitrosative stress", "reactive oxygen species", "reactive nitrogen species", and "antioxidants" were strategically combined using Boolean operators (AND, OR) to enhance the specificity of the search outcomes.The databases queried included PubMed, EBSCO (EDS), and Google Scholar to ensure a comprehensive review of the available scholarly literature.The search strategy is presented in Figure 1.
These insights into the interplay between exercise, oxidative and nitrosative stress, and sociodemographic factors are vital for crafting personalized exercise and dietary interventions.Such tailored recommendations aim to optimize health benefits and minimize oxidative damage, accommodating individual differences in physiology and life circumstances.

Research Design
This general review was formulated to evaluate the effects of physical exercise on oxidative and nitrosative stress, with a particular emphasis on the role of antioxidants.A comprehensive narrative synthesis methodology was employed to integrate and analyze the findings from diverse studies.This section delineates our systematic approach to the literature selection.We concentrated on empirical research, encompassing both quantitative and qualitative studies, to thoroughly investigate the impacts of physical exercise on oxidative and nitrosative stress.Furthermore, our analysis included a review of the existing reviews, systematic reviews, and meta-analyses to provide a holistic examination of the subject matter.

Search Strategy Description
The literature search was confined to studies published within the last two decades (2004-2024) to incorporate the most recent data to reflect contemporary insights, practices, and findings regarding the impact of physical exercise on oxidative and nitrosative stress as well as the mitigative effects of antioxidants.Search terms such as "physical exercise", "oxidative stress", "nitrosative stress", "reactive oxygen species", "reactive nitrogen species", and "antioxidants" were strategically combined using Boolean operators (AND, OR) to enhance the specificity of the search outcomes.The databases queried included PubMed, EBSCO (EDS), and Google Scholar to ensure a comprehensive review of the available scholarly literature.The search strategy is presented in Figure 1.

Roles of Authors and Conflict Resolution
Each author was assigned specific roles: initiating the search, screening the articles, extracting data, and drafting the manuscript sections.Disagreements among authors regarding study inclusion were resolved through discussion until consensus was achieved.If consensus could not be reached, a third-party expert in exercise physiology was consulted to make the final decision.

Inclusion and Exclusion Criteria
The initial selection commenced with a corpus of 6531 studies subjected to a stringent multistage filtering process based on explicit inclusion criteria.The initial filtering at the abstract level assessed studies for (i) the employment of quantitative and qualitative research methodologies, (ii) inclusion of human or animal subjects, (iii) open access or peerreviewed status, (iv) publication dates ranging from 2004 to 2024; and (v) articles penned in English.This phase accommodated various research designs including descriptive, experimental, quasi-experimental, ex post facto, and instrumental studies.Subsequently, the second filtering stage, conducted at the full-text level, specifically targeted studies that presented systematic reviews, meta-analyses, and those providing detailed statistical analyses or were review studies pertinent to the focal topics.Exclusions during this phase were made for document types such as editorials, brief reports, communications, perspectives, concept papers, and opinion pieces.The final filtering phase concentrated on studies examining the impacts of exercise on producing reactive oxygen species (ROS), reactive nitrogen species (RNS), and the corresponding antioxidant responses.Following this comprehensive selection process, 41 studies were deemed suitable for inclusion in this systematic review.

Data Extraction
Data extraction was conducted using a standardized template that captured key elements of each study including descriptions of the study, the participants' demographics, details of the study design and interventions, results examined, conclusions drawn, practical implications, and a typical ranking of different types of studies.Two reviewers independently executed this process to ensure the precision and dependability of the data extracted.

Quality Assessment
Our research focused primarily on general and narrative reviews, developing a quality assessment framework through an extensive review of existing methodologies for evaluating narrative and systematic reviews.This process identified essential elements to ensure integrity and reliability, adapting and innovating traditional methods to include measures for assessing narrative coherence and argumentative structure-key aspects often neglected in standard tools.We collaborated with research methodology and academic publishing experts to validate and refine our criteria, ensuring relevance and comprehensiveness.Pilot testing on a sample of reviews further confirmed the practical applicability of our framework in discerning quality differences among narrative reviews.The rationale behind our framework was built on four pivotal criteria: clarity of objectives, coherence of arguments, comprehensiveness of literature coverage, and depth of critical analysis.These were designed to clarify the review's goals, enhance persuasiveness and logical flow, ensure exhaustive literature coverage, and promote critical engagement with the material, advancing scholarly dialogue and improving the utility of narrative reviews in academic communication.This consolidated approach is detailed in Table 1, which outlines the quality assessment of the reviewed studies.Column Descriptions: Authors and Publishing Year-A unique identifier for each review; Clarity of Objectives-Assesses whether the objectives of the review are clearly defined and specific; Coherence of Arguments-Evaluates the logical consistency and flow of the arguments presented in the review; Comprehensiveness of Literature-Measures the scope and breadth of the literature referenced in the review, considering whether it adequately represents the field being discussed; Critical Analysis of Findings-Examines the depth and thoughtfulness of the review's analysis concerning the findings and their implications; Overall Quality Rating-A summary rating based on the assessment of the other four criteria, typically rated as Low, Moderate, High, or Very High.

Sources of Free Radicals during Exercise
During physical activity, the body's metabolic rate increases, leading to higher oxygen consumption and the production of reactive oxygen species (ROS), which escalate oxidative stress potential.This is crucially managed by the body's antioxidant defense systems in muscle fibers, emphasizing the importance of maintaining redox homeostasis [19].Mitochondria, essential for ATP production, become significant sources of ROS due to electron leakage from their electron transport chain during increased activity, potentially causing oxidative damage.However, exercise also triggers protective mechanisms such as the superassembly of mitochondrial complex I in rats, which has been shown to reduce lipid peroxidation and mitochondrial oxidative damage, presenting potential therapeutic benefits for metabolic diseases [20,21].
Ischemia-reperfusion injury, which occurs due to temporary blood flow restriction followed by reoxygenation in muscle tissues, contributes to ROS generation, highlighting the role of oxidative stress in exercise-induced muscle damage and the potential mitigating effects of antioxidant supplementation [22].The inflammatory response to exercise activates immune cells such as neutrophils and macrophages, which produce free radicals essential for muscle repair and regeneration.This inflammatory process is crucial for recovery, particularly after exercise-induced muscle damage, exacerbated by eccentric muscle contractions that cause severe disruptions in sarcomeres and increase inflammation, leading to strength loss and delayed-onset muscle soreness (DOMS).The recovery timeline from such damage varies with the severity of the damage and the muscle's prior adaptation [23].
Additionally, catecholamines like adrenaline can autoxidize to form free radicals.However, enzymatic reactions and metal ions are more typical sources at physiological pH, with a potential risk of oxidative damage in cardiac cells [24].Despite the risks of excessive free radical production, moderate levels can initiate adaptive responses that confer health benefits.This underscores the need to understand these mechanisms to optimize antioxidant defenses and muscle health [25].Regular physical activity boosts the body's antioxidant capacity, protecting against oxidative stress and illustrating the complex adaptations to exercise-induced oxidative stress.These responses including oxidative stress and inflammatory responses may depend on exercise intensity, influencing the activation of inflammatory cytokines and sirtuin (SIRT) family members [26].

Antioxidant Responses to Acute and Chronic Exercise Conditions
The body combats exercise-induced oxidative stress using enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and non-enzymatic antioxidants including vitamins C and E. These antioxidants are pivotal in neutralizing reactive oxygen species (ROS).While acute exercise transiently enhances these antioxidants for immediate protection, chronic exercise stimulates genetic adaptations that progressively augment the body's antioxidant capacity, an effect known as hormesis.This phenomenon shows that moderate oxidative stress can fortify the body's defenses over time [19].
Computational studies have further demonstrated how antioxidants can influence enzyme structures, thereby contributing to disease prevention.This underscores the critical role of antioxidants in controlling cellular ROS levels and maintaining redox homeostasis, highlighting potential avenues for novel therapeutic strategies against ROS-related diseases [27].ROS production during exercise is driven by factors like mitochondrial activity and inflammation, which are essential for muscle adaptations such as angiogenesis, hypertrophy, and enhanced mitochondrial function, all of which vary according to the type and intensity of exercise [28].
For athletes, it is crucial to balance antioxidant intake with training to optimize both performance and recovery.This balance is vital for activating signaling pathways that regulate muscle hypertrophy, angiogenesis, and mitochondrial biogenesis-fundamental processes that underpin training adaptation and sports performance.Therefore, understanding the equilibrium between ROS production and antioxidant defenses is essential to maximize the exercise benefits and minimize potential oxidative damage.Careful consideration of antioxidant supplementation is necessary to preserve this balance, as excessive intake might disrupt the natural adaptive responses to exercise and impair athletic performance [29].Table 2 briefly overviews the exercise-induced oxidative stress mechanisms and antioxidant responses.[29]: D The level of evidence of each reference is graded as B: Randomized controlled trials (RCTs); C: Cohort studies, case-control studies, cross-sectional surveys, case studies, and/or observational studies; D: Review or evidence insufficient for categories A to C.

Exploration of the Role of Nitric Oxide in Exercise Physiology
Nitric oxide (NO) enhances blood flow, oxygen delivery, and muscle nutrient supply during exercise, improving performance and endurance.NO production increases with physical activity, facilitated by enzymes such as endothelial and neuronal nitric oxide synthase (eNOS and nNOS), which promote vasodilation and muscular perfusion.Notably, the bioavailability of NO decreases with age, impacting exercise capacity.However, regular aerobic exercise combined with dietary supplements like inorganic nitrate, nitrite, l-arginine, and l-citrulline can counteract these age-related declines, mainly benefiting older adults [30,31].
Exercise-induced NO release also benefits vascular function and cardiovascular health including in patients with vascular diseases.Moreover, NO contributes to mitochondrial biogenesis and efficiency, which is crucial for enhancing endurance and reducing fatigue during extended physical activities [32].While a meta-analysis highlighted a significant boost in mitochondrial oxidative capacity following exercise, results regarding antioxidant capacity and quality were less definitive.This research primarily investigated conditions such as heart failure, peripheral artery disease, and hypertension, where exercise improved mitochondrial function [32].Therefore, regular physical activity helps sustain NO levels as we age and capitalizes on its benefits for cardiovascular and muscular health, underscoring the integrated role of NO in exercise physiology and health maintenance.

Examination of the Consequences of Excessive Nitrosative Stress Due to Physical Activity
While moderate nitric oxide (NO) levels benefit health and exercise adaptation, excessive NO can cause nitrosative stress, leading to cellular damage.High NO levels react with superoxide anions to form peroxynitrite, a potent oxidant that can damage lipids, DNA, and proteins, altering cell function and integrity.Such stress is linked to various diseases including cardiovascular and neurodegenerative disorders and inflammation.Too much NO can impair recovery, increase muscle fatigue, and reduce performance in exercise.The body has mechanisms like protein nitrosation and denitrosylation to regulate NO effects; however, an imbalance in these processes can lead to health issues, significantly affecting the central nervous system [33,34].Additionally, the body produces reactive oxygen species (ROS) in different locations including the mitochondria and endoplasmic reticulum, impacting cellular activities and contributing to pathological conditions when mismanaged.Understanding how to control NO and ROS levels is crucial for preventing oxidative and nitrosative stress-related diseases, emphasizing the importance of maintaining a balance to support cellular function and health [35].For comprehensive information on the mechanisms, benefits, and regulatory strategies of exercise-induced nitrosative stress, please refer to Table 3.The level of evidence of each reference is graded as A: Systematic reviews and meta-analyses; C: Cohort studies, case-control studies, cross-sectional surveys, case studies, and/or observational studies; D: Review or evidence insufficient for categories A to C.

Introduction to the Concept of Hormesis within the Context of Exercise Physiology
Hormesis, a concept in exercise physiology, suggests that moderate oxidative and nitrosative stress from exercise can stimulate beneficial adaptations in the body.This principle is particularly relevant in addressing the increasing prevalence of neurodegenerative diseases in the aging population.Neurohormesis refers to the brain's adaptive responses to low-level stress, showing the potential to slow and mitigate the impact of neurodegenerative conditions.Herbal compounds like resveratrol, curcumin, and sulforaphane have been identified for their neurohormetic effects, activating stress response pathways to enhance cellular defense against injury and improve immune function.These findings suggest promising avenues for managing neurological disorders and supporting healthy aging [36].
The article also touches on the role of reactive oxygen species (ROS) in maintaining cellular redox balance and how shifts toward oxidative stress can contribute to chronic diseases such as cardiovascular issues and cancer.While direct antioxidant supplementation has shown limited efficacy and potential risks, strategies to induce mild oxidative stress like hormesis could improve the body's natural defense mechanisms and increase sensitivity to cancer treatments [37].Key transcription factors, NF-κB and Nrf2, regulate the expression of antioxidant enzymes, demonstrating how low-level stress can enhance health and longevity by triggering protective responses against various stressors [60].Additionally, the body's adaptation to environmental, physical, and nutritional stress through hormesis involves epigenetic changes, highlighting the importance of understanding these responses for health and longevity.Such adaptations underline the potential benefits of controlled environmental exposures to activate defense mechanisms against diseases and aging [61].This holistic view of hormesis underscores the intricate balance between stress and adaptive response, offering insights into leveraging these mechanisms for health benefits.

Moderation in Exercise Intensity and Duration
Regular exercise is crucial in triggering adaptive stress responses and bolstering the body's antioxidant defenses, providing numerous health benefits.However, intense or prolonged physical activity can elevate the production of reactive oxygen species (ROS), leading to oxidative stress in critical tissues like blood and skeletal muscles, which are significant sources of ROS during exercise.This oxidative stress is associated with muscle fatigue and plays a crucial role in muscle adaptation through biochemical signaling.The effects of exercise-induced ROS on health, whether beneficial or harmful, are still subjects of debate.The body's antioxidant systems, which include enzymes such as superoxide dismutase, glutathione peroxidase, and catalase are essential for neutralizing ROS and maintaining cellular redox balance.
A study involving 25 sedentary adults investigated how various intensities and durations of exercise impacted oxidative stress and antioxidant responses.The study revealed that oxidative stress markers increased following exercise sessions at 50%, 60%, and 70% of peak aerobic capacity across 10-, 20-, and 30-minute durations, showing different effects on antioxidant enzyme activities.These findings suggest that sedentary adults should limit exercise to 70% of their peak capacity to manage oxidative stress effectively [38,39].
Excessive exercise intensity and duration can lead to an overproduction of free radicals like ROS and reactive nitrogen species (RNS), potentially causing cellular damage.While free radicals are a normal part of cellular processes, their accumulation beyond the body's capacity to neutralize them can damage proteins, DNA, and lipids, contributing to diseases and accelerating aging.Oxidative stress may also trigger mitochondrial dysfunction and impair mitochondrial biogenesis, which is particularly significant in aging.To combat oxidative stress, regular physical activity and antioxidants such as quercetin, resveratrol, and curcumin are recommended for their protective effects.Chronic inflammation and oxidative stress are interconnected and lead to various health issues.Managing oxidative stress through DNA repair mechanisms, antioxidants like glutathione and superoxide dismutase, and engaging in physical activity are crucial for maintaining cellular health.Structured and moderate exercise is vital to mitigating the adverse effects of oxidative stress.
Research also highlights high dropout rates in health clubs, particularly within the initial months, with enjoyment playing a critical role in exercise persistence.A study demonstrated that aligning exercise intensity with personal preferences enhances the enjoyment and supports exercise commitment, positively affecting exercise habits and the desire to continue exercising [62,63].This insight is valuable for health club professionals in tailoring exercise programs that maximize adherence by aligning with the individuals' intensity preferences.
Ultimately, this article examines the balance between benefiting from exercise-induced stress adaptations and avoiding oxidative damage, particularly in high-intensity exercise, and its association with muscle damage.It focuses on how free radicals contribute to oxidative stress responses and offers insights for athletes, coaches, and the general population on recovery strategies from intense workouts and the health implications of such activities.The role of antioxidants in aiding the recovery process and mitigating the effects of oxidative stress is emphasized, highlighting their importance in protecting cells and preventing oxidative stress-related diseases [40].By customizing exercise intensity and duration based on individual capacities, it is possible to optimize the benefits of exercise while minimizing the risks of oxidative stress-related harm.This personalized approach helps individuals maintain a healthy exercise routine that promotes overall well-being and long-term fitness goals.

Nutritional Support
A diet rich in antioxidants from fruits, vegetables, and nuts plays a vital role in boosting the body's defense against oxidative stress.This topic continues to be explored in research.Antioxidants are essential in protecting the body from damage caused by free radicals.Found naturally in plant-based foods, antioxidants contribute significantly to disease prevention, while industrial antioxidants are used to prevent the oxidation of various products.By neutralizing free radicals and acting as reducing agents, antioxidants are not only integral to supplements in the food industry, but are also researched for their potential in combating heart disease and cancer.The antioxidant properties of foods like apples and grains, which may inhibit cancer growth and disease development, underline the importance of further investigation into how the body absorbs and benefits from these compounds [41].The article also discusses the critical role of antioxidants in eye health, detailing how different molecules protect against oxidative stress in both the anterior and posterior segments of the eye.This protection is crucial for preventing eye disorders like dry eye disease, cataracts, and age-related macular degeneration, among others.Despite ongoing research, the effectiveness of antioxidant supplementation in avoiding eye diseases remains uncertain, calling for more detailed studies [42].Moreover, the consumption of vitamin C, especially among athletes, is debated regarding its necessity and impact on performance.Vitamin C is crucial for immune health and combating free radicals, but there is evidence that high doses might impede athletic performance by affecting training adaptations and vascular function.For athletes, consuming less than 1 g per day and prioritizing vitamin C intake through diet over supplements is advised, with the relationship between vitamin C and athletic performance necessitating further research to optimize dosage and timing [43].Oxidative stress, characterized by the imbalance between pro-oxidants and antioxidants, underscores the importance of managing this balance to prevent cellular damage and dysfunction [62].Studies have explored using antioxidants like zinc, selenium, and vitamin C to counteract oxidative stress induced by environmental pollutants like cadmium, highlighting the potential of dietary interventions in mitigating oxidative damage.Incorporating a variety of antioxidants through diet and supplements can help maintain a healthy oxidative balance and support overall well-being [64,65].

Adequate Recovery Periods
Adequate recovery periods are essential for mitigating chronic oxidative stress and facilitating the body's repair mechanisms.Research by Mahendra Wahyu Dewangga and Djoko Pekik Irianto explored how varying exercise frequencies impacted the serum antioxidant levels and muscle damage in male Wistar rats.Their study, which divided the rats into four groups subjected to different exercise frequencies, found that exercising four times a week or daily without sufficient recovery decreased the serum antioxidant levels and increased muscle tissue damage.This underscores the importance of integrating adequate rest days into exercise routines to preserve the body's antioxidant capacity and muscle health [44].
Active recovery techniques and sufficient sleep are critical in enhancing recovery and boosting antioxidant defenses, effectively counteracting exercise-induced oxidative stress.A specific study examined the fluctuations of oxidative stress biomarkers in ten males performing cycling exercises under hot conditions, analyzing blood samples for oxidative stress indicators.The results did not support the expected increase in exercise-induced oxidative stress, possibly due to the severe heat stress during rest, delayed recovery, or dehydration, with the study's limited sample size potentially influencing the variability of results.This suggests a need for further research to understand the impacts of oxidative stress when exercising in hot environments [45].
Another study highlighted that strenuous exercise induced beneficial changes in skeletal muscle such as enhanced endurance and strength gains through processes like mitochondrial biogenesis and muscle hypertrophy.However, these benefits were heavily dependent on the recovery phase post-exercise.An imbalance between intense training and inadequate recovery can lead to performance declines, overreaching, and potentially overtraining syndrome (OTS), characterized by prolonged low-frequency force depression (PLFFD) from muscle damage and glycogen depletion.Reactive oxygen, nitrogen species, and inflammatory pathways likely contribute to the development of OTS [46].
Additionally, the autonomic nervous system (ANS) plays a significant role in health by responding to environmental stressors.Imbalances between the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS can contribute to chronic stress and unhealthy lifestyles.The interaction of the ANS with the hypothalamic-pituitary-adrenal axis is crucial in managing immune function, cardiovascular health, oxidative stress, and metabolic imbalances.High-intensity exercise can disrupt this balance, inducing oxidative stress that affects the ANS equilibrium.Maintaining an optimal SNS and PNS balance through exercise is emphasized as it helps reduce oxidative stress and inflammation [66].
Therefore, ensuring the inclusion of appropriate recovery periods in training regimes is vital for optimizing health and performance, highlighting the need to balance exercise intensity with adequate rest to support physiological functions and overall well-being.

Hydration and Electrolyte Balance
Proper hydration and electrolyte balance are critical for optimizing physiological functions and reducing oxidative stress during exercise, especially in conditions that elevate the risk of dehydration such as high temperatures.A study involving 12 healthy men demonstrated that isotonic drinks were more effective than water in protecting muscles from exercise-induced heat stress, highlighting the importance of tailored hydration strategies for enhancing performance and recovery in hot environments [47].In demanding work settings like those encountered by agricultural workers in Latin America, dehydration and related health complications such as rhabdomyolysis and acute kidney injury are prevalent due to strenuous labor and harsh climate conditions.Despite general water intake and rest guidelines, replenishing electrolytes is critical to maintain proper hydration and prevent electrolyte imbalance.A field trial with sugarcane cutters in Guatemala showed that enhanced electrolyte intake effectively sustained hydration and minimized health risks without compromising productivity [67].Additionally, data from the National Health and Nutrition Examination Survey indicate that many U.S. adults fail to meet hydration standards, associating insufficient hydration with chronic diseases and increased mortality rates, emphasizing the public health implications of inadequate hydration [48].This evidence points to the necessity of further research on hydration requirements and the monitoring of hydration status [68].Thus, ensuring adequate hydration and appropriate electrolyte supplementation is essential for maintaining health, optimizing performance during physical activities, and preventing chronic health issues.For in-depth insights into the comprehensive strategies for optimizing health benefits and mitigating exercise-induced oxidative and nitrosative stress, refer to Table 4 for a detailed overview.The level of evidence of each reference is graded as B: Randomized controlled trials (RCTs); C: Cohort studies, case-control studies, cross-sectional surveys, case studies, and/or observational studies; D: Review or evidence insufficient for categories A to C.

Investigation into How Diet Influences Exercise-Induced Oxidative and Nitrosative Stress
The research underscores the significance of incorporating antioxidant-rich foods into diets to combat exercise-induced oxidative stress.Studies suggest that whole dietary strategies involving foods like dark chocolate, cocoa, oatmeal, and various fruits and juices can enhance the body's ability to scavenge reactive oxygen species generated during exercise, thereby reducing oxidative stress and inflammation.However, the diverse protocols across these studies call for more standardized research to solidify the evidence supporting the antioxidant benefits of these dietary approaches on exercise-induced oxidative stress [49].Intense physical activity without adequate recovery can imbalance the body's free radical production and antioxidant defenses, leading to oxidative damage.However, moderateintensity exercises such as Taekwondo have been shown to initiate an adaptive response that improves the body's oxidative balance, emphasizing the importance of exercise type, intensity, and duration in influencing oxidative stress levels and potential cellular damage [50].Antioxidants from vitamins C and E, selenium, flavonoids, and carotenoids are pivotal in neutralizing harmful reactive species and supporting cellular health during strenuous activities.While supplementation is standard, the correct dosage and timing are crucial to avoid potential pro-oxidant effects and effectively reduce oxidative/nitrosative stress [51].
Diets rich in fruits, vegetables, and whole grains, known for their high antioxidant content, have been linked to improved antioxidant defenses and protection against oxidative stress from exercise.Polyphenols, in particular, found in berries and green tea, may boost antioxidant enzyme activity and lower inflammation and muscle damage markers.The relationship between diet, gut microbiota, and chronic disease development also highlights the role of dietary antioxidants in managing conditions like cardiovascular disease and cancer, promoting plant-based diets like the Mediterranean for their preventive benefits.The discussion extends to the potential of polyphenol supplements in enhancing the recovery and performance of athletes, though the effectiveness and optimal usage of such supplements require further exploration [52,69].Thus, a balanced diet rich in natural antioxidants and regular exercise is recommended for mitigating oxidative stress and preventing chronic health issues.

Evidence-Based Recommendations for Antioxidant Supplementation to Support Exercise Recovery and Performance
The effectiveness of antioxidant supplementation, especially exceptionally high doses of vitamin C, for athletic performance and recovery presents mixed results.While some research indicates reduced muscle damage post-exercise, other studies highlight neutral or negative impacts on performance and muscle soreness.Consequently, long-term high-dose vitamin C supplementation is not universally recommended due to inconsistent findings and the potential to dampen training adaptations.Athletes are instead encouraged to focus on a diet rich in nutrients for their antioxidant needs [53].In addition, antioxidants from natural fruit sources, especially those high in polyphenols, are recognized for their anti-inflammatory and antioxidant capabilities, offering a promising approach to muscle recovery and performance enhancement.Strenuous exercise can disrupt the balance between reactive oxygen species (ROS) and antioxidants, leading to delayed-onset muscle soreness (DOMS), which peaks 24 to 72 h after activity.Due to their potent properties, fruit-derived antioxidants have been explored as an effective means to protect muscle cells from ROS-induced damage, showcasing the potential of antioxidant-rich fruit juices in aiding muscle recovery and boosting sports performance.Research on beetroot, grape, and pomegranate juices has shown positive outcomes in minimizing muscle damage and enhancing antioxidant capacity, underlining the role of natural fruit juice supplementation as a viable nutritional strategy for athletes [54].While the body's natural training adaptations involve ROS, incorporating specific antioxidants like vitamins C, E, and resveratrol can positively contribute to recovery and athletic outcomes.
Vitamin C and E supplementation: Research on the effects of vitamins C and E on athletic performance and recovery has presented mixed outcomes.Some studies have highlighted the potential of these vitamins to decrease oxidative stress markers and inflammation following intense exercise.However, others caution that high doses might disrupt the body's natural adjustments to training, possibly limiting gains in endurance and strength.The review delves into the impact of antioxidant and vitamin supplementation across various exercise types including endurance activities and resistance training.
Findings generally indicate that such supplementation does not significantly enhance performance, mitigate exercise-induced oxidative stress, or aid recovery.There are concerns that vitamin supplementation could impede the cellular adaptation processes essential for endurance training improvements.The need for further research to clarify the effectiveness and possible downsides of antioxidant and vitamin supplements for athletes is underscored [55,56].Additionally, a specific focus on the supplementation's impact on delayed-onset muscle soreness (DOMS) through a review of 14 randomized trials involving 280 participants, mostly young, active individuals revealed that only a few studies had reported a notable reduction in muscle soreness from vitamin C and E supplementation.This inconsistent evidence calls for more comprehensive studies to ascertain the role of these antioxidant vitamins in alleviating DOMS.
Polyphenol supplementation: Polyphenol supplements such as quercetin and resveratrol are gaining attention for their potential to boost endurance performance and enhance the body's antioxidant defense mechanisms.These compounds might also aid muscle recovery by reducing inflammation.Although widely used by athletes to minimize exerciseinduced oxidative stress and speed up recovery, definitive evidence on the effectiveness of dietary polyphenols for athletes remains sparse.This review examines the bioavailability of polyphenols, their efficacy in combating oxidative stress, and their role in improving the antioxidant status and recovery strategies of athletes.Despite indications that polyphenols can bolster antioxidant defenses and mitigate oxidative stress, debates and mixed results persist regarding their efficacy.The need for further research to pinpoint the effects of polyphenols on oxidative stress, antioxidant status in athletes, and the best dosing practices is highlighted.The review also discusses the significance of standardized polyphenol extracts for more reliable research outcomes, alongside the anti-inflammatory properties and contribution to vascular function and recovery enhancement of polyphenols through mechanisms like free radical scavenging and Nrf2 pathway activation.Suggested dosing includes acute supplementation of approximately 300 mg before exercise to boost performance and over 1000 mg daily for several days pre-and post-exercise to aid recovery.However, the complexity of polyphenol absorption and metabolism calls for more in-depth studies to validate these recommendations and fully understand the potential of polyphenols to support rapid recovery between intensive training sessions or competitions [52,57].
Selenium and coenzyme Q10: Selenium and coenzyme Q10 (CoQ10) have been studied for their potential to enhance physical performance and reduce oxidative stress.Selenium is crucial for producing glutathione peroxidase (GPX) and thioredoxin reductase (TxnRd), selenoproteins involved in reducing lipid peroxides and regulating cell death, thus maintaining immune homeostasis and heart function.TxnRd, existing in cytosolic and mitochondrial forms, plays roles in DNA synthesis, angiogenesis, and reducing mitochondrial oxidative stress.These selenoproteins also possess anti-inflammatory properties, potentially suppressing the production of inflammatory mediators.However, the pro-inflammatory effects of some selenoproteins suggest a complex role in inflammation regulation, necessitating further research to clarify selenium's mechanisms in immunity and inflammation [58].CoQ10 is vital for the electron transport chain and antioxidant defense, with natural deficiencies linked to aging and exacerbated by certain medications.At the same time, CoQ10 supplementation has shown promise for cardiovascular health; its effectiveness for statin-associated muscle symptoms varies, indicating the need for more research to establish its benefits across different health conditions [59].This overview highlights the need for further studies to better understand the impact of selenium and CoQ10 on athletic performance, oxidative stress, and health outcomes.For an in-depth analysis of the enhanced understanding of the role of dietary antioxidants in exercise-induced oxidative stress mitigation, refer to Table 5.  [59]: D The level of evidence of each reference is graded as A: Systematic reviews and meta-analyses;C: Cohort studies, case-control studies, cross-sectional surveys, case studies, and/or observational studies; D: Review or evidence insufficient for categories A to C.

Discussion
This review analyzed the impact of physical exercise on oxidative and nitrosative stress, emphasizing how antioxidant interventions and demographic factors modulate exercise-induced responses.

Modulation of Oxidative Stress through Exercise Intensity
The intricate relationship between exercise intensity and the balance of oxidative and nitrosative stress is crucial for understanding the dual impacts of physical activity on health.Moderate exercise enhances antioxidant defenses, primarily through upregulating enzymes such as superoxide dismutase and catalase [70].These play critical roles in scavenging free radicals and reducing oxidative damage, thus demonstrating the hermetic effects that promote cellular resilience and longevity [38,39].This exercise intensity also triggers the NRF2 signaling pathway, a vital regulator of cellular antioxidant mechanisms, thereby boosting the body's ability to mitigate oxidative stress and protect against cardiovascular and metabolic disorders [25,52,57,60].Conversely, high-intensity exercise can lead to an overload of reactive oxygen and nitrogen species, overwhelming the antioxidant defense and resulting in cellular damage, muscle fatigue, and impaired recovery, conditions often exacerbated during continuous intense training without adequate rest [26,40,66].Such scenarios are associated with overtraining syndrome in athletes, characterized by persistent fatigue and reduced performance [29,33,44,46].Thus, it is critical to design training programs that include proper recovery and nutritional support to moderate the physiological impacts of exercise [34,40,50].For the general population, incorporating moderate exercise into daily routines significantly enhances health and reduces the risk of chronic diseases related to oxidative stress [40].This nuanced understanding underscores the importance of personalized exercise regimens, with future research needed to explore these dynamics through longitudinal studies, aiming to clarify the long-term effects of different exercise intensities on oxidative stress and overall health outcomes.

Role of Dietary Antioxidants in Exercise
The interplay between dietary antioxidants and exercise-induced oxidative stress is complex, involving significant biological interactions.The body's endogenous antioxidant systems respond to moderate exercise by enhancing defense mechanisms to alleviate oxidative damage [37,61].However, administering exogenous antioxidants like vitamins C and E shows mixed outcomes [71,72].At the same time, these can diminish oxidative stress markers, and excessive intake may inhibit critical adaptive responses such as mitochondrial biogenesis and the activation of necessary stress response pathways [19,51,55,56,[73][74][75][76].Powers et al. noted that although antioxidants can reduce acute oxidative damage, they might also impede long-term physiological adaptations such as improvements in the body's natural antioxidant capacity and mitochondrial efficiency, indicating a possible trade-off between immediate oxidative stress reduction and delayed muscular adaptations [19,38].The effectiveness of antioxidants appears more pronounced when sourced from natural foods, with dietary polyphenols enhancing antioxidant status and supporting recovery and performance effectively when part of a balanced diet, possibly due to the synergistic effects of nutrients within natural food matrices [52,54,57,69,77,78].These sources like fruits, vegetables, and whole grains deliver complex nutrients that supplements might not replicate [41].Furthermore, individual factors such as age, gender, fitness level, and exercise type also influence the interaction between dietary antioxidants and exercise-induced oxidative stress; for instance, older adults might need more nutritional antioxidants due to diminished endogenous production, whereas athletes should manage their intake not to counteract essential physiological stress responses [3,12,26,79].Ongoing research is vital to ascertain the optimal forms, timing, and dosages of antioxidants across various exercise modalities, aiming to enhance the health and performance benefits of exercise without compromising the adaptive responses essential to exercise physiology.

Demographic Variability in Oxidative Stress Response
Understanding how demographic factors such as age, gender, health status, ethnicity, and socioeconomic background influence oxidative and nitrosative stress responses to exercise is crucial for developing personalized health and fitness programs [80][81][82][83][84]. Older adults, who naturally experience declines in antioxidant production and mitochondrial function, may benefit from moderate-intensity exercises combined with antioxidant-rich diets to counteract age-related oxidative stress [85].Additionally, gender differences, often influenced by hormonal variations like estrogen in women, may necessitate adjustments in exercise intensities or modalities to optimize health outcomes across genders [86].Individuals with chronic conditions need specially tailored exercise plans to avoid exacerbating oxidative stress, while ethnic and socioeconomic disparities can impact susceptibility to oxidative damage and access to necessary resources, highlighting the importance of public health initiatives aimed at providing equitable health opportunities [87][88][89].Future research should employ longitudinal studies and personalized medicine principles to thoroughly investigate these demographic distinctions, thereby improving our ability to tailor exercise and dietary interventions to optimize individual health outcomes.

Future Research Directions
Future research should focus on developing precise, personalized guidelines that integrate exercise with antioxidant supplementation, tailored to the specific needs and demographic characteristics of the individuals.This should involve longitudinal studies to monitor long-term physiological adaptations to various exercise intensities and assess the roles of dietary and supplemental antioxidants in diverse populations.Moreover, a deeper exploration into the molecular mechanisms by which exercise impacts redox balance in different tissues will enhance our understanding of how antioxidants influence exercise-induced physiological responses.Integrating advanced technologies such as genomics, proteomics, and metabolomics will provide detailed insights into individual responses to exercise-induced oxidative stress, supporting the development of customized exercise and nutrition strategies.Clinical perspectives on these interventions are essential, particularly in considering how such strategies can be implemented in routine clinical practice to manage or prevent health conditions.Additionally, recognizing the influence of social, psychological, and environmental factors on exercise behaviors and outcomes is crucial for designing effective and culturally sensitive interventions.Collaborative efforts among researchers, healthcare providers, and policymakers are vital to ensure that scientific findings are translated into practical, accessible health applications that promote healthier lifestyles across various communities.

Conclusions
In conclusion, this review has comprehensively analyzed the impacts of physical exercise on oxidative and nitrosative stress, particularly emphasizing the role of antioxidants.Our findings underscore that exercise generally promotes health by enhancing the body's antioxidant defenses and redox balance; it can also induce oxidative stress, mainly when intense or improperly managed.These effects are significantly influenced by age, gender, ethnicity, and socioeconomic status, which can affect the generation of reactive species during exercise and the body's capacity to manage them.
The evidence suggests that moderate exercise stimulates beneficial adaptive responses through mechanisms like the activation of the NRF2 and ARE pathways, improving antioxidant defenses and cellular function.Conversely, excessive physical activity can lead to harmful levels of oxidative stress, suggesting the need for well-balanced exercise regimes.Additionally, the interaction between exercise-induced ROS and RNS production and the use of dietary antioxidants presents a complex but critical area for developing effective interventions.
Clinically, these insights advocate for personalized exercise programs that consider individual demographic factors and baseline oxidative stress levels to maximize the health benefits and minimize potential harm.Healthcare providers should consider these factors when prescribing exercise regimes and recommend dietary adjustments that enhance the body's natural antioxidant capacity.Further research is needed to develop more precise guidelines tailored to individual needs, improving the overall effectiveness of physical activity as a preventive and therapeutic tool in managing oxidative and nitrosative stress.This approach aligns with the initial purpose of our study, aiming to enhance the understanding and management of exercise-induced biochemical changes across diverse populations.

Table 1 .
Quality assessment of the reviewed studies.

Table 2 .
Detailed overview of exercise-induced oxidative stress mechanisms and antioxidant responses.

Description Participant Demographics Study Design and Intervention Details Examined Result Conclusions Practical Implications Typical Ranking of Different Types of Studies
[26]: B

Table 3 .
Detailed insights into exercise-induced nitrosative stress: mechanisms, benefits, and regulatory strategies.

Table 4 .
Comprehensive strategies for optimizing health benefits and mitigating.

Table 5 .
Enhanced understanding of the role of dietary antioxidants in exercise-induced oxidative stress mitigation.