Effects of antioxidant consumption on physical rehabilitation variables and quality of life in people with osteoarthritis: Protocol for a systematic review with meta-analysis

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Present in both foods and supplements, these molecules can neutralize free radicals and modulate inflammatory processes, both of which are implicated in the pathophysiology of osteoarthritis. Although the results of antioxidants have been promising, the current evidence remains heterogeneous and sometimes inconsistent. Therefore, it is necessary to integrate and critically analyze the available data. Objective This systematic review protocol with meta-analysis aims to describe the methodology necessary to analyze the effects of antioxidant intervention compared with usual medical care on pain, physical function, and quality of life in people with osteoarthritis. Methods In conducting this literature synthesis, a comprehensive search will be executed across the Medline databases via PubMed, Scopus, Web of Sciences, ScienceDirect, and EBSCO to identify randomized clinical trials that satisfy the predetermined eligibility criteria. Primary outcomes, including pain, physical function, and quality of life, and secondary outcomes, such as clinical modifications, will be analyzed. The quality of the selected studies will be evaluated using the ROB-2 risk of bias tool, and the certainty of the evidence will be assessed through the GRADE method. A meta-analysis will be conducted using either a fixed- or random-effects model, depending on the degree of heterogeneity. Heterogeneity will be assessed using the I2 statistic. If the outcome assessment method is homogeneous, the mean difference (MD) with a 95% confidence interval will be utilized; otherwise, the standardized mean difference (SMD) will be employed to calculate the effect size. Discussion Osteoarthritis imposes a substantial clinical and socioeconomic burden, and antioxidants are increasingly recognized as potential adjuvants owing to their safety and anti-inflammatory properties. The findings of this systematic review and meta-analysis based on this protocol will aid in determining the extent of the impact of antioxidant consumption in pertinent clinical practice. PROSPERO registration: CRD420251035393 " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-1380/v1", "name": "Effects of antioxidant consumption on physical rehabilitation variables..." } } ] } Home Browse Effects of antioxidant consumption on physical rehabilitation variables... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Riquelme-Hernández C, Reyes-Barría JP, Vargas A et al. Effects of antioxidant consumption on physical rehabilitation variables and quality of life in people with osteoarthritis: Protocol for a systematic review with meta-analysis [version 1; peer review: awaiting peer review] . F1000Research 2025, 14 :1380 ( https://doi.org/10.12688/f1000research.173013.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Effects of antioxidant consumption on physical rehabilitation variables and quality of life in people with osteoarthritis: Protocol for a systematic review with meta-analysis [version 1; peer review: awaiting peer review] Cristóbal Riquelme-Hernández https://orcid.org/0000-0002-1563-7229 1 , Juan Pablo Reyes-Barría 2 , Abner Vargas https://orcid.org/0000-0003-0909-2127 3,4 , [...] Luz Ortiz 5 , Caroline Yans 5 , Iván Cuyul-Vásquez 6 , Daniel Reyes-Molina 7 , Rafael Zapata-Lamana 7 , Carolina Muñoz Pérez https://orcid.org/0000-0002-1556-4250 8 , Igor Cigarroa 1,9 Cristóbal Riquelme-Hernández https://orcid.org/0000-0002-1563-7229 1 , Juan Pablo Reyes-Barría 2 , [...] Abner Vargas https://orcid.org/0000-0003-0909-2127 3,4 , Luz Ortiz 5 , Caroline Yans 5 , Iván Cuyul-Vásquez 6 , Daniel Reyes-Molina 7 , Rafael Zapata-Lamana 7 , Carolina Muñoz Pérez https://orcid.org/0000-0002-1556-4250 8 , Igor Cigarroa 1,9 PUBLISHED 09 Dec 2025 Author details Author details 1 Escuela de Kinesiología, Departamento de Salud, Arturo Prat, Victoria, Region de la Araucanía, Chile 2 Clínica de Fisioterapia, Club Domus, Montevideo, Uruguay 3 Universidad de los Lagos - Campus Puerto Montt, Puerto Montt, Region de Los Lagos, Chile 4 Nüwa Rehabilitación Física y Rendimiento, Puerto Montt, Los Lagos Region, Chile 5 Escuela de Nutrición y Dietética, Facultad de Salud, Universidad Santo Tomas Facultad de Salud, Puerto Montt, Region de Los Lagos, Chile 6 Departamento de Procesos Terapéuticos, Facultad de Ciencias de la Salud, Universidad Catolica de Temuco, Temuco, Araucania, Chile 7 Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomas, Los Ángeles, Region del Biobío, Chile 8 Escuela de Educación, Universidad de Concepcion, Los Ángeles, Region del Biobío, Chile 9 Escuela de Kinesiología, Facultad de Ciencias de la Salud, Universidad Catolica Silva Henriquez - Campus Lo Cañas, La Florida, Región Metropolitana, Chile Cristóbal Riquelme-Hernández Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Juan Pablo Reyes-Barría Roles: Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Abner Vargas Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Luz Ortiz Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Caroline Yans Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Iván Cuyul-Vásquez Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Daniel Reyes-Molina Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Rafael Zapata-Lamana Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Carolina Muñoz Pérez Roles: Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Igor Cigarroa Roles: Conceptualization, Investigation, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW REVIEWER STATUS AWAITING PEER REVIEW Abstract Introduction Antioxidants have emerged as potentially beneficial options. Present in both foods and supplements, these molecules can neutralize free radicals and modulate inflammatory processes, both of which are implicated in the pathophysiology of osteoarthritis. Although the results of antioxidants have been promising, the current evidence remains heterogeneous and sometimes inconsistent. Therefore, it is necessary to integrate and critically analyze the available data. Objective This systematic review protocol with meta-analysis aims to describe the methodology necessary to analyze the effects of antioxidant intervention compared with usual medical care on pain, physical function, and quality of life in people with osteoarthritis. Methods In conducting this literature synthesis, a comprehensive search will be executed across the Medline databases via PubMed, Scopus, Web of Sciences, ScienceDirect, and EBSCO to identify randomized clinical trials that satisfy the predetermined eligibility criteria. Primary outcomes, including pain, physical function, and quality of life, and secondary outcomes, such as clinical modifications, will be analyzed. The quality of the selected studies will be evaluated using the ROB-2 risk of bias tool, and the certainty of the evidence will be assessed through the GRADE method. A meta-analysis will be conducted using either a fixed- or random-effects model, depending on the degree of heterogeneity. Heterogeneity will be assessed using the I 2 statistic. If the outcome assessment method is homogeneous, the mean difference (MD) with a 95% confidence interval will be utilized; otherwise, the standardized mean difference (SMD) will be employed to calculate the effect size. Discussion Osteoarthritis imposes a substantial clinical and socioeconomic burden, and antioxidants are increasingly recognized as potential adjuvants owing to their safety and anti-inflammatory properties. The findings of this systematic review and meta-analysis based on this protocol will aid in determining the extent of the impact of antioxidant consumption in pertinent clinical practice. PROSPERO registration: CRD420251035393 READ ALL READ LESS Keywords Osteoarthritis, Antioxidants, Curcuminoid, Pain, Quality of Life, Physical fitness, Rehabilitation, Anti-Inflammatory Agents, Non-Steroidal Corresponding Author(s) Igor Cigarroa ( [email protected] ) Close Corresponding author: Igor Cigarroa Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Riquelme-Hernández C et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Riquelme-Hernández C, Reyes-Barría JP, Vargas A et al. Effects of antioxidant consumption on physical rehabilitation variables and quality of life in people with osteoarthritis: Protocol for a systematic review with meta-analysis [version 1; peer review: awaiting peer review] . F1000Research 2025, 14 :1380 ( https://doi.org/10.12688/f1000research.173013.1 ) First published: 09 Dec 2025, 14 :1380 ( https://doi.org/10.12688/f1000research.173013.1 ) Latest published: 09 Dec 2025, 14 :1380 ( https://doi.org/10.12688/f1000research.173013.1 ) Introduction Osteoarthritis (OA) is characterized by clinical symptoms and radiological indicators. While cartilage plays a pivotal role in its development, OA is a multifactorial disorder that affects the joint tissue components and its periphery. 1 This condition is often accompanied by bone neoformation and synovial proliferation, which can result in pain, loss of joint function, and disability. 2 , 3 Globally, the prevalence of osteoarthritis is 22.9% among individuals aged > 40 years. 4 It is one of the most common and disabling forms of the disease, followed by hip osteoarthritis. 5 This condition involves systemic factors such as increased body mass, chronic low-grade inflammation, progressive functional disability, and oxidative stress. 6 – 8 The primary risk factors include age, obesity, history of injuries, and abnormal load, with these factors interacting concurrently. 9 Collectively, osteoarthritis is a prevalent cause of pain, functional impairment, and diminished quality of life in adults. 10 , 11 In accordance with the guidelines set forth by the National Institute for Health and Care Excellence (NICE), the therapeutic management of osteoarthritis primarily emphasizes symptom control. In terms of non-pharmacological strategies, the guidelines advocate for therapeutic exercise, patient education, and weight reduction. 12 Regarding pharmacological interventions, analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are the principal pharmacological strategies. 13 Nevertheless, the extended or unsupervised use of these medications poses considerable risks, including adverse gastrointestinal, cardiovascular, and renal effects. 14 – 16 This scenario has led to the pursuit of safer, more sustainable, and long-term therapeutic alternatives. Excessive production of reactive oxygen species (ROS) and ROS-induced lipid peroxidation are implicated in the pathogenesis of osteoarthritis. 2 As oxidative stress intensifies, there is a concomitant increase in collagen degradation, indicating that ROS play a crucial role in the catabolism of the collagen matrix. 17 Antioxidants have emerged as a potentially advantageous intervention. 18 , 19 Antioxidants, which are naturally found in foods and supplements, 20 can neutralize free radicals and modulate inflammatory processes, both of which are integral to the pathophysiology of osteoarthritis. 21 Compounds such as curcumin, vitamin D, resveratrol, and other antioxidants have been investigated for their potential beneficial effects on chronic diseases, including osteoarthritis. 22 – 24 Specifically, turmeric, owing to its anti-inflammatory and antioxidant properties, has demonstrated positive effects in alleviating pain associated with osteoarthritis 25 by suppressing the expression of various pro-inflammatory cytokines, thereby mitigating pain and cartilage degeneration. 17 Similarly, the consumption of flavonoids has been shown to reduce TNF-α expression, as evidenced by existing research. 26 A recent systematic review indicated promising outcomes concerning the use of oral antioxidants for the prevention and alleviation of symptoms in individuals with osteoarthritis. Nevertheless, the existing evidence is characterized by heterogeneity and inconsistency, which complicates the generalization of these findings. 27 Consequently, a systematic review with meta-analysis, as derived from this protocol, is intended to evaluate the effects of antioxidant-based interventions compared to standard medical care on pain, physical function, and quality of life in individuals with hip and knee osteoarthritis. Research question In individuals with hip and knee osteoarthritis, does an intervention involving the consumption of oral antioxidants demonstrate greater efficacy than conventional medical treatments in alleviating pain, enhancing physical function, and improving quality of life? Methods Protocol and registration This systematic review protocol and meta-analysis were prospectively registered in PROSPERO (CRD420251035393). Its development adhered to the guidelines established by the PRISMA P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) statement. 28 (Supplementary 1, https://doi.org/10.6084/m9.figshare.30510332.v1 ). The methodology employed was in accordance with the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions. 29 Furthermore, a systematic review derived from this protocol will be conducted following the most recent version of the PRISMA statement. 30 Eligibility criteria Types of participants Randomized Clinical Trials involving adult males and females with a clinical diagnosis of knee or hip osteoarthritis will be included. Participants must be diagnosed according to established clinical criteria, such as those of the American College of Rheumatology (ACR). 31 Eligible studies must feature interventions involving the oral consumption of antioxidants compared to non-steroidal anti-inflammatory drugs (NSAIDs), placebo, or other standard medical treatments, and must analyze at least one variable related to physical rehabilitation and quality of life (QoL). Studies will be excluded if they involve participants exposed to antioxidants in combination with other uncontrolled therapies, as this would preclude the isolation of the antioxidant effects. Additionally, studies including individuals with severe comorbidities that may affect treatment response or functional capacity (e.g., cancer, advanced renal or hepatic failure, and active autoimmune diseases) will be excluded. Furthermore, studies utilizing supplements without detailed information on their composition, dosage, or purity, as well as those involving mixed populations (e.g., rheumatoid arthritis and osteoarthritis) without stratified analysis by diagnosis will also be excluded. Type of intervention Dietary antioxidants directly interact with free radicals and mitigate lipid peroxidation (LP). LP can compromise the integrity of the cell membrane and is implicated in osteoarthritis (OA). 32 Antioxidants, such as vitamins A and C, can attenuate LP by diminishing the levels of oxidation-reduction (REDOX) reactions through the elimination of reactive oxygen species (ROS). 33 Furthermore, antioxidants such as curcuminoids exhibit anti-inflammatory properties, 34 which partially elucidates their beneficial effects in osteoarthritis. The selected studies must include a prescribed regimen of therapy through controlled oral intake of antioxidants, whether in the form of food, dietary supplements, or extracts, with a minimum intervention duration of four weeks. Type of comparison Randomized clinical trials will be included in which the control group receives oral NSAID interventions, placebo, or standard medical care for osteoarthritis. Types of studies Randomized clinical trials (RCTs) assessing the effects of interventions involving the oral administration of antioxidants, in comparison to nonsteroidal anti-inflammatory drugs (NSAIDs), placebo, or standard medical care in individuals with hip or knee osteoarthritis, will be included. No language restrictions were applied. Sources of information A comprehensive and sensitive systematic search will be performed using the following databases: Medline via PubMed, Scopus, Web of Science, ScienceDirect, and EBSCO. Furthermore, a manual search will be conducted within the reference lists of the included studies, as well as systematic and narrative reviews and clinical practice guidelines pertinent to the subject matter. If additional data are necessary, the authors of the included studies will be contacted via email. Search strategy The search strategy implemented in the MEDLINE database employed both controlled vocabulary (Medical Subject Headings [MeSH]) and free-text terms. The search terms were systematically combined using the Boolean operators “OR” and “AND.” This search string will be tailored to each respective database. Table 1 delineates the search strategy used in the MEDLINE database via the PubMed search engine. Furthermore, the table has been disseminated on the figshare ( figshare.com ) information platform to enhance the transparency and reproducibility of the search process. Table 1. PubMed search strategy. Database Search descriptors MEDLINE/Pubmed #1 (“Osteoarthritis”[Mesh]) OR (osteoarthrosis) #2 (((((((((“Antioxidants”[Mesh]) OR (“Curcuma”[Mesh])) OR (“Vitamin A”[Mesh])) OR (“Carotenoids”[Mesh])) OR (“beta Carotene”[Mesh])) OR (“Ascorbic Acid”[Mesh])) OR (vitamin c)) OR (“Vitamin E”[Mesh])) OR (“Tocopherols”[Mesh])) OR (“Selenium”[Mesh]))))))))) #1 AND #2 Note: https://figshare.com/ : DOI. https://doi.org/10.6084/m9.figshare.30506216.v1 . Source: Own creation 2025. Study registration Selection process All studies identified through the literature search will be uploaded to the Rayyan web application, 35 where duplicates will be removed, and the study selection process will commence. Four reviewers will independently and blindly select articles by applying the inclusion and exclusion criteria based on their titles and abstracts. Subsequently, articles that meet these criteria will undergo full-text reviews. In instances of discrepancies during the selection process, a consensus will be achieved among the reviewers. The entire article selection process will be documented using a PRISMA flow diagram. Data extraction Data extraction will be independently performed by four reviewers, and the collected information will be documented in a standardized and previously piloted form. Subsequently, pertinent data will be organized and presented in summary tables and figures. The information gathered will include the general characteristics of the articles, such as author, year, country, population, sex, intervention, variables, and type of design; characteristics of the interventions, including frequency, treatment, scope, and duration; and a description of the effects of the interventions, encompassing pain, physical function, and QoL. For outcomes of interest, the mean and standard deviation will be recorded for continuous variables both pre- and post-intervention. In instances where studies report results using graphs, ImageJ software will be used to extract the data. Outcome measures Types of outcomes The Core Outcome Set (COS) recommended by the COMET initiative was used to select the primary and secondary outcomes. Specifically, the OMERACT-OARSI collaborative proposal for clinical trials in knee and hip osteoarthritis was employed, encompassing pain, physical function, quality of life, and the patient’s global assessment of the target joint. 36 Primary outcomes a) The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”. 37 It is evaluated using instruments with validated generic or specific questionnaires, such as the visual analog scale (VAS), WOMAC-PAIN, and KOOS-PAIN. b) According to the Penn State College of Medicine, physical function is defined as the ability to perform basic and instrumental activities of daily living. 38 It is assessed using instruments with validated generic or specific questionnaires, including WOMAC function, Time Up and Go (TUG), 6-minute walk test, KOOS function, 40-meter fast-paced walk test, and Lequesne Functional Index (LFI). c) The WHO defines quality of life as the perception an individual has of their position in life within the context of the culture and value system in which they live, and in relation to their goals, expectations, standards, and concerns. 39 It is measured using instruments with validated generic or specific questionnaires, such as the KOOS-qol, WHOqol-bref, and SF-36. Secondary outcomes a) Clinical modifications are defined as alterations in objective outcome variables pertaining to physical function and the clinical status of the joints. 40 These modifications are evaluated using instruments that incorporate validated generic or specific questionnaires, such as the Patient’s Global Assessment of Disease Activity (PGADA) and Clinical Disabilities Scale (KSS-clinical). Risk of bias assessment The methodological quality of the studies will be evaluated using the Cochrane Risk of Bias 2.0 (ROB II) tool. This tool assesses studies across six key domains: D1) bias arising from the randomization process, D2) bias due to deviations from intended interventions, D3) bias due to missing outcome data, D4) bias in the measurement of the outcome, and D5) bias in the selection of the reported result, as well as the overall risk of bias. To determine the overall risk of bias for each article, the following criteria will be considered: low risk of bias—all domains evaluated as “low risk”; High risk of bias—one or more domains evaluated as “high risk,” or multiple domains with a “concern for bias” that affect the credibility of the result; Some concerns—at least one domain with “concern for bias,” but no domains at “high risk”. 41 , 42 The ROB II tool will be applied independently by two reviewers, and any discrepancies will be resolved through discussion until a consensus is achieved. Summary of results A quantitative synthesis will be conducted utilizing Jamovi 2.2 software. The Revman calculator will be employed to ascertain the mean and standard deviation when studies report results using alternative measures of central tendency and data dispersion. A quantitative synthesis will be conducted using Jamovi 2.2 software. The Revman calculator will be used to ascertain the mean and standard deviation when studies report results using alternative measures of central tendency and data dispersion. A fixed-effects or random-effects model will be selected based on statistical heterogeneity, which will be assessed using the I 2 statistic. If the method for evaluating results is homogeneous, the mean difference (MD) with a 95% confidence interval will be utilized; otherwise, the standardized mean difference (SMD) will be employed to calculate the effect size (adjusted Hedges’ g). In cases of substantial (I2 = 50%–90%) or considerable (I2 = 75%–100%) heterogeneity, a DerSimonian and Laird random-effects model will be applied. Conversely, if heterogeneity is low (I2 = 0%–40%) or moderate (I2 = 30%–60%), a Mantel-Haenszel fixed-effects model will be applied. 29 A p-value < 0.05 will be considered statistically significant. Subgroup analyses will be conducted based on the type of antioxidant, osteoarthritis, and duration of the interventions. Moderator variable analysis will be performed on studies reporting data such as age, body mass index, pain duration, and others. If sufficient data are available, a dose-response analysis will be conducted based on the antioxidant dose for the variables, following the recommendations by Crippa and Orsini (2016). 43 Sensitivity analyses will also be conducted if clinical and methodological heterogeneity justifies it, such as restricting studies with a high risk of bias or imputing missing data for the main variables. If the studies presented show clinical heterogeneity, are insufficient, or there are not enough studies to perform a meta-analysis, a narrative synthesis of the effects of the intervention for each variable will be performed. Any deviations from the protocol will be documented and justified in the final report, in accordance with the PRISMA 2020 guidelines. Additionally, the corresponding information will be updated on the PROSPERO platform. Finally, synthesis and assessment of the certainty of evidence will be performed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Meta-biases The meta-biases to be examined will include publication bias, the potential presence of which will be assessed through observation of funnel plots and the application of Egger’s test. 44 Reporting bias will be analyzed by identifying discrepancies between published data and registered protocols of each study. If discrepancies are detected, the corresponding authors will be contacted via email to resolve any information queries. 44 Certainty of the evidence The certainty of the evidence will be assessed using the GRADE methodology through the GRADEpro CDT online tool ( https://gdt.gradepro.org/app/ ). The certainty of the evidence will initially be considered high for randomized controlled trials and may decrease for five reasons or domains: risk of bias, inconsistency in results, indirectness of evidence, imprecision of estimates, and publication bias. For each outcome, the quality of evidence will be applied and stratified into one of four levels: high, moderate, low, and very low. 45 Dissemination Once the systematic review with meta-analysis is completed, we will submit the manuscript to relevant peer-reviewed academic journals for publication. Study status This systematic review with meta-analysis is currently in the data collection phase for the selected articles. Discussion Osteoarthritis is a significant source of pain, disability, and socioeconomic costs. 7 , 46 Previously, it was believed to be simply due to wear and tear; however, it is now understood to be a complex interaction of local and systemic factors. 47 The usual management of the disease involves traditional palliative measures, such as topical and systemic analgesics, including nonsteroidal anti-inflammatory drugs, therapeutic exercise, weight loss, education, and orthoses. However, researchers continue to discover new therapeutic targets that are effective in osteoarthritis. 48 In this context, the possible outcomes of this research indicate that antioxidants may be potentially beneficial owing to their effects on variables such as pain, inflammatory biomarkers, and overall assessment of disease activity, as well as their safety and low incidence of serious adverse effects in therapeutic applications. 49 Furthermore, this addresses a clinical and scientific need, as well as the possibility that antioxidants may represent a low-cost and relatively safe adjuvant therapeutic approach. 50 Their appeal lies in their ability to neutralize reactive oxygen species and modulate key inflammatory pathways, 51 which can not only alleviate symptoms but also help slow the structural progression of the disease. Unlike conventional drugs, such as nonsteroidal anti-inflammatory drugs, the long-term use of which is associated with gastrointestinal, cardiovascular, and renal adverse effects, 52 , 53 antioxidants generally have a more favorable safety profile, positioning them as useful adjuncts to reduce medication dosages and improve treatment tolerability. 27 Likewise, the systematic review with meta-analysis developed from this protocol will help identify the effect sizes of antioxidant consumption on relevant clinical variables in the context of physical rehabilitation in adults with osteoarthritis. Similarly, it will allow for the identification of the most studied types of antioxidants and those that show the greatest effectiveness, as well as analyze whether their use provides additional benefits beyond standard medical care in this population group. The synthesis of the resulting evidence may guide clinicians and decision-makers in choosing therapeutic strategies aimed at improving the quality of life of people with osteoarthritis. Nevertheless, despite the increase in studies on antioxidants in osteoarthritis, the evidence remains inconsistent and is characterized by marked heterogeneity in study design, populations, interventions, dosages, durations, and outcome measures. 21 This variability makes it difficult to draw solid conclusions about their effectiveness, as the reported effects differ considerably between studies, limiting both the evaluation of their actual clinical impact and their general applicability. Along these lines, a foreseeable limitation is that methodological and clinical heterogeneity among the included studies may restrict the comparability of different antioxidant interventions. Finally, our results will open various lines of research for future projects, as this is a topic about which there is very little knowledge. Ethical considerations This systematic review protocol with meta-analysis is based on the use of secondary data from previously published articles; therefore, it does not require approval from an ethics committee. The analysis and interpretation of the information will be carried out independently by the authors, ensuring that there is no external interference with the results. Data availability Underlying data There are no data associated with this article. Extended data Figshare: Table with the search string developed for the PubMed database. This project contains the following extended data files: 1. PubMed search strategy 2. PRISMA-P checklist 3. ICMJE form Name of the repository: Figshare Project title: Effects of antioxidant consumption on physical rehabilitation variables and quality of life in people with osteoarthritis: Protocol for a systematic review with meta-analysis. 53 – 55 DOI: https://doi.org/10.6084/m9.figshare.30506216.v1 53 Project title: Checklist PRISMA P DOI: https://doi.org/10.6084/m9.figshare.30510332.v1 54 Project title: ICMJE DOI: https://doi.org/10.6084/m9.figshare.30510509.v1 55 License: CC BY 4.0 Acknowledgements None. References 1. Bliddal H: Definition, pathology and pathogenesis of osteoarthritis. Ugeskr. Laeger. 2020 Oct 12; 182 (42): V06200477. 2. Abramson SB, Attur M: Developments in the scientific understanding of osteoarthritis. Arthritis Res. Ther. 2009 May 19; 11 (3): 227. PubMed Abstract | Publisher Full Text | Free Full Text 3. Wei G, Lu K, Umar M, et al. : Risk of metabolic abnormalities in osteoarthritis: a new perspective to understand its pathological mechanisms. Bone Res. 2023 Dec 6; 11 (1): 63. PubMed Abstract | Publisher Full Text | Free Full Text 4. Cui A, Li H, Wang D, et al. : Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020 Dec; 29-30 : 100587. PubMed Abstract | Publisher Full Text | Free Full Text 5. Long H, Liu Q, Yin H, et al. : Prevalence trends of site-specific osteoarthritis from 1990 to 2019: findings from the Global Burden of Disease Study 2019. Arthritis Rheumatol. 2022 Jul; 74 (7): 1172–1183. PubMed Abstract | Publisher Full Text | Free Full Text 6. Messier SP: Obesity and osteoarthritis: disease genesis and nonpharmacologic weight management. Rheum. Dis. Clin. N. Am. 2008 Aug; 34 (3): 713–729. PubMed Abstract | Publisher Full Text | Free Full Text 7. Martel-Pelletier J, Barr AJ, Cicuttini FM, et al. : Osteoarthritis. Nat. Rev. Dis. Primers. 2016 Oct 13; 2 : 16072. Publisher Full Text 8. Amalia PBA, Astuti D, Widyastuti R: Analisis faktor risiko terjadinya osteoarthritis. CoMPHI J. Community Med. Public Health Indones. J. 2023 [cited 2025 Jul 23]; 4 (2). Publisher Full Text Reference Source 9. Blümel JE, Aedo S, Arteaga E, et al. : Risk factors for the development of osteoarthritis in middle-aged women. Rev. Med. Chile. 2022 Jan; 150 (1): 46–53. PubMed Abstract | Publisher Full Text 10. Pang J, Cao YL, Zheng YX, et al. : Influence of pain severity on health-related quality of life in Chinese knee osteoarthritis patients. Int. J. Clin. Exp. Med. 2015 Mar 15; 8 (3): 4472–4479. PubMed Abstract 11. Araujo ILA, Castro MC, Daltro C, et al. : Quality of life and functional independence in patients with osteoarthritis of the knee. Knee Surg. Relat. Res. 2016 Sep; 28 (3): 219–224. PubMed Abstract | Publisher Full Text | Free Full Text 12. National Institute for Health and Care Excellence (NICE): Osteoarthritis in over 16s: diagnosis and management. Guidance NG226. London: NICE; 2022 [cited 2025 Sep 28]. Reference Source 13. McAlindon TE, Bannuru RR, Sullivan MC, et al. : OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr. Cartil. 2014 Mar; 22 (3): 363–388. PubMed Abstract | Publisher Full Text 14. Cooper C, Chapurlat R, Al-Daghri N, et al. : Safety of oral non-selective non-steroidal anti-inflammatory drugs in osteoarthritis: What does the literature say?. Drugs Aging. 2019 Apr; 36 (Suppl 1): 15–24. PubMed Abstract | Publisher Full Text | Free Full Text 15. Domper Arnal MJ, Hijos-Mallada G, Lanas A: Gastrointestinal and cardiovascular adverse events associated with NSAIDs. Expert Opin. Drug Saf. 2022 Mar; 21 (3): 373–384. Publisher Full Text 16. Liang S, Wang X, Zhu X: Insights from pharmacovigilance and pharmacodynamics on cardiovascular safety signals of NSAIDs. Front. Pharmacol. 2024 Sep 4 [cited 2025 Jul 23]; 15 . PubMed Abstract | Publisher Full Text | Free Full Text 17. Ansari MY, Ahmad N, Haqqi TM: Oxidative stress and inflammation in osteoarthritis pathogenesis: role of polyphenols. Biomed. Pharmacother. 2020 Sep 1; 129 : 110452. PubMed Abstract | Publisher Full Text | Free Full Text 18. Hsueh HC, Ho GR, Tzeng SI, et al. : Effects of curcumin on serum inflammatory biomarkers in patients with knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Med. Ther. 2025 Jul 4; 25 (1): 237. PubMed Abstract | Publisher Full Text | Free Full Text 19. Bhol NK, Bhanjadeo MM, Singh AK, et al. : The interplay between cytokines, inflammation, and antioxidants: mechanistic insights and therapeutic potentials of various antioxidants and anti-cytokine compounds. Biomed. Pharmacother. 2024 Sep 1; 178 : 117177. PubMed Abstract | Publisher Full Text 20. Grover AK, Samson SE: Benefits of antioxidant supplements for knee osteoarthritis: rationale and reality. Nutr. J. 2016 Jan 5; 15 (1): 1. Publisher Full Text 21. Valsamidou E, Gioxari A, Amerikanou C, et al. : Dietary interventions with polyphenols in osteoarthritis: a systematic review directed from the preclinical data to randomized clinical studies. Nutrients. 2021 Apr 23; 13 (5): 1420. PubMed Abstract | Publisher Full Text | Free Full Text 22. Srivastava S, Saksena A, Khattri S, et al. : Curcuma longa extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of the knee: a four-month, double-blind, randomized, placebo-controlled trial. Inflammopharmacology. 2016 Dec; 24 (6): 377–388. PubMed Abstract | Publisher Full Text 23. Sanghi D, Mishra A, Sharma A, et al. : Does vitamin D improve osteoarthritis of the knee: a randomized controlled pilot trial. Clin. Orthop. Relat. Res. 2013 Nov; 471 (11): 3556–3562. PubMed Abstract | Publisher Full Text | Free Full Text 24. Nguyen C, Coudeyre E, Boutron I, et al. : Oral resveratrol in adults with knee osteoarthritis: a randomized placebo-controlled trial (ARTHROL). PLoS Med. 2024 Aug; 21 (8): e1004440. PubMed Abstract | Publisher Full Text | Free Full Text 25. Zeng L, Yu G, Hao W, et al. : The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis. Biosci. Rep. 2021 May 15; 41 (6): 1–20. Publisher Full Text 26. Kasprzyk N, Nandy S, Grygiel-Górniak B: Diet in knee osteoarthritis-myths and facts. Nutrients. 2025 Jan; 17 (11): 1872. PubMed Abstract | Publisher Full Text | Free Full Text 27. Nejadhosseinian M, Djalalinia S, Haerian H, et al. : The effects of antioxidants on knee osteoarthritis: a systematic review and meta-analysis. Front. Nutr. 2022; 9 : 1026450. PubMed Abstract | Publisher Full Text | Free Full Text 28. Moher D, Shamseer L, Clarke M, et al. : Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev. 2015 Jan 1; 4 (1): 1. PubMed Abstract | Publisher Full Text | Free Full Text 29. Cochrane Collaboration: Cochrane Handbook for Systematic Reviews of Interventions.[cited 2025 Apr 22]. Reference Source 30. Page MJ, McKenzie JE, Bossuyt PM, et al. : The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29; 372 : n71. PubMed Abstract | Publisher Full Text | Free Full Text 31. Zhang X, Hou L, Guo Z, et al. : Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis. Cell Death Dis. 2023 Aug 29; 9 (1): 1–13. Publisher Full Text 32. Canals-Garzón C, Guisado-Barrilao R, Martínez-García D, et al. : Effect of antioxidant supplementation on markers of oxidative stress and muscle damage after strength exercise: a systematic review. Int. J. Environ. Res. Public Health. 2022 Jan; 19 (3): 1803. PubMed Abstract | Publisher Full Text | Free Full Text 33. Buhrmann C, Mobasheri A, Busch F, et al. : Curcumin modulates nuclear factor kappaB (NF-kappaB)-mediated inflammation in human tenocytes in vitro: role of the phosphatidylinositol 3-kinase/Akt pathway. J. Biol. Chem. 2011 Aug 12; 286 (32): 28556–28566. PubMed Abstract | Publisher Full Text | Free Full Text 34. Ouzzani M, Hammady H, Fedorowicz Z, et al. : Rayyan-a web and mobile app for systematic reviews. Syst. Rev. 2016 Dec 5; 5 (1): 210. PubMed Abstract | Publisher Full Text | Free Full Text 35. Smith TO, Hawker GA, Hunter DJ, et al. : The OMERACT-OARSI core domain set for measurement in clinical trials of hip and/or knee osteoarthritis. J. Rheumatol. 2019 Aug; 46 (8): 981–989. PubMed Abstract | Publisher Full Text | Free Full Text 36. Raja SN, Carr DB, Cohen M, et al. : The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020 Sep 1; 161 (9): 1976–1982. PubMed Abstract | Publisher Full Text | Free Full Text 37. Penn State College of Medicine Research: Improving physical function with exercise.[cited 2025 Jul 30]. Reference Source 38. The WHOQOL Group: Development of the World Health Organization WHOQOL-BREF quality of life assessment. Psychol. Med. 1998 May; 28 (3): 551–558. Publisher Full Text 39. Silva ALPE, Demange MK, Gobbi RG, et al. : Translation and validation of the Knee Society Score (KSS) for Brazilian Portuguese. Acta Ortop Bras. 2012; 20 (1): 25–30. PubMed Abstract | Publisher Full Text | Free Full Text 40. Higgins JPT, Savović J, Page MJ, et al. : Revised Cochrane risk-of-bias tool for randomized trials (RoB 2).[cited 2024 Dec 18]. Reference Source 41. Sterne JAC, Savović J, Page MJ, et al. : RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019 Aug 28; 366 : l4898. Publisher Full Text 42. Crippa A, Orsini N: Multivariate dose–response meta-analysis: the dosresmeta R package. J. Stat. Softw. 2016 Aug 16; 72 : 1–15. Publisher Full Text 43. Sterne JAC, Egger M, Smith GD: Investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001 Jul 14; 323 (7304): 101–105. PubMed Abstract | Publisher Full Text | Free Full Text 44. Xie CX, Machado GC: Clinimetrics: grading of recommendations, assessment, development and evaluation (GRADE). J. Physiother. 2021 Jan; 67 (1): 66. PubMed Abstract | Publisher Full Text 45. Glyn-Jones S, Palmer AJR, Agricola R, et al. : Osteoarthritis. Lancet. 2015 Jul 25; 386 (9991): 376–387. Publisher Full Text 46. Abramoff B, Caldera FE: Osteoarthritis: pathology, diagnosis, and treatment options. Med. Clin. North Am. 2020 Mar; 104 (2): 293–311. Publisher Full Text 47. Siddiq MAB, Oo WM, Hunter DJ: New therapeutic strategies in osteoarthritis. Joint Bone Spine. 2024 Dec; 91 (6): 105739. Publisher Full Text 48. Henrotin Y, Malaise M, Wittoek R, et al. : Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo-controlled three-arm study. Arthritis Res. Ther. 2019 Dec; 21 (1): 179. PubMed Abstract | Publisher Full Text | Free Full Text 49. Feng J, Li Z, Tian L, et al. : Efficacy and safety of curcuminoids alone in alleviating pain and dysfunction for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. BMC Complement. Med. Ther. 2022 Oct 19; 22 (1): 276. PubMed Abstract | Publisher Full Text | Free Full Text 50. Manful CF, Fordjour E, Subramaniam D, et al. : Antioxidants and reactive oxygen species: shaping human health and disease outcomes. Int. J. Mol. Sci. 2025 Aug 4; 26 (15): 7520. PubMed Abstract | Publisher Full Text | Free Full Text 51. Schaffer D, Florin T, Eagle C, et al. : Risk of serious NSAID-related gastrointestinal events during long-term exposure: a systematic review. Med. J. Aust. 2006 Nov 6; 185 (9): 501–506. PubMed Abstract | Publisher Full Text 52. Soliman S, Ahmed RM, Ahmed MM, et al. : Non-steroidal anti-inflammatory drugs: what is the actual risk of chronic kidney disease? A systematic review and meta-analysis. Rom. J. Intern. Med. 2025 Mar 1; 63 (1): 3–27. PubMed Abstract | Publisher Full Text 53. Riquelme C: Effects of antioxidant consumption on physical rehabilitation variables and quality of life in people with osteoarthritis: Protocol for a systematic review with meta-analysis. figshare. Figure. 2025. Publisher Full Text 54. Riquelme C: Checklist PRISMA P. figshare. Figure. 2025. Publisher Full Text 55. Riquelme C: ICMJE. figshare. Figure. 2025. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 09 Dec 2025 ADD YOUR COMMENT Comment Author details Author details 1 Escuela de Kinesiología, Departamento de Salud, Arturo Prat, Victoria, Region de la Araucanía, Chile 2 Clínica de Fisioterapia, Club Domus, Montevideo, Uruguay 3 Universidad de los Lagos - Campus Puerto Montt, Puerto Montt, Region de Los Lagos, Chile 4 Nüwa Rehabilitación Física y Rendimiento, Puerto Montt, Los Lagos Region, Chile 5 Escuela de Nutrición y Dietética, Facultad de Salud, Universidad Santo Tomas Facultad de Salud, Puerto Montt, Region de Los Lagos, Chile 6 Departamento de Procesos Terapéuticos, Facultad de Ciencias de la Salud, Universidad Catolica de Temuco, Temuco, Araucania, Chile 7 Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomas, Los Ángeles, Region del Biobío, Chile 8 Escuela de Educación, Universidad de Concepcion, Los Ángeles, Region del Biobío, Chile 9 Escuela de Kinesiología, Facultad de Ciencias de la Salud, Universidad Catolica Silva Henriquez - Campus Lo Cañas, La Florida, Región Metropolitana, Chile Cristóbal Riquelme-Hernández Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Juan Pablo Reyes-Barría Roles: Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Abner Vargas Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Luz Ortiz Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Caroline Yans Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Iván Cuyul-Vásquez Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Daniel Reyes-Molina Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Rafael Zapata-Lamana Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Carolina Muñoz Pérez Roles: Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Igor Cigarroa Roles: Conceptualization, Investigation, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 09 Dec 2025, 14:1380 https://doi.org/10.12688/f1000research.173013.1 Copyright © 2025 Riquelme-Hernández C et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Riquelme-Hernández C, Reyes-Barría JP, Vargas A et al. 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