Osteoarthritis (OA) is a degenerative joint disease characterized by pain, stiffness, and reduced flexibility, often assessed or classified using radiographic imaging [1]. It typically affects the articular cartilage and underlying bone within synovial joints [2]. Symptomatic OA is defined as the coexistence of radiographic OA and symptoms attributable to the disease [3]. As a prevalent chronic condition, OA presents a major clinical and economic challenge, particularly in aging populations. The global burden of OA is substantial, with a rapidly increasing economic impact on healthcare systems [4]. The primary symptoms include joint pain, aching, and stiffness, leading to limitations in mobility and quality of life. Against this background, there is growing interest in accessible adjunctive strategies that may target inflammatory pathways and improve OA-related symptoms. The present review focuses specifically on polyphenol- and anthocyanin-rich dark fruits, which have been proposed as food-based interventions with potential antioxidant and anti-inflammatory properties.

OA is the most common joint disorder globally and the leading cause of walking-related disability among older adults in the United States [5]. It is increasingly recognized as an inflammatory disease of synovial joints, where the associated structural changes negatively impact gait performance and limit physical activity [6]. Epidemiological studies in the United States indicate that OA affects approximately 13.9% of adults aged 25 and older, and 33.6% of those over 65 years [7]. A range of systemic and local biomechanical factors contribute to OA development. Systemic factors include age, gender, race or ethnicity, genetics, obesity, osteoporosis, bone density, and nutrition, while local factors encompass joint injury, occupation, physical activity levels, limb-length discrepancies, neuromuscular function, bone characteristics, and joint space integrity [8]. Among these, obesity, aging, and female gender are the most prominent risk factors [9].

Although OA is a highly prevalent and disabling condition, no pharmacological treatment has been shown to modify the underlying disease mechanisms or alter its natural progression [10]. Current management strategies focus on symptom relief and improving quality of life through therapeutic approaches with minimal adverse effects. Pharmacologic therapies, including oral and topical nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors, are considered first-line treatments due to their effectiveness in reducing pain and improving function [11]. Intra-articular corticosteroid injections are also frequently used and are generally well tolerated [11], although their effects are often short-lived [12]. For advanced cases, surgical interventions such as joint replacement remain the most effective options for restoring function and improving quality of life [13]. However, long-term use of pharmacological agents is associated with serious adverse effects, including cardiovascular and gastrointestinal complications [14, 15]. Furthermore, these treatments impose considerable financial burdens on healthcare systems and contribute to an overreliance on prescription medications [16]. There is, therefore, a pressing need for OA-specific public health strategies focused on prevention, personalized conservative treatments, and gender-sensitive care models to ensure sustainable management of OA within aging societies.

Inflammation plays a central role in the initiation and progression of OA [17]. Several inflammatory pathways, including the activity of cytokines and matrix metalloproteinases (MMPs), contribute to cartilage degradation and disease advancement [18]. Contemporary OA research increasingly conceptualises OA as a heterogeneous whole-joint disease involving interactions between cartilage, synovium, subchondral bone, mechanical loading, metabolic dysfunction, and chronic low-grade inflammation [19, 20]. In this context, molecular endotypes and biomarkers of inflammatory activity, cartilage matrix turnover, and subchondral bone remodelling are increasingly being investigated to improve patient stratification, monitor progression, and support the development of disease-modifying OA therapies [21–24]. This is relevant to the present review because the included trials assessed not only patient-reported symptoms, but also inflammatory and cartilage-related biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, IL-10, MMP-3, and MMP-13.

Importantly, elevated levels of inflammatory and cartilage-related biomarkers have been observed in individuals with OA [24–26] and are known to accelerate disease progression [27, 28]. Conversely, anti-inflammatory cytokines such as IL-10 and IL-13 exhibit chondroprotective effects that can help slow OA progression [29, 30]. Given the central role of inflammation, growing attention has been directed toward dietary interventions that modulate inflammatory pathways. Anti-inflammatory dietary patterns, including the Mediterranean and plant-based diets, which emphasize fruits, vegetables, whole grains, and healthy fats, have shown potential to influence inflammatory responses and improve OA symptoms [31, 32]. Evidence supports that these dietary approaches can reduce systemic inflammation independent of weight loss [33], suggesting they may offer a cost-effective strategy for managing OA. However, adherence to such dietary modifications over long periods has proven challenging [34].

Given these challenges, dietary supplementation has emerged as a promising adjunctive or alternative approach for OA management. Nutraceuticals such as glucosamine, chondroitin sulfate, and methylsulfonylmethane have been linked to modest improvements and delayed progression of knee OA [35–37], though clinical benefits depend on pharmaceutical-grade formulations and appropriate dosing [38]. Other nutrients and bioactive compounds have also been investigated in OA. Vitamin D has been evaluated in several randomized controlled trials (RCTs) [39–41], with larger trials reporting no clear benefit for pain, function, stiffness, or structural progression, whereas ginger [42–44] and turmeric-containing formulations [43] have shown some symptom-related benefits in selected studies; overall, the evidence remains heterogeneous and further high-quality trials are needed.

Natural antioxidants and anti-inflammatory compounds have been proposed as promising supplementary strategies for OA due to their potential to reduce inflammation with minimal side effects [44, 45]. Among these, anthocyanins, a subclass of polyphenols abundant in darkly pigmented fruits, have attracted significant attention. These compounds possess potent antioxidant properties [46] and may modulate inflammatory pathways implicated in OA [17]. Randomized intervention studies have demonstrated the efficacy of anthocyanin-rich fruits in alleviating inflammation and oxidative stress across a range of chronic conditions, including cardiovascular disease [47], certain cancers [48], metabolic syndrome [49], dyslipidemia [45, 50], hypertension [51, 52], and inflammatory bowel disease [53]. There is now a growing body of RCTs evaluating their effects specifically in OA, assessing both symptomatic improvements and biochemical markers of disease activity.

Despite increasing interest in polyphenol-rich dark fruits as a therapeutic approach for OA, no systematic review or meta-analysis has yet synthesized the evidence from randomized trials evaluating their effects on OA-related outcomes. Several studies have investigated their impact on pain and other symptomatic measures, as well as on biomarkers reflective of inflammation and cartilage metabolism. A systematic synthesis of this literature is therefore timely and necessary to determine the overall efficacy of these interventions. Accordingly, the core question addressed in this review is whether polyphenol-rich dark fruit supplementation improves OA-related symptoms and inflammatory or cartilage-related biomarkers compared with placebo, usual care, or no intervention. By integrating available RCT evidence, this meta-analysis aims to clarify the potential role of these interventions in OA clinical management and to identify priorities for future research.

This systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including the checklist, flow diagram, and accompanying Explanation and Elaboration document [54]. In addition, the Cochrane Handbook for Systematic Reviews of Interventions was consulted to inform the methodological approach [55]. This meta-analysis was registered prospectively via a database of systematic reviews in health-related research (CRD420251148988; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251148988).

The present systematic review and meta-analysis critically evaluated and quantified the effects of polyphenol-rich dark fruit supplementation on clinical and biochemical outcomes in individuals with OA. To our knowledge, this is the first systematic review and meta-analysis to examine the role of polyphenol-rich dark fruits in OA. By synthesising available RCT evidence, this review aimed to provide an integrated understanding of the potential therapeutic utility of these natural compounds and to inform future research and clinical practice. Six RCTs met the inclusion criteria [66–71], all of which investigated knee OA. The interventions varied in duration, formulation, and fruit type, ranging from 3–16 weeks and including blueberry, tart cherry, strawberry, and pomegranate in powder or juice form.

With respect to the primary clinical outcome of overall OA symptom severity, which was assessed across four RCTs [66, 68, 69, 71], polyphenol-rich dark fruit supplementation was associated with a small but statistically significant improvement compared with placebo (g = –0.309). This aligns with prior meta-analytic evidence demonstrating beneficial effects of antioxidant supplementation in knee OA [72], suggesting that dark fruit supplementation may help to alleviate disease-related OA symptoms. Given the major clinical and socioeconomic burden of OA [4], such findings, though modest, may have meaningful implications for patient care and the development of accessible adjunctive therapies. No statistically significant effects were found for WOMAC pain or stiffness subscales, although a small but significant benefit was observed for WOMAC physical function (g = –0.335). Both of these outcomes exhibited low heterogeneity, yet GRADE evaluation indicated low certainty of evidence, and RoB 2.0 assessments identified moderate to high risk of bias across trials. These results therefore suggest potential, but not definitive, therapeutic efficacy of dark fruit supplementation, warranting cautious interpretation. The magnitude of the observed clinical effects should also be considered in patient-centred terms. Although statistically significant, the pooled effects for overall symptom severity and physical function were small, suggesting that any average symptomatic benefit is likely to be modest. Because outcomes were synthesized using SMDs across different clinical scales, and because absolute changes relative to established minimal clinically important differences were not consistently available, it is not possible to determine whether these effects would be clearly perceptible or clinically meaningful for individual patients. The findings should therefore be interpreted as evidence of possible short-term adjunctive benefit rather than as evidence of a large patient-perceived improvement.

In relation to biochemical outcomes, five RCTs [66–70] examined one or more inflammatory biomarkers. For IL-6 specifically, three RCTs [66, 68, 70] provided extractable data, and the pooled meta-analysis demonstrated a small but statistically significant reduction favouring polyphenol-rich dark fruit supplementation compared with placebo/control (g = –0.398). Joint inflammation is present in most individuals with OA [17], and IL-6 is known to play a key role in disease pathophysiology by promoting cartilage degradation and pain via matrix-degrading enzymes and downstream mediators of IL-6 signalling. Elevated IL-6 levels correlate with OA incidence and symptom severity, indicating its importance as a therapeutic target. The reduction in IL-6 observed here suggests that polyphenol-rich dark fruits may influence inflammatory pathways relevant to OA pathophysiology [73, 74]. However, this finding should not be interpreted as evidence of disease modification because intervention durations were short, structural outcomes were not assessed, heterogeneity was substantial (I² = 80.2%), certainty of evidence was low, and all included studies exhibited moderate risk of bias. The heterogeneity in the IL-6 analysis may plausibly reflect differences between the three contributing interventions: Du et al. [66] used 40 g/day freeze-dried blueberry powder for 16 weeks, with polyphenol/anthocyanin composition not reported; Schell et al. [68] used 50 g/day freeze-dried strawberry powder for 12 weeks, containing 1,585 mg total polyphenols and approximately 66 mg anthocyanins; and Kuehl et al. [70] used two 10.5-oz bottles/day of tart cherry juice for 3 weeks, providing at least 1,200 mg phenolics and 80 mg anthocyanins per day. These differences in fruit type, formulation, bioactive composition, dose, intervention duration, and biomarker assessment context may have contributed to the observed variability in IL-6 effects. Therefore, although the pooled analysis suggests a possible short-term reduction in IL-6, confidence in this estimate is limited.

Taken together, the findings provide limited and preliminary evidence that dark fruit supplementation may influence selected short-term clinical and biochemical outcomes in OA. However, the certainty of the evidence was low for several key outcomes, and moderate-to-high risk of bias across the included trials limits confidence in the pooled estimates. Across included studies, adherence was generally high where reported, and adverse events were relatively infrequent; however, safety conclusions should remain cautious because adverse-event reporting was incomplete, reasons for withdrawal were not always specified, and all trials were small and short in duration. The sugar content of juice-based interventions may also be relevant for individuals with diabetes, metabolic syndrome, or impaired glycaemic control and should certainly be reported systematically in future trials.

While methodological inconsistencies restrict the strength of inference, the convergence of evidence across symptom-related and biochemical endpoints suggests that polyphenol-rich dark fruits may warrant further investigation as an adjunctive nutritional strategy for OA; however, the current evidence is insufficient to support firm clinical recommendations. In light of the increasing emphasis on multimodal management strategies, incorporating nutritional interventions of this nature could enhance symptom control and improve patient well-being. Nevertheless, these promising findings must be substantiated through rigorously designed, adequately powered clinical trials employing standardised measures of efficacy and compliance.

The methodological strengths of this review include adherence to PRISMA and Cochrane guidelines [54, 55], the exclusive inclusion of RCTs, and the combined assessment of both clinical symptoms and inflammatory biomarkers to provide a comprehensive overview of dark fruit supplementation effects in OA. However, several limitations should be acknowledged. Restricting inclusion to English-language studies may have introduced publication bias, and all eligible RCTs investigated knee OA, limiting the generalisability of findings to other OA phenotypes. The small number of studies precluded subgroup analyses, preventing evaluation of the differential effects of specific fruit types, dosages, formulations, polyphenol/anthocyanin content, comparator composition, or intervention duration. This is important because “polyphenol-rich dark fruits” represents a broad intervention category rather than a single standardized product, and the included blueberry, strawberry, pomegranate, and tart cherry interventions may differ in bioactive composition, bioavailability, glycaemic load, adherence, and biological effects.

Reporting of intervention composition and implementation was inconsistent across the included trials. Polyphenol and anthocyanin content was not reported for some interventions, comparator matching varied, one study used usual care rather than a matched placebo, numerical adherence data were unavailable in several trials, and blinding efficacy was formally assessed in only one study. The usual-care study by Ghoochani et al. [71] was the only unblinded, non-placebo-controlled trial and contributed to the pooled analyses for overall symptom severity, WOMAC stiffness, WOMAC physical function, and MMP-13. Leave-one-out sensitivity analyses excluding this study were conducted for outcomes with at least three contributing studies and are reported in Supplementary material 2 (1007133_sup_2); however, this was not possible for MMP-13 because only two studies contributed to that pooled analysis. These factors limit reproducibility, reduce confidence in comparator equivalence, and constrain interpretation of dose-response relationships. Moreover, the number of studies contributing to each meta-analysis was modest, with as few as two trials for some biomarkers. All included RCTs were assessed as moderate to high risk of bias using RoB 2.0, and GRADE assessments indicated very low to moderate certainty of the evidence. Substantial heterogeneity for IL-6, CRP and MMP-3 further reduces confidence in the pooled biomarker estimates and indicates that the observed effects may not be consistent across intervention types, populations or measurement approaches.

Intervention durations were short, ranging from 3 to 16 weeks, which is a major limitation given that OA is a chronic, progressive condition. Consequently, the present findings should be interpreted as short-term effects only and cannot determine whether polyphenol-rich dark fruit supplementation provides sustained symptom relief, long-term safety, or disease-modifying effects. In particular, the included trials did not provide sufficient evidence on structural progression, radiographic or MRI-based outcomes, cartilage preservation, or durability of response after cessation of supplementation. These methodological constraints limit the strength of conclusions that can be drawn from the pooled estimates and highlight the need for more rigorous, longer-duration experimental designs in future investigations.

Future research should prioritise large-scale, well-controlled RCTs with longer intervention periods and post-intervention follow-up to determine whether any clinical or biochemical improvements are sustained. Trials should also include outcomes capable of assessing potential disease-modifying effects, such as radiographic progression, MRI-based cartilage and synovitis measures, joint-space narrowing, and validated biomarkers of cartilage turnover. Given the high heterogeneity and low certainty of the current evidence base, studies must implement robust randomization, allocation concealment, and blinding procedures to reduce bias. Standardization of dosage regimens, polyphenol and anthocyanin quantification, supplement form (juice, powder, or extract), intervention duration, comparator composition, adherence assessment, and core outcome measures is essential to improve comparability across studies and enable dose-response analyses. Future trials should use consistent clinical outcomes, such as WOMAC or KOOS pain and function domains, alongside harmonised inflammatory and cartilage-related biomarker panels. Expanding research beyond knee OA to include other common OA phenotypes is also critical to evaluate whether the observed benefits are joint-specific or generalisable [75].

In addition, future trials should report blinding efficacy, supplement composition, and patient-reported outcomes such as taste, acceptability, and long-term compliance, as these factors may influence treatment adherence and clinical applicability. Currently, dark fruit supplementation is not included in non-surgical management guidelines for OA [76–78]. Integrating cost-effectiveness and patient-centred outcomes into trial design will be vital to guide evidence-based recommendations and support the potential adoption of these nutritional strategies within comprehensive OA management frameworks.

In conclusion, in the available knee OA trials, polyphenol-rich dark fruits were associated with small statistically significant improvements in overall symptom severity, WOMAC physical function, and IL-6 compared with placebo. However, these findings should be interpreted cautiously given the small number of trials, short intervention durations, low certainty of evidence, substantial heterogeneity for some biomarker outcomes, incomplete reporting of intervention composition and adherence, and moderate-to-high risk of bias. The interventions appeared generally well tolerated within the included short-term trials; however, adherence, withdrawals, and adverse-event reporting were incomplete, so tolerability should be interpreted cautiously. Further large-scale, rigorously designed RCTs with longer intervention durations, standardised protocols, comprehensive safety reporting, and clinically interpretable outcome measures are required to determine whether polyphenol-rich dark fruit supplementation provides meaningful adjunctive benefits for people with OA.