Abstract
Tart cherry (Prunus cerasus L.) extracts are plant extracts rich in polyphenolic compounds, particularly anthocyanins, which exhibit antioxidant and anti-inflammatory properties. These bioactives may help reduce plasma urate and C-reactive protein (CRP) levels, supporting cardiovascular and the management of hyperuricemia. Processing and formulation methods can influence tart cherry products stability and efficacy. To evaluate the effects of a standardized tart cherry extract on plasma urate and CRP levels. In a randomized, double-blind, placebo-controlled, crossover trial, 10 healthy subjects (n = 10; 6 male, 4 female, age: 34.9 ± 6.6 years, height: 155.3 ± 2.9 cm, weight: 67.1 ± 5.2 kg) consumed 500 mg of a European tart cherry (Prunus cerasus L.) extract powder or placebo for 4 wk, with a 14-day washout between treatment. Venous blood samples were collected at baseline and at 2-, 4-, and 8-h post-ingestion on day 1, as well as at 8 h post-ingestion on day 28, and were analyzed for plasma urate and CRP concentrations. Acute administration did not alter CRP or urate concentrations. Chronic supplementation significantly reduced CRP by 23.0% (– 1.36 ± 0.44 mg/L) and urate by 37.4% (–2.62 ± 0.44 mg/dL) compared to placebo (both p < 0.001). Four weeks of daily supplementation with 500 mg of tart cherry extract significantly reduced systemic inflammation and urate levels in healthy adults, supporting its potential as a polyphenol-rich, foodbased strategy for managing low-grade inflammation and hyperuricemia.
Introduction
Tart cherries (Prunus cerasus L.) are rich in polyphenolic compounds, particularly flavonoids such as anthocyanins, which exhibit potent antioxidant and anti-inflammatory properties (Jawad et al. Citation2025). Polyphenols from tart cherry have been shown to attenuate markers of muscle breakdown, improve functional recovery, and reduce post-exercise soreness, likely through modulation of oxidative and inflammatory pathways (Hill et al. Citation2021; Dehghani et al. Citation2025). These bioactive components have been linked to improvements in exercise-induced muscle damage, oxidative stress, and systemic inflammation, mechanisms relevant to both athletic recovery and chronic disease risk mitigation (Connolly et al. Citation2006; Bell et al. Citation2014; Citation2016; Keane et al. Citation2016). Processing and encapsulation conditions can markedly influence anthocyanin stability and total-polyphenol retention, making standardized extract characterization essential (Hillman and Chrismas Citation2021); however, the present study investigated a single standardized extract.
Among their proposed benefits, tart cherries have also been investigated for their potential role in modulating plasma uric acid levels, which, when elevated, are associated with a range of cardiometabolic and renal disorders (Johnson et al. Citation2013; Kanbay et al. Citation2013). Uric acid is the final breakdown product of purine metabolism and is normally excreted by the kidneys (Borghi et al. Citation2015; Sanchez-Lozada et al. Citation2019; Song et al. Citation2021). Under physiological conditions, uric acid exists primarily in its ionized form, urate, at the normal blood pH (∼7.4). Accordingly, the two terms are often used interchangeably in clinical and biochemical literature, as most assays measure total urate (the soluble ionized form) rather than undissociated uric acid. While it can serve as a circulating antioxidant under physiological conditions, excessive accumulation leads to hyperuricemia, a state that promotes oxidative stress, endothelial dysfunction, and inflammation (Du et al. Citation2024). Elevated uric acid also activates immune and oxidative pathways that stimulate hepatic C-reactive-protein (CRP) synthesis, linking urate metabolism to systemic inflammatory status (Amiya Citation2021; Du et al. Citation2024).
Hyperuricemia, defined as serum urate concentrations exceeding 6 mg/dL in women and 7 mg/dL in men, is increasingly prevalent worldwide (Du et al. Citation2024). Although often asymptomatic, elevated uric acid may contribute to the pathophysiology of hypertension, obesity, hypothyroidism, and chronic kidney disease (Du et al. Citation2024). While pharmacologic agents such as xanthine oxidase inhibitors (e.g. allopurinol) and uricosuric drugs are commonly prescribed to manage symptomatic hyperuricemia and gout, they are not routinely indicated for asymptomatic individuals (Cicero et al. Citation2021). As such, there is a growing interest in identifying safe, food-based interventions that may support healthy urate metabolism without pharmacological side effects.
Several studies have reported that tart cherry juice or extract may reduce plasma urate and inflammatory biomarkers, such as CRP, potentially via mechanisms involving xanthine oxidase inhibition and enhanced renal urate excretion (Jacob et al. Citation2003; Schumacher et al. Citation2013; Martin and Coles Citation2019). In overweight and obese adults, four to six weeks of tart cherry juice consumption (240 mL/day) reduced CRP by ∼0.8–1.2 mg/L and lowered triglycerides and inflammatory cytokines (Martin and Coles Citation2019; Desai et al. Citation2021). Similarly, Sinclair et al. (Citation2022) reported a ∼0.5 mg/L decrease in CRP following 20 days of 60 mL/day tart cherry juice intake in healthy adults. Trials assessing urate outcomes suggest small (0.3–0.8 mg/dL) but consistent reductions after 2–6 wk of intake (Jacob et al. Citation2003; Schumacher et al. Citation2013). Collectively, these findings indicate that sustained tart cherry consumption, at doses of 240–480 mL juice or 500–1000 mg extract daily, may beneficially influence urate and inflammatory markers, supporting its potential role in metabolic health maintenance. While Connolly et al. (Citation2006) and Desai et al. (Citation2021) did not measure urate directly, their findings of reduced oxidative stress and inflammation provide supportive mechanistic evidence for the potential pathways by which tart cherry supplementation could influence uric-acid–related processes. However, acute supplementation trials show mixed outcomes: Hillman and Uhranowsky (Citation2021) reported decreased serum uric acid but no CRP change after a single dose, whereas a 30-day study observed no significant effects on gut-microbiota composition or inflammatory markers (Hillman and Chrismas Citation2021). These findings suggest that tart cherries may confer a dual benefit by lowering serum uric acid while concurrently attenuating systemic inflammation. Beyond these endpoints, prior investigations have also evaluated changes in metabolic and clinical-chemistry parameters, such as lipid profile, glucose regulation and hematological indices, as indicators of broader physiological adaptation and product tolerability (Kimble et al. Citation2021; Martin et al. Citation2022; Sinclair et al. Citation2022; Wang et al. Citation2023). Nevertheless, formulation differences, particularly between juice and powder forms, can lead to wide variability in polyphenol and anthocyanin contrations (Jawad et al. Citation2025) and caloric and glycemic load. Consequently, the long-term effects of encapsulated, concentrated, and standardized tart cherry powder on urate metabolism and inflammatory markers remain insufficiently characterized and warrant further investigation.
The present study aimed to evaluate the effects of a standardized, whole-fruit tart cherry extract on plasma urate and CRP concentrations in a healthy adult population. While uric acid modulation was a primary endpoint, this investigation also provides insight into broader anti-inflammatory actions and the tolerability of tart cherry supplementation in an otherwise healthy cohort, addressing a critical gap in the current literature on polyphenol-based interventions for metabolic health.
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Ralf Jäger (Conceptualization) (Writing – review & editing), Martin Purpura (Conceptualization) (Writing – review & editing), Sebastian, T. Balcombe (Conceptualization), Ashok Godavarthi (Conceptualization) (Investigation) (Writing – review & editing), Suda A. Reddy (Investigation), Ecaterina Vasenina (Writing – original draft) & Grant M. Tinsley (Formal analysis) (Writing – review & editing) (2025) Effects of Tart Cherry Extract Supplementation on Plasma Urate and C-Reactive Protein Levels in Healthy Adults: a Randomized Controlled Trial, Journal of Dietary Supplements, DOI: 10.1080/19390211.2025.2589787
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