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Randomized Controlled Trial
. 2023 Sep 7;25(1):164.
doi: 10.1186/s13075-023-03152-1.

Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study

Can Wang #  1   2   3 , Wenyan Sun #  2 , Nicola Dalbeth #  4 , Zhongjun Wang  5 , Xuefeng Wang  1   2   3 , Xiaopeng Ji  1   2   3 , Xiaomei Xue  1   2   3 , Lin Han  1   2   3 , Lingling Cui  1   2   3 , Xinde Li  1   2   3 , Zhen Liu  1   2   3 , Aichang Ji  1   2   3 , Yuwei He  1   2   3 , Mingshu Sun  6   7 , Changgui Li  8   9   10
Affiliations
Randomized Controlled Trial

Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study

Can Wang et al. Arthritis Res Ther. .

Abstract

Background: Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied.

Objectives: This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate.

Methods: A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 μmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints.

Results: Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups.

Conclusion: The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT.

Trial registration: This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.

Keywords: Citrate; Gout; Sodium bicarbonate; Tart cherry; Urine alkalization.

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Conflict of interest statement

The authors declare that they have no competing interests. Nicola Dalbeth has received consulting fees, speaker fees, or grants from AstraZeneca, Dyve Biosciences, Horizon, Amgen, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, PTC Therapeutics, Protalix, Cello Health, Abbvie, and Janssen, outside the submitted work.

Other authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Flow of study participants. Totally 354 participants were screened, and then 282 eligible patients were enrolled and randomized into sodium bicarbonate, citrate mixture, and TaCCi mixture groups. Nine participants withdrew before receiving at least 1 dose of treatment medication and were excluded from ITT analysis; furthermore, 19 participants were excluded from PP analysis for loss to follow-up. Sb, sodium bicarbonate; TaCCi mixture, tart cherry supplementary citrate mixture, ITT, intention to treat; PP, per protocol
Fig. 2
Fig. 2
Urine pH categories and UACR changes. A Proportion of patients with pH < 5.5 or ≥ 5.5 at baseline. B Proportion of patients with pH < 5.5, 5.5–6.2, or > 6.2 at week 12. C UACR at baseline and week 12. TaCCi mixture, tart cherry supplementary citrate mixture group; UACR, 24-h urinary albumin-creatinine ratio
See this image and copyright information in PMC

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