Tart Cherry Citrate for Gout: What a 12-Week Trial Found

The study “ Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study” by Can Wang et al. (2023) is a clinical trial that looks at a tart cherry supplementary citrate (TaCCi) mixture as part of gout care. The authors compared this mixture with a standard citrate mixture and with sodium bicarbonate in men with gout who had low urine pH and were just starting urate-lowering therapy (ULT) with the xanthine oxidase inhibitor (XOI) febuxostat. The scientific paper focuses on how these different alkalizing treatments affect urine pH, serum urate (sUA), kidney markers, inflammation, and gout flares over 12 weeks.

Gout is described in the scientific paper as the most common inflammatory arthritis worldwide and is often linked with metabolic syndrome (MetS) and chronic kidney disease (CKD). Many patients with gout have acidic urine (low urine pH), which is associated with kidney problems such as nephrolithiasis, renal cysts, hematuria, and proteinuria. In a large earlier cross-sectional study from the same group, almost half of gout patients had aciduria with urine pH below 5.5, and low pH was independently linked to different types of kidney injury.

The authors note growing interest in tart cherries as a complementary supplement. Tart cherries are rich in anthocyanins and other polyphenols with anti-inflammatory and antioxidant activity. Prior work suggested benefits for metabolic syndrome and cardiovascular markers, such as blood pressure and lipids, and some small studies showed that cherry products can lower serum urate, although findings are not consistent. Observational research also found that cherry intake was associated with about a 35% lower risk of gout flares, but those data cannot prove cause and effect.

Urine alkalinization itself is debated in gout guidelines. Some groups suggest considering it to reduce uric acid stone risk, while the 2020 American College of Rheumatology (ACR) guideline recommends against routine use because of limited evidence. The same research team had already shown that a citrate mixture worked as well as sodium bicarbonate for urine alkalization and might lower hematuria and gout flares, but that earlier trial did not measure urinary albumin/creatinine ratio (twenty-four-hour urinary albumin/creatinine ratio (UACR)) or many metabolic outcomes.

In this new scientific paper, the authors tested whether adding tart cherry powder to a citrate mixture (creating TaCCi) could offer extra benefits for urine pH, serum urate, kidney markers, and inflammation in gout patients starting febuxostat.

This was an open-label, prospective, randomized, parallel-controlled trial carried out at a gout clinic in the Affiliated Hospital of Qingdao University between September 2021 and June 2022. The research team screened 354 men with gout, and 282 eligible participants with fasting urine pH at or below 6 were randomized in a 1:1:1 ratio into three groups:

• Sodium bicarbonate group: 1 g three times daily.
• Citrate mixture group: 3.5 g twice daily (citric acid, sodium citrate, potassium citrate, sodium carbonate, and excipients).
• TaCCi mixture group: 3.5 g twice daily containing tart cherry powder (25%), citric acid, sodium citrate, potassium citrate, sodium carbonate, and excipients.

All participants were male, aged 18–70 years, met the 2015 ACR/European League Against Rheumatism (EULAR) gout classification criteria, had serum urate between 420 and 600 μmol/L, and were about to start urate lowering therapy. They began febuxostat at 20 mg daily, which could be increased to 40 mg daily if serum urate stayed at or above 360 μmol/L at the first follow-up.

Before baseline, there was a 14-day washout phase. Participants stopped other urate-lowering drugs and followed a low-purine diet. During the 12-week study, visits occurred every 4 weeks. At each visit, the team collected data on urine pH, serum urate, blood pressure (BP), body mass index (BMI), blood lipids, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and kidney function (including estimated glomerular filtration rate (eGFR) and UACR). C-reactive protein (CRP) and dual-energy computed tomography (DECT) urate volumes were measured at baseline and week 12.

Gout flares were recorded using patient reports and a visual analogue scale (VAS) score above 3 out of 10. The primary outcomes were changes in urine pH and serum urate over 12 weeks. Key secondary outcomes included CRP, UACR, gout flares, DECT monosodium urate (MSU) volume, metabolic markers, and adverse events.

Statistical analyses used repeated measures mixed models for primary outcomes, with additional models for UACR and gout flares. Both intention-to-treat (ITT) and per-protocol (PP) analyses were reported.

All three treatments raised urine pH to a similar degree. Median fasting urine pH increased from about 5.4–5.6 at baseline to around 5.8–6.0 at week 12 in every group, and there were no significant differences between groups in absolute pH or in pH categories.

Serum urate levels also fell in all groups after febuxostat initiation. Mean serum urate dropped from about 524–538 μmol/L at baseline to around 360–370 μmol/L at week 12, again without meaningful differences between the three treatment arms or in the proportions reaching targets below 360 μmol/L or 300 μmol/L. The authors wrote that “sUA levels declined in all three groups as well, with no significant differences observed between the groups.”

A key difference appeared in the urinary albumin/creatinine ratio. UACR improved in all groups, but the reduction was greatest in the TaCCi mixture group. Median UACR fell from 7.42 to 0.89 mg/g with TaCCi, compared with 3.29 to 1.17 mg/g in the citrate group and 3.01 to 1.72 mg/g in the sodium bicarbonate group. Between-group comparisons showed significantly lower UACR at week 12 in the TaCCi group than in both the citrate and sodium bicarbonate groups.

Estimated glomerular filtration rate stayed generally stable across all groups, with only a temporary rise at week 8 in the TaCCi arm.

Participants taking the TaCCi mixture or the citrate mixture experienced fewer gout flares over 12 weeks than those receiving sodium bicarbonate. Mean numbers of flares per participant were about 0.56–0.58 in the TaCCi and citrate groups versus 0.94 in the sodium bicarbonate group. However, there was no difference in flare rate between the TaCCi and citrate groups.

For inflammation, CRP levels were similar at baseline. By week 12, CRP had decreased more in the TaCCi mixture group than in either of the other two groups. The authors noted that “the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups.”

DECT measured urate volumes decreased from baseline in all three groups, and no clear differences appeared between the treatment arms.

Within the TaCCi group, systolic blood pressure, diastolic blood pressure, total cholesterol, fasting blood glucose, and HOMA-IR improved compared with baseline, although these changes did not differ significantly from the other groups. In the sodium bicarbonate group, systolic blood pressure and BMI slightly increased over time.

Safety findings were similar across groups. Serum electrolytes (sodium, potassium, chloride) remained stable. Rates of new hemoglobinuria, nephrolithiasis, renal cysts, hypertension, and liver enzyme elevations did not differ significantly among the three treatments, and no serious events led to treatment interruption or hospitalization.

This scientific paper suggests that in men with gout and acidic urine who are starting febuxostat, a tart cherry supplementary citrate mixture performs much like citrate or sodium bicarbonate for its main goals: urine alkalization and serum urate reduction. The key co-primary outcomes did not differ between groups.

Where TaCCi suggests a larger reduction in systemic inflammatory markers. The larger drop in UACR is consistent with greater improvement in a marker of glomerular health, and the stronger fall in CRP suggests a larger reduction in systemic inflammatory markers over 12 weeks. The authors connect these findings with antioxidant and anti-inflammatory properties of tart cherry anthocyanins that have been described in previous research, along with experimental data in animals, while noting that the clinical importance of these mechanisms still needs more study.

However, there are important limits. The trial was open-label and conducted at a single center, which can raise bias concerns. Only male participants with preserved kidney function (eGFR above 60 mL/min/1.73 m²) were included, and the follow-up lasted only 12 weeks. The authors emphasize that longer, double-blind, placebo-controlled trials in more diverse patient groups are needed before firm clinical recommendations can be made.

In summary, this scientific paper reports that a tart cherry supplementary citrate mixture had similar efficacy and safety to the citrate mixture and sodium bicarbonate for raising urine pH and lowering serum urate in men with gout starting febuxostat. At the same time, TaCCi was linked with greater improvements in UACR and CRP and with fewer gout flares than sodium bicarbonate over 12 weeks. Taken together, the findings point to potential kidney and anti-inflammatory effects of tart cherry-based citrate mixtures that warrant further clinical research, in addition to urine alkalization. Because the study was open-label, short in duration, and limited to a specific group of men with gout, more trials are needed before clear clinical recommendations can be made. For now, TaCCi is best viewed as an option under investigation rather than a proven standalone treatment for gout.