Quercetin, Rutin, Bromelain, and L-Carnosine for Borderline Uric Acid: What a 2020 Clinical Trial Found

Overview:The study Evaluation of the Effects of a Supplement Composed by Quercetin, Rutin, Bromelain and L-Carnosine in Patients with Borderline Uricemia by Derosa et al. (2020) evaluates whether a combined nutraceutical (Uricemin®) was associated with changes in uric acid and inflammation markers in people whose uric acid is elevated but still below the typical hyperuricemia cutoff. In the scientific paper, the authors frame hyperuricemia as clinically important because urate crystal buildup can contribute to gout and joint problems, and they also describe links seen in observational research between higher uric acid and cardio-metabolic conditions. Their main goal is stated plainly: The authors state that the aim was to evaluate whether the nutraceutical was associated with reductions in uric acid levels after 3 months of therapy.

In the Introduction, the authors define hyperuricemia as uric acid above 7 mg/dL, calling this “the saturation point of monosodium uric acid at physiological levels of temperature and pH.” When uric acid is high, monosodium urate crystals can deposit in and around joints, which the paper links to acute gout attacks and chronic arthropathy (long-term joint disease).

The scientific paper also explains that uric acid can act as an antioxidant under certain conditions, helping scavenge excess free radicals, but in hyperuricemia, it may shift toward pro-oxidant effects.

For this trial, the focus is “borderline uricemia,” defined in the paper as uric acid values between ≥6 and <7 mg/dL. The authors point out that epidemiological and observational studies have reported associations between uric acid ≥6 mg/dL and several cardio-metabolic diseases. Against that backdrop, they test whether a supplement could represent a complementary nutritional approach in individuals not using hypouricemic medication.

This scientific paper reports a 3-month, double-blind, randomized, placebo-controlled clinical trial conducted at the Centre of Diabetes and Metabolic Diseases (University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy). The protocol followed the Declaration of Helsinki and Good Clinical Practice, and all participants gave written informed consent. The trial is registered on ClinicalTrials.gov (Identifier: NCT04161872).

Participants. The investigators enrolled adults with uric acid levels between ≥6 and <7 mg/dL who were not using hypouricemic agents and had no previous gout attack. The paper lists multiple exclusions, including impaired hepatic or renal function, endocrine disorders (including type 1 and type 2 diabetes mellitus), major cardiovascular history (ischemic heart disease, heart failure, stroke), and several medication exclusions.

Intervention: Participants were randomized to Uricemin® or placebo for 3 months. Tablets were identical and coded to maintain blinding. Dosing was once daily: “1 tablet during breakfast.” Medication compliance was checked by pill counts.

Outcomes and measurements: At baseline and again at 3 months, the team measured body weight and body mass index (BMI), fasting plasma glucose (FPG), and a full lipid profile, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (Tg). They also measured uric acid (UA) and high-sensitivity C-reactive protein (Hs-CRP). For safety monitoring, liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatinine levels, and any reported adverse events were recorded.

Analysis: The authors describe an intention-to-treat approach with analysis of variance and analysis of covariance (ANCOVA), using p < 0.05 as statistically significant.

A total of 116 patients were enrolled (59 assigned to Uricemin® and 57 to placebo). The analysis included 107 completers; the paper notes losses to follow-up and exclusions due to low compliance.

The primary reported outcome was a statistically significant difference in uric acid levels in the Uricemin® group compared with both baseline and placebo (p < 0.05 for both comparisons). According to the published data, mean uric acid levels in the Uricemin® group changed from 6.5 ± 0.4 mg/dL at baseline to 5.9 ± 0.3 mg/dL after 3 months. In contrast, the placebo group showed no statistically significant change, with mean values moving from 6.6 ± 0.5 mg/dL to 6.7 ± 0.6 mg/dL over the same period.

The paper also describes a shift in participant distribution across uric acid categories within the Uricemin® group. At baseline, 55.9 percent of participants were in the 6.5 to 7.0 mg/dL range. After 3 months, none remained in that category. At the end of the study period, 67.3 percent were in the 6.0 to 6.4 mg/dL range and 32.7 percent were in the 5.5 to 5.9 mg/dL range. These categorical changes are presented by the authors as part of the overall statistical findings observed during the trial.

The scientific paper reports that Hs-CRP decreased in the Uricemin® group (p < 0.05 vs baseline) but not with placebo, and that the Uricemin® value was lower than placebo at 3 months (p < 0.05).

In the table, Hs-CRP in the Uricemin® group dropped from 1.1 ± 0.5 mg/L to 0.6 ± 0.3 mg/L (significant). Placebo was 1.0 ± 0.4 mg/L at baseline and 1.1 ± 0.5 mg/L at 3 months.

The authors state, “We did not record any change in glycemia,” and “No changes in lipid profile were recorded.” In the table, FPG and lipid measures (TC, LDL-C, HDL-C, Tg) appear similar from baseline to 3 months in both groups.

The scientific paper explains tolerability monitoring using transaminases and creatinine, plus adverse event recording. In the table, AST, ALT, and creatinine values do not show large shifts from baseline to 3 months in either group.

In the Discussion section, the authors review previously published research to explain how each ingredient in the uric acid supplement may interact with biological pathways measured in the trial. These explanations are based largely on laboratory and animal studies, along with limited human research.

For quercetin, the authors describe in vitro findings showing inhibition of xanthine oxidoreductase, the enzyme involved in the final step of uric acid production. Animal studies are cited in which quercetin exposure was associated with changes in circulating uric acid levels. The paper also notes that human evidence remains mixed and describes the effect of quercetin in humans as “still much debated.” One cited study in healthy men with uric acid levels ≥6 mg/dL reported reductions after four weeks of supplementation, without reported changes in fasting glucose or blood pressure.

Regarding rutin, the authors reference in vitro data showing inhibition of xanthine oxidoreductase similar to quercetin. Rutin is also described as having antioxidant properties in laboratory models, including the ability to bind divalent iron (Fe2+) involved in lipid peroxidation processes.

For bromelain, the paper discusses prior research examining its influence on inflammatory signaling pathways, including prostaglandin-related activity. The authors reference studies conducted in research settings involving rheumatoid arthritis and osteoarthritis, where bromelain-containing formulations were compared with non-steroidal anti-inflammatory drugs (NSAIDs). These references are presented as part of the broader scientific background rather than as clinical recommendations.

L-carnosine is described as an imidazole-containing compound studied for its potential role in buffering pH and influencing enzymes involved in glycogenolysis and gluconeogenesis. The authors suggest that these metabolic interactions may relate to how uric acid is processed in the body, based on cited experimental research.

Overall, the mechanisms discussed in the paper are presented as proposed biological pathways derived from prior studies, many of which are preclinical. The authors emphasize that further clinical research is needed to clarify how these mechanisms translate to measurable outcomes in humans.

Based on the reported findings, the authors conclude that the combination was associated with reductions in uric acid levels in individuals with borderline uricemia. They also discuss the observed decrease in Hs-CRP as consistent with changes in inflammatory markers measured during the trial. The study emphasizes that results should be interpreted within the context of the trial’s duration and design.