Beyond Symptoms: Urinary Succinate Emerges as Metabolic Signal in Women With Overactive Bladder

Your patient has no diabetes, no hypertension, no dyslipidemia — and yet she's rushing to the bathroom more than eight times a day. Sound familiar? For clinicians managing overactive bladder (OAB), symptom burden often seems disconnected from any identifiable biological mechanism. New research published in *BMC Women's Health* raises an intriguing possibility: the answer might be hiding in the urine, at a metabolic level we don't routinely measure.

**What the Researchers Set Out to Do**

Investigators from Ankara University enrolled 186 women attending a gynecology outpatient clinic — 81 with probable OAB (identified via the validated OAB-V8 screening questionnaire) and 105 symptom-free controls. Crucially, women with known cardiometabolic conditions — diabetes, hypertension, dyslipidemia — were excluded. The goal was to determine whether two specific urine chemicals, succinate and malate, differed between groups even in the absence of overt metabolic disease.

Both are intermediates of the tricarboxylic acid (TCA) cycle — essentially byproducts of the body's cellular energy production process. When mitochondrial function is disrupted or metabolic stress occurs, these compounds can accumulate. Urine samples were analyzed using gas chromatography-mass spectrometry, a highly sensitive technique, and normalized against urinary creatinine to account for dilution differences.

**What the Data Showed**

Women with OAB had significantly higher urinary succinate levels compared to controls (4.33 vs. 3.09 µmol/mmol creatinine). After adjusting for age, BMI, parity, and menopausal status — since OAB patients were older and more often postmenopausal — the association held firm. Women with OAB had approximately 1.69 times higher succinate levels than controls (95% CI: 1.34–2.12). This finding remained consistent even in subgroup analyses limited to premenopausal women and those with BMI under 30.

Urinary malate was also elevated in the OAB group, but the association was weaker and less consistent across sensitivity analyses, suggesting it plays a secondary role at best.

**How Well Does Succinate Discriminate OAB?**

An exploratory receiver operating characteristic (ROC) analysis — a statistical tool used to evaluate how well a marker separates two groups — yielded an area under the curve (AUC) of 0.678 for succinate. To put that in clinical context, an AUC of 0.5 is no better than a coin flip, while 1.0 is perfect. At a cut-off of 2.22 µmol/mmol creatinine, succinate achieved 79% sensitivity but only 51% specificity. In other words, it catches most OAB cases but generates too many false positives to function as a standalone diagnostic tool right now. Malate barely edged above chance with an AUC of 0.560.

**Why This Matters Clinically — and What It Doesn't Mean Yet**

This is hypothesis-generating research, not practice-changing guidance. The authors are not proposing a urine succinate test for OAB clinics. What they are doing is opening a biologically plausible door: succinate isn't just an energy metabolite — it also activates a receptor on bladder lining cells (SUCNR1/GPR91) that may influence inflammatory signaling and detrusor function. If subclinical metabolic stress is elevating succinate even in women without diagnosed disease, it could be contributing to bladder dysfunction through pathways we've largely ignored.

There are important caveats. The study is cross-sectional, so causality cannot be determined. Urine sampling wasn't standardized for fasting or diet, which can influence metabolite levels. The urinary microbiome — increasingly recognized as relevant in OAB — wasn't assessed. And the sample size, while adequate for detecting moderate effects, limits the precision of subgroup findings and diagnostic thresholds.

**Takeaway for Clinicians**

OAB in metabolically "healthy" women may not be as purely neurological or structural as once assumed. Subclinical metabolic alterations — invisible to standard history-taking — might be contributing to symptom burden through measurable urinary changes. Future research combining metabolomics, microbiome profiling, and comprehensive cardiometabolic phenotyping could reshape how we subclassify and ultimately treat OAB.

Key points -

- Urinary succinate was significantly elevated in women with OAB compared to controls, even after adjusting for age, BMI, parity, and menopausal status — and even in the absence of known cardiometabolic disease.

- The association with urinary malate was weaker and inconsistent across sensitivity analyses, making succinate the more biologically credible candidate for future investigation.

- Succinate's exploratory diagnostic performance (AUC 0.678, sensitivity 79%, specificity 51%) is promising but insufficient for clinical use as a standalone OAB biomarker at this stage.

- The findings suggest OAB may involve subclinical metabolic or mitochondrial dysregulation — potentially mediated via SUCNR1 signaling in urothelial cells — even in women who appear metabolically well on standard clinical assessment.

- Larger prospective studies incorporating standardized metabolic screening, dietary control, bladder diary data capturing urgency episodes, and urinary microbiome profiling are needed before these findings can inform clinical practice.

**Citation:** Öz ÖF, Seval MM, Doğan Ö, Varli B, Çetinkaya ŞE, Dökmeci F. Elevated urinary succinate in women with symptom-defined overactive bladder without clinically recognized cardiometabolic disease: a cross-sectional study. *BMC Women's Health*. 2026. DOI: https://doi.org/10.1186/s12905-026-04596-8