A randomized placebo-controlled study evaluating the efficacy of a multi‑nutrient supplement on lower urinary tract health in male cats with feline idiopathic cystitis

Feline idiopathic cystitis (FIC) is the most common diagnosis within the spectrum of feline lower urinary tract disease (FLUTD), accounting for approximately 60–65% of cases presenting with lower urinary tract signs (LUTS), particularly in male cats with narrow urethras. FIC is now recognized as a systemic stress-sensitive disorder characterized by neuroendocrine dysregulation and urothelial barrier dysfunction, rather than a purely local bladder disease. Multimodal environmental modification (MEMO) is the cornerstone of therapy, but recurrence rates remain high, and many cats experience repeated episodes despite environmental optimization. This prospective, randomized, placebo-controlled trial evaluated the efficacy of a novel multi-nutrient supplement (HT-3) containing cranberry extract and marigold extract, docosahexaenoic acid (DHA), inulin, spirulina, and L-lysine as an adjunct to standardized MEMO in neutered male cats with recurrent FIC. We hypothesized that HT-3 would significantly reduce LUTS severity, prolong the disease-free interval (DFI), reduce the recurrence rate, and favorably modulate urinary biomarkers and behavior compared with MEMO plus placebo. Thirty neutered male cats with documented recurrent FIC were enrolled in a 6‑month randomized placebo‑controlled exploratory pilot study. All cats received a strictly standardized MEMO protocol and were randomized in a 1:1 ratio to receive either HT-3 or an isocaloric placebo. The primary endpoints were cumulative LUTS scores, recurrence rate, and DFI at 6 months. The secondary endpoints included urinalysis parameters, urinary cortisol: creatinine ratio (UCCR), urinary glycosaminoglycan: creatinine ratio (GAG: Cr), and behavioral scores. Short‑term (2‑week), intermediate (3‑month), and long‑term (6‑month) responses were analyzed. The baseline characteristics were comparable between the groups. Both groups showed early improvement at 2 weeks following MEMO implementation; however, the HT-3 group demonstrated a significantly greater reduction in LUTS scores by week 4 (− 63.8% vs. −39.3%, p = 0.01) and maintained lower scores through month 6 (1.2 ± 0.6 vs. 2.8 ± 1.0, p = 0.002). The recurrence rate over 6 months was 13.3% (2/15) in the HT-3 group versus 40.0% (6/15) in the placebo group ( p = 0.05). Mean DFI was longer in the HT-3 group (162 ± 15 vs. 110 ± 35 days, p = 0.01), and Kaplan–Meier analysis showed a significantly higher recurrence-free probability over 6 months (log-rank p = 0.03). The HT-3 group showed greater reductions in UCCR (− 45% vs. −20%, p = 0.05) and a significant increase in urinary GAG: Cr (+ 25% vs. no change, p = 0.02). Behavioral scores showed greater reductions in fear-related and hiding behaviors, together with greater improvements in social interaction, in the HT-3 group than in the placebo group ( p < 0.01). The multi-nutrient supplement HT-3, when implemented alongside a standardized MEMO protocol, offers a practical supportive option for reducing symptom burden and recurrence risk in male cats with recurrent FIC. These preliminary pilot findings require confirmation in larger, more tightly standardized studies.