VetPlus Cystaid Capsules for Cats | N-Acetyl D-Glucosamine, Hyaluronic Acid & Chondroitin | GAG Layer Bladder Support for FIC & FLUTD | 30 & 180 Capsules

FOR ANIMAL USE ONLY — Administer as directed by a veterinarian or as per label instructions. Cystaid is a veterinary nutraceutical supplement — not a veterinary medicine; it does not require a prescription but veterinary guidance is strongly recommended for all cats presenting with haematuria, dysuria, stranguria, or periuria (inappropriate urination outside the litter box). EMERGENCY WARNING: male cats with feline lower urinary tract disease (FLUTD) are at risk of complete urethral obstruction (UO) — a life-threatening emergency requiring immediate veterinary attention; signs of urethral obstruction include: multiple failed attempts to urinate producing no urine or only drops, vocalising in the litter box, distended painful abdomen, lethargy, vomiting, and collapse; if a male cat shows these signs do NOT wait — seek emergency veterinary care immediately. Cystaid is not a treatment for urethral obstruction, urinary tract infection (UTI), urinary calculi (bladder stones), or neoplasia — these must be excluded by veterinary examination, urinalysis, urine culture, and imaging before attributing clinical signs to FIC alone. Keep out of reach of children. Store in a cool, dry place.

VetPlus Cystaid Capsules for Cats | N-Acetyl D-Glucosamine, Hyaluronic Acid & Chondroitin | GAG Layer Bladder Support for FIC & FLUTD | 30 & 180 Capsules

VetPlus Cystaid is a veterinary nutraceutical urinary supplement manufactured by VetPlus Ltd (UK) for cats, formulated to support and replenish the bladder glycosaminoglycan (GAG) layer — the critical protective mucosal lining of the feline urothelium. Cystaid delivers a combination of N-acetyl D-glucosamine (NAG), Hyaluronic Acid (HA), and Chondroitin Sulphate — the three principal GAG-family components of the bladder’s uroepithelial protective coat — to address the well-documented GAG layer deficiency and urothelial barrier dysfunction that underlies feline idiopathic cystitis (FIC), the most common cause of feline lower urinary tract disease (FLUTD) in indoor cats. Available in 30-capsule (approximately 1-month) and 180-capsule (approximately 6-month) packs.

Feline Lower Urinary Tract Disease (FLUTD) & Feline Idiopathic Cystitis (FIC) Pathophysiology

• FLUTD — a syndrome, not a diagnosis: FLUTD (feline lower urinary tract disease) is a clinical syndrome encompassing all causes of lower urinary tract signs (LUTS) in cats: haematuria (blood in urine), dysuria (painful/difficult urination), stranguria (straining to urinate), pollakiuria (increased frequency of small-volume urinations), and periuria (urination outside the litter box); the differential diagnosis of FLUTD includes: (a) feline idiopathic cystitis (FIC) — the most common cause (~55–70% of FLUTD cases, particularly in cats under 10 years); (b) urolithiasis (struvite — magnesium ammonium phosphate, and calcium oxalate stones — together accounting for ~95% of feline uroliths); (c) urethral plugs (matrix-crystalline plugs — predominantly in male cats due to the narrow penile urethra); (d) urinary tract infection (UTI — uncommon as primary cause in cats under 10 years, more common in older cats and diabetic cats; caused predominantly by Escherichia coli, Staphylococcus spp., Streptococcus spp., and Pasteurella multocida in cats); (e) anatomical abnormalities and neoplasia (uncommon); veterinary diagnosis should always precede long-term supplementation to exclude surgical and infectious causes
• Feline Idiopathic Cystitis (FIC) — Pandora Syndrome: FIC (previously termed interstitial cystitis in cats by analogy with the human condition) is now preferentially called ‘Pandora Syndrome’ (coined by Buffington et al., Ohio State University) to reflect its complex neuroendocrine-urothelial pathogenesis that extends beyond the bladder; FIC is fundamentally a disorder of the stress-response system in genetically susceptible cats: (a) the HPA axis and sympatho-adrenal response to environmental stressors (inter-cat conflict, new animals, changes in routine, owner absence, novel environments, loud noises, changes in food or litter type) in FIC cats shows an abnormal HPA axis activation: reduced cortisol response but paradoxically exaggerated sympatho-adrenal (sympathetic nervous system + adrenal medullary) catecholamine response; FIC cats have smaller adrenal glands with reduced cortex-to-medulla ratio (reduced glucocorticoid-secreting cortical tissue relative to catecholamine-secreting medullary tissue) — the result is insufficient cortisol-mediated ‘dampening’ of the sympathetic stress response → excessive, prolonged catecholamine (noradrenaline/adrenaline) release; (b) elevated sympathetic tone → increased noradrenaline release from sympathetic nerve endings in the bladder wall → noradrenaline acts on α-adrenergic receptors on mast cells in the subepithelial lamina propria → mast cell degranulation → histamine, substance P, and prostaglandins released into the bladder submucosa → vasodilation, oedema, neurogenic inflammation, and urothelial permeability increase; (c) substance P (SP) — a neuropeptide released from capsaicin-sensitive C-fibre sensory afferents (TRPV1+ unmyelinated nociceptors) in the bladder → SP acts on NK-1 (neurokinin 1) receptors on urothelial cells, inflammatory cells, and blood vessels → amplifies neurogenic inflammation; FIC cats have elevated SP levels in urine and increased SP-immunoreactive nerve fibre density in the bladder wall vs healthy cats; (d) deficient GAG layer → urothelial permeability increase: the uroepithelium is normally protected from the toxic, hyperosmolar, acidic urine by the GAG layer (see below); in FIC, the GAG layer is qualitatively and quantitatively deficient → urine-derived noxious substances (urea, creatinine, potassium ions — the high luminal K+ of cat urine is particularly relevant; normal feline urine K+ ~100–150 mEq/L) penetrate the leaky urothelium → subepithelial afferent C-fibre sensitisation (K+ depolarises the C-fibre terminals) → pain, urgency, and neurogenic inflammation amplification; this is the ‘potassium leak’ hypothesis of FIC; (e) environmental enrichment and stress reduction (MEMO — Multimodal Environmental Modification) is the cornerstone of FIC management and reduces recurrence rates by ~70–80% in responsive cats; Cystaid addresses the GAG layer deficiency component of FIC pathophysiology
• The urothelial GAG layer: the bladder urothelium (transitional epithelium — a specialised stratified epithelium of umbrella cells/facet cells overlying intermediate and basal layers) is coated on its luminal surface by a GAG layer — a hydrated, negatively charged, mucus-gel matrix composed of: (a) uroplakins (UP1a, UP1b, UP2, UP3a, UP3b — tetraspanin and single-pass transmembrane proteins that form the crystalline 16nm urothelial plaques covering the apical membrane of umbrella cells; uroplakins are unique to the urothelium and form the physical basis of the impermeable umbrella cell apical membrane); (b) glycosaminoglycans — heparan sulphate (the principal GAG of the umbrella cell apical glycocalyx), chondroitin sulphate, and hyaluronic acid — extending from the uroplakin scaffold into the bladder lumen; (c) the Tamm-Horsfall protein (uromodulin — the most abundant urinary protein, secreted by the thick ascending limb of Henle in the kidney and present in bladder urine; forms a gel-like layer that traps bacteria and prevents them from adhering to the urothelium via mannose residues binding type 1 fimbriated E. coli FimH adhesins); the combined GAG/uroplakin/uromodulin layer prevents: (i) bacteria from adhering to the urothelium; (ii) urine solutes (urea, K+, Ca2+, H+) from penetrating the epithelium; (iii) nociceptive activation of subepithelial sensory afferents; GAG layer disruption in FIC → ‘leaky bladder’ → urine-to-subepithelium penetration → pain and inflammation

Active Ingredients & Mechanisms of Action

• N-Acetyl D-Glucosamine (NAG) — key biosynthetic precursor for heparan sulphate and GAG chain synthesis in urothelial cells: NAG (2-acetamido-2-deoxy-D-glucose) is the activated monosaccharide unit (as UDP-GlcNAc — uridine diphosphate-N-acetylglucosamine) that serves as the direct substrate for: (a) heparan sulphate biosynthesis — heparan sulphate chains are GlcUA–GlcNAc alternating disaccharide repeats synthesised by EXT1/EXT2 copolymerase on a tetrasaccharide linker (GlcUA-Gal-Gal-Xyl) attached to core proteoglycan proteins (syndecan-1, syndecan-4, glypicans) on the umbrella cell surface; exogenous NAG supplementation provides UDP-GlcNAc substrate to support heparan sulphate chain elongation in urothelial cells — directly replenishing the principal GAG component of the urothelial glycocalyx; (b) hyaluronic acid biosynthesis — HA (the only non-sulphated GAG — an alternating GlcUA–GlcNAc disaccharide synthesised at the plasma membrane by hyaluronan synthases HAS1, HAS2, HAS3 without a protein core) requires both UDP-GlcNAc and UDP-GlcUA as alternating substrates; NAG supplementation supports UDP-GlcNAc availability for HA synthesis in the bladder interstitium and submucosa; (c) O-GlcNAc modification of proteins — many nuclear and cytoplasmic proteins are dynamically modified by O-linked N-acetylglucosamine (O-GlcNAc transferase — OGT) at serine and threonine residues, competing with phosphorylation for the same residues; O-GlcNAc modification of uroplakin proteins and tight junction proteins (occludin, claudin-4, ZO-1) in umbrella cells may stabilise the urothelial barrier; importantly, NAG bypasses the hexosamine biosynthesis pathway rate-limiting step (GFAT — glutamine:fructose-6-phosphate amidotransferase, which converts fructose-6-phosphate + glutamine → glucosamine-6-phosphate; this step is rate-limited by available glutamine and is regulated by insulin) by being directly phosphorylated to GlcNAc-6-phosphate by GlcNAc kinase and then converted to UDP-GlcNAc, bypassing GFAT and providing substrate more efficiently than non-acetylated Glucosamine
• Hyaluronic Acid (HA — Hyaluronan) — non-sulphated GAG providing viscoelastic barrier protection and CD44-mediated anti-inflammatory signalling in the bladder wall: HA in the bladder context acts as: (a) a direct component of the luminal GAG protective layer — HA’s high negative charge density (due to the carboxylate groups of GlcUA residues) and its high water-binding capacity (HA binds up to 1000× its weight in water) creates a hydrated, viscous gel barrier on the urothelial surface that impedes ion and macromolecule permeation; (b) a signalling molecule via CD44 (the principal HA receptor — a type I single-pass transmembrane glycoprotein of the hyaladherins family expressed on umbrella cells, inflammatory cells, and subepithelial fibroblasts): high-MW HA (>1MDa — the native form) binding to CD44 activates anti-inflammatory signalling: CD44 → Rac1 GTPase activation → suppression of NF-κB p65 nuclear translocation → reduced IL-1β, IL-6, IL-8, and COX-2 expression in urothelial cells; additionally, CD44-HA interaction activates PI3K → Akt (protein kinase B) → anti-apoptotic survival signalling in urothelial cells (protecting against stress-induced urothelial apoptosis which contributes to barrier disruption in FIC); contrast: low-MW HA fragments (generated by reactive oxygen species and hyaluronidase in the inflamed bladder — HYAL1 and HYAL2 hyaluronidases) act as DAMPs (damage-associated molecular patterns) via TLR2 and TLR4 on urothelial cells → pro-inflammatory NF-κB activation; exogenous supplementation with intact high-MW HA in Cystaid aims to replenish the protective anti-inflammatory high-MW HA pool in the bladder
• Chondroitin Sulphate (CS) — sulphated GAG contributing to the urothelial charge barrier and anti-inflammatory signalling: CS in the bladder context: (a) contributes sulphate groups to the strongly negative fixed charge density of the urothelial GAG layer — the Donnan potential established by the negatively charged GAG layer electrostatically repels negatively charged urinary components (phosphate, oxalate, citrate) and bacterial surface lipopolysaccharide (LPS — negatively charged at physiological pH) preventing adhesion; (b) CS directly inhibits NF-κB activation in urothelial cells by reducing IκBα degradation (CS sulphate groups chelate the IKKβ kinase catalytic Zn2+ ion, reducing IKKβ activity → IκBα remains intact → NF-κB p65 retained in cytoplasm → reduced inflammatory cytokine transcription); (c) CS inhibits mast cell degranulation in the bladder submucosa — reducing histamine, heparin, and tryptase release from subepithelial mast cells (which are markedly increased in number in FIC bladder biopsies compared to healthy cats — a FIC histopathological feature); the NAG + HA + CS triad in Cystaid provides all three major components of the urothelial GAG protective layer simultaneously, each addressing the barrier defect from a complementary structural and signalling perspective

Indications

• Feline idiopathic cystitis (FIC) / Pandora Syndrome — adjunctive GAG layer support alongside multimodal environmental modification (MEMO), increased water intake, and wet diet; use as a long-term maintenance supplement in recurrent FIC cats
• Feline lower urinary tract disease (FLUTD) — after exclusion of UTI, urolithiasis, and urethral obstruction by veterinary examination, urinalysis, urine culture, and imaging
• Cats with recurrent haematuria, dysuria, pollakiuria, or periuria attributable to FIC
• Post-obstructive support in male cats following urethral obstruction relief and catheterisation — to support urothelial barrier recovery
• Preventive supplementation in indoor cats at high risk of FIC — multi-cat households, stressed cats, cats on dry-food-only diets

Directions for Use

• Administer orally as directed by a veterinarian or per VetPlus label instructions
• Capsules can be opened and sprinkled onto food if the cat will not accept the whole capsule
• Supplement long-term continuously for best results — do not discontinue after a single FIC episode resolves; FIC is a recurrent condition and continuous supplementation reduces recurrence frequency
• Complement with: wet diet (increases water intake → dilutes urine → reduces urothelial exposure to concentrated urinary noxious compounds), water fountains, litter tray management, and multimodal environmental enrichment (MEMO)
• 180-capsule pack — approximately 6-month supply at 1 capsule daily

Safety Information

• For animal use only — keep out of reach of children
• Always exclude UTI, urolithiasis, and urethral obstruction before attributing LUTS to FIC
• Not a treatment for urethral obstruction — seek immediate emergency veterinary care if urethral obstruction is suspected
• Store in a cool, dry place; keep container tightly closed