CYSTITIS (Interstitial, Infection)

J Urol 1997 Dec;158(6):2045-50

Effect of long-term oral L-arginine on the nitric oxide synthase pathway in the urine from patients with interstitial cystitis.
Wheeler MA, Smith SD, Saito N, Foster HE Jr, Weiss RM

Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.

PURPOSE: We attempted to determine whether oral L-arginine, the substrate for nitric oxide synthase, increases nitric oxide synthase activity and cyclic guanosine monophosphate (cGMP) levels in the urine from interstitial cystitis patients. Nitric oxide and cGMP are decreased in urine from interstitial cystitis patients and both induce smooth muscle relaxation and immunological responses. Increasing urinary nitric oxide and cGMP may ameliorate interstitial cystitis symptoms. MATERIALS AND METHODS: Eight patients with interstitial cystitis were given L-arginine (1,500 mg. a day) orally for 6 months. Before and during treatment nitric oxide synthase activity and inducible nitric oxide synthase protein, cGMP, nitrate plus nitrite and interleukin 8 (IL-8) levels were measured in urine. RESULTS: After 2 weeks to 1 month of oral L-arginine treatment, urinary levels of nitric oxide synthase related enzymes and products increased significantly, while levels of the cytokine IL-8 were not changed significantly. IL-8 was significantly elevated in interstitial cystitis patients with leukocyte esterase positive urine. CONCLUSIONS: Long-term oral administration of L-arginine increases nitric oxide related enzymes and metabolites in the urine of patients with interstitial cystitis, which is associated with a decrease in interstitial cystitis related symptoms.

J Urol 1999 Feb;161(2):558-65

A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis.
Korting GE, Smith SD, Wheeler MA, Weiss RM, Foster HE Jr

Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8041, USA.

PURPOSE: Nitric oxide synthase activity is decreased in the urine of patients with interstitial cystitis compared to the urine of controls. In a preliminary trial oral L-arginine, the substrate for nitric oxide synthase, increased urinary nitric oxide synthase activity and improved interstitial cystitis symptoms. This randomized, double-blind, placebo controlled study further investigates the efficacy of L-arginine treatment for interstitial cystitis. MATERIALS AND METHODS: A total of 53 interstitial cystitis patients were assigned to receive daily 1,500 mg. L-arginine or placebo orally for 3 months. Interstitial cystitis symptoms were assessed by interviews at 2 weeks, and 1, 2 and 3 months. RESULTS: The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26 in the placebo group. Using per protocol analysis 29% (6 of 21 patients) in the L-arginine group and 8% (2 of 25) in the placebo group were clinically improved by the end of the trial (p = 0.07). A Likert scale showed greater global improvement in the L-arginine group (48%, 10 of 21) compared to the placebo group (24%, 6 of 25) at 3 months (p = 0.05) with a decrease in pain intensity (p = 0.04), and tendency toward improvement in urgency (p = 0.06) and frequency of pain (p = 0.09). Using an intention to treat approach to analysis there were no differences between groups. CONCLUSIONS: Oral L-arginine (1,500 mg. daily) may decrease pain and urgency in a subset of interstitial cystitis patients.