Serum uric acid and risk of multiple sclerosis.
ABSTRACT Because of evidence implicating oxidative stress in multiple sclerosis pathogenesis, it has been postulated that high levels of urate, a potent antioxidant, could reduce risk or favorably influence disease progression. We conducted a prospective study to determine whether serum urate levels contribute to prediction of multiple sclerosis risk. Analyses included 31 cases with blood collected a median of 1.9 years before multiple sclerosis onset from the Nurses' Health Study and Nurses' Health Study II cohorts, and 42 cases with collection a median of 14.5 years before onset from the Kaiser Permanente Northern California health plan cohort. Relative risks were estimated by unconditional logistic regression, including 26 controls in the Nurses' cohorts and 130 controls in the Kaiser cohort. In analyses including only cases in the Nurses' cohorts where blood was collected shortly before onset, there was a trend toward a lower risk of multiple sclerosis among individuals with higher serum urate, but the association was not significant (multivariable relative risk 0.52, 95% CI 0.22, 1.20, p value 0.13). In contrast, there was no evidence of a decline in risk with increasing serum urate in the Kaiser cohort where there was a longer period of time between blood collection and onset (multivariable relative risk 1.36, 95% CI 0.87, 2.14, p value 0.18). The results of this study suggest that serum urate is not a strong predictor of MS risk. This lack of association is consistent with the interpretation that the lower urate levels among multiple sclerosis cases are a consequence rather than a cause of the disease.
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ABSTRACT: Urate is a natural antioxidant and may prevent CNS tissue damage and the clinical manifestations of experimental autoimmune encephalitis. Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain. To evaluate serum urate levels in MS patients and their relationships with clinical, demographic and MRI variables. Levels of non-fasting serum uric acid and creatinine were determined by an automated enzymatic assay and glomerular filtration rate was assessed in 245 MS patients, in 252 age/sex-matched neurological controls (NC) and in 59 Healthy controls (HC). Median serum urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02), whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5 mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL), compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR ≤2: 3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female sex (beta: -0.53; p<0.00001) was the most significant determinant of serum urate concentrations in MS patients on multivariate regression analysis. Our findings suggest that low urate levels could be of significance in predominantly inflammatory phases of MS even at the early stage and mainly in females.PLoS ONE 01/2012; 7(7):e40608. · 4.09 Impact Factor
Article: Oxidative stress is increased in serum from Mexican patients with relapsing-remitting multiple sclerosis.[show abstract] [hide abstract]
ABSTRACT: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress.Disease markers 02/2009; 26(1):35-9. · 1.64 Impact Factor