Journal of Neurology

, Volume 258, Issue 2, pp 238–243 | Cite as

An exploratory study of serum urate levels in patients with amyotrophic lateral sclerosis

  • Stefano Zoccolella
  • Isabella Laura Simone
  • Rosa Capozzo
  • Rosanna Tortelli
  • Antonio Leo
  • Eustachio D’Errico
  • Giancarlo Logroscino
Original Communication

Abstract

Urate is a natural antioxidant, and high serum urate levels could be protective against the development of amyotrophic lateral sclerosis (ALS). To determine if serum urate concentrations were lower in ALS patients than in healthy controls, we compared serum urate levels in 132 ALS patients and 337 age/sex-matched controls. Median urate levels were lower in ALS patients compared to controls (4.2mgl/dL [range:1.4–8.2], vs. 4.7 [1.7–13.1]; p = 0.04). In univariate analysis, high urate levels were less likely to be associated with ALS (odds ratio [OR]: 0.53; 95% CI: 0.29–0.97; p = 0.04), but after adjusting for age, sex and kidney function, the association was not statistically significant (OR: 0.63; 95% CI: 0.32–1.24; p = 0.18). Urate levels were lower in bulbar-onset ALS (3.9 mg/dL), compared to limb-onset ALS (4.3; p = 0.001), and in cases with longer disease duration compared to controls (4.1 mg/dL, vs. 4.7; p = 0.01). In this cross-sectional study, lower levels of serum urate were evident in ALS cases with bulbar-onset and longer disease duration, but were likely to be related to the malnutrition induced by ALS.

Keywords

Amyotrophic lateral sclerosis Urate Oxidative stress Progression Phenotype 

References

  1. 1.
    Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700CrossRefPubMedGoogle Scholar
  2. 2.
    Goodall EF, Morrison KE (2006) Amyotrophic lateral sclerosis (motor neuron disease): proposed mechanisms and pathways to treatment. Expert Rev Mol Med 8:1–22CrossRefPubMedGoogle Scholar
  3. 3.
    Oda M, Satta Y, Takenaka O et al (2002) Loss of urate oxidase activity in hominoids and its evolutionary implications. Mol Biol Evol 19:640–653PubMedGoogle Scholar
  4. 4.
    Ames BN, Cathcart R, Schwiers E et al (1981) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Nal Acad Sci USA 78:6858–6862CrossRefGoogle Scholar
  5. 5.
    Yu ZF, Bruce-Keller AJ, Goodman Y et al (1998) Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo. J Neurosci Res 53:613–625CrossRefPubMedGoogle Scholar
  6. 6.
    Church WH, Ward VL (1994) Uric acid is reduced in the substantia nigra in Parkinson’s disease: effect on dopamine oxidation. Brain Res Bull 33:419–425CrossRefPubMedGoogle Scholar
  7. 7.
    Beal MF (2005) Mitochondria take center stage in aging and neurodegeneration. Ann Neurol 58:495–505CrossRefPubMedGoogle Scholar
  8. 8.
    Davis JW, Grandinetti A, Waslien CJ et al (1996) Observations on serum uric acid and the risk for idiopathic Parkinson’s disease. Am J Epidemiol 144:480–484PubMedGoogle Scholar
  9. 9.
    Weisskopf MG, O’Reilly E, Chen H et al (2007) Plasma urate and risk of Parkinson’s disease. Am J Epidemiol 166:561–567CrossRefPubMedGoogle Scholar
  10. 10.
    De Vera M, Rahman MM, Rankin J et al (2008) Gout and the risk of Parkinson’s disease: a cohort study. Arthritis Rheum 59:1549–1554CrossRefPubMedGoogle Scholar
  11. 11.
    de Lau LM, Koudstaal PJ, Hofman A et al (2005) Serum uric acid levels and the risk of Parkinson disease. Ann Neurol 58:797–800CrossRefPubMedGoogle Scholar
  12. 12.
    Gao X, Chen H, Choi HK et al (2008) Diet, urate, and Parkinson’s disease risk in men. Am J Epidemiol 167:831–838CrossRefPubMedGoogle Scholar
  13. 13.
    Alonso A, Rodríguez LA, Logroscino G et al (2007) Gout and risk of Parkinson disease: a prospective study. Neurology 69:1696–1700CrossRefPubMedGoogle Scholar
  14. 14.
    Irizarry MC, Raman R, Schwarzschild MA et al (2009) Plasma urate and progression of mild cognitive impairment. Neurodegener Dis 6:23–28CrossRefPubMedGoogle Scholar
  15. 15.
    Euser SM, Hofman A, Westendorp RG et al (2009) Serum uric acid and cognitive function and dementia. Brain 132:377–382CrossRefPubMedGoogle Scholar
  16. 16.
    Schretlen DJ, Inscore AB, Jinnah HA et al (2007) Serum uric acid and cognitive function in community-dwelling older adults. Neuropsychology 21:136–140CrossRefPubMedGoogle Scholar
  17. 17.
    Ruggiero C, Cherubini A, Miller E et al (2007) Usefulness of uric acid to predict changes in C-reactive protein and interleukin-6 in 3-year period in Italians aged 21 to 98 years. Am J Cardiol 100:115–121CrossRefPubMedGoogle Scholar
  18. 18.
    Keizman D, Ish-Shalom M, Berliner S et al (2009) Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress? J Neurol Sci 285:95–99CrossRefPubMedGoogle Scholar
  19. 19.
    Sohmiya M, Tanaka M, Suzuki Y et al (2005) An increase of oxidized coenzyme Q-10 occurs in the plasma of sporadic ALS patients. J Neurol Sci 228:49–53CrossRefPubMedGoogle Scholar
  20. 20.
    Kokic AN, Stevic Z, Stojanovic S et al (2005) Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Redox Rep 10:265–270CrossRefPubMedGoogle Scholar
  21. 21.
    Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124(Suppl):96–107CrossRefPubMedGoogle Scholar
  22. 22.
    Miller RG, Munsat TL, Swash M et al (1999) Consensus guidelines for the design and implementation of clinical trials in ALS. J Neurol Sci 169:2–12CrossRefPubMedGoogle Scholar
  23. 23.
    Bos MJ, Koudstaal PJ, Hofman A et al (2006) Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke 37:1503–1507CrossRefPubMedGoogle Scholar
  24. 24.
    Brooks BR (2003) Functional scales: summary. Amyotroph Lateral Scler Other Motor Neuron Disord 3(suppl1):S13–S18Google Scholar
  25. 25.
    Kimura F, Fujimura C, Ishida S et al (2006) Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS. Neurology 66:265–267CrossRefPubMedGoogle Scholar
  26. 26.
    Levey AS, Coresh J, Greene T et al (2007) Chronic kidney disease epidemiology collaboration. expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 53:766–772CrossRefPubMedGoogle Scholar
  27. 27.
    Reynolds A, Laurie C, Lee Mosley R et al (2007) Oxidative stress and the pathogenesis of neurodegenerative disorders. Intern Rev Neurobiol 82:297–325CrossRefGoogle Scholar
  28. 28.
    Hervias I, Beal MF, Manfredi G (2006) Mitochondrial dysfunction and amyotrophic lateral sclerosis. Muscle Nerve 33:598–608CrossRefPubMedGoogle Scholar
  29. 29.
    Pacher P, Beckman KS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424CrossRefPubMedGoogle Scholar
  30. 30.
    Tohgi H, Abe T, Yamazaki K et al (1999) Increase in oxidized NO products and reduction in oxidized glutathione in cerebrospinal fluid from patients with sporadic form of amyotrophic lateral sclerosis. Neurosci Lett 260:204–206CrossRefPubMedGoogle Scholar
  31. 31.
    Du Y, Chen CP, Tseng CY et al (2007) Astroglia-mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity. Glia 55:463–472CrossRefPubMedGoogle Scholar
  32. 32.
    Ruggiero C, Cherubini A, Lauretani F et al (2009) Uric acid and dementia in community-dwelling older persons. Dement Geriatr Cogn Disord 27:382–389CrossRefPubMedGoogle Scholar
  33. 33.
    Schiess M, Oh I (2008) Serum uric acid and clinical progression in Parkinson disease. Potential biomarker for nigrostriatal failure. Arch Neurol 65:698–699CrossRefPubMedGoogle Scholar
  34. 34.
    Ruggiero C, Cherubini A, Ble A et al (2006) Uric acid and inflammatory markers. Eur Heart J 27:1174–1181CrossRefPubMedGoogle Scholar
  35. 35.
    Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–521CrossRefPubMedGoogle Scholar
  36. 36.
    Hayden MR, Tyagi SC (2004) Uric acid: a new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: the urate redox shuttle. Nutr Metab (Lond) 1(1):10CrossRefGoogle Scholar
  37. 37.
    Gasteyger C, Suter M, Calmes JM et al (2006) Changes in body composition, metabolic profile and nutritional status 24 months after gastric banding. Obes Surg 16:243–250CrossRefPubMedGoogle Scholar
  38. 38.
    Traynor BJ, Bruijn L, Conwit R et al (2006) Neuroprotective agents for clinical trials in ALS: a systematic assessment. Neurology 67:20–27CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Stefano Zoccolella
    • 1
  • Isabella Laura Simone
    • 2
  • Rosa Capozzo
    • 2
  • Rosanna Tortelli
    • 2
  • Antonio Leo
    • 2
  • Eustachio D’Errico
    • 2
  • Giancarlo Logroscino
    • 2
    • 3
  1. 1.Azienda Ospedaliero-Universitaria Ospedali Riuniti, Medical and Neurological Sciences, Clinic of Nervous System DiseasesUniversity of FoggiaFoggiaItaly
  2. 2.Department of Neurological SciencesUniversity of BariBariItaly
  3. 3.Department of Neurology and PsychiatryUniversity of BariBariItaly

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