American Journal of Epidemiology Advance Access originally published online on February 17, 2008
American Journal of Epidemiology 2008 167(6):753-754; doi:10.1093/aje/kwn009
American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.
THE AUTHORS REPLY
M. G. Weisskopf1,2,
E. O'Reilly3,
H. Chen4,
M. A. Schwarzschild5 and
A. Ascherio2,3
1 Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115
2 Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115
3 Department of Nutrition, Harvard School of Public Health, Boston, MA 02115
4 Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
5 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114
(e-mail: mweissko{at}hsph.harvard.edu)
We appreciate Dr. Wise's thoughtful comments (1). We agree that it would have been premature—based on the epidemiologic data we presented (2)—to recommend that plasma urate levels be increased in order to reduce the risk and delay the progression of Parkinson's disease. Accordingly, we did not make such a recommendation. Our statement simply raised the possibility of a therapeutic effect and was intentionally cautious.
In his second point, Dr. Wise notes that urate may not be acting as an antioxidant, and that even if it does confer neuroprotection through its antioxidant properties, other antioxidants with a lower risk of side effects might be better candidates as neuroprotectants for Parkinson's disease. We strongly agree (as referenced in our article (2)) that a urate-elevating strategy would carry with it a significant potential for adverse events, and that this would have to be carefully weighed against its potential disease-modifying benefits. Moreover, because urate does not act only as an antioxidant, other antioxidant agents may not offer relevant alternatives to urate. In addition, even if urate were protective through its antioxidant properties, these properties are not necessarily interchangeable with those of other antioxidants. Thus, for example, the negative results obtained with the lipophilic antioxidant alpha-tocopherol in an earlier Parkinson's disease neuroprotection trial (3) should not preclude consideration of hydrophilic urate as a neuroprotectant candidate for Parkinson's disease.
We also thank Dr. Wise for pointing out the discrepancy in part A of figure 1 (2, p. 564). While the text and the point estimates were correct, it appears that due to a graphical error the bars in part B were inadvertently duplicated in part A. The rate ratio for subjects in the highest quartile of urate level as compared with those in the lowest quartile was not quite statistically significant (rate ratio = 0.43, 95 percent confidence interval: 0.18, 1.02), although the continuous trend was significant (p = 0.017). The corrected panel A is shown here (figure 1). In addition, the dates in the figure legend should have read 1993–2000.
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FIGURE 1. A) Rate ratio for Parkinson's disease by quartile of urate concentration among all cases and controls, adjusted for age, pack-years of smoking, and quintile of caffeine intake, Health Professionals Follow-up Study, 1993–2000. Rate ratios are indicated next to the black diamonds, and 95% confidence intervals are indicated by the vertical lines. The numbers of cases and controls in each quartile of urate concentration are shown in the box below the figure.
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ACKNOWLEDGMENTS
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Conflict of interest: none declared.
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References
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- Wise BL, Neogi T, Zhang Y. Re: "Plasma urate and risk of Parkinson's disease." (Letter). Am J Epidemiol (2008) 167:752–3.[Free Full Text]
- Weisskopf MG, O'Reilly E, Chen H, et al. Plasma urate and risk of Parkinson's disease. Am J Epidemiol (2007) 166:561–7.[Abstract/Free Full Text]
- Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med (1993) 328:176–83.[Abstract/Free Full Text]
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