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. 2014 May 6;82(18):1666. doi: 10.1212/01.wnl.0000449750.81263.7d

Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study

Raja Mehanna 1
PMCID: PMC10845904  PMID: 24799519

Ding et al.1 concluded that a significant proportion of patients with Parkinson disease (PD) are vitamin D deficient, and the severity of deficiency is correlated to the severity and duration of the disease. The authors should be praised for admitting that this association does not mean causation and that PD might predispose to vitamin D deficiency by limiting outdoor activity. The authors should also be commended for not suggesting vitamin D supplementation to all patients with PD.

However, after the analysis was corrected for covariates, the overall relation between total 25[OH] vitamin D and PD was lost, but the authors considered the relation between 25[OH]D3 and PD at a p value of 0.047. Even though this is close to the 0.05 cutoff, the authors did not mention any correction for multiple statistical analyses, which may have affected the value of p and rendered this relation not statistically significant. Ultimately, this could affect the conclusion that their study “reveals an association between 25[OH]D3 and PD.”

Neurology. 2014 May 6;82(18):1666.

Author Response

Clemens R Scherzer, Hongliu Ding, Joseph J Locascio 1

We thank Dr. Mehanna for commenting on our study, where we used liquid chromatography/tandem mass spectrometry to investigate an association specifically between deficiency of the transcriptionally active human hormone 25[OH]D3 and PD. Our goal was to directly measure 25[OH]D3.

We chose this method because it is advantageous compared to other methods that assay total 25[OH]D (a composite measure of 25[OH]D2 and 25[OH]D3). Total 25[OH]D may be confounded by exogenous vitamin 25[OH]D2 that is not produced in humans but ingested through diet or supplements. In the primary analysis, plasma levels of 25[OH]D3 were associated with the prevalence of PD with an unadjusted p value of 0.0034 and a p value of 0.047 after adjusting for the baseline inequalities including age, sex, race, and vitamin D supplementation.

Dr. Mehanna noted that we did not mention any correction for multiple hypothesis testing and speculated that this may have affected the value of p and rendered the relation between 25[OH]D3 and PD not statistically significant. Although the adjusted p value of 0.047 is from a multivariate test (i.e., 25[OH]D3 adjusted for important covariates), it is from only one test: one p value that specifically answered the predefined primary scientific question. We agree with Dr. Mehanna that adjustment for multiple testing in the appropriate settings is vital2,3 but it does not apply here.

The data shown in our study, consistent with several previous independent cross-sectional and prospective investigations, confirm the view that vitamin D deficiency is both common and significant in PD.

References

  • 1.Ding H, Dhima K, Lockhart KC, et al. Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study. Neurology 2013;81:1531–1537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Scherzer CR. Chipping away at diagnostics for neurodegenerative diseases. Neurobiol Dis 2009;35:148–156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Hennecke G, Scherzer CR. RNA biomarkers of Parkinson's disease: developing tools for novel therapies. Biomark Med 2008;2:41–53. [DOI] [PubMed] [Google Scholar]

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