Response to “importance of C-3 epimer of 25-hydroxyvitamin D in dried blood spots of neonatal population”
Year: 2015
Type: letter
Abstract: We thank Dr. Tapan and coworkers for their letter stressing the importance of considering the contribution of the C3-epimer of vitamin D in epidemiologic studies of the health impacts of vitamin D status. In our pilot study of neonatal vitamin D and childhood brain tumor (CBT) risk, we used liquid-chromatography-tandem mass spectrometry (LC-MS/MS) to obtain high-quality and distinct measurements of 25-hydroxyvitamin D2 [25-(OH)D2] and 25-hydroxyvitamin D3 [25-(OH)D3] in archived dried blood spots (DBS).1 Unfortunately, the LC-MS/MS assay that we used did not differentiate the C3-epimer of 25(OH)D3 [3-epi-25(OH)D3],2 though it has recently been suggested that separation of 3-epi-25(OH)D3 could be attained by a modification to the run-time of the method.3 To our knowledge, however, validation studies of any of the various LC-MS/MS methods proposed to measure 3-epi-25(OH)D3 in archived DBS have not yet been conducted. Despite recent findings suggesting that C-3 epimers of vitamin D can contribute significantly to overall vitamin D levels, particularly among infants,4 the clinical utility of obtaining separate measurements of C-3 epimers remains uncertain.5 There is, however, a growing body of mechanistic evidence suggesting differential effects of the C-3 epimers of vitamin D at the molecular level. For example, of particular relevance to our study is research demonstrating significantly reduced anti-proliferative and differentiation impacts of the C-3 epimer of vitamin D in cancer cells.6 Given such findings, we agree that future epidemiologic studies, particularly among infant populations, should endeavor to obtain and separately analyze measurements of 3-epi-25(OH)D3, pending validation of the assay methods. The potential impact of unmeasured 3-epi-25(OH)D3 on our results is difficult to estimate. We originally speculated that the birth weight specific effects of vitamin D on CBT risk were due to the impact of vitamin D on circulating insulin-like growth factor 1 (IGF-1) levels. The exact mechanism by which vitamin D promotes IGF-1 secretion is not understood, but it is thought to occur through direct interaction of vitamin D with liver cells through the vitamin D receptor (VDR). Given that 3-epi-25(OH)D3 has been observed to have less binding affinity to the VDR,6 accounting for between-subject variation in the levels of 3-epi-25(OH)D3 might have potentially strengthened the associations we observed. Additional studies of vitamin D and CBT risk are needed to disentangle any epimer-specific effects. Yours sincerely, Parveen Bhatti David R. Doody Roberta Mckean-Cowdin and Beth A. Mueller
Source: International Journal of Cancer
DOI: 10.1002/ijc.29422
Language: English
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1982015162