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Existing and potentially novel functional markers of vitamin D status: a systematic review^1,2,3,4,5

¹ From the Departments of Food and Nutritional Sciences (KMS and KDC) and Medicine (KDC), University College Cork, Cork, Ireland.

² This manuscript does not necessarily reflect the views of the Commission of the European Communities and in no way anticipates the future policy in this area.

³ Presented at the EURRECA workshop "Biomarkers of Micronutrient Status," held in Sveti Stefan, Montenegro, 9 June 2008.

⁴ Supported by the Commission of the European Communities, specific RTD Programme, "Quality of Life and Management of Living Resources," within the 6th Framework Programme (contract no. FP6-036196-2 EURRECA: EURopean micronutrient RECommendations Aligned).

⁵ Address correspondence to KD Cashman, Department of Food and Nutritional Sciences and Department of Medicine, University College Cork, Cork, Ireland. E-mail: k.cashman{at}ucc.ie.

Background: Although serum 25-hydroxyvitamin D [25(OH)D] is the currently accepted vitamin D status marker of choice, use of other biomarkers or functional endpoints have been suggested.

Objective: The objective was to systematically review the effectiveness of 25(OH)D, parathyroid hormone (PTH), bone turnover markers, bone mineral density (BMD), and calcium absorption as biomarkers of vitamin D status.

Design: Methods included a structured search on Ovid MEDLINE, EMBASE (Ovid), and Cochrane CENTRAL; rigorous inclusion/exclusion criteria; data extraction; quality assessment; meta-analysis; and meta-regression.

Results: Thirty-six vitamin D supplementation randomized controlled trials (RCTs) and 4 before-after studies were included. Vitamin D supplementation significantly raised circulating 25(OH)D in all but one RCT, but the response was highly heterogeneous [weighted mean difference (WMD): 34.1 nmol/L; 95% CI: 28.9, 39.2; 32 RCTs; I² = 97%). Vitamin D supplementation (without calcium) significantly lowered circulating PTH (WMD: –0.29 pmol/L; 95% CI: –0.56, –0.02; 11 RCTs; I² = 29%), but this was not apparent in the presence of calcium supplementation. There was a suggestion that whole-body or lumbar spine BMD may be a useful biomarker in older people but not in adolescents. Bone turnover markers were not useful biomarkers of vitamin D status, but 4 before-after studies suggested that intestinal calcium absorption may respond to vitamin D status.

Conclusions: This systematic review confirmed that circulating 25(OH)D is a robust and reliable marker of vitamin D status. Further research is needed to clarify which population subgroups show responses of PTH, BMD, and/or calcium absorption in response to changes in vitamin D status.

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