Elsevier

Journal of Clinical Densitometry

Volume 16, Issue 4, October–December 2013, Pages 402-408
Journal of Clinical Densitometry

Special Section on Bone and Nutrition
Clinical Controversies in Vitamin D: 25(OH)D Measurement, Target Concentration, and Supplementation

https://doi.org/10.1016/j.jocd.2013.08.006Get rights and content

Abstract

Despite a plethora of recent research and systematic reviews of available data, controversy continues to surround the definition of optimal vitamin D status, the daily intake needed, and the potential adverse health consequences of “insufficiency.” Efforts to standardize vitamin D measurement and improve understanding of the physiologic consequences of other vitamin D metabolites such as 3-epi and 24,25(OH)2D (and potentially other vitamin D compounds) are needed. Currently, measurement of circulating 25(OH)D is accepted as the approach to define an individual's vitamin D status. However, existing 25(OH)D assays may include other vitamin D metabolites such as the 3-epimer of 25(OH)D and 24,25(OH)2D. It seems unlikely that the controversy will soon be resolved.

Introduction

This quote seems an apt description of the controversy surrounding vitamin D; there is much that we simply do not know. Despite a plethora of recent research and systematic reviews of available data, controversy continues to surround the definition of optimal vitamin D status, the daily intake needed, and the potential adverse health consequences of “insufficiency.” Indeed, current evidence-based recommendations regarding vitamin D dose and 25-hydroxyvitamin D (25(OH)D) concentration to achieve for optimal health are not concordant and have engendered passionate disagreement among vitamin D experts 1, 2, 3. In such a situation, it is hardly surprising that clinicians and the public are confused regarding vitamin D. Importantly, challenges continue to vex 25(OH)D measurement, despite this being recognized as the best clinical indicator of vitamin D status. It is the author's perspective that improved vitamin D laboratory measurement, and understanding of these results is essential to advance definition of what constitutes vitamin D deficiency, insufficiency, and optimal vitamin D status. Given our current inadequate knowledge, what is the clinician to do? The following provides an approach to the clinical assessment and management of vitamin D status.

Section snippets

Vitamin D Inadequacy

Inadequate vitamin D status, however, one wishes to define it, is common because of low dietary intake and the current lifestyle of widespread sun avoidance or use of sunscreen, thereby blocking vitamin D production (4). Vitamin D has long been known to be important in bone and muscle health with deficiency causing osteomalacia/rickets. In addition, vitamin D deficiency is associated with muscle weakness, an obvious risk factor for falls. As falls directly cause many fragility fractures, it is

Current Assessment of Vitamin D Status

Measurement of circulating 25(OH)D (not 1, 25 dihydroxyvitamin D) is universally considered to be the best approach to assess an individual's vitamin D status. Nonetheless, caveats and substantial confounders exist with this measurement. Importantly, 25(OH)D is not subject to tight physiologic feedback regulation (in contrast, for example, to thyroid stimulating hormone), and as such, it does not provide direct insight into adequacy on an individual patient level. Moreover, other issues

How Much Is Enough? What 25(OH)D Level Defines Vitamin D “Deficiency” and “Insufficiency?” and How to Deal With Clinical 25(OH)D Measurement Variability

Is there a “right” 25(OH)D level to target in clinical practice? The short answer is no. When attempting to answer this question, experts remain passionate but divided; some advocate 20 ng/mL, whereas others favor 30–32 ng/mL. A major contributor to this controversy is the 25(OH)D assay variability noted earlier. These assay issues substantially confound all existing literature, importantly including the numerous systematic reviews/meta-analyses that relate 25(OH)D level to various

Approaches to Vitamin D Supplementation

How to optimally use vitamin D supplementation has received inadequate attention. Daily supplementation with 1000–4000 IU and intermittent pharmacologic dose approaches have been studied. Although obviously an oversimplification and not applicable to all patients, a reasonable “rule of thumb” is that addition of 1000 IU of vitamin D3 daily can be expected to increase circulating 25(OH)D by approx 6–10 ng/mL (18). It is common to see “high-dose” pharmacologic approaches used to treat vitamin D

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