Vitamin D testing and treatment: a narrative review of current evidence

Abstract

Vitamin D testing and treatment is a subject of controversial scientific discussions, and it is challenging to navigate through the expanding vitamin D literature with heterogeneous and partially opposed opinions and recommendations. In this narrative review, we aim to provide an update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues. Vitamin D is critical for bone and mineral metabolism, and it is established that vitamin D deficiency can cause rickets and osteomalacia. While many guidelines recommend target serum 25-hydroxyvitamin D (25[OH]D) concentrations of ≥50 nmol/L (20 ng/mL), the minimum consensus in the scientific community is that serum 25(OH)D concentrations below 25-30 nmol/L (10-12 ng/mL) must be prevented and treated. Using this latter threshold of serum 25(OH)D concentrations, it has been documented that there is a high worldwide prevalence of vitamin D deficiency that may require public health actions such as vitamin D food fortification. On the other hand, there is also reason for concern that an exploding rate of vitamin D testing and supplementation increases costs and might potentially be harmful. In the scientific debate on vitamin D, we should consider that nutrient trials differ from drug trials and that apart from the opposed positions regarding indications for vitamin D treatment we still have to better characterize the precise role of vitamin D for human health.

Keywords: evidence-based medicine; guideline; recommendation; vitamin D.

Figure 1

Vitamin D endogenous synthesis and metabolism. Endogenous vitamin D synthesis occurs primarily through sunlight exposure which produces pre-vitamin D3. It is hydroxylated in the liver and then in the kidney, producing 1,25D (1,25 dihydroxyvitamin D), the physiologically active form of vitamin D which acts in target sites in bone and immune cells, as well as liver cells. Abbreviations: CYP (cytochrome P450), UV-B (ultraviolet-B), hν (denotes photochemical reaction). Reproduced from Keane et al. (14) under the terms of the CC Attribution 4.0 International (CC BY 4.0) licence.

Figure 2

Three children with rickets (reproduced, with permission, from Wellcome Library, London. Wellcome Images images@wellcome.ac.uk http://wellcomeimages.org; Three children with rickets; anon., Friends’ Relief Mission, Vienna XII, n.d.; Photograph circa 1920–1930; reproduced under the terms of the CC Attribution 4.0 International (CC BY 4.0) licence).

Figure 3

Dose–response trend of hazard ratios of death from all causes by standardized 25-hydroxyvitamin D. Dose–response trend of hazard ratios of all-cause mortality by standardized 25-hydroxyvitamin D were adjusted for age, sex, BMI and season of blood drawing concentrations. Hazard ratios (blue line with 95% confidence interval as the dotted blue lines) are referring to the 25-hydroxyvitamin D concentration of 83.4 nmol/L (i.e. the median 25-hydroxyvitamin D concentration for the group with 25-hydroxyvitamin D concentrations from 75 to 99.99 nmol/L). Reproduced from Gaksch et al. (16) under the terms of the CC0 1.0 Universal (CC0 1.0) Public Domain Dedication.