How Should We Define Vitamin D Deficiency?
July 21, 2015: Dr. Anders Berg presented at the Northeast Laboratory Conference in October 2014 regarding a much debated topic: vitamin D deficiency and how this should be defined. Dr. Berg referenced over one thousand studies, reports and expert testimonials suggesting vitamin D is related to various health outcomes. Despite the large body of evidence supporting the role of vitamin D in the fields of cancer, CVD and diabetes, Dr. Berg finds the evidence mixed and inconclusive. Berg suggested that current evidence only supports the role of vitamin D in bone health, but not in other health conditions. The reasoning behind his conclusion lies in the metabolism and availability of vitamin D, as well as how vitamin D deficiency is defined.
Following the uptake of vitamin D2 and D3 through sunlight contacting bare skin or through dietary means, it is quickly metabolized into 25-OH vitamin D, the major storage form of vitamin D. While in circulation, the majority (85-90%) of 25-OH vitamin D is bound vitamin D binding protein (VDBP) which prevents it from acting on target cells. Of the 10-15% of 25-OHVD that is not bound by VDBP, less than one percent exists in the unbound or free form with the remaining 25-OHVD bound by albumin. When levels of 25-OH vitamin D are quantified, the number reflects the following: Total = Free 25-OH + 25-OH bound to albumin + 25-OH bound to VDBP Dr. Berg believes free 25-OH vitamin D levels are more indicative of vitamin D status. Deficiency is related to low free 25-OH vitamin D levels rather than total 25-OHVD levels. This concept relates to the free hormone hypothesis which states that only unbound hormones can cross cell membranes and have biological action.
To illustrate this point, Dr. Berg presented a schematic of Free T4 as the active form binding to the thyroid hormone receptor and eliciting a response. TBG- bound T4, in turn, is not free to act on target tissues. Berg presented data from a collection of publications showing that, despite the reported lower total 25-OHVD levels in blacks than whites, their bone mineral density (BMD) is actually higher. Therefore, he concluded that because levels of functional VDBP are lower in blacks, free 25-OHVD levels are higher and it is the free 25-OHVD impacting BMD. In summary, Dr. Berg suggested free vitamin D levels are more predictive of disease. Additionally, Berg proposed that direct measurement of free vitamin D levels is needed, rather than quantifying total 25-OHVD levels.