Effect of Vitamin D Supplementation on Free and Total Vitamin D

A Comparison of Asians and Caucasians

Jaya Sujatha Gopal-Kothandapani; Lucy Faith Evans; Jennifer S. Walsh; Fatma Gossiel; Alan S. Rigby; Richard Eastell; Nick J. Bishop


Clin Endocrinol. 2019;90(1):222-231. 

In This Article


Vitamin D deficiency is a term widely used but rarely defined in terms of functional outcomes. Based on synthesized evidence, thresholds for low-dose supplementation or higher dose treatment have been suggested. The Scientific Advisory Committee on Nutrition Department (SACN) recommends a threshold of 25 nmol/L for serum 25OHD for all individuals at any time of the year to protect the musculoskeletal health.[3] The Institute of Medicine defines the threshold for vitamin D deficiency as ≤30 nmol/L.[2] The Endocrine Society defines the threshold for vitamin D deficiency as <50 nmol/L, which would likely include more than half the population of the UK during winter months.[1]

What remains unclear is the extent to which "one size fits all" in providing vitamin D supplementation or treatment. In the UK, vitamin D deficiency is widely reported, more so in those with darker skin including those of African or Asian descent. The effect of ethnicity, independently of other factors, has not previously been considered when devising strategies and recommendations for either low-dose supplementation or higher dose treatment.

Vitamin D status is currently assessed by measuring circulating 25-hydroxyvitamin D (25OHD), which exists either free in the circulation (<1%), or bound to albumin or the vitamin D binding protein (DBP). The terms "free" vitamin D and "bioavailable" vitamin D refer, respectively, to unbound 25OHD, or unbound plus 25OHD bound to albumin. The extent to which the total measurement adequately reflects either free or bioavailable serum 25OHD and whether any relationship between "total" and "free" varies following supplementation, or with other factors such as ethnicity, is unclear. Reports of higher free and bioavailable serum 25OHD for the same total serum 25OHD in African Americans have been challenged because of concerns regarding DBP measurement accuracy.[4–8]

In the light of this, we sought to investigate whether there were differences between serum total and directly measured free 25OHD concentrations between Asians and White Caucasians and the changes in these parameters following administration of a single dose of 150 000 IU of vitamin D3. In addition, we aimed to determine the effect of covariates including DBP concentration and genotype, concurrent diet and skin colour on both the free and total 25OHD responses, and the extent of parathyroid hormone (PTH) suppression following dosing.