Calcifediol – Advanced Vitamin D Supplementation

We all know the importance of the ‘sunshine vitamin’ as a support for immune and bone health as well as for a healthy pregnancy and foetal development.1 However, the fact that is often brushed over is that deficiency of vitamin D is still very common, even in sunny Australia. In fact, just under 1 in 4 or 23% of Australians are thought to be deficient in vitamin D.2 Given the Aussie slip, slop slap culture, as well as an increasingly indoor lifestyle in modern times, it is not unreasonable to consider a vitamin D supplement as a more reliable source over sun exposure.3,4 However, most supplements on the market provide a form of vitamin D that is known as colecalciferol.  Yet D3 or colecalciferol still needs to be converted in the liver to a usable form by the body. Calcifediol is a novel form that has recently become available as a supplement in Australia. Calcifediol is the circulating form of vitamin D in the body, so that it does not need to be metabolised by the liver and is immediately available for use.1

Calcifediol, is the result of the hydroxylation of colecalciferol in its carbon 25 position, forming 25-hydroxy-vitamin D3 (calcifediol). As an intermediate metabolite within the vitamin D cycle, calcifediol is the active, circulating form of vitamin D in the blood. Several structural, physical and metabolic properties of calcifediol differentiates it from the colecalciferol form, enabling direct and more rapid enhancement of endogenous vitamin D concentrations. These properties include being 25-hydroxylated (i.e. not requiring hepatic carbon-25 hydroxylation) and more hydrophilic, and absorption occurring more efficiently via portal vein circulation compared with the more complex lymphatic pathway that colecalciferol absorption requires.5-11

 Calcifediol has been clinically demonstrated to increase and optimise endogenous vitamin D status at least 3x more rapidly than the colecalciferol form. In a randomised, controlled intervention study in apparently healthy, free-living adults, it was investigated whether the intake of 25-hydroxyvitamin D3 is 5 times more potent in raising serum 25-hydroxyvitamin D [25(OH)D] during winter compared with an equivalent amount of vitamin D3. The study was conducted in adults aged ≥50 y (n = 56) who consumed a placebo, 20 μg vitamin D3, or 7 or 20 μg 25-hydroxyvitamin D3 daily throughout 10 weeks of winter. Serum 25(OH)D was then measured. It was concluded that each microgram of orally consumed 25 hydroxyvitamin D3 was about 5 times more effective in raising serum 25(OH)D in older adults in winter than an equivalent amount of vitamin D3.12

 In another sixteen-week randomised controlled trial, thirty-five adults ≥18 years of age with 25D levels <20 ng/mL were given sixty micrograms (2400 IU)/d of D3 or 20 μg/d of calcifediol (25D3). Calcifediol increased total and free 25D levels more rapidly than D3, regardless of race/ethnicity. Free and total 25D were similarly associated with change in PTH.13 

Lastly, the conduction of a seven-arm, randomised, double-blind, controlled parallel-group study, ensured 35 healthy females aged 50–70 years (5 per group) received 20 μg calcifediol or vitamin D(3) daily, 140 μg calcifediol or vitamin D(3) weekly, for 15 weeks, or a single bolus of either 140 μg calcifediol, or vitamin D(3), or both. 25(OH)D3 plasma concentrations were quantified using LC–MS/MS in 14 clinical visits among all participants. The results showed that calcifediol given daily, weekly, or as a single bolus is about 2–3 times more potent in increasing plasma 25(OH)D3 concentrations than vitamin D3. The trial concluded also that plasma 25(OH)D3 concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol. When summarised, the clinical trials shown above, collectively make a strong argument for the efficiency of calcifediol over colecalciferol in raising vitamin D levels.14

*References available on request