DSM Nutritional Products

Novel Food Application: Calcidiol

2.12 Concluding remarks

Calcidiol (25-hydroxycholecalcifediol, or 25-hydroxy vitamin D3) is a normal metabolite of
vitamin D3 in mammalian, avian and other species and is the principal circulating form of
vitamin D3, the primary source of vitamin D activity in humans and animals. The metabolism
of vitamin D in humans is well understood and is documented in the literature. Vitamin D
regulates calcium and phosphorus homeostasis, bone growth and other endocrine system
functions. Humans have been exposed to calcidiol in their diet for as long as they have
consumed animal products for example meat, milk and eggs. Circulating 25-hydroxy vitamin
D3 is considered as the best biomarker of vitamin D status; a serum 25-hydroxy vitamin D3
level above 50 nmol/L is considered as being sufficient, however, for optimal fracture
prevention at older age a threshold of 75 nmol/L is desirable.

There is evidence from studies of an association between circulating calcidiol concentrations

with bone health outcomes (established rickets, parathyroid hormone, falls, bone mineral
density). Published non-clinical and clinical trials demonstrate that substitution of vitamin D3
with calcidiol is effective and well tolerated and has a potential advantage over vitamin D
administration. The benefit of consuming calcidiol rather than vitamin D3 itself is that the
metabolite, calcidiol, is preferentially bound by the vitamin D binding protein (DBP) and
bypasses the vitamin D3 to calcidiol conversion step in the liver.

The assessment of the safety of calcidiol has been clearly established since its discovery as a
metabolite of Vitamin D3 over 40 years ago.

Toxicological studies using DSM's calcidiol showed no potential for mutagenicity in the Ames
Test and the MLA Test. No indication of clastogenicity or aneugenicity was noted in the in vitro
CA and in vivo MNT. No adverse effects were noted in a repeated dose toxicity study (OECD
408 compliant 90-day study), and the NOAEL was 180 µg calcidiol/kg bw/d, the highest dose
level tested. Comparative ADME studies show that oral calcidiol is absorbed faster and also
cleared and eliminated faster than oral cholecalciferol. Oral calcidiol results in wide tissue
distribution with highest concentration in plasma and lower retention in tissues as compared
to vitamin D3. Apart from the first step of 25-hydroxylation of vitamin D3, further metabolism is
qualitatively the same for calcidiol and cholecalciferol, but metabolism is faster and more
efficient with calcidiol. The relatively faster elimination and lower retention supports the safety
of oral calcidiol supplementation.

Clinical studies have been performed with calcidiol in comparison to vitamin D3 to determine
the safety and efficacy of the use of the substances as a source of vitamin D3 activity. Each of
the studies support the use of calcidiol at the proposed dose and at two to five times the
proposed dose as being safe and effective. The studies clearly indicate that calcidiol is three
times more effective on average than vitamin D3 in raising the circulating level of 25-hydroxy
vitamin D3, the internationally accepted maker for vitamin D nutritional status.

Concluding remarks Page 1 of 2

[Calcidiol, © DSM Nutritional Products Ltd., 2018]
May 2018 / DSM5051-001
DSM Nutritional Products
Novel Food Application: Calcidiol

Calcidiol is a new form of Vitamin D for use in food supplements. It complies with the current
Ph.Eur and USP monographs. The use of Calcidiol will provide manufacturers with the
opportunity to develop new and more efficient vitamin D-containing food supplements.

Concluding remarks Page 2 of 2

[Calcidiol, © DSM Nutritional Products Ltd., 2018]
May 2018 / DSM5051-001