Dosing recommendations

Clinically effective dose: Clinical trials demonstrate that doses of 10-20 mcg/day of calcifediol to be effective in raising serum levels of 25-hydroxyvitamin D (25(OH)D)

Duration: Calcifediol has been used in clinical trials lasting between 2 weeks to 6 months with more extensive trials being undertaken for 12 months

Form: Calcifediol

Drug interactions: Calcium channel blockers: caution - vitamin D supplementation may increase risk of hypercalcaemia which may reduce drug effectiveness. Monitor serum vitamin D and calcium levels

Safe dosing: Long-term safety of 20 µg and 30 µg of calcifediol taken daily over 6 months has been confirmed in patients with low serum levels of 25(OH)D

Colecalciferol has long been regarded as the gold standard for vitamin D supplementation, however, thanks to emerging evidence and availability of ingredients, calcifediol is now becoming a more suitable alternative in patients with low vitamin D status.

In a randomized, double-blind, active comparator trial of 91 participants, researchers compared the pharmacokinetics of 3 different daily doses of calcifediol to 20 μg of colecalciferol. Participants were administered either 10, 15 or 20 μg of calcifediol or 20 μg of colecalciferol daily for 6 months followed by a 6-month washout period. Blood was drawn to determine serum 25(OH)D at baseline and at multiple stages throughout the study.

After 6 months of supplementation, serum 25(OH)D levels were significantly higher in the 10, 15 and 20 µg calcifediol/day groups compared to the 20 µg colecalciferol/day group. Demonstrating calcifediol’s enhanced ability to raise serum vitamin D levels compared to colecalciferol, even at lower doses.

Response time to increase serum levels

By performing ongoing blood tests, researchers were able to determine the time at which serum 25(OH)D concentrations reached 75 nmol/L (30 ng/mL) for each group.
Results found all 3 daily doses of calcifediol to be superior to 20 μg colecalciferol in increasing serum 25(OH)D to 75 nmol/L.  

10 μg/day calcifediol group, 26 days

15 μg/day calcifediol group, 10 days

20 μg/day calcifediol group, 7 days

20 μg/day colecalciferol, 40 days

Enhanced Bioavailability

Researchers believe that the increases in serum vitamin D seen with calcifediol supplementation may be due to enhanced bioavailability through improved absorption and distribution.

Gastrointestinal absorption is of great importance when assessing the effectiveness of various supplements. Previous studies have found calcifediol peaked earlier and had greater absorption than colecalciferol.

Furthermore, colecalciferol has been shown to have less affinity for vitamin D-binding protein than calcifediol. Therefore, calcifediol will diffuse more readily into tissues, lowering the amount available to be hydroxylated by cytochrome P450 enzymes.

Rate of Elimination

30 days after cessation of supplementation, testing found rates of elimination to be significantly higher in all 3 calcifediol groups compared to colecalciferol. However, there was no difference in serum 25(OH)D concentrations between all 4 interventions after the 6-month washout period.

Higher doses of calcifediol were found to have higher rates of elimination, however similar concentrations were seen by 2 months. Researchers hypothesised this may be a result of the 25-hydroxyvitamin D-24-hydroxylase enzyme (CYP24A1) being upregulated by larger doses, resulting in a faster elimination rate of calcifediol. Another possibility is the lipophilic nature of colecalciferol, resulting in slower elimination due to higher retention in tissues, providing continuous release into circulation.

Clinical Take-Aways

Researchers concluded that, per microgram dose, calcifediol was 3 times more effective than colecalciferol in raising serum 25(OH)D concentrations. Based on this evidence, practitioners should consider the use of calcifediol in cases where there is a need to rapidly increase vitamin D levels, such as seen in deficiency states, intestinal malabsorption syndromes and obesity to name a few clinical scenarios. In contrast, due to its slower elimination rate, colecalciferol may be ideal to maintain vitamin D status in healthy individuals, or once serum levels have been sufficiently raised.