Is cholecalciferol (Vitamin D3) more effective than ergocalciferol (Vitamin D2)?

From the Guidelines

Vitamin D3 is generally considered more effective than vitamin D2 for raising and maintaining vitamin D levels in the blood. The difference in effectiveness between the two forms is attributed to their distinct metabolism, with vitamin D3 being more efficient in raising 25(OH) D concentrations and maintaining those levels for a longer time when longer dosing intervals are employed 1.

Key Points to Consider

• Vitamin D3 could be more effective in raising 25(OH) D concentrations and maintaining those levels for a longer time when longer dosing intervals are employed 1.
• No difference in maintaining 25(OH) D levels was found when daily dosing was studied, suggesting that for consistent, daily supplementation, both forms may be equally effective 1.
• A common regimen for patients with serum 25(OH) D levels below 30 ng/mL is prescription vitamin D (ergocalciferol) 50,000 IU weekly for 8 weeks, followed by a recheck of the serum 25(OH) D level, with subsequent dosing based on the results 1.
• For patients with 25(OH) D levels between 20 and 30, an alternative is adding 1000 IU over the counter vitamin D2 or D3 per day to the patient's current intake and rechecking the level in 3 months 1.

Recommendations for Supplementation

• Current expert opinion on supplementation for adults older than age 50 is 1200 mg of calcium (from all sources) and 800 to 1000 IU of vitamin D daily 1.
• The NCCN Bone Health in Cancer Care Task Force also recommends these ranges for younger patients at risk for cancer treatment–associated bone loss 1.
• Many patients need more than the recommended amount of vitamin D and should be repleted based on serum 25(OH) D level 1.

From the Research

Comparison of Vitamin D2 and D3

• Vitamin D3 is considered more effective than vitamin D2 in increasing serum levels of 25(OH)D 2
• A study comparing the effectiveness of vitamin D2 and D3 replacement therapy found that vitamin D3 injection alone or with a D2 tablet increased serum vitamin D levels more than vitamin D2 injection alone 3
• The study also found that using vitamin D3 in an injectable form is the best choice to restore severe vitamin D deficiency, and it was superior to the injectable form of vitamin D2, even though vitamin D2 has double the molar units 3

Pharmacological Differences

• Vitamin D2 has a shorter plasma half-life and a lower affinity for the vitamin D binding protein, the hepatic vitamin D hydroxylase, and the vitamin D receptor compared to vitamin D3 2
• These differences may contribute to the greater effectiveness of vitamin D3 in increasing serum levels of 25(OH)D

Supplementation Guidelines

• The Institute of Medicine recommends that most North Americans receive sufficient vitamin D from their diet and sun exposure, and that supplementation is not necessary for indications other than musculoskeletal health 4
• However, other studies suggest that vitamin D supplementation may be necessary for individuals with severe vitamin D deficiency, and that vitamin D3 may be a better choice than vitamin D2 for supplementation 3, 2

Health Effects of Vitamin D Supplementation

• Vitamin D supplementation can prevent and cure nutritional rickets in infants and children, and may have extra-skeletal benefits for individuals with vitamin D deficiency 5
• However, the causal link between vitamin D and many extra-skeletal outcomes remains unclear, and supplementation of vitamin D-replete individuals does not provide demonstrable health benefits 5