What is the difference between Vitamin D2 (Ergocalciferol) and Vitamin D3 (Cholecalciferol)?

From the Guidelines

Vitamin D3 (cholecalciferol) is generally considered the preferred form for supplementation due to its higher bioefficacy compared to Vitamin D2 (ergocalciferol) in raising and maintaining vitamin D levels in the body. The main difference between Vitamin D2 and Vitamin D3 lies in their sources and effectiveness. Vitamin D2 is derived from plant sources and fungi, particularly from UV-irradiated mushrooms and yeast, while Vitamin D3 comes from animal sources and is also produced in human skin when exposed to sunlight.

Key Differences and Recommendations

• Vitamin D3 is more effective at raising and maintaining vitamin D levels because it binds more efficiently to vitamin D-binding proteins and has a longer half-life in the bloodstream 1.
• When supplementing, Vitamin D3 is typically recommended in doses of 600-2000 IU daily for most adults, though individuals with deficiency may require higher doses (up to 5000 IU daily) under medical supervision.
• The body must convert both forms to the active hormone calcitriol (1,25-dihydroxyvitamin D) through processes in the liver and kidneys before they can regulate calcium absorption and bone health.
• For those following strict vegan diets, Vitamin D2 may be preferred as it contains no animal products, though plant-derived D3 supplements are now available as well.

Clinical Considerations

• The optimal serum level of 25-hydroxyvitamin D (25(OH)D) needed for optimal health is unknown, but a recent benefit-risk assessment of vitamin D suggested that it may be similar or possibly higher than needed for optimal bone health and calcium metabolism 1.
• Vitamin D deficiency may attenuate the efficacy of bisphosphonates and increase the risk of bisphosphonate-related hypocalcemia, thus it should be corrected prior to initiation of bisphosphonates therapy, particularly intravenous therapy 1.
• Guidelines on vitamin D replacement in bariatric surgery recommend at least 3,000 IU of vitamin D daily, titrated to therapeutic 25-dihydroxy vitamin D levels, with some cases requiring higher doses of up to 50,000 IU daily 1.

From the FDA Drug Label

The first hydroxylation of ergocalciferol takes place in the liver (to 25-hydroxyvitamin D) and the second in the kidneys (to 1,25-dihydroxy- vitamin D). The main difference between Vitamin D2 (Ergocalciferol) and Vitamin D3 (Cholecalciferol) is the source and the way they are metabolized in the body.

• Vitamin D2 is derived from fungi and is also known as Ergocalciferol.
• Vitamin D3 is derived from animals and is also known as Cholecalciferol. The drug label does not provide a direct comparison of the two, but it mentions the hydroxylation of Ergocalciferol in the liver, implying that Vitamin D2 and Vitamin D3 have different metabolic pathways 2.

From the Research

Difference between Vitamin D2 and Vitamin D3

• Vitamin D2 (ergocalciferol) and Vitamin D3 (cholecalciferol) are two forms of vitamin D, with different effectiveness in correcting vitamin D deficiency 3, 4, 5, 6
• Vitamin D3 is considered more effective than Vitamin D2 in increasing serum 25-hydroxyvitamin D (25(OH)D) concentrations 3, 5, 6
• Vitamin D2 supplements may be less effective and may enhance the degradation of 25-hydroxyvitamin D3 (25(OH)D3) metabolite 3
• Cholecalciferol (Vitamin D3) has pharmacokinetic properties that allow for daily or weekly, fortnightly, or monthly administration, which can facilitate adherence to treatment 4
• The optimal values of 25(OH)D range between 75-125 nmol/L, and ensuring optimal levels of vitamin D in the population is a challenge 7

Biochemical Effects

• High-dose bolus vitamin D2 and D3 supplementation can be effective in patients with vitamin D insufficiency, but vitamin D3 has greater potency than equimolar vitamin D2 5
• Vitamin D3 can achieve serum levels of 25(OH)D of 30-50 ng/mL, considered optimal for maximum benefit at the lowest risk 4
• Vitamin D2 may not be as effective in suppressing parathyroid hormone (PTH) levels as vitamin D3 5

Treatment Recommendations

• Vitamin D3 is recommended as the form of vitamin D for exogenous supplementation, with calcifediol reserved for patients with liver failure or severe intestinal malabsorption syndromes 4
• Administering 300,000 IU oral vitamin D3 approximately three times per year may be an effective treatment for vitamin D insufficiency 5