What is the difference between vitamin D3 (Cholecalciferol) 25-hydroxyvitamin D and dehydroxyvitamin D?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: May 2, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Vitamin D3 25-OH and dehydroxyvitamin D are distinct forms of vitamin D, with vitamin D3 25-OH being the main circulating form in the bloodstream and dehydroxyvitamin D referring to vitamin D molecules lacking hydroxyl groups. The difference between these two forms is crucial in understanding vitamin D's role in the body. Vitamin D3 25-OH, also known as 25-hydroxyvitamin D or calcidiol, is created when the liver adds a hydroxyl group to vitamin D3 (cholecalciferol) from sun exposure or dietary sources 1. In contrast, dehydroxyvitamin D refers to vitamin D molecules that lack hydroxyl groups, with the most common forms being vitamin D2 (ergocalciferol) from plant sources and vitamin D3 (cholecalciferol) from animal sources or sun exposure. These must be converted to 25-OH vitamin D in the liver and then to the active form, 1,25-dihydroxyvitamin D (calcitriol), in the kidneys before they can regulate calcium absorption and bone health 1. Key points to consider include:

  • The main circulating form of vitamin D in the bloodstream is vitamin D3 25-OH.
  • Dehydroxyvitamin D refers to vitamin D molecules lacking hydroxyl groups.
  • Vitamin D2 and vitamin D3 must be converted to 25-OH vitamin D and then to 1,25-dihydroxyvitamin D to regulate calcium absorption and bone health.
  • The distinction between these forms matters clinically, as 25-OH vitamin D levels reflect overall vitamin D status, while the active 1,25-dihydroxyvitamin D is tightly regulated and not useful for assessing vitamin D sufficiency.

From the FDA Drug Label

The initial transformation is catalyzed by a vitamin D3-25-hydroxylase enzyme present in the liver, and the product of this reaction is 25-(OH)D3 (calcifediol). The difference between vitamin D3 25-OH (also known as calcifediol) and dehydroxyvitamin D is that:

  • Vitamin D3 25-OH refers to the metabolite of vitamin D3 that has undergone hydroxylation in the liver, resulting in the addition of a hydroxyl group (-OH) at the 25th carbon atom.
  • Dehydroxyvitamin D is not explicitly defined in the provided text, but based on the context, it can be inferred to refer to a form of vitamin D that has not undergone hydroxylation, such as vitamin D3 itself. 2

From the Research

Vitamin D3 25-OH and Dehydroxyvitamin D Difference

  • Vitamin D3 25-OH, also known as calcifediol, is a metabolite of vitamin D3 (cholecalciferol) that is produced in the liver by hydroxylation of cholecalciferol 3.
  • Dehydroxyvitamin D is not a commonly used term in the context of vitamin D supplementation, but it can be inferred to refer to the precursor of hydroxylated vitamin D metabolites, such as cholecalciferol (vitamin D3) itself.
  • The key difference between vitamin D3 25-OH (calcifediol) and cholecalciferol (vitamin D3) is that calcifediol is a more potent and rapidly acting form of vitamin D, with a higher rate of intestinal absorption and a more linear dose-response curve 4, 5.
  • Cholecalciferol, on the other hand, is the form of vitamin D that is most commonly used in supplements and is considered the gold standard for vitamin D supplementation by some studies 6, 7.

Comparison of Efficacy and Safety

  • Studies have shown that calcifediol is more efficacious than cholecalciferol in increasing serum 25(OH)D levels, with a faster onset of action and greater potency 4, 5.
  • Calcifediol has also been found to have a more predictable efficacy profile, with the increase in 25OHD levels depending primarily on the dose and frequency of administration 5.
  • Cholecalciferol, while effective, may have a more variable efficacy profile, with the increase in 25OHD levels depending on multiple factors, including dose, frequency of administration, and individual phenotypic and genotypic factors 5.

Clinical Use

  • Calcifediol is often used in patients with liver failure or severe intestinal malabsorption syndromes, as it can bypass the liver hydroxylation step and provide a more direct source of 25(OH)D 6.
  • Cholecalciferol, on the other hand, is widely used in the general population for vitamin D supplementation and is considered safe and effective by many studies 6, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Is calcifediol better than cholecalciferol for vitamin D supplementation?

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2018

Research

Vitamin D supplementation: cholecalciferol, calcifediol, and calcitriol.

European journal of clinical nutrition, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.