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Calcifediol (25-hydroxyvitamin D)

Vitamin D analogue (25-hydroxy metabolite)

ATC code: A11CC06(Calcifediol (25-OH-D))

Brand names: Rayaldee

Updated · Methodology

Indications

B

Postmenopausal osteoporosis

Adjunct

Adjunct to bisphosphonates, denosumab, and zoledronate in osteoporosis to ensure adequate vitamin D status before and during antiresorptive therapy. In patients with low baseline 25(OH)D, calcifediol restores levels faster, reducing hypocalcemia risk on bisphosphonates. AACE/ACE 2020 and SEIOMM 2024 set 25(OH)D target above 30 ng/mL before antiresorptive therapy.

Sources

  1. AEMPS: Ficha técnica de Calcifediol (25-hidroxivitamina D) (2024)

ICD-10: M81.0 · ICD-11: FB83.11

B

Vitamin D deficiency

First line

Used in confirmed vitamin D deficiency (25(OH)D under 20 ng/mL) when fast target response is needed, with hepatic dysfunction or malabsorption. SEEN 2021 and SEEDO 2024 place calcifediol in first-line therapy in Spain. Standard dose 0.266 mg (266 mcg) orally once or twice monthly, or 0.1 mg (100 mcg) weekly depending on baseline. Target 25(OH)D 30–50 ng/mL. In most patients without specific causes, cholecalciferol 800–2000 IU/day suffices; routine calcifediol use without documented deficiency is not indicated.

Sources

  1. AEMPS: Ficha técnica de Calcifediol (25-hidroxivitamina D) (2024)
  2. Endocrine Society: Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline (2024)

ICD-10: E55.9 · ICD-11: 5B57

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

F

Anti-aging and longevity

Not recommended

Calcifediol (25-hydroxyvitamin D) is an intermediate metabolite of vitamin D that raises blood 25(OH)D faster than cholecalciferol. It is prescribed for vitamin D deficiency, especially with malabsorption (AEMPS Ficha Técnica). Healthy adults take calcifediol in drops and capsules for an anti-aging level of vitamin D. With normal 25(OH)D (above 20 ng/mL per most international guidelines), no clinical studies of prophylactic use exist. Vitamin D overdose causes hypercalcemia (nausea, vomiting, weakness, kidney dysfunction, arrhythmias). If calcifediol is being taken without confirmed 25(OH)D deficiency on blood test, consider seeking a second opinion and getting tested.

Sources

  1. AEMPS: Ficha técnica de Calcifediol (25-hidroxivitamina D) (2024)
  2. Cochrane: Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases (2012)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

25-hydroxycholecalciferol – an intermediate vitamin D metabolite formed in the liver from cholecalciferol. Drives 1,25-dihydroxyvitamin D synthesis in the kidneys and regulates intestinal calcium and phosphorus absorption and bone mineralization. Compared with cholecalciferol (D3), it bypasses hepatic 25-hydroxylation – faster increases in serum 25(OH)D (hours to days versus weeks). Particularly useful with hepatic dysfunction, malabsorption, or very low baseline 25(OH)D. In Spain it is the dominant form of vitamin D under the brand Hidroferol, unlike most countries where cholecalciferol prevails.

Safety

Contraindications

  • Calcifediol or excipient hypersensitivity
  • Hypercalcemia
  • Hypervitaminosis D
  • Active calcium-containing urolithiasis
  • Severe hypercalciuria
  • Pseudohypoparathyroidism

Serious adverse effects

  • Hypercalcemia and its complications (polyuria, dehydration, arrhythmia)
  • Hypercalciuria and nephrocalcinosis
  • Acute kidney injury
  • Soft-tissue calcification with prolonged overdose

Common adverse effects

  • Nausea
  • Constipation
  • Dry mouth
  • Metallic taste

Pregnancy: can you take Calcifediol (25-hydroxyvitamin D)?

With confirmed vitamin D deficiency in pregnancy, use is acceptable at doses that restore 25(OH)D without exceeding normal range. Calcium and 25(OH)D monitoring is mandatory. Overdose is hazardous due to maternal and fetal hypercalcemia.

Breastfeeding: can you take Calcifediol (25-hydroxyvitamin D)?

Compatible with breastfeeding at standard doses. Monitor calcium in mother and infant with high doses.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take orally, ideally with a fat-containing meal for optimal absorption (although calcifediol absorption depends less on fat than cholecalciferol). Check 25(OH)D at 3 months after start, then every 6–12 months on a stable maintenance dose. At high doses, monitor serum and urinary calcium – hypercalcemia and hypercalciuria risk. Before starting bisphosphonates, check 25(OH)D and calcium.

Common myths

Myth: «Hidroferol is a powerful vitamin D every Spaniard needs for immunity.» Fact: routine vitamin D supplementation without documented deficiency does not reduce infection, cancer, cardiovascular events, or mortality (VITAL 2019, BMJ Bouillon 2022 meta-analysis). Indications are documented 25(OH)D deficiency, risk factors (older age, low sun exposure, dark skin, obesity, malabsorption), or specific comorbidities (osteoporosis, CKD). Calcifediol overdose is dangerous – hypercalcemia, nephrocalcinosis, kidney injury. Myth: «one ampoule of Hidroferol is a year's dose of vitamin D.» Fact: pharmacokinetics vary individually; regimen is set by 25(OH)D level, not by «one-ampoule» protocols.

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Frequently asked

What is Calcifediol (25-hydroxyvitamin D) used for?

Calcifediol (25-hydroxyvitamin D) is evaluated for the following indications with varying evidence strength: Vitamin D deficiency (evidence tier B), Postmenopausal osteoporosis (evidence tier B), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Calcifediol (25-hydroxyvitamin D)?

Common side effects of Calcifediol (25-hydroxyvitamin D) (≥ 1 in 100): Nausea, Constipation, Dry mouth, Metallic taste. See the Safety section for uncommon and serious reactions.

Is Calcifediol (25-hydroxyvitamin D) safe during pregnancy?

With confirmed vitamin D deficiency in pregnancy, use is acceptable at doses that restore 25(OH)D without exceeding normal range. Calcium and 25(OH)D monitoring is mandatory. Overdose is hazardous due to maternal and fetal hypercalcemia.

Is Calcifediol (25-hydroxyvitamin D) compatible with breastfeeding?

Compatible with breastfeeding at standard doses. Monitor calcium in mother and infant with high doses.

Who should not take Calcifediol (25-hydroxyvitamin D)?

Calcifediol (25-hydroxyvitamin D) is contraindicated in: Calcifediol or excipient hypersensitivity; Hypercalcemia; Hypervitaminosis D; Active calcium-containing urolithiasis; Severe hypercalciuria. Full list in the Safety section.

Other drugs in this group

Chaga (Inonotus obliquus), Chlorella, Cholecalciferol, Choline (umbrella: bitartrate, phosphatidylcholine, lecithin), Grape seed extract (Vitis vinifera, oligomeric proanthocyanidins), Olive leaf extract (Olea europaea, oleuropein), Rhodiola rosea (golden root), Stinging nettle root (Urtica dioica, radix)