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Saturday, July 26, 2025

Colecalciferol



Colecalciferol, also known as cholecalciferol or vitamin D3, is a fat-soluble secosteroid hormone precursor that plays a pivotal role in calcium and phosphate homeostasis and the maintenance of healthy bone and immune function. It is synthesized endogenously in the skin upon exposure to ultraviolet B (UVB) radiation from sunlight or acquired through dietary intake and supplements.

Colecalciferol is the preferred form of vitamin D for supplementation due to its superior bioavailability and potency compared to ergocalciferol (vitamin D2). It is biologically inert and undergoes two hydroxylation steps in the liver and kidneys to become calcitriol (1,25-dihydroxyvitamin D3), the hormonally active form.

1. Classification and Nature

  • Chemical name: (3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-3-ol

  • Synonyms: Vitamin D3, Cholecalciferol

  • Drug class: Vitamin D analog, dietary supplement, endocrine hormone precursor

  • ATC code: A11CC05

  • Available forms:

    • Oral tablets

    • Capsules (softgel or hard)

    • Oral solution

    • Chewable tablets

    • Granules/sachets

    • Injectable solution (rare)

    • Combined formulations with calcium, alendronate, or multivitamins

2. Mechanism of Action

Colecalciferol is inactive until metabolized:

  • Liver: Colecalciferol → 25-hydroxyvitamin D3 (calcifediol) via CYP2R1

  • Kidney: Calcifediol → 1,25-dihydroxyvitamin D3 (calcitriol) via CYP27B1

Calcitriol then acts by binding to the vitamin D receptor (VDR), a nuclear receptor found in target tissues (intestine, bone, kidney, immune cells). This complex modulates transcription of genes involved in:

  • Calcium and phosphate absorption from the gut

  • Bone mineralization

  • Parathyroid hormone (PTH) regulation

  • Immune modulation

  • Cell proliferation and differentiation

3. Physiological Roles of Vitamin D3

  • Calcium absorption: Enhances calcium transport in the intestines

  • Phosphate homeostasis: Increases serum phosphate by enhancing reabsorption in the kidneys

  • Bone health: Promotes osteoblast differentiation and mineralization

  • Suppression of PTH: Reduces PTH overactivity (secondary hyperparathyroidism)

  • Immune regulation: Modulates innate and adaptive immunity

  • Anti-inflammatory: Inhibits pro-inflammatory cytokines (e.g., IL-6, TNF-α)

4. Therapeutic Indications

A. Approved Medical Uses

  • Prevention and treatment of vitamin D deficiency

  • Osteomalacia and rickets

  • Osteoporosis (as adjunct with calcium)

  • Hypoparathyroidism

  • Chronic kidney disease (CKD)–related secondary hyperparathyroidism

  • Malabsorption syndromes (e.g., celiac disease, IBD, pancreatic insufficiency)

  • Long-term anticonvulsant therapy

  • Elderly with limited sun exposure

B. Off-label and Emerging Uses

  • Autoimmune diseases: MS, SLE

  • Chronic pain syndromes: fibromyalgia

  • Respiratory infections: may reduce risk and severity

  • COVID-19: explored as adjunctive therapy for immune modulation (inconclusive evidence)

5. Dosage and Administration

A. General Adult Supplementation

StatusDose (oral)
Maintenance (normal levels)400–1,000 IU/day
Prevention (at-risk individuals)800–2,000 IU/day
Mild deficiency2,000 IU/day
Moderate to severe deficiency20,000–50,000 IU/week or 100,000 IU/month (short term)



B. Specific Clinical Situations

  • Osteoporosis (with calcium): 800–1,200 IU/day

  • CKD/secondary hyperparathyroidism: Higher doses required; monitor calcium, phosphate, PTH

  • Pediatric dosing:

    • <1 year: 400–1,000 IU/day

    • 1–18 years: 600–1,000 IU/day

  • Elderly or institutionalized: 800–2,000 IU/day

  • Pregnancy/lactation: 600–2,000 IU/day

C. Routes of Administration

  • Oral: Preferred route; good absorption with fat-containing meals

  • Intramuscular: Used in severe malabsorption or non-compliance

  • Combined Products: Calcium + vitamin D combinations widely available (e.g., Calci-D, Adcal-D3)

6. Pharmacokinetics

  • Absorption: Fat-soluble; absorbed in jejunum and ileum with bile salts

  • Onset: Slow; plasma 25(OH)D rises over weeks

  • Half-life:

    • Colecalciferol: ~24 hours

    • 25(OH)D3: ~15 days

  • Storage: In adipose tissue and liver

  • Excretion: Fecal (via bile), minimal renal

7. Contraindications

  • Hypercalcemia

  • Hypervitaminosis D

  • Severe renal impairment with hyperphosphatemia

  • Sarcoidosis or other granulomatous diseases (may increase endogenous vitamin D production)

  • Hypersensitivity to colecalciferol or any excipients

8. Precautions

  • Renal disease: Risk of hypercalcemia; use active analogs (e.g., calcitriol) if GFR <30 mL/min

  • Malabsorption: May require high-dose or parenteral therapy

  • Elderly: Monitor calcium levels, especially if taking thiazides or digoxin

  • Pregnancy and lactation: Safe within RDA limits

  • Pediatric: Overdose can cause serious toxicity; dose carefully

9. Adverse Effects

At therapeutic doses, colecalciferol is well tolerated. However, high doses or prolonged supplementation can lead to:

  • Hypercalcemia: nausea, vomiting, constipation, fatigue, polyuria, kidney stones

  • Hypercalciuria

  • Hyperphosphatemia

  • Nephrocalcinosis

  • Renal impairment

  • Calcification of soft tissues

  • Headache, muscle weakness

Signs of toxicity: serum 25(OH)D >150 ng/mL with hypercalcemia

10. Drug Interactions

A. Reduced Absorption or Effect

  • Orlistat, cholestyramine, colestipol: fat-soluble vitamin malabsorption

  • Corticosteroids: reduce vitamin D metabolism

  • Antiepileptics (phenytoin, carbamazepine, phenobarbital): induce hepatic enzymes, reduce vitamin D

  • Rifampin: hepatic enzyme inducer

  • Weight-loss surgeries: reduce absorption

B. Increased Risk of Hypercalcemia

  • Thiazide diuretics: reduce urinary calcium excretion

  • Calcium supplements: monitor total intake

  • Digoxin: hypercalcemia may increase risk of arrhythmias

C. Supplements

  • Monitor concurrent intake of vitamin A, magnesium, or phosphate.

11. Monitoring Parameters

  • Serum 25(OH)D levels

    • Deficiency: <20 ng/mL (<50 nmol/L)

    • Insufficiency: 20–30 ng/mL (50–75 nmol/L)

    • Optimal: 30–50 ng/mL (75–125 nmol/L)

    • Toxicity: >150 ng/mL

  • Serum calcium and phosphate

  • Renal function

  • Urinary calcium (if prolonged high-dose therapy)

12. Comparative Efficacy: Vitamin D2 vs D3

FeatureVitamin D2 (Ergocalciferol)Vitamin D3 (Colecalciferol)
SourcePlant-basedAnimal-based or synthesized from lanolin
Half-lifeShorterLonger
PotencyLessMore
Binding to DBPLowerHigher
Clinical useLess effective in maintaining 25(OH)D levelsPreferred for supplementation



13. Commercial Brand Names

A. UK and EU

  • Fultium-D3

  • Desunin

  • InVita D3

  • Accrete D3 (with calcium)

  • Adcal-D3 (chewable tablets with calcium)

  • Calcichew D3 Forte

B. United States

  • D3-50

  • Vitamin D3 Softgels

  • Cholecalciferol Liquid

  • Os-Cal D3 (with calcium)

  • Citracal D

C. Middle East

  • Sunvit-D3

  • D-Vit3

  • Vita D3

  • Devit-3

14. Storage and Stability

  • Store below 25°C

  • Protect from light and moisture

  • Keep tightly closed to prevent oxidation

  • Injectable forms: refrigerate if required, avoid freezing

15. Regulatory and Safety Considerations

  • FDA and EMA approved for prevention/treatment of deficiency

  • Listed in WHO Model List of Essential Medicines

  • Vitamin D is not a controlled substance

  • Over-the-counter availability in many regions

  • Prescription-only for high-dose forms or injectable formulations

16. Research and Emerging Applications

  • COVID-19: Investigated for role in reducing disease severity

  • Cancer prevention: Mixed evidence for colorectal, prostate, breast cancers

  • Autoimmune modulation: Under investigation in MS, type 1 diabetes

  • Cardiovascular disease: Low levels associated with increased risk, but supplementation trials are inconclusive



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