Introduction
Vitamin D is a fat-soluble vitamin that functions as a prohormone in the human body. Unlike other vitamins, vitamin D can be synthesized endogenously through sunlight exposure to the skin. It exists in two major forms: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), with both forms requiring hepatic and renal hydroxylation to become biologically active. Vitamin D plays a crucial role in calcium homeostasis, bone metabolism, and various other physiological processes.
Mechanism of Action
Vitamin D exerts its effects through binding to the vitamin D receptor (VDR), a nuclear receptor that regulates gene expression. The active form, 1,25-dihydroxyvitamin D (calcitriol), promotes intestinal absorption of calcium and phosphorus, facilitates bone mineralization, and regulates parathyroid hormone secretion. It also modulates cell proliferation, differentiation, and immune function through genomic and non-genomic pathways.
Indications
- Treatment and prevention of vitamin D deficiency
- Management of hypocalcemia in hypoparathyroidism
- Prevention and treatment of osteoporosis (in combination with calcium)
- Management of renal osteodystrophy in chronic kidney disease
- Prevention of rickets in children and osteomalacia in adults
- Adjunctive therapy in psoriasis (topical formulations)
Dosage and Administration
General supplementation: 600-800 IU daily for adults Vitamin D deficiency treatment: 50,000 IU weekly for 8 weeks, then maintenance dosing Osteoporosis prevention: 800-1,000 IU daily with calcium Renal impairment: Dosage adjustment required; may need active vitamin D metabolites Special populations:- Elderly: 800-1,000 IU daily
- Infants: 400 IU daily
- Pregnancy/lactation: 600 IU daily
- Obesity: Higher doses may be required (2-3 times standard dose)
Available forms: Oral tablets, capsules, drops, injectable solutions, and topical formulations.
Pharmacokinetics
Absorption: Well absorbed from gastrointestinal tract (especially with fatty meals); requires bile salts for optimal absorption Distribution: Stored in adipose tissue and liver; widely distributed throughout body Metabolism: Hydroxylated in liver to 25-hydroxyvitamin D [25(OH)D], then in kidneys to active 1,25-dihydroxyvitamin D Elimination: Primarily excreted in bile; half-life of 25(OH)D is approximately 2-3 weeksContraindications
- Hypervitaminosis D
- Hypercalcemia
- Hypersensitivity to vitamin D or product components
- Malabsorption syndromes (for oral formulations without appropriate adjustment)
Warnings and Precautions
- Risk of hypercalcemia with excessive dosing
- Use caution in patients with renal impairment, sarcoidosis, or other granulomatous diseases
- Monitor patients with atherosclerosis or history of kidney stones
- May exacerbate hyperphosphatemia in renal failure patients
- Increased risk of toxicity in immobilized patients
Drug Interactions
- Thiazide diuretics: May increase risk of hypercalcemia
- Corticosteroids: May reduce vitamin D effects
- Anticonvulsants (phenytoin, phenobarbital): Increase vitamin D metabolism
- Cholestyramine/orlistat: May decrease absorption
- Calcium supplements: Increased risk of hypercalcemia
- Digoxin: Hypercalcemia may potentiate digitalis toxicity
Adverse Effects
Common:- Nausea
- Constipation
- Headache
- Weakness
- Hypercalcemia (symptoms: confusion, polyuria, polydipsia, nausea, vomiting)
- Hypercalciuria
- Nephrocalcinosis
- Renal impairment
- Soft tissue calcification
Monitoring Parameters
- Serum 25-hydroxyvitamin D levels (target 20-50 ng/mL for most indications)
- Serum calcium (total and ionized) regularly
- Phosphorus levels
- Renal function (BUN, creatinine)
- Urine calcium excretion (24-hour collection if indicated)
- Bone mineral density in osteoporosis patients
- Parathyroid hormone levels in specific indications
Patient Education
- Take with food for better absorption, especially containing fat
- Do not exceed recommended dosage without medical supervision
- Report symptoms of hypercalcemia: nausea, vomiting, constipation, weakness, confusion
- Maintain adequate calcium intake as recommended by healthcare provider
- Sun exposure (15-20 minutes several times weekly) can help maintain vitamin D levels
- Inform all healthcare providers about vitamin D supplementation
- Store properly away from heat and light
References
1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281. 2. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011. 3. Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011;364(3):248-254. 4. Pludowski P, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality. Endocrine. 2018;61(2):218-239. 5. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. 2019. 6. Martineau AR, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. 7. UpToDate. Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment. 2023. 8. American Association of Clinical Endocrinologists. Guidelines for the management of vitamin D deficiency. Endocr Pract. 2020;26(5):1-29.