VITAMIN D
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VITAMIN D (VITAMIN D).
Vitamin D (cholecalciferol) is a secosteroid that binds to the vitamin D receptor (VDR), which heterodimerizes with the retinoid X receptor (RXR) to regulate gene transcription. It enhances intestinal calcium and phosphate absorption, promotes renal tubular reabsorption of calcium, and stimulates osteoclast activity to mobilize calcium from bone, thereby maintaining serum calcium and phosphate homeostasis.
| Metabolism | Vitamin D is hydroxylated in the liver by CYP2R1 (25-hydroxylase) to 25-hydroxyvitamin D, then in the kidney by CYP27B1 (1α-hydroxylase) to the active form 1,25-dihydroxyvitamin D. It is further metabolized by CYP24A1 (24-hydroxylase) to inactive metabolites. |
| Excretion | Primarily fecal via bile (approximately 50-60% of metabolites), renal excretion accounts for <4% of unchanged vitamin D and its metabolites, mainly as water-soluble conjugates. |
| Half-life | Terminal elimination half-life of 25-hydroxyvitamin D is 2-3 weeks (15-21 days), reflecting slow turnover and tissue storage, clinically important for dosing intervals. |
| Protein binding | ~85-90% bound to vitamin D-binding protein (DBP), ~10-15% to albumin; free fraction <0.1%. |
| Volume of Distribution | 0.17 L/kg for 25-hydroxyvitamin D in normal weight individuals; increases with obesity; reflects distribution to adipose tissue and muscle. |
| Bioavailability | Oral: ~60-90% for ergocalciferol and cholecalciferol; absorption is bile-dependent; IM: high but variable (close to 100% if injected into muscle); topical: negligible systemic absorption. |
| Onset of Action | Oral: 10-24 hours for increased intestinal calcium absorption; IM: similar onset as absorption depends on formulation; topical: not applicable. |
| Duration of Action | Oral: 2-3 months for single large dose (e.g., 600,000 IU) due to storage in adipose tissue and slow release; chronic dosing maintains steady state after 3-5 half-lives. |
| Molecular Weight | 384.64 |
600-800 IU (15-20 mcg) orally once daily for adults 19-70 years; 800 IU (20 mcg) orally once daily for adults >70 years. For deficiency: 50,000 IU (1.25 mg) orally once weekly for 8 weeks, then maintenance as above.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min. For GFR <15 mL/min or dialysis: use calcitriol or paricalcitol; cholecalciferol may be ineffective. Monitor calcium and phosphate levels. |
| Liver impairment | No dose adjustment required for any Child-Pugh class. Impaired 25-hydroxylation in severe cirrhosis may necessitate use of calcifediol (25-hydroxyvitamin D) instead of cholecalciferol for treatment of deficiency. |
| Pediatric use | Infants 0-12 months: 400 IU (10 mcg) orally once daily. Children 1-18 years: 600 IU (15 mcg) orally once daily. For deficiency: 1000-2000 IU/day for 12 weeks or 50,000 IU once weekly for 6 weeks; adjust based on serum levels. |
| Geriatric use | Recommended dose: 800 IU (20 mcg) orally once daily. Lower starting doses may be considered due to increased sensitivity; monitor serum calcium and 25-hydroxyvitamin D levels regularly. |
| 1st trimester | Safe at recommended doses. High doses may be teratogenic (hypercalcemia risk). |
| 2nd trimester | Safe at recommended doses. Monitor for hypercalcemia if high doses used. |
| 3rd trimester | Safe at recommended doses. High doses may cause neonatal hypercalcemia. |
Clinical note
Comprehensive clinical and safety monograph for VITAMIN D (VITAMIN D).
| Placental transfer | Crosses placenta efficiently; 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are present in fetal circulation at approximately 60-80% of maternal levels. |
| Breastfeeding | Vitamin D is excreted in breast milk in low amounts. Maternal supplementation up to 4000 IU/day is considered safe. High maternal doses may increase milk levels but rarely cause adverse effects in infants. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
HypercalcemiaVitamin D toxicityMalabsorption syndrome with severe hypercalciuria
| Precautions | Hypercalcemia risk, especially in patients with hyperparathyroidism, granulomatous diseases, or on thiazide diuretics, Renal impairment: monitor calcium and phosphate levels, Digitalis toxicity risk due to hypercalcemia, Serum calcium and 25-hydroxyvitamin D monitoring recommended during treatment |
| Food/Dietary | Vitamin D is fat-soluble, so absorption is enhanced when taken with fatty foods. Avoid taking with mineral oil or orlistat, as they can reduce absorption. No specific dietary restrictions; however, maintaining adequate calcium intake is important for bone health when using vitamin D supplements. |
Loading safety data…
| Lactation Rating |
| L1 (Compatible) |
| Teratogenic Risk | Vitamin D is not teratogenic at recommended doses. High doses (≥4000 IU/day) may be associated with fetal hypercalcemia, supracalcified aorta, and cardiac abnormalities, particularly in the first trimester. The risk is dose-dependent. |
| Fetal Monitoring | Monitor maternal serum 25-hydroxyvitamin D levels if high-dose therapy is used; assess for signs of hypercalcemia (e.g., nausea, weakness). In the fetus, ultrasonography may be indicated if hypercalcemia is suspected, looking for aortic calcification. |
| Fertility Effects | Vitamin D deficiency is associated with reduced fertility in both sexes and may contribute to polycystic ovary syndrome (PCOS) and endometriosis. Supplementation may improve outcomes, but high doses are not recommended. No direct evidence of impairment at standard doses. |
| Clinical Pearls | Cholecalciferol (D3) is more potent and has a longer half-life than ergocalciferol (D2). For vitamin D deficiency, treat with 50,000 IU D2 weekly for 8 weeks or equivalent D3 dosing. Monitor serum 25-hydroxyvitamin D levels after 3 months. Caution in sarcoidosis or other granulomatous diseases due to extrarenal 1α-hydroxylase activity. Avoid high-dose vitamin D in patients with hypercalcemia or metastatic calcification. |
| Patient Advice | Take with the largest meal of the day to enhance absorption due to its fat-soluble nature. · Do not exceed the recommended dose unless instructed by your healthcare provider, as extremely high doses can cause toxicity. · Report symptoms of hypercalcemia: nausea, vomiting, constipation, weakness, or confusion. · Exposure to sunlight helps your body produce vitamin D, but dietary supplements are necessary for deficiency. · Store at room temperature, away from moisture and heat. |