Vitamin
B-Complex
A group of eight B vitamins that work together to support energy metabolism, nervous system function, and red blood cell production.
Moderate Evidence
Strong Evidence Vitamin
Vitamin D3
A fat-soluble vitamin produced by the skin in response to sunlight, critical for bone health, immune function, and mood regulation.
Updated February 20, 2026This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication regimen.
Benefits & Uses
- Prevents and treats rickets/osteomalacia by correcting vitamin D deficiency and improving intestinal calcium/phosphate absorption (strong evidence from decades of clinical use and trials).
- Supports bone mineral density and reduces hip/any fracture risk when combined with calcium in older, institutionalized, or vitamin D–deficient adults; vitamin D alone shows little to no fracture benefit in community-dwelling adults (moderate evidence; mixed results across meta-analyses and large RCTs).
- May modestly reduce risk of acute respiratory infections, particularly in those with low baseline vitamin D when taken daily or weekly (not large intermittent bolus dosing) (moderate evidence from meta-analyses).
- May modestly reduce incidence of autoimmune diseases over several years of use (emerging-to-moderate evidence from large RCT data).
- May reduce cancer mortality slightly without affecting cancer incidence (moderate evidence from meta-analyses of RCTs).
- Muscle function: correcting deficiency can improve proximal muscle weakness; effects on fall prevention are inconsistent, and very high intermittent bolus dosing has been linked to increased falls in older adults (mixed evidence).
Side Effects & Precautions
- Generally well tolerated at typical supplemental doses.
- Common/mild (uncommon overall): gastrointestinal upset, constipation, nausea, headache, fatigue.
- Dose-related hypercalcemia (rare; usually with prolonged high-dose use or 25(OH)D >150 ng/mL): anorexia, nausea/vomiting, constipation, polyuria/polydipsia, dehydration, muscle weakness, confusion, arrhythmias; can lead to nephrocalcinosis or kidney injury.
- Nephrolithiasis (kidney stones): small increased risk observed when vitamin D is combined with calcium supplements in some trials (uncommon; small absolute increase).
- Falls/fractures: some RCTs report increased falls with large intermittent bolus regimens in older adults; daily moderate dosing does not show this signal.
- Laboratory changes: elevated serum calcium and/or phosphate; suppressed PTH; in severe toxicity, elevated creatinine. Frequency notes: clinically significant toxicity is rare and typically associated with chronic intakes well above the tolerable upper intake level or with disorders causing increased vitamin D activation.
Dosage & Administration
- Typical supplemental intakes used in studies: 600–800 IU (15–20 mcg) daily for general maintenance; 800–2000 IU (20–50 mcg) daily commonly studied for bone and immune outcomes. Optimal dosing varies by baseline 25(OH)D, body weight, sun exposure, and indication.
- Deficiency correction in clinical trials: regimens such as 1000–4000 IU/day (25–100 mcg) or 50,000 IU weekly for 6–8 weeks have been used, followed by maintenance dosing; these require monitoring and clinical oversight.
- Acute respiratory infection prevention trials typically used daily or weekly dosing (e.g., 400–1000+ IU/day), not large intermittent boluses.
- Tolerable Upper Intake Level (adults): 4000 IU/day (100 mcg/day) per several authorities; higher doses have been used short term under medical supervision with monitoring of serum 25(OH)D and calcium.
- Target serum 25(OH)D considered sufficient varies by guideline (approx. 20–30+ ng/mL [50–75 nmol/L]); individualized targets and monitoring are recommended for at-risk groups.
Contraindications
- Hypercalcemia or hypercalciuria (contraindicated).
- Primary hyperparathyroidism or other causes of hypercalcemia (contraindicated or specialist-supervised use only).
- Granulomatous diseases (e.g., sarcoidosis, some lymphomas, tuberculosis) due to extrarenal 1-α-hydroxylase activity and risk of hypercalcemia (use only with medical supervision and calcium monitoring).
- Severe chronic kidney disease: altered vitamin D metabolism and risk of hyperphosphatemia/hypercalcemia; often requires active forms (calcitriol) and specialist guidance (caution/medical supervision).
- History of calcium-containing kidney stones: avoid high doses and combinations with high-dose calcium unless medically indicated (caution).
- Williams syndrome (predisposition to hypercalcemia) (contraindicated without specialist oversight).
- Pregnancy and breastfeeding: generally considered safe within recommended dietary allowances; avoid high-dose regimens unless prescribed and monitored by a clinician.
- Surgery: no known direct effect on coagulation. Many clinicians advise holding nonessential high-dose supplements 1–2 weeks before surgery; inform your surgical team, especially if taking calcium or thiazide diuretics due to hypercalcemia risk.
Known Interactions
| Substance | Type | Severity | Description |
|---|---|---|---|
| Thiazide diuretics (e.g., hydrochlorothiazide) | synergistic | moderate | Both reduce urinary calcium excretion/increase serum calcium; combined with vitamin D can precipitate hypercalcemia, especially in older adults or those with hyperparathyroidism. |
| Digoxin (digitalis) | caution | severe | Vitamin D–induced hypercalcemia can potentiate digoxin toxicity and precipitate arrhythmias; monitor calcium and cardiac status. |
| Orlistat | antagonistic | moderate | Reduces absorption of fat and fat-soluble vitamins, decreasing vitamin D absorption and status; stagger dosing and consider monitoring. |
| Bile acid sequestrants (e.g., cholestyramine, colesevelam) | antagonistic | moderate | Bind fat-soluble vitamins in the gut and reduce vitamin D absorption; separate dosing and consider monitoring vitamin D levels. |
| Anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital) | antagonistic | moderate | Induce hepatic enzymes increasing vitamin D catabolism, lowering 25(OH)D and impairing calcium balance; may require monitoring and dose adjustment. |
| Rifampin | antagonistic | moderate | CYP induction increases vitamin D breakdown, reducing circulating levels and effectiveness. |
| Systemic corticosteroids (e.g., prednisone) | antagonistic | moderate | Reduce intestinal calcium absorption and interfere with vitamin D metabolism, diminishing its skeletal benefits; monitor bone health. |
| Calcium supplements | synergistic | moderate | Co-supplementation can improve bone outcomes in some populations but increases risk of hypercalcemia and may slightly raise kidney stone risk; use judiciously. |
Sources
- Vitamin D with or without calcium for preventing fractures in adults: Cochrane systematic review and meta-analysis (meta-analysis) , 2014
- Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults (NEJM VITAL ancillary analysis) (rct) , 2022
- Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of individual participant data (BMJ) (meta-analysis) , 2017
- Vitamin D and marine omega-3 fatty acids and prevention of autoimmune disease: results from the VITAL randomized trial (BMJ) (rct) , 2022
- Effect of vitamin D supplementation on cancer incidence and mortality: meta-analysis of randomized controlled trials (meta-analysis) , 2019
- Calcium plus vitamin D supplementation and the risk of kidney stones (Women’s Health Initiative, NEJM) (rct) , 2006
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This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication regimen.