Vitamin D
Deficiency is near-universal. Optimal repletion is not as simple as the guidelines suggest.
Evidence highlight
Optimal 25-OH-D for immune and autoimmune benefit is 40-60 ng/mL, not the conventional "sufficient" threshold of 20 ng/mL. Levels >40 ng/mL reduce TPO antibody titers in Hashimoto's and significantly reduce upper respiratory infection rates.
Therapeutic dosing
Vitamin D3 (cholecalciferol) — maintenance
2000-5000 IU/day
Always use D3, not D2; take with fat-containing meal for absorption
Vitamin D3 — repletion (deficient <20 ng/mL)
5000-10,000 IU/day for 8-12 weeks, then maintenance
Recheck 25-OH-D at 12 weeks; adjust to maintain 40-60 ng/mL
Loading protocol (severe deficiency)
50,000 IU weekly x 8 weeks (D3 preferred)
Then retest and transition to daily maintenance; D3 50k IU available by prescription
Drug interactions
Thiazide diuretics — increase calcium reabsorption; hypercalcemia risk with high-dose vitamin D
Digoxin — hypercalcemia from vitamin D toxicity increases digoxin toxicity risk
Corticosteroids — reduce vitamin D absorption and increase requirements
Anticonvulsants (phenytoin, phenobarbital) — increase vitamin D metabolism; higher doses often needed
Orlistat / cholestyramine — reduce fat-soluble vitamin absorption including D
Contraindications
Hypercalcemia
Sarcoidosis / granulomatous disease (unregulated vitamin D activation)
Williams syndrome
Lymphoma (similar to sarcoidosis mechanism)
Labs to monitor
Mechanism of action
Vitamin D is a steroid hormone precursor, not a simple micronutrient. Its receptor (VDR) is expressed in nearly every cell type. Adequate magnesium is required for two of the hydroxylation steps in vitamin D activation — patients with magnesium deficiency may show apparent vitamin D resistance even with supplementation. Vitamin K2 (MK-7) is required to direct calcium to bone and away from arteries when supplementing at doses above 2000 IU/day.
Clinical note
Always co-prescribe magnesium glycinate and vitamin K2 (MK-7, 100-200mcg/day) with vitamin D at doses above 2000 IU. Magnesium is required for activation; K2 handles calcium directionality. A patient on 5000 IU/day without these cofactors may not be getting the full benefit — and may be directing calcium to arterial walls. Test 25-OH-D, not the active 1,25-OH form.
Conditions commonly using Vitamin D
Commonly combined with
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