All supplements
Grade A Evidence

Vitamin D

Deficiency is near-universal. Optimal repletion is not as simple as the guidelines suggest.

Deficiency repletionImmune modulation (autoimmune, infection resistance)Bone densityMood / seasonal depressionHashimoto's / thyroid autoimmunityInsulin resistance / diabetes preventionCancer risk reductionMuscle function and fall prevention

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

25-OH Vitamin D (not 1,25-OH; that measures active form, not stores)Serum calciumPTH (elevated PTH is a functional marker of vitamin D insufficiency)Urine calcium (with high-dose supplementation)

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.

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