When to Stop

• Hypercalcemia + vitamin D toxicity (hypervitaminosis D): Real but rare. Requires sustained intake of >10,000 IU/day for months without monitoring, OR a single accidental mega-dose (>50,000 IU/day prolonged), OR genetic CYP24A1 loss-of-function mutations (idiopathic infantile hypercalcemia in adults). Threshold serum 25(OH)D for symptomatic toxicity is usually >150 ng/mL. Symptoms: nausea, vomiting, polyuria, polydipsia, confusion, weakness, kidney stones, soft-tissue/vascular calcification (especially without K2). Treatable: stop D3, hydrate, sometimes corticosteroids/bisphosphonates.
• Kidney stones: Rare with D3 alone; risk rises with co-administered high calcium intake. Mitigation: don't co-supplement calcium unless dietary intake is low, and pair with K2.
• Vascular calcification: Theoretical risk from D3-driven intestinal Ca²⁺ absorption without K2-mediated MGP activation to route Ca to bone. The Rotterdam Study epidemiology supports K2 protection. No RCT has shown D3-alone causes net vascular calcification in humans, but the mechanistic argument for K2 co-supplementation is strong.
• Granulomatous disease exacerbation: Sarcoidosis, TB, lymphoma — macrophages in granulomas express CYP27B1 unregulated by normal feedback, producing calcitriol independent of feedback. Supplementing D3 in these patients can cause hypercalcemia at much lower doses than expected. Hard contraindication: sarcoidosis, active TB, primary hyperparathyroidism.
• Weeks 1-2 of high-dose loading: monitor for headache, cramps, anxiety — usually Mg-related, add Mg before assuming D toxicity.
• 8-12 weeks post-start: first lab redraw, calibrate dose.
• First year: if any history of kidney stones, monitor urinary calcium 24-hr collection annually.