What are the symptoms and signs of vitamin D toxicity?

Symptoms of Vitamin D Toxicity

Vitamin D toxicity manifests primarily through hypercalcemia-related symptoms including fatigue, weakness, nausea, vomiting, constipation, altered mental status, polyuria, and polydipsia, typically occurring when 25(OH)D levels exceed 150 ng/mL. 1

Generalized Symptoms

• Fatigue and weakness are among the earliest manifestations of vitamin D toxicity, resulting from elevated calcium levels that impair cellular function 1
• These nonspecific symptoms may present for days to weeks before more severe manifestations develop 2

Gastrointestinal Manifestations

• Nausea, vomiting, and constipation occur frequently as the gastrointestinal tract responds to hypercalcemia 1
• Recurrent vomiting and abdominal pain are commonly noted clinical symptoms in established vitamin D toxicity 3

Neurological Symptoms

• Altered mental status, irritability, and confusion develop as hypercalcemia affects neurological function 1, 3
• In severe cases, encephalopathy, apathy, and even coma may occur 1, 3

Endocrinological Manifestations

• Polyuria and polydipsia result from hypercalcemia-induced nephrogenic diabetes insipidus 1
• These symptoms reflect the kidney's impaired ability to concentrate urine in the setting of elevated calcium 1

Renal Complications

• Acute kidney injury may develop as a serious complication of vitamin D toxicity 2
• Kidney stones and nephrocalcinosis can occur with prolonged hypercalcemia and hypercalciuria 4, 1
• Dehydration from polyuria compounds renal injury risk 3

Laboratory Thresholds for Toxicity

• Vitamin D toxicity typically occurs at 25(OH)D levels >150 ng/mL (>375 nmol/L), with acute toxicity associated with levels >200 ng/mL (>500 nmol/L) 1
• The upper safety limit for serum 25(OH)D is 100 ng/mL, above which toxicity risk increases substantially 1
• Hypercalcemia in generally healthy adults has been observed only when daily intake exceeded 100,000 IU or when 25(OH)D levels exceeded 100 ng/mL 1

Important Clinical Caveats

Toxicity can occur without hypervitaminosis D: Prolonged vitamin D supplementation may induce hypercalcemia, hypercalciuria, and hyperphosphatemia—the initial signs of toxicity—even when serum 25(OH)D levels remain below traditionally toxic ranges 5. Tissue and organ damage may already be underway when calcium and phosphorus dysregulation becomes apparent 5.

Variable individual response: Most subjects with hypercalcemia from vitamin D present at serum concentrations <375 nmol/L, demonstrating highly variable individual responses 6. Genetic, phenotypic, and environmental factors cause substantial inter-individual differences in vitamin D metabolism, meaning some persons may experience toxicity at doses safe for others 1.

Asymptomatic presentation is possible: Laboratory testing may reveal hypercalcemia even with vitamin D doses considered safe for the general population, reflecting hypersensitivity to vitamin D from dysregulated metabolism 3. In rare cases, extremely high serum vitamin D levels (>700 ng/mL) have been documented without clinical symptoms or hypercalcemia 7.

Diagnostic Evaluation

When vitamin D toxicity is suspected, obtain:

• Serum 25(OH)D to confirm diagnosis 1
• Serum calcium, phosphorus, and intact PTH (PTH is typically suppressed) 1
• Spot urine calcium-to-creatinine ratio to assess hypercalciuria 1
• Renal ultrasonography if hypercalciuria is present to screen for nephrocalcinosis and kidney stones 1

High-Risk Populations

• Patients with chronic kidney disease face increased risk due to impaired calcium and phosphorus regulation 1
• Patients with hyperparathyroidism have altered calcium homeostasis requiring particularly cautious supplementation 1
• Immobilized patients require dose reduction of active vitamin D formulations to prevent hypercalciuria and hypercalcemia 1