Can propranolol or sumatriptan cause elevated vitamin D levels in a 46-year-old male?

Can Propranolol or Sumatriptan Cause Elevated Vitamin D Levels?

No, neither propranolol nor sumatriptan causes elevated vitamin D levels—these medications have no known mechanism or documented effect on vitamin D metabolism or serum concentrations.

Propranolol and Vitamin D

• Propranolol is a non-cardioselective beta-blocker used for hypertension, migraine prophylaxis, and other cardiovascular conditions, with well-characterized pharmacology that does not involve vitamin D pathways 1
• The drug undergoes extensive first-pass hepatic metabolism primarily through glucuronidation and oxidation to 4-hydroxypropranolol, with no interaction with vitamin D synthesis, metabolism, or transport 1
• Published pharmacokinetic studies demonstrate interactions with vitamin C (which decreases propranolol absorption and first-pass metabolism) but show no effect on vitamin D levels or metabolism 2
• No clinical or pharmacological evidence exists linking propranolol to alterations in 25-hydroxyvitamin D [25(OH)D] concentrations 1

Sumatriptan and Vitamin D

• Sumatriptan is a selective 5-HT1 receptor agonist used for acute migraine treatment, with a pharmacokinetic profile that includes rapid clearance (elimination half-life ~2 hours) and metabolism to an indole acetic acid analogue excreted in urine 3
• The drug has 96% bioavailability after subcutaneous injection and 14% after oral administration due to first-pass metabolism, but these metabolic pathways do not involve vitamin D 3
• Pharmacokinetic interaction studies with propranolol, flunarizine, pizotifen, naproxen, and alcohol show no significant drug interactions, and none of these studies report effects on vitamin D metabolism 3, 4
• There is no biological mechanism by which a 5-HT1 agonist would affect vitamin D synthesis, hydroxylation, or serum levels 3

Actual Causes of Elevated Vitamin D Levels

• Excessive supplementation is the most common cause, with toxicity typically occurring only with prolonged daily doses exceeding 10,000 IU or serum levels above 100 ng/mL 5
• Manufacturing errors in supplements can cause inadvertent hypervitaminosis D—a recent case series documented two adolescents with severe hypercalcemia from a creatine supplement containing 425,000 IU vitamin D per serving (100 times the upper tolerable dose) despite the product label not claiming to contain vitamin D 6
• Granulomatous diseases (sarcoidosis, tuberculosis) can cause elevated 1,25-dihydroxyvitamin D through extrarenal conversion by activated macrophages, though this typically does not elevate 25(OH)D 5

Clinical Approach to Unexplained Elevated Vitamin D

• Obtain a detailed supplement history, including all over-the-counter products, protein powders, and "natural health products" that may not list vitamin D on the label 6
• Measure serum calcium, phosphorus, and PTH to assess for hypercalcemia and distinguish vitamin D toxicity from other causes 5
• If 25(OH)D exceeds 100 ng/mL with suppressed PTH and hypercalcemia, immediately discontinue all vitamin D and calcium-containing supplements 5
• Consider sending supplements for mass spectrometry analysis if no obvious source is identified, as manufacturing errors can occur even in products not claiming to contain vitamin D 6

Important Caveat

• The upper safety limit for 25(OH)D is 100 ng/mL, with toxicity symptoms (hypercalcemia, hyperphosphatemia, suppressed PTH, hypercalciuria) typically occurring only at levels above 150 ng/mL 5, 7
• Daily doses up to 4,000 IU are generally safe for adults, with some evidence supporting up to 10,000 IU daily for several months without adverse effects in specific clinical contexts 5, 7