Dietary Supplements

Overdiagnosed and oversupplemented: the iatrogenic rise of vitamin D toxicity.

TL;DR

Annual vitamin D testing increased 54.1% and very high results more than doubled over 5 years at a Barcelona tertiary hospital, with hypercalcemia occurring in 4.3% of cases with very elevated 25(OH)D, predominantly associated with calcifediol supplementation.

Key Findings

Annual vitamin D testing volume increased substantially over the study period at a Barcelona tertiary hospital.

  • Study analyzed 185,604 serum 25(OH)D results from 2020 to 2025
  • Annual testing increased by 54.1% over the study period
  • Measurements were performed using a VDSCP-certified immunoassay
  • The study was conducted retrospectively at a single tertiary hospital in Barcelona, Spain

Median serum 25(OH)D levels rose over the study period, indicating a rightward population-level shift in vitamin D status.

  • Median 25(OH)D rose from 25.3 to 28.6 ng/mL over the study period
  • The authors describe this as a 'rightward shift and expanding high-concentration tail'
  • This shift occurred in parallel with rapid test growth

The number of very high vitamin D results (>100 ng/mL) more than doubled during the study period.

  • Very high results (>100 ng/mL or >250 nmol/L) increased from 31 (0.14%) to 108 (0.31%) annually
  • Total number of very high results was 393 across the full study period
  • The proportion of results exceeding the very high threshold more than doubled (0.14% to 0.31%)

Hypercalcemia occurred in 4.3% of cases where calcium measurements were available alongside very elevated vitamin D levels.

  • Hypercalcemia was defined as albumin-corrected calcium >10.5 mg/dL
  • Calcium data were available in 324 of 393 very high 25(OH)D results
  • Hypercalcemia occurred in 14 of 324 cases (4.3%)
  • Concomitant measurements retrieved included calcium, phosphorus, albumin, alkaline phosphatase, and parathyroid hormone

Calcifediol supplementation was the predominant supplement associated with hypervitaminosis D and hypercalcemia cases.

  • Calcifediol was documented in 183 of 201 (91.0%) hypervitaminosis D patients with available supplementation data
  • Calcifediol was documented in 12 of 14 (85.7%) hypercalcemic cases
  • Calcifediol use was often associated with short-interval dosing regimens
  • Supplementation data were available for 201 of the 393 very high result cases

Spanish pharmacovigilance alerts have highlighted vitamin D overdosing as a recognized safety concern.

  • The study was motivated in part by existing Spanish pharmacovigilance alerts regarding vitamin D overdosing
  • The authors frame the phenomenon as 'iatrogenic rise of vitamin D toxicity'
  • The findings support calls for 'evidence-based requesting, clearer intermittent-dosing and supplementation instructions'

The authors recommend selective serum calcium surveillance when 25(OH)D is greatly elevated.

  • Selective serum calcium surveillance is recommended specifically when 25(OH)D is 'greatly elevated'
  • The authors also support evidence-based requesting practices
  • Clearer intermittent-dosing and supplementation instructions are recommended as corrective measures

What This Means

This research suggests that vitamin D testing and supplementation have increased substantially in recent years, with potentially harmful consequences for some patients. Analyzing over 185,000 vitamin D blood test results from a large hospital in Barcelona between 2020 and 2025, the researchers found that the number of tests performed grew by more than half, average vitamin D levels in patients rose, and the number of people with dangerously high vitamin D levels more than doubled. Among those with very high vitamin D levels, about 1 in 23 also had high blood calcium (hypercalcemia), a condition that can cause symptoms such as fatigue, nausea, kidney problems, and confusion. The research also suggests that a specific form of vitamin D supplement called calcifediol was involved in the vast majority of cases with very high vitamin D levels and in most of the cases where high blood calcium developed. Calcifediol is a more potent and faster-acting form of vitamin D than the more commonly known cholecalciferol (vitamin D3), and it appears to have been frequently prescribed in dosing schedules that may not have provided enough time between doses, potentially leading to accumulation in the body. The practical implication of this research is that vitamin D testing may be occurring more often than is medically necessary, and that supplementation — particularly with calcifediol — may sometimes be prescribed without sufficient caution about dosing intervals or follow-up monitoring. The authors suggest that clearer prescribing guidelines, more selective use of vitamin D testing, and monitoring of blood calcium levels in patients with very high vitamin D results could help reduce the risk of toxicity.

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Citation

Fabregat-Bolufer A, Martín-Alonso C, Escolà-Rodríguez A, Morales-Ruiz M. (2026). Overdiagnosed and oversupplemented: the iatrogenic rise of vitamin D toxicity.. European journal of endocrinology. https://doi.org/10.1093/ejendo/lvag088