The Safety Profile of Vitamin D Supplements Using Real-World Data from 445,493 Participants of the UK Biobank: Slightly Higher Hypercalcemia Prevalence but Neither Increased Risks of Kidney Stones nor Atherosclerosis.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Hypercalcemia*/epidemiology ; Hypercalcemia*/chemically induced ; Vitamin D*/analogs & derivatives ; Vitamin D*/blood ; Vitamin D*/administration & dosage ; Dietary Supplements*/adverse effects ; Kidney Calculi*/epidemiology ; Kidney Calculi*/blood ; Atherosclerosis*/epidemiology ; Atherosclerosis*/etiology; Humans ; Middle Aged ; Male ; Female ; United Kingdom/epidemiology ; Aged ; Adult ; Prevalence ; Biological Specimen Banks ; Risk Factors ; Calcium/blood ; Calcium/administration & dosage ; UK Biobank

Background : Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40-69, we examined associations of high 25-hydroxyvitamin (25(OH)D) levels ≥ 100 nmol/L and vitamin D supplementation with hypercalcemia (serum calcium > 2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% was diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46 [1.32-1.62] and 1.11 [1.04-1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusions: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without a higher atherosclerosis prevalence or risk of kidney stones.

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Keywords: adverse events; atherosclerosis; hypercalcemia; kidney stone risk; real-world evidence; serum 25-hydroxyvitamin D levels; vitamin D supplementation

1406-16-2 (Vitamin D)
A288AR3C9H (25-hydroxyvitamin D)
SY7Q814VUP (Calcium)

Date Created: 20240727 Date Completed: 20240727 Latest Revision: 20240729

20240729

PMC11279740

10.3390/nu16142251

39064694