Long-term supplementation with 3200 to 4000 IU of vitamin D daily and adverse events

  • \(\bf Purpose\) The upper tolerable intake level for vitamin D in the general population has been set at 4000 international units (IU) daily, but considerable uncertainty remains. We summarized reported harmful effects of a daily vitamin D supplement of 3200–4000 IU in trials lasting \(\geq\) 6 months. \(\bf Methods\) We performed a systematic review and meta-analysis of randomized controlled trials in several databases and identified 22 trials reporting safety data. Parameters of calcium metabolism, falls, hospitalization, and mortality were assessed. \(\bf Results\) The selected trials comprised a total number of 12,952 participants. All trials used supplemental vitamin \(D_3\). The relative risk (RR) of hypercalcemia in the vitamin D vs. control arm was 2.21 (95%CI: 1.26–3.87; 10 studies), with a vitamin D-induced frequency of hypercalcemia of 4 cases per 1000 individuals. Subgroup analysis in trials with > 100 and \(\leq\) 100 study participants revealed an RR of 2.63 (95%CI: 1.30–5.30; 7 studies) and 0.80 (95%CI: 0.24–2.62; 3 studies), respectively (\(P_{interaction}\) = 0.06). Risks of falls and hospitalization were also significantly increased in the vitamin D arm with an RR of 1.25 (95%CI: 1.01–1.55; 4 studies) and 1.16 (95%CI: 1.01–1.33; 7 studies), respectively. Risks of hypercalciuria, kidney stones, and mortality did not differ significantly between study arms. Quality assessment revealed high risk of incomplete reporting of safety-related outcome data. \(\bf Conclusion\) Supplemental vitamin D doses of 3200–4000 IU/d appear to increase the risk of hypercalcemia and some other adverse events in a small proportion of individuals, indicating that this dose is not completely safe. In future studies, rigorous reporting of safety-related outcomes is needed when using moderately high doses of vitamin D.

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Author:Armin ZittermannORCiDGND, Christian TrummerGND, Verena Theiler-SchwetzGND, Stefan PilzGND
Parent Title (English):European journal of nutrition
Subtitle (English):a systematic review and meta-analysis of randomized controlled trials
Publisher:Springer Nature
Place of publication:Berlin
Document Type:Article
Date of Publication (online):2024/04/08
Date of first Publication:2023/02/28
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Adverse events; Harmful effects; Hypercalcemia; Intoxication; Upper tolerable intake level; Vitamin D
First Page:1833
Last Page:1844
Dieser Beitrag ist auf Grund des DEAL-Springer-Vertrages frei zugänglich.
Institutes/Facilities:Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International