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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Zittermann, A; Trummer, C; Theiler-Schwetz, V; Pilz, S.
Long-term supplementation with 3200 to 4000 IU of vitamin D daily and adverse events: a systematic review and meta-analysis of randomized controlled trials.
Eur J Nutr. 2023; 62(4):1833-1844
Doi: 10.1007/s00394-023-03124-w
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- Co-authors Med Uni Graz
- Pilz Stefan
- Theiler-Schwetz Verena
- Trummer Christian
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- Abstract:
- 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 ≥ 6 months. 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. RESULTS: The selected trials comprised a total number of 12,952 participants. All trials used supplemental vitamin D3. 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 ≤ 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 (Pinteraction = 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. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Vitamin D - administration & dosage
- Hypercalcemia - chemically induced
- Randomized Controlled Trials as Topic - administration & dosage
- Vitamins - administration & dosage
- Dietary Supplements - adverse effects
- Find related publications in this database (Keywords)
- Vitamin D
- Hypercalcemia
- Intoxication
- Harmful effects
- Upper tolerable intake level
- Adverse events