Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum NRW, Ruhr University Bochum, Georgstraße 11, 32545, Bad Oeynhausen, Germany.
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
Eur J Nutr. 2023 Jun;62(4):1833-1844. doi: 10.1007/s00394-023-03124-w. Epub 2023 Feb 28.
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.
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.
The selected trials comprised a total number of 12,952 participants. All trials used supplemental vitamin D. 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 (P = 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.
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.
一般人群的维生素 D 可耐受最高摄入量设定为每天 4000 国际单位（IU），但仍存在相当大的不确定性。我们总结了持续时间≥6 个月的每日补充 3200-4000 IU 维生素 D 的试验报告的有害影响。
我们在多个数据库中进行了系统评价和荟萃分析，确定了 22 项报告安全性数据的随机对照试验。评估了钙代谢、跌倒、住院和死亡率等参数。
入选的试验共纳入 12952 名参与者。所有试验均使用补充维生素 D。与对照组相比，维生素 D 组高钙血症的相对风险（RR）为 2.21（95%CI：1.26-3.87；10 项研究），每 1000 人中发生 4 例维生素 D 引起的高钙血症。在纳入超过 100 人和≤100 名研究参与者的试验中进行亚组分析，RR 分别为 2.63（95%CI：1.30-5.30；7 项研究）和 0.80（95%CI：0.24-2.62；3 项研究）（P=0.06）。维生素 D 组跌倒和住院的风险也显著增加，RR 分别为 1.25（95%CI：1.01-1.55；4 项研究）和 1.16（95%CI：1.01-1.33；7 项研究）（P=0.01）。高钙尿症、肾结石和死亡率在研究组之间无显著差异。质量评估显示，安全性相关结局数据报告不完整的风险较高。
每天补充 3200-4000 IU 的维生素 D 似乎会增加一小部分人发生高钙血症和其他一些不良事件的风险，表明该剂量并非完全安全。在未来的研究中，当使用中高剂量的维生素 D 时，需要严格报告安全性相关结局。
