McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Research Facilitation, Alberta Health Services, Calgary, Canada.
JAMA. 2019 Aug 27;322(8):736-745. doi: 10.1001/jama.2019.11889.
Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day.
To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength.
DESIGN, SETTING, AND PARTICIPANTS: Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L.
Daily doses of vitamin D3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day.
Co-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis.
Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (-3.9 mg HA/cm3 [95% CI, -6.5 to -1.3]) and 10 000 IU group (-7.5 mg HA/cm3 [95% CI, -10.1 to -5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of -1.2% (400 IU group), -2.4% (4000 IU group), and -3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were -1.8 mg HA/cm3 (95% CI, -3.7 to 0.1) in the 4000 IU group and -4.1 mg HA/cm3 in the 10 000 IU group (95% CI, -6.0 to -2.2), with mean percent change values of -0.4% (400 IU), -1.0% (4000 IU), and -1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12).
Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful.
ClinicalTrials.gov Identifier: NCT01900860.
很少有研究评估每日维生素 D 剂量在可耐受上限或更高水平持续 12 个月或更长时间的效果，但有 3%的美国成年人报告每天摄入至少 4000IU 的维生素 D。
评估维生素 D 补充剂对体积骨密度 (BMD) 和骨强度的剂量依赖性影响。
设计、地点和参与者：这是一项为期 3 年的、在加拿大卡尔加里的一个单一中心进行的、双盲、随机临床试验，包括 311 名无骨质疏松症的、年龄在 55 至 70 岁之间的、社区居住的健康成年人，其基线 25-羟维生素 D (25[OH]D) 水平为 30 至 125nmol/L。
3 年来每天服用维生素 D3，剂量分别为 400IU（n=109）、4000IU（n=100）或 10000IU（n=102）。对于每天饮食摄入少于 1200mg 钙的参与者，给予钙补充剂。
主要联合结局是桡骨和胫骨的总体积 BMD，采用高分辨率外周定量计算机断层扫描评估；通过有限元分析估计桡骨和胫骨的骨强度（失效负荷）。
在随机分组的 311 名参与者中（53%为男性；平均[SD]年龄 62.2[4.2]岁），有 287 名（92%）完成了研究。基线、3 个月和 3 年时，25(OH)D 水平分别为 400IU 组 76.3、76.7 和 77.4nmol/L；4000IU 组 81.3、115.3 和 132.2nmol/L；10000IU 组 78.4、188.0 和 144.4nmol/L。3 个月和 3 年时，体积 BMD 存在显著的组间交互作用。试验结束时，与 400IU 组相比，4000IU 组（-3.9mgHA/cm3[95%CI，-6.5 至-1.3]）和 10000IU 组（-7.5mgHA/cm3[95%CI，-10.1 至-5.0]）的桡骨体积 BMD 降低，400IU 组体积 BMD 的平均百分比变化为-1.2%，4000IU 组为-2.4%，10000IU 组为-3.5%。与 400IU 组相比，胫骨体积 BMD 的差异分别为 4000IU 组-1.8mgHA/cm3（95%CI，-3.7 至 0.1）和 10000IU 组-4.1mgHA/cm3（95%CI，-6.0 至-2.2），400IU 组的平均百分比变化值为-0.4%，4000IU 组为-1.0%，10000IU 组为-1.7%。桡骨（P=0.06）和胫骨（P=0.12）的失效负荷变化无显著差异。
在健康成年人中，与每天 400IU 相比，每天 4000IU 或 10000IU 的维生素 D 治疗 3 年，导致桡骨 BMD 统计学上显著降低；仅在每天 10000IU 剂量下，胫骨 BMD 显著降低。桡骨和胫骨的骨强度均无显著差异。这些发现不支持高剂量维生素 D 补充对骨骼健康有益；还需要进一步的研究来确定它是否有害。
ClinicalTrials.gov 标识符：NCT01900860。
