加拿大卡尔加里大学Steven K. Boyd研究组的最新研究分析了高剂量维生素D对骨密度和骨强度的影响。 这一研究成果发表在2019年8月27日出版的《美国医学会杂志》上。

2013年8月至2017年12月，这项为期三年的双盲、随机、临床试验共招募了311名健康参与者，53%为男性，平均年龄为62.2岁，治疗前25羟基维生素D水平为30-125nmol/L，所有参与者均没有骨质疏松症。随机分为三组，每日服用维生素D400 IU组109人，4000 IU组100人，10000 IU组102人，对每日摄入钙含量低于1200毫克的参与者提供补钙。

400 IU组的基线、3个月和3年的25羟基维生素D水平分别为76.3、76.7和77.4nmol/L；4000 IU组分别为81.3、115.3和132.2nmol/L；10000 IU组分别为78.4、188.0和144.4nmol/L。体积骨密度存在显著的分组-时间交互作用。

在试验结束时，与400 IU组相比，4000 IU组的桡骨体积骨密度减少了3.9 mg HA/cm^₃，10000 IU组减少了7.5 mg HA/cm³，其中400 IU组的平均百分比变化为−1.2%，4000 IU组为−2.4%，10000IU组为−3.5%；4000 IU组胫骨体积骨密度减少了1.8 mg HA/cm³，10000 IU组减少了4.1 mg HA/cm³，其中400 IU组的平均百分比变化为−0.4%，4000 IU组为−1.0%，10000 IU组为−1.7%。三组参与者的骨强度变化均无显著性差异。

综上，每天摄入4000 IU或10000 IU维生素D，与每天摄入400 IU相比，桡骨骨密度显著降低，而胫骨骨密度仅在每日摄入10000 IU时显著降低，但桡骨和胫骨的骨强度均无明显变化。该发现不支持补充高剂量维生素D对骨骼健康有益，相反，还需进一步研究来确定它是否有害。

据了解，3%的美国成年人报告称每天应至少补充4000 IU维生素D，但很少有研究评估每日摄入维生素D 4000 IU及以上持续12个月或更长时间的真实效果。

附：英文原文

Title: Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength

Author: Lauren A. Burt, Emma O. Billington, Marianne S. Rose, Duncan A. Raymond, David A. Hanley, Steven K. Boyd

Issue&Volume: August 27, 2019, Vol 322, No. 8

Abstract:

Importance  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.

Objective  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.

Interventions  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.

Main Outcomes and Measures  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.

Results  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).

Conclusions and Relevance  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.

DOI: 10.1001/jama.2019.11889

Source: https://jamanetwork.com/journals/jama/article-abstract/2748796