Monthly High-Dose Vitamin D Supplementation and Cancer Risk A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial
Monthly High-Dose Vitamin D Supplementation and Cancer Risk A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial
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DOI：
10.1001/jamaoncol.2018.2178
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发表时间：
2018-11-01
期刊：
影响因子：
28.4
通讯作者：
Camargo, Carlos A., Jr.
中科院分区：
文献类型：
--
作者：
Scragg, Robert;Khaw, Kay-Tee;Camargo, Carlos A., Jr.
重要性 先前的随机临床试验报告了维生素 D 补充剂对癌症发病率影响的不一致结果。目的 检验每月补充高剂量维生素 D（不含钙）是否与普通人群中癌症发病率和癌症死亡率的降低相关。设计、设置。和参与者 这是对维生素 D 评估 (ViDA) 研究数据的事后分析，该研究是一项随机、双盲、安慰剂对照试验，从 2011 年 4 月 5 日至 2012 年 11 月 6 日期间从新西兰奥克兰的家庭诊所和社区团体中招募参与者，并于 2015 年 12 月 31 日完成随访。参与者是年龄在 50 至 84 岁的成年社区居民。在受家庭诊所邀请的 47,905 名成年人和来自社区团体的 163 名成年人中，5110 名参与者被随机分配接受维生素 D-3 (n = 2558) 或安慰剂 (n = 2552)。两名参与者撤回同意，所有其他参与者 (n = 5108) 均纳入主要分析。数据分析按意向治疗进行。 干预措施 口服维生素 D-3，初始推注剂量为 200 000 IU，随后每月剂量为 100 000 IU，或安慰剂，中位时间为 3.3 年（范围为 2.5-42 年）。 主要结果和措施 事后主要结果是所有原发性侵袭性和原位恶性肿瘤的数量（不包括非黑色素瘤皮肤癌）从随机分组开始诊断，直到 2015 年 7 月 31 日停止研究药物为止。 结果 在分析中纳入的 5108 名参与者中，平均 (SD) 年龄为 65.9 (8.3) 岁。 58.1% 为男性，4253 人 (83.3%) 为欧洲或其他种族/民族。其余为波利尼西亚或南亚人。平均 (SD) 基线去季节化 25-羟基维生素 D 浓度为 26.5 (9.0) ng/mL。在 438 名参与者的随机样本中，维生素 D 组的平均随访 25-羟基维生素 D 浓度始终比安慰剂组高出 20 ng/mL 以上。癌症的主要结局包括 328 例癌症（259 例侵袭性肿瘤和 69 例原位恶性肿瘤），维生素 D 组 2558 名参与者中有 165 名（6.5%）发生癌症，安慰剂组 2550 名参与者中有 163 名（6.4%）发生癌症，调整后的风险比为 1.01（95% CI，0.81-1.25；P = .95),结论和相关性 每月服用大剂量维生素 D 补充剂长达 4 年而不加钙可能无法预防癌症。这项研究表明，较长时间内每日或每周给药可能需要进一步研究。
IMPORTANCE Previous randomized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence.OBJECTIVE To examine whether high-dose vitamin D supplementation received monthly, without calcium, is associated with a reduction in cancer incidence and cancer mortality in the general population.DESIGN, SETTING. AND PARTICIPANTS This is a post hoc analysis of data from the Vitamin D Assessment (ViDA) study, a randomized, double-blind, placebo-controlled trial that recruited participants from family practices and community groups in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up completed December 31, 2015. Participants were adult community residents aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D-3 (n = 2558) or placebo (n = 2552). Two participants withdrew consent, and all others (n = 5108) were included in the primary analysis. Data analysis was by intention to treat.INTERVENTIONS Oral vitamin D-3, in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-42 years).MAIN OUTCOMES AND MEASURES Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms (excluding nonmelanoma skin cancers) diagnosed from randomization until the study medication was discontinued on July 31, 2015.RESULTS Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years. 58.1% were male, and 4253 (83.3%) were of European or another race/ethnicity. with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 (9.0) ng/mL. In a random sample of 438 participants, the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of cancer comprised 328 total cases of cancer (259 invasive and 69 in situ malignant neoplasms) and occurred in 165 of 2558 participants (6.5%) in the vitamin D group and 163 of 2550 (6.4%) in the placebo group, yielding an adjusted hazard ratio of 1.01(95% CI, 0.81-1.25; P = .95),CONCLUSIONS AND RELEVANCE High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer. This study suggests that daily or weekly dosing for a longer period may require further study.