McCullough Patrick, Amend Jeffrey
Department of Psychiatry, Wright State University, School of Medicine, Dayton, OH, 45435, United States; Summit Behavioral Healthcare, Cincinnati, OH, 45237, United States.
Summit Behavioral Healthcare, Cincinnati, OH, 45237, United States.
J Steroid Biochem Mol Biol. 2017 Oct;173:308-312. doi: 10.1016/j.jsbmb.2016.12.009. Epub 2016 Dec 21.
In the 1930's and 1940's, vitamin D was reported to be an effective treatment for a number of diseases, including asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. High doses were used, 60,000 to 300,000 IU a day for asthma, and 200,000 to 600,000 IU a day for rheumatoid arthritis. Toxicity from hypercalcemia occurred after prolonged oral dosing with these supraphysiologic doses. Assays for measuring vitamin D in the blood were not available, and blood levels of vitamin D associated with hypercalcemia were unknown. A 2011 report on vitamin D toxicity showed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400ng/ml in 2 patients with blood levels ranging from 645ng/ml to 1220ng/ml after accidental ingestion of massive doses of vitamin D. We now know that vitamin D is made in the skin in amounts ranging up to 25,000 IU a day with exposure to UVB radiation. There is little data on the safety and blood levels of 25OHD and calcium after prolonged daily intake of amounts of vitamin D in this range. In this report, one subject took increasing daily doses of vitamin D3 for 6 years starting in April 2009: 6500 IU for 6 months; increasing to 10,000 IU for 13 months; 20,000 IU for 24 months; 40,000 IU for 12 months; 50,000 IU for 10 months, and 60,000 IU since October 2014. 25OHD blood levels were 28, 81, 204, 216, 225, 166, and 218ng/ml. Subject 2 began 10,000 IU in Nov 2011, increased to 20,000 IU in Feb 2014, 25,000 IU in June 2014, and 30,000 IU in Oct 2014, and then decreased to 20,000 IU in June 2015. 25OHD blood levels were 96.6, 161.1 and 106.9ng/ml. He reported marked clinical improvement in his asthma. Subject 3 started on daily 10,000 IU in Sept 2013, increasing to 20,000 IU on Nov 2013. 25OHD blood levels were 31.4, 102, 164, 148, and 143ng/ml. No one developed hypercalcemia or any adverse events. The major finding of this case series is prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU was safely tolerated.
在20世纪30年代和40年代，据报道维生素D对多种疾病有效，包括哮喘、银屑病、类风湿性关节炎、佝偻病和结核病。使用的是高剂量，哮喘患者每天60,000至300,000国际单位，类风湿性关节炎患者每天200,000至600,000国际单位。长期口服这些超生理剂量后会出现高钙血症毒性。当时尚无测量血液中维生素D的检测方法，与高钙血症相关的维生素D血液水平也不清楚。一份2011年关于维生素D毒性的报告显示，2例意外摄入大量维生素D后血液水平在645纳克/毫升至1220纳克/毫升之间的患者，当25-羟维生素D（25OHD）血液水平降至400纳克/毫升以下时，高钙血症得到缓解。我们现在知道，皮肤在暴露于中波紫外线辐射时每天可产生高达25,000国际单位的维生素D。关于长期每日摄入该范围内维生素D量后25OHD和钙的安全性及血液水平的数据很少。在本报告中，一名受试者从2009年4月开始连续6年每日增加维生素D3剂量：6个月内每天6500国际单位；增加到每天10,000国际单位，持续13个月；每天20,000国际单位，持续24个月；每天40,000国际单位，持续12个月；每天50,000国际单位，持续10个月，自2014年10月起每天60,000国际单位。25OHD血液水平分别为28、81、204、216、225、166和218纳克/毫升。受试者2于2011年11月开始每天服用10,000国际单位，2014年2月增加到每天20,000国际单位，2014年6月增加到每天25,000国际单位，2014年10月增加到每天30,000国际单位，然后在2015年6月降至每天20,000国际单位。25OHD血液水平分别为96.6、161.1和106.9纳克/毫升。他报告哮喘症状有明显临床改善。受试者3于2013年9月开始每天服用10,000国际单位，2013年11月增加到每天20,000国际单位。25OHD血液水平分别为31.4、102、164、148和143纳克/毫升。没有人出现高钙血症或任何不良事件。该病例系列的主要发现是，每日长期服用10,000至60,000国际单位的维生素D3可被安全耐受。
