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The results demonstrated that daily 4000\u00a0IU vitamin D3 is required to achieve blood levels associated with lowest disease risks, and this dose should be tested in future trials for fracture prevention.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Introduction<\/jats:title>\n            <jats:p>The aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000\u00a0IU (100\u00a0\u03bcg), 2000\u00a0IU (50\u00a0\u03bcg) or placebo for 1\u00a0year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This is a randomized placebo-controlled trial in 305 community-dwelling people aged 65\u00a0years or older in Oxfordshire, UK. Outcomes included biochemical markers of vitamin D status (plasma 25-hydroxy-vitamin D [25[OH]D], parathyroid hormone [PTH], calcium and alkaline phosphatase), cardiovascular risk factors and tests of physical function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Mean (SD) plasma 25(OH)D levels were 50 (18) nmol\/L at baseline and increased to 137 (39), 102 (25) and 53 (16) nmol\/L after 12\u00a0months in those allocated 4000\u00a0IU, 2000\u00a0IU or placebo, respectively (with 88%, 70% and 1% of these groups achieving the pre-specified level of &gt;90\u00a0nmol\/L). Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium. The additional effect on 25(OH)D levels of 4000 versus 2000\u00a0IU was similar in all subgroups except for body mass index, for which the further increase was smaller in overweight and obese participants compared with normal-weight participants. Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>After accounting for average 70% compliance in long-term trials, doses of 4000\u00a0IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00198-016-3833-y","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T08:28:14Z","timestamp":1481963294000},"page":"841-851","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care"],"prefix":"10.1007","volume":"28","author":[{"given":"H.","family":"Hin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Tomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Kurien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Emberson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Armitage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,16]]},"reference":[{"key":"3833_CR1","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/S8756-3282(01)00614-7","volume":"29","author":"TP van Staa","year":"2001","unstructured":"van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England and Wales. 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The British Heart Foundation (PG\/12\/32\/29544) and British Heart Foundation Centre for Research Excellence provided partial funding for the study. The Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) at the University of Oxford receives funding from the UK Medical Research Council, the British Heart Foundation and Cancer Research UK.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}