{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:51:44Z","timestamp":1773658304527,"version":"3.50.1"},"reference-count":44,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2014,11,5]],"date-time":"2014-11-05T00:00:00Z","timestamp":1415145600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["journals.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Public Health Nutr."],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Two recent studies published in <jats:italic>The Lancet<\/jats:italic> (Autier <jats:italic>et al.<\/jats:italic> (2013) <jats:italic>Lancet Diabetes Endocrinol<\/jats:italic><jats:bold>2<\/jats:bold>, 76\u201389 and Bolland <jats:italic>et al.<\/jats:italic> (2014) <jats:italic>Lancet Diabetes Endocrinol<\/jats:italic><jats:bold>2<\/jats:bold>, 307\u2013320) have concluded that low levels of vitamin D are not a cause but a consequence of ill health brought about by reduced exposure to the sun, an association known as \u2018reverse causality\u2019. The scientific evidence and reasoning for these conclusions are examined here and found to be faulty. A null result in a clinical trial of vitamin D in adults need not lead to a conclusion of reverse causation when low vitamin D is found in observational studies of the same disease earlier in life. To assume an explanation of reverse causality has close similarities with type 2 statistical error.<\/jats:p><jats:p>For example, a null result in providing vitamin D for treatment of adult bones that are deformed in the pattern of the rachitic rosary would not alter the observation that lack of vitamin D can cause rickets in childhood and may have lasting consequences if not cured with vitamin D. Other examples of diseases considered on a lifetime basis from conception to adulthood are used to further illustrate the issue, which is evidently not obvious and is far from trivial.<\/jats:p><jats:p>It is concluded that deficiency of vitamin D in cohort studies, especially at critical times such as pregnancy and early life, can be the cause of a number of important diseases. Denial of the possible benefits of vitamin D, as suggested by insistent interpretation of studies with reverse causation, may lead to serious harms, some of which are listed.<\/jats:p>","DOI":"10.1017\/s1368980014002304","type":"journal-article","created":{"date-parts":[[2014,11,5]],"date-time":"2014-11-05T03:41:20Z","timestamp":1415158880000},"page":"409-414","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":13,"title":["Controlled trials of vitamin D, causality and type 2 statistical error"],"prefix":"10.1017","volume":"19","author":[{"given":"OIiver","family":"Gillie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2014,11,5]]},"reference":[{"key":"S1368980014002304_ref43","doi-asserted-by":"publisher","DOI":"10.1517\/17530059.2013.786040"},{"key":"S1368980014002304_ref42","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.29094"},{"key":"S1368980014002304_ref44","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f1169"},{"key":"S1368980014002304_ref23","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-012-0166-2"},{"key":"S1368980014002304_ref12","doi-asserted-by":"publisher","DOI":"10.1308\/003588413X13629960046192"},{"key":"S1368980014002304_ref16","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.054676"},{"key":"S1368980014002304_ref14","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.112.000298"},{"key":"S1368980014002304_ref37","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.167.16.1730"},{"key":"S1368980014002304_ref6","unstructured":"Anon. (2014) New analysis suggests that further trials of vitamin D have little chance of showing health benefits. Press release promoting Bolland et al. (2014); available at http:\/\/www.thelancet.com\/press-room"},{"key":"S1368980014002304_ref17","first-page":"39","article-title":"The presence of high-risk chromosome aberrations in chronic lymphocytic leukaemia does not correlate with centrosome aberrations","volume":"26","author":"Ottaggio","year":"2008","journal-title":"Hematol Oncol Clin North Am"},{"key":"S1368980014002304_ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.10.016"},{"key":"S1368980014002304_ref40","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis697"},{"key":"S1368980014002304_ref33","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0385"},{"key":"S1368980014002304_ref7","doi-asserted-by":"publisher","DOI":"10.1111\/nure.12090"},{"key":"S1368980014002304_ref26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034866"},{"key":"S1368980014002304_ref15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082109"},{"key":"S1368980014002304_ref5","unstructured":"Anon. (2014) Further doubt cast on benefit of vitamin D supplementation for disease prevention. Press release promoting Autier et al. (2013); available at http:\/\/www.thelancet.com\/press-room"},{"key":"S1368980014002304_ref24","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-171"},{"key":"S1368980014002304_ref22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000369"},{"key":"S1368980014002304_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70164-5"},{"key":"S1368980014002304_ref13","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12007"},{"key":"S1368980014002304_ref18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-1984"},{"key":"S1368980014002304_ref28","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-013-9462-8"},{"key":"S1368980014002304_ref11","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20256"},{"key":"S1368980014002304_ref34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2011.04147.x"},{"key":"S1368980014002304_ref35","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e3283310767"},{"key":"S1368980014002304_ref39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200072109"},{"key":"S1368980014002304_ref8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29449"},{"key":"S1368980014002304_ref10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1985.tb00157.x"},{"key":"S1368980014002304_ref32","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2704"},{"key":"S1368980014002304_ref9","first-page":"226","article-title":"Distribution of Paget\u2019s disease in England, Wales and Scotland and a possible relationship with vitamin D deficiency in childhood","volume":"28","author":"Barker","year":"1974","journal-title":"Br J Prev Soc Med"},{"key":"S1368980014002304_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70165-7"},{"key":"S1368980014002304_ref20","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12020"},{"key":"S1368980014002304_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06580-1"},{"key":"S1368980014002304_ref31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197607082950204"},{"key":"S1368980014002304_ref4","first-page":"353","article-title":"Vitamin D for health: global perspsective","volume":"81","author":"Hossein-Nezhad","year":"2006","journal-title":"Mayo Clin Proc"},{"key":"S1368980014002304_ref19","doi-asserted-by":"publisher","DOI":"10.1177\/1756285612473513"},{"key":"S1368980014002304_ref27","doi-asserted-by":"publisher","DOI":"10.4161\/derm.1.4.9500"},{"key":"S1368980014002304_ref36","first-page":"1075","article-title":"25-Hydroxyvitamin D levels and all-cause mortality","volume":"169","author":"Zittermann","year":"2009","journal-title":"Arch Intern Med"},{"key":"S1368980014002304_ref41","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-3029"},{"key":"S1368980014002304_ref38","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2011.68"},{"key":"S1368980014002304_ref25","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-10-69"},{"key":"S1368980014002304_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70212-2"},{"key":"S1368980014002304_ref29","doi-asserted-by":"publisher","DOI":"10.2174\/138945011793591653"}],"updated-by":[{"DOI":"10.1017\/s1368980015000130","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2015,1,28]],"date-time":"2015-01-28T00:00:00Z","timestamp":1422403200000}},{"DOI":"10.1017\/s1368980015000166","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T00:00:00Z","timestamp":1423612800000}}],"container-title":["Public Health Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1368980014002304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T18:53:56Z","timestamp":1555700036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1368980014002304\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,5]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["S1368980014002304"],"URL":"https:\/\/doi.org\/10.1017\/s1368980014002304","relation":{"correction":[{"id-type":"doi","id":"10.1017\/S1368980015000166","asserted-by":"object"},{"id-type":"doi","id":"10.1017\/S1368980015000130","asserted-by":"object"}]},"ISSN":["1368-9800","1475-2727"],"issn-type":[{"value":"1368-9800","type":"print"},{"value":"1475-2727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,5]]},"assertion":[{"value":"Copyright \u00a9 The Author 2014\u00a0","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}