Controlled trials of vitamin D, causality and type 2 statistical error.

Two recent studies published in The Lancet (Autier et al. (2013) Lancet Diabetes Endocrinol 2, 76-89 and Bolland et al. (2014) Lancet Diabetes Endocrinol 2, 307-320) 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 'reverse causality'. 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. 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. 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.