Errors in Table 1 and Figure 2

Abstract

To the Editor In a recent article in JAMA Neurology, Hendriks et al 1 report that low vitamin D status is associated with a higher risk for young-onset dementia in participants in the UK Biobank. The authors note that in a number of similar studies, vitamin D status is associated with various types of mental and motor disorders. The term vitamin D is highly misleading and incorrect, even if meant as an overarching term for vitamin D 3 metabolites. Vitamin D 3 (cholecalciferol) is either produced in skin or taken up from the diet, then hydroxylated in the liver to form calcidiol (25-OH vitamin D 3 ) and further hydroxylated in the kidneys to 1,25-OH2 vitamin D 3 (calcitriol). Only the latter is biologically active and relevant. 2 As apparent from the supplement, Hendriks et al 1 used calcidiol (also there termed vitamin D)-but not vitamin D 3 levelsfor their association study. Even more, the relevance of lower calcidiol levels in individuals with higher risk for youngonset dementia is questionable as the conversion of calcidiol to calcitriol is highly regulated, and the correlation between calcidiol and calcitriol levels is weak in the general population and modulated by age, sex, season, body mass index, and the presence of various diseases, including kidney disease and also motor and mental disorders. 3,4 A detailed analysis whether calcitriol is associated with or even causative for mental disorders would be very important as animal experiments indeed suggest a strong influence of calcitriol on brain development, function, and pathology. Using the correct terminology and concepts of vitamin D metabolism is of outmost importance in this context as recent trials have been testing the effects of calcidiol supplements on dementia and other neurological disorders and lack justification if epidemiological association studies operate with inaccurate concepts and terms. 5 Thus, the concept that calcitriol may modulate central nervous system functions is plausible; however, it lacks strong evidence from epidemiological studies, and the use of incorrect nomenclature may produce rather conceptual confusion than help addressing this important issue.