Vitamin D and brain volumetric changes: Systematic review and meta-analysis

Vitamin D has multiple functions in the nervous system. Our objective was to systematically review and quantitatively synthesize evidence on the location and nature of brain morphometric changes linked to vitamin D depletion or repletion. A Medline search was conducted in February 2014, without limit of date and language restriction, using the MeSH terms "Vitamin D" OR "Ergocalciferols" combined with "Brain Mapping" OR "Magnetic Resonance Imaging" OR "Tomography, X-ray Computed" OR "Tomography, Emission-Computed, Single-Photon" OR "Positron-Emission Tomography" OR "Nuclear Medicine" OR "Radionucleide Imaging". Of the 376 selected studies, nine observational studies - two animal and seven human studies - met the selection criteria. The number of participants ranged from 20 to 333 (40-79% female). Three studies were eligible for fixed-effects meta-analysis of bias-corrected effect size of the difference in lateral ventricle volume between cases with vitamin D depletion and controls. Results showed that vitamin D depletion was associated with lower brain volume, specifically larger lateral ventricles. The pooled effect size was 1.01 [95% CI: 0.62; 1.41], a 'large' effect size indicating that the ventricle volume was 1.01 SD higher with vitamin D depletion. Results on brain subvolumes were mixed, and indicated that brain atrophy with vitamin D depletion could be explained not by temporal lobe atrophy but rather by loss of matter at the cranial vertex, possibly in the precuneus cortex. In conclusion, despite increasing evidence arguing for an action of vitamin D in the brain, data is sparse regarding brain morphological changes related to vitamin D depletion. The retrieved association between vitamin D depletion and brain atrophy provides a scientific base for vitamin D replacement trials.