Several studies have confirmed that vitamin D can increase cognitive function in mild cognitive impairment and dementia. However, there are still a number of limitations to these studies. Specifically, the studies are cross-sectional and lack prospective data on healthy individuals. A long-term placebo-controlled trial is needed to assess the effects of pharmacologic and lifestyle interventions.
The current review aims to summarize the existing evidence on the effects of vitamin D on cognitive function. It covers animal models of brain impairment, as well as interventional clinical studies on vitamin D deficiency and brain functioning. It also discusses the possible pitfalls of translating preclinical findings into clinical benefit.
The vitamin D receptor (VDR) is found in the central nervous system (CNS) and has a zinc finger and ligand-binding domain. It is localized in the hippocampus and the limbic system. It is involved in the regulation of cell proliferation and apoptosis. It also contributes to the turnover of the dopaminergic system in adults. In addition, it is a potent therapeutic target. It has been shown to be present in the midbrain of the 12-day-old embryo. It may play a role in the development of stem cells and neuronal proliferation.
Recent epidemiological studies have revealed an association between maternal serum calcidiol levels during pregnancy and cognitive development disorders in offspring. These results are in accordance with previous studies on children. It has been proposed that the optimal levels of neonatal vitamin D are likely to be between 30 and 50 nmol/L.
Vitamin D may also play an important role in maintaining cognitive function. The antioxidant properties of vitamin D have been demonstrated in numerous preclinical studies. It can reduce oxidative stress and amyloid deposits in the brain. It also increases telomere length and reduces phosphorylated tau. Its effects on memory and learning are known to be hippocampal-dependent. In a study conducted in the Morris water maze, mice lacking vitamin D were less able to remember and learn. It is therefore possible that the vitamin D receptor plays a role in the maintenance of cognitive function in the elderly.
The role of vitamin D in brain function was also investigated in middle-aged F344 rats fed a medium-fat diet. They were deprived of vitamin D for 5-6 mo. The animals showed no muscle weakness, but they did show impaired performance on cognitive tests. They showed impairments on the active place-avoidance test and memory tests. It was also shown that VDD mice exhibited reduced hippocampus activity.
The effects of vitamin D supplementation in middle-aged rodents were not well-characterized. It was assumed that diffusion of vitamin D and its metabolites was responsible for the action. However, it is also suggested that alternative pathways might be responsible. Moreover, vitamin D supplements are not yet shown to increase calcitriol levels in the brain. These studies suggest that some critical elements of the signaling process in the brain are still unknown.
The review also highlights the need for a large and representative sample size in clinical trials. For example, it is not known if vitamin D increases telomere length in the brain. A larger sample size might enable more robust analyses and be able to detect more significant effects. Moreover, it is important to include patients from a community-based population in clinical studies.