Beyond the classical roles of vitamin D in Calcium Homeostasis and regulation of Musculoskeletal Health (maintain normal blood levels of calcium and phosphorus), there is emerging facts that shows a range of effects of vitamin D in the central nervous system. There are cross sectional studies which serve as the evidence for considering vitamin D as a ‘neurosteroid hormone’ and as a potential biomarker of Alzheimer’s disease (AD) (1, 4). Experimental and pre-clinical data suggest a link between vitamin D status and cognitive function.
Vitamin D receptors have been found in several types of human brain cells; where they receive chemical signals. There are only fewer vitamin D receptors in the hippocampus (involved in forming memories) of the Alzheimer’s patients. Studies show that vitamin D levels are lower in people with AD than those without AD. The biologically active form of vitamin D [1,25(OH)(2)D3] has shown neuroprotective effects including the clearance of amyloidal plaques, regulate inflammation in the brain and helps in preventing the development of tangles (2). Action of vitamin D and AD-type pathology overlap. Therefore, hypovitaminosis D have been frequently associated with cognitive decline and may contribute to diseases of the nervous system. Hypovitaminosis D is also considered to contribute to the risk of hip fractures in elderly patients with Alzheimer’s disease (3, 6). Lack of vitamin D deteriorates type II fibers in the muscle, resulting in a reduction in motor function and an increase in the risk of falls in elderly patients with Alzheimer’s disease.
Hypovitaminosis D also decreases intestinal calcium absorption, resulting in an increase in bone resorption, and a decrease in bone mineral density (8). Why should we seriously consider “simple” vitamin D as a “fundamental factor” in AD? Potential correlation of vitamin D status with the vulnerability of neurons to aging and neurodegeneration is supported by evidence that the disruption of vitamin D pathways mimic amyloid pathology. Vitamin D molecule as a secosteroid could be considered as one of the important factor in the development of Alzheimer’s, due to long term hormonal imbalance. Any variation in vitamin D-related genes would lead to insufficient utilization of the vitamin D molecule (5). Case study on VDR polymorphisms in 255 AD cases and 260 cognitively screened elderly controls from the longitudinal cohort of the Oxford Project to Investigate Memory and Ageing showed that the presence of each of the linked alleles was associated with the risk of AD. These associations seem to be biologically plausible and are consistent with a role for vitamin D in AD (6).
Supplementation with vitamin D is protective against biological processes associated with Alzheimer’s disease (AD) and enhances learning and memory performance in various animal models of aging and AD. These experimental observations support multiple mechanisms by which vitamin D can act against neurodegenerative processes (7). The numerous functions of vitamin D inducing genomic and non genomic effects include calcium homeostasis, neurotransmission, vascularization, oxidative stress, and inflammation. Future studies examining the effects of serum vitamin D levels on neurocognitive function is of high importance which could be used as therapeutic or preventive interventional tool. Vitamin D plays significant role in physiological processes and need to be considered as a significant factor in the nervous system development and function, in a broader perspective as we are moving towards personalized medicine.
References
1. Annweiler, Cedric, David J. Llewellyn, and Olivier Beauchet. “Low serum vitamin D concentrations in Alzheimer’s disease: a systematic review and meta-analysis.” Journal of Alzheimer’s Disease 33.3 (2013): 659-674.
2. https://www.vitamindcouncil.org/health-conditions/alzheimers-disease/
3. Soni, Maya, et al. “Vitamin D and cognitive function.” Scandinavian Journal of Clinical and Laboratory Investigation 72.sup243 (2012): 79-82.
4. Oudshoorn, Christian, et al. “Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer’s disease.” Dementia and geriatric cognitive disorders 25.6 (2008): 539-543.
5. Gezen-Ak, Duygu, Selma Y?lmazer, and Erdinç Dursun. “Why vitamin D in Alzheimer’s disease? The hypothesis.” Journal of Alzheimer’s Disease 40.2 (2014): 257-269.
6. Lehmann, Donald J., et al. “The vitamin D receptor gene is associated with Alzheimer’s disease.” Neuroscience letters 504.2 (2011): 79-82.
7. Landel, Véréna, et al. “Vitamin D, Cognition and Alzheimer’s Disease: The Therapeutic Benefit is in the D-Tails.” Journal of Alzheimer’s Disease 53.2 (2016): 419-444.
8. Iwamoto, Jun, and Yoshihiro Sato. “Strategy for Prevention of Hip Fractures in Patients with Alzheimer’s Disease.” General Medicine: Open Access 2013 (2013).