Vitamin D and Parkinson’s Disease

Abstract

Vitamin D is a fat-soluble secosteroid, traditionally considered a key regulator of bone metabolism, calcium and phosphorous homeostasis. Its action is made possible through the binding to the vitamin D receptor (VDR), after which it directly and indirectly modulates the expression of thousands of genes. Vitamin D is important for brain development, mature brain activity and associated with many neurological diseases, including Parkinson’s disease (PD). High frequency of vitamin D deficiency in patients with Parkinson’s disease compared to control population was noted nearly twenty years ago. This finding is of interest given vitamin D’s neuroprotective effect, exerted by the action of neurotrophic factors, regulation of nerve growth or through protection against cytotoxicity. Vitamin D deficiency seems to be related to disease severity and disease progression, evaluated by Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale, but not with age of PD onset and duration of disease. Additionally, fall risk has been associated with lower vitamin D levels in PD. However, while the association between vitamin D and motor-symptoms seems to be possible, results of studies investigating the association with non-motor symptoms are conflicting. In addition, very little evidence exists regarding the possibility to use vitamin D supplementation to reduce clinical manifestations and disability in patients with PD. However, considering the positive balance between potential benefits against its limited risks, vitamin D supplementation for PD patients will probably be considered in the near future, if further confirmed in clinical studies.

Vitamin D Status and Parkinson’s Disease

“…Studies on animal models and, more recently, on the human brain emphasize the role of vitamin D on neuroprotection. Recently, Pignolo et al [ 118 ] have extensively investigated the role of vitamin D in PD, describing its relevance in neuroprotection, its implication in all clinical aspects which characterize the disease, and suggesting a possible role of vitamin D supplementation as a possible therapeutic strategy.…”

“…Vitamin D depletion is responsible for the death of dopaminergic neurons [ 118 ]. On the other hand, vitamin D supplementation protects against dopamine depletion in SNpc in rats.…”

“…The expression of VDR and 1α-hydroxylase in the brain suggests as vitamin D hydroxylation occurs in the brain, reinforcing the concept of the protective role of vitamin D against dopaminergic cells loss, and therefore PD. All these findings suggest the potential role of vitamin D as a biomarker in PD [ 36 , 37 , 41 , 118 ].…”

“…In the literature, no investigations regarding the potential role of vitamin D in PD linked with cancer have been conducted. Vitamin D has a well-recognized protective role in a large number of cancers (e.g., breast cancer, gastrointestinal malignancies, melanoma), since it is implicated in tumors cell growth, inflammation, and immune surveillance [ 115 , 116 , 117 , 118 ]. However, the role of vitamin D in recent years has been widely discussed in malignant melanoma, whose occurrence has been reported with a higher frequency in PD, independently by dopaminergic therapy [ 93 , 117 ].…”

Association of vitamin D receptor gene haplotypes with late‑onset Alzheimer's disease in a Southeastern European Caucasian population

“…The role of vitamin D in the development and protection of neural cells has been described in a number of studies both in vitro and in vivo (1)(2)(3)(4). In parallel, over the past years, an increasing interest has emerged for the beneficial effects of vitamin D in neurodegenerative disorders, such as Parkinson's disease, Multiple sclerosis and Alzheimer's disease (AD) (5)(6)(7)(8)(9)(10)(11)(12)(13). Studies have concluded that there may be a close interaction between the molecular pathways of vitamin D mechanisms of action and the molecular pathways of AD pathology (14,15).…”