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.

Keywords: 1,25-dihydroxyvitamin D; Parkinson’s disease; balance; cognition; disease progression; motor symptoms; neurodegeneration; neuroprotection; vitamin D; vitamin D receptor.

Figure 1

Principal neurotrophic and neuroprotective effects of Vitamin D on CNS. nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), transforming growth factor (TGF)-b2, ciliary neurotrophic factor (CNTF), neurotrophin 4 (NT4), neurotrophin 3 (NT3), brain-derived neurotrophic factor (BDNF), proto-oncogene tyrosine-protein kinase receptor Ret (C-Ret), p75 neurotrophin receptors (p75 NTR), L-type voltage sensitive Ca2+ channel (LVSCC), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS), increased activity (↑), decreased activity(↓).