cholecalciferol and Parkinson-Disease

Vitamin D has long been synonymous with bone health. More recently, new health benefits are continually being associated with vitamin D, including a burgeoning field on neuroprotective properties. This has generated a huge explosion of interest in recent years in the potential for vitamin D to be used not only as a therapeutic in neurodegenerative disease, including Parkinson's disease, but also as biomarkers and for risk association. With an emphasis on Parkinson's disease, this chapter will discuss recent evidence supporting the assertion that vitamin D can be a useful therapeutic agent used as an intervention therapy to be combined with existing treatments; and the case for further development of novel treatments utilizing the potential of vitamin D. In addition, we present novel, previously unpublished evidence showing that in a unilateral model of Parkinson's disease, vitamin D can not only reduce the extent of denervation, but that this is also reflected in functional benefit to the animals. The potential of vitamin D is slowly being realized; in the future, it will be widely associated with far more than just bone health and may even contribute to an elusive treatment of neurodegenerative illness.

Topics: Animals; Cholecalciferol; Dopaminergic Neurons; Humans; Mesencephalon; Neuroprotective Agents; Parkinson Disease

Although initially thought to be important primarily in neural development, a number of trophic proteins have been found to have neuroprotective and neuroregenerative activity in the adult central nervous system, particularly for midbrain dopamine neurons (MDN). Neurorestoration is potentially feasible for MDN since there is an initial loss of phenotype for these neurons in Parkinson's disease (PD) rather than neuronal death. There is a considerable recent literature on trophic properties of TGF-β superfamily proteins for MDN's, including glial cell-derived neurotrophic factor (GDNF), neurturin, and bone morphogenetic proteins (BMPs). This paper will review studies with the factors listed above, as well as describe more recent studies with two newly described trophic proteins, MANF and CDNF. Data will be presented from various animal models of PD suggesting that these trophic proteins may eventually lead to PD therapeutics in man. In addition, some data on small molecules with neuroprotective properties (AP(4)A, retinoic acid and vitamin D(3)) will also be described.

Topics: Animals; Cholecalciferol; Dopaminergic Neurons; Humans; Mesencephalon; Nerve Growth Factors; Neuroprotective Agents; Parkinson Disease; Tretinoin

We evaluated the efficacy of muscle-targeted nutritional support on the functional outcomes of multidisciplinary intensive rehabilitation treatment (MIRT) in patients with Parkinson disease (PD) or parkinsonism.. We conducted a pragmatic, bicentric, randomized (1:1), assessor-blind controlled trial (Protein, Leucine and Vitamin D Enhancing Rehabilitation [PRO-LEADER]; April 2017 to January 2018) in cognitively intact patients with PD or parkinsonism and undergoing a 30-day MIRT. Patients (n = 150) received a standard hospital diet with or without a whey protein-based nutritional supplement enriched with leucine and vitamin D twice daily. The primary efficacy endpoint was the increase in the distance walked during a 6-minute walking test (6MWT). Secondary endpoints were changes in 4-meter walking speed, Timed Up and Go test (TUG), Berg balance scale, handgrip strength, Self-assessment Parkinson's Disease Disability Scale, body weight, and skeletal muscle mass (SMM).. Nutritional support resulted in greater increase in the distance walked during 6MWT (mean 69.6 meters [95% confidence interval (CI) 60.7-78.6]) than no support (51.8 meters [95% CI 37.0-66.7]): center-adjusted mean difference, 18.1 meters (95% CI 0.9-35.3) (. The consumption of a whey protein-based nutritional formula enriched with leucine and vitamin D with MIRT improved lower extremity function and preserved muscle mass in patients with PD or parkinsonism.Clinicaltrials.gov IDENTIFIER: NCT03124277.. This study provides Class I evidence that for patients with parkinsonism undergoing intensive rehabilitation, a whey protein-based nutritional formula enriched with leucine and vitamin D increased distance walked on the 6MWT.

Topics: Aged; Amino Acids, Essential; Body Weight; Cholecalciferol; Dietary Proteins; Dietary Supplements; Female; Food, Fortified; Humans; Leucine; Male; Middle Aged; Muscle, Skeletal; Nutritional Support; Parkinson Disease; Parkinsonian Disorders; Physical Functional Performance; Treatment Outcome; Vitamins; Walk Test; Walking Speed; Whey Proteins

In our previous study, higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and the vitamin D receptor (VDR) FokI CC genotype were associated with milder Parkinson disease (PD).. We evaluated whether vitamin D3 supplementation inhibits the progression of PD on the basis of patient VDR subgroups.. Patients with PD (n = 114) were randomly assigned to receive vitamin D3 supplements (n = 56; 1200 IU/d) or a placebo (n = 58) for 12 mo in a double-blind setting. Outcomes were clinical changes from baseline and the percentage of patients who showed no worsening of the modified Hoehn and Yahr (HY) stage and Unified Parkinson's Disease Rating Scale (UPDRS).. Compared with the placebo, vitamin D3 significantly prevented the deterioration of the HY stage in patients [difference between groups: P = 0.005; mean ± SD change within vitamin D3 group: +0.02 ± 0.62 (P = 0.79); change within placebo group: +0.33 ± 0.70 (P = 0.0006)]. Interaction analyses showed that VDR FokI genotypes modified the effect of vitamin D3 on changes in the HY stage (P-interaction = 0.045), UPDRS total (P-interaction = 0.039), and UPDRS part II (P-interaction = 0.021). Compared with the placebo, vitamin D3 significantly prevented deterioration of the HY stage in patients with FokI TT [difference between groups: P = 0.009; change within vitamin D3 group: -0.38 ± 0.48 (P = 0.91); change within placebo group, +0.63 ± 0.77 (P = 0.009)] and FokI CT [difference between groups: P = 0.020; change within vitamin D3 group: ±0.00 ± 0.60 (P = 0.78); change within placebo group: +0.37 ± 0.74 (P = 0.014)] but not FokI CC. Similar trends were observed in UPDRS total and part II.. Vitamin D3 supplementation may stabilize PD for a short period in patients with FokI TT or CT genotypes without triggering hypercalcemia, although this effect may be nonspecific for PD. This trial was registered at UMIN Clinical Trials Registry as UMIN000001841.

Topics: Aged; Blood Pressure; Body Mass Index; Calcium, Dietary; Cholecalciferol; Dietary Supplements; Disease Progression; Double-Blind Method; Endpoint Determination; Female; Follow-Up Studies; Genotype; Humans; Male; Middle Aged; Parathyroid Hormone; Parkinson Disease; Receptors, Calcitriol; Surveys and Questionnaires

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic cells in the substantia nigra pars compacta. PD patients' brains show neuroinflammation, oxidative stress, and mitochondrial dysfunction. The present study aims to evaluate the neuroprotective activity of VD3 on astrocytes after their exposure to rotenone (ROT) a natural pesticide known to exhibit neurotoxic potential via the inhibition of mitochondrial complex I. Cell viability parameters were evaluated by the MTT test and staining with 7-AAD in cultures of astrocytes treated and untreated with VD3 (0.1, 0.5, and 1.0 ng/mL) and/or ROT (10 µg/mL or 5 µg/mL), and the cytoplasmic production of ROS and the cell death profile were measured by flow cytometry. Glutathione accumulation and ultrastructural changes were evaluated and immunocytochemistry assays for NF-kB and Nrf2 were also carried out. The results showed that VD3 improved the viability of cells previously treated with VD3 and then exposed to ROT, reducing the occurrence of necrotic and apoptotic events. Furthermore, cells exposed to ROT showed increased production of ROS, which decreased significantly with previous treatment with VD3. Importantly, the decrease by ROT in the mitochondrial transmembrane potential was significantly prevented after treating cells with VD3, especially at a concentration of 1 ng/mL. Therefore, treatment with VD3 protected astrocytes from damage caused by ROT, decreasing oxidative stress, decreasing NF-kB and Nrf2 expressions, and improving mitochondrial function. However, further investigation is needed regarding the participation and mechanism of action of VD3 in this cellular model of PD focusing on the crosstalk between Nrf2 and NF-kB.

Topics: Astrocytes; Cholecalciferol; Dopaminergic Neurons; Humans; Neurodegenerative Diseases; Neuroprotective Agents; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Parkinson Disease; Reactive Oxygen Species; Rotenone

Topics: Cholecalciferol; Cross-Sectional Studies; Female; Humans; Parkinson Disease; Quality of Life; Sexual Dysfunction, Physiological; Testosterone

Topics: Cholecalciferol; Female; Humans; Male; Parkinson Disease; Vitamin D Deficiency

Topics: Cholecalciferol; Female; Humans; Male; Parkinson Disease; Vitamin D Deficiency

Topics: Cholecalciferol; Dietary Supplements; Female; Humans; Male; Parkinson Disease

To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D3, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD).. We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D3 and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study.. Plasma levels of 25-hydroxy-vitamin D3 were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D3 as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson's Disease Rating Scale scores at baseline and during follow-up.. Our study reveals an association between 25-hydroxy-vitamin D3 and PD and suggests that thousands of patients with PD in North America alone may be vitamin D-deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association.

Topics: Aged; Biomarkers; Case-Control Studies; Cholecalciferol; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Middle Aged; Parkinson Disease; Prevalence; Severity of Illness Index; Vitamin D Deficiency

Previous reports have demonstrated that exogeneous administration of glial cell line-derived neurotrophic factor (GDNF) reduces ventral mesencephalic (VM) dopaminergic (DA) neuron damage induced by 6-hydroxydopamine (6-OHDA) lesioning in rats. Recent studies have shown that 1,25-dihydroxyvitamin D(3) (D3) enhances endogenous GDNF expression in vitro and in vivo. The purpose of present study was to investigate if administration of D3 in vivo and in vitro would protect against 6-OHDA-induced DA neuron injury. Adult male Sprague-Dawley rats were injected daily with D3 or with saline for 8 days and then lesioned unilaterally with 6-OHDA into the medial forebrain bundle. Locomotor activity was measured using automated activity chambers. We found that unilateral 6-OHDA lesioning reduced locomotor activity in saline-pretreated animals. Pretreatment with D3 for 8 days significantly restored locomotor activity in the lesioned animals. All animals were sacrificed for neurochemical analysis 6 weeks after lesioning. We found that 6-OHDA administration significantly reduced dopamine (DA), 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanilic acid (HVA) levels in the substantia nigra (SN) on the lesioned side in the saline-treated rats. D3 pretreatment protected against 6-OHDA-mediated depletion of DA and its metabolites in SN. Using primary cultures obtained from the VM of rat embryos, we found that 6-OHDA or H(2)O(2) alone caused significant cell death. Pretreatment with D3 (10(-10) M) protected VM neurons against 6-OHDA- or H(2)O(2)-induced cell death in vitro. Taken together, our data indicate that D3 pretreatment attenuates the hypokinesia and DA neuronal toxicity induced by 6-OHDA. Since both H(2)O(2) and 6-OHDA may injure cells via free radical and reactive oxygen species, the neuroprotection seen here may operate via a reversal of such a toxic mechanism.

Topics: Animals; Cells, Cultured; Cholecalciferol; Dopamine; Drug Interactions; Glial Cell Line-Derived Neurotrophic Factor; Immunohistochemistry; Male; Mesencephalon; Motor Activity; Nerve Degeneration; Nerve Growth Factors; Nerve Tissue Proteins; Neurons; Neuroprotective Agents; Neurotoxins; Oxidopamine; Parkinson Disease; Rats; Rats, Sprague-Dawley; Substantia Nigra; Sympatholytics; Tyrosine 3-Monooxygenase; Ventral Tegmental Area