Vitamin D and Parkinson's disease--a hypothesis.
Newmark Harold L,Newmark Jonathan
Movement disorders : official journal of the Movement Disorder Society
Parkinson's disease (PD), a common disease of the elderly, is a movement disorder characterized by tremor, akinesia, and loss of postural reflexes, leading to immobility and frequent falls. It results from selective loss (death) of dopaminergic neurons in the substantia nigra region of the brain, largely developed prior to clinical diagnosis, and continuous after diagnosis, despite use of current therapeutic modalities. In PD in the United States the cause and mechanism of continued neuron cell death in the substantia nigra is currently unknown. We hypothesize, based upon several lines of evidence, that documented chronically inadequate vitamin D intake in the United States, particularly in the northern states and particularly in the elderly, is a significant factor in the pathogenesis of PD. This hypothesis implies that dietary aid for prevention and therapy for PD is possible.
Lack of association of dairy food, calcium, and vitamin D intake with the risk of Parkinson's disease: a case-control study in Japan.
Miyake Y,Tanaka K,Fukushima W,Sasaki S,Kiyohara C,Tsuboi Y,Yamada T,Oeda T,Miki T,Kawamura N,Sakae N,Fukuyama H,Hirota Y,Nagai M,
Parkinsonism & related disorders
Three previous cohort studies in the USA reported that dairy product consumption was significantly associated with an increased risk of Parkinson's disease (PD) in men, but not in women. We examined the relationship between consumption of dairy products, calcium, and vitamin D and the risk of PD using data from a multicenter hospital-based case-control study in Japan. Included were 249 cases within 6 years of onset of PD based on the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, and dietary factors including cholesterol, dietary glycemic index, vitamin E, β-carotene, vitamin B(6), caffeine, iron, and alcohol. Total dairy product consumption was not materially associated with the risk of PD (P for trend = 0.62). No evident relationships were observed between intake of milk, yogurt, cheese, or ice cream and the risk of PD (P for trend = 0.75, 0.63, 0.59, and 0.35, respectively). There were no measurable associations between consumption of calcium or vitamin D and PD (P for trend = 0.37 and 0.69, respectively). No significant interactions were observed between the dietary exposures and sex regarding PD. Our results suggest that intake of dairy products, calcium, and vitamin D was not related to PD, regardless of sex. However, such null relationships might be a consequence of PD.
Role of vitamin d in Parkinson's disease.
L Ng Khanh,Nguyễn Lan
Parkinson's disease (PD) is the second most common form of neurodegeneration in the elderly population. Clinically, it is characterized by tremor, rigidity, slowness of movement, and postural imbalance. A significant association between low serum vitamin D and PD has been demonstrated, suggesting that elevated vitamin D levels might provide protection against PD. Genetic studies have helped identify a number of proteins linking vitamin D to PD pathology, including the major histocompatibility complex (MHC) class II, the vitamin D receptor (VDR), cytochrome P450 2D6 (CYP2D6), chromosome 22, the renin-angiotensin system (RAS), heme oxygenase-1 (HO-1), poly(ADP-ribose) polymerase-1 gene (PARP-1), neurotrophic factor (NTF), and Sp1 transcription factor. Vitamin D has also been implicated in PD through its effects on L-type voltage-sensitive calcium channels (L-VSCC), nerve growth factor (NGF), matrix metalloproteinases (MMPs), prostaglandins (PGs) and cyclooxygenase-2 (COX-2), reactive oxygen species (ROS), and nitric oxide synthase (NOS). A growing body of evidence suggests that vitamin D supplementation may be beneficial for PD patients. Among the different forms of vitamin D, calcitriol (1,25-dihydroxyvitamin D(3)) is best indicated for PD, because it is a highly active vitamin D(3) metabolite with an appropriate receptor in the central nervous system (CNS).
25-hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson's disease.
Suzuki Masahiko,Yoshioka Masayuki,Hashimoto Masaya,Murakami Maiko,Kawasaki Keiichi,Noya Miki,Takahashi Daisuke,Urashima Mitsuyoshi
Movement disorders : official journal of the Movement Disorder Society
We aimed to examine associations among serum 25-hydroxyvitamin D levels, 1,25-dihyroxyvitamin D levels, vitamin D receptor polymorphisms, vitamin D binding protein gene polymorphisms, and the severity of Parkinson's disease. In 137 patients, the severity of Parkinson's disease was evaluated using Hoehn & Yahr stage and Unified Parkinson's Disease Rating Stage by neurologists and compared with 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, vitamin D receptor polymorphisms, ie, FokI (rs10735810), BsmI (rs1544410), Cdx2 (rs11568820), ApaI (rs7976091), and TaqI (rs731236), and vitamin D binding protein gene polymorphisms GC1 (rs7041)/GC2 (rs4588) in a cross-sectional study. Mean ± standard deviation levels of 25-hydroxyvitamin D were 21.1 ± 9.0 ng/mL. Levels were deficient (<20 ng/mL) in 49% of patients. In contrast, 1,25-hydroxyvitamin D levels were considered normal in all patients. Higher circulating 25-hydroxyvitamin D levels were significantly associated with milder Parkinson's disease evaluated by Hoehn & Yahr stage (P = .002) and total Unified Parkinson's Disease Rating Stage (P = .004) even after multivariate adjustment for 8 covariates, including disease duration. However, significant associations were not observed in 1,25-hydroxyvitamin D levels. Under multivariate analysis with 25-hydroxyvitamin D as well as other 8 covariates including disease duration, carriers of vitamin D receptor FokICC genotype had a milder form of Parkinson's disease: odds ratio, 0.32; 95% confidence interval, 0.16 to 0.66, P = 0.002. These results suggest that higher 25-hydroxyvitamin D levels and the vitamin D receptor FokICC genotype may be independently associated with milder forms of Parkinson's disease. However, significant associations were not observed in 1,25-hydroxyvitamin D levels.
Vitamin D receptor gene polymorphism and its association with Parkinson's disease in Chinese Han population.
Han Xun,Xue Li,Li Yongsheng,Chen Biao,Xie Anmu
Vitamin D plays an important role in neurodegenerative disorders as a crucial neuro-immunomodulator, and accumulating data have provided evidence for that vitamin D receptor (VDR) gene is a candidate gene for susceptibility to Parkinson's disease (PD). In this study, we performed a case-control study to demonstrate whether the risk for the development of onset of sporadic PD might be influenced by VDR gene polymorphisms in a Chinese cohort. Two hundred and sixty PD patients and 282 matched-healthy controls were genotyped for two representative single nucleotide polymorphisms (SNPs) in VDR gene (FokI C/T and BsmI G/A) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis in. Results from our study revealed that FokI C allele carriers were likely to associate with an increased risk of PD (P=0.004) as well as early-onset PD (EOPD) (P=0.010). Moreover, the frequency of FokI C allele was significantly increased in PD group and late-onset PD (LOPD) group relative to the control groups respectively (P=0.023 and P=0.033, respectively). For BsmI polymorphisms, no significant difference in genotype or allele distribution was found between PD patients and the controls, as well as gender- and age-related differences between PD patients and the controls subgroup. This study demonstrated a possible association between the VDR FokI T/C polymorphism and PD, indicating that VDR polymorphisms may well change genetic susceptibility to sporadic PD in a Han Chinese population.
Vitamin D and Parkinson's disease.
Vinh Quôc Luong Khanh,Thi Hoàng Nguyên Lan
Journal of neuroscience research
Parkinson's disease (PD) is the second most common form of neurodegeneration among the elderly population. PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance. Interestingly, a significant association has been demonstrated between PD and low levels of vitamin D in the serum, and vitamin D supplement appears to have a beneficial clinical effect on PD. Genetic studies have provided the opportunity to determine which proteins link vitamin D to PD pathology, e.g., Nurr1 gene, toll-like receptor, gene related to lipid disorders, vascular endothelial factor, tyrosine hydroxylase, and angiogenin. Vitamin D also exerts its effects on cancer through nongenomic factors, e.g., bacillus Calmette-Guerin vaccination, interleukin-10, Wntβ-catenin signaling pathways, mitogen-activated protein kinase pathways, and the reduced form of the nicotinamide adenine dinucleotide phosphate. In conclusion, vitamin D might have a beneficial role in PD. Calcitriol is best used for PD because it is the active form of the vitamin D(3) metabolite and modulates inflammatory cytokine expression. Further investigation with calcitriol in PD is needed.
Memory, mood, and vitamin D in persons with Parkinson's disease.
Peterson Amie L,Murchison Charles,Zabetian Cyrus,Leverenz James B,Watson G Stennis,Montine Thomas,Carney Natasha,Bowman Gene L,Edwards Karen,Quinn Joseph F
Journal of Parkinson's disease
BACKGROUND:Research in recent years has suggested a role of vitamin D in the central nervous system. The final converting enzyme and the vitamin D receptor are found throughout the human brain. From animal studies vitamin D appears important in neurodevelopment, up-regulation of neurotrophic factors, stabilization of mitochondrial function, and antioxidation. OBJECTIVE:To examine the relationship between serum vitamin D and neuropsychiatric function in persons with Parkinson's disease (PD). METHODS:This is an add-on study to a longitudinal study following neuropsychiatric function in persons with PD. Baseline neuropsychiatric performance and serum 25-hydroxyvitamin D were examined for 286 participants with PD. Measures of global cognitive function (MMSE, MOCA, Mattis Dementia Scale), verbal memory (Hopkins Verbal Learning Test), fluency (animals, vegetables, and FAS words), visuospatial function (Benton Line Orientation), executive function (Trails Making Test and Digit-Symbol Substitution), PD severity (Hoehn & Yahr and Unified Parkinson's Disease Rating Scale) and depression (Geriatric Depression Scale (GDS)) were administered. Multivariate linear regression assessed the association between vitamin D concentration and neuropsychiatric function, in the entire cohort as well as the non-demented and demented subsets. RESULTS:Using a multivariate model, higher vitamin D concentrations were associated with better performance on numerous neuropsychiatric tests in the non-demented subset of the cohort. Significant associations were specifically found between vitamin D concentration and verbal fluency and verbal memory (t = 4.31, p < 0.001 and t = 3.04, p = 0.0083). Vitamin D concentrations also correlated with depression scores (t = -3.08, p = 0.0083) in the non-demented subset. CONCLUSIONS:Higher plasma vitamin D is associated with better cognition and better mood in this sample of PD patients without dementia. Determination of causation will require a vitamin D intervention study.
Vitamin D reduces falls and hip fractures in vascular Parkinsonism but not in Parkinson's disease.
Sato Yoshihiro,Iwamoto Jun,Honda Yoshiaki,Amano Nobuko
Therapeutics and clinical risk management
PURPOSE:Vitamin D supplementation is suggested to reduce the risk of falls in older institutionalized or ambulatory individuals by 20%. The present study was undertaken to address the reduced risk, by vitamin D supplementation, of falls and hip fractures in patients with vascular Parkinsonism (VP) and Parkinson's disease (PD). PATIENTS AND METHODS:In the open-label-study, 94 elderly patients with VP and 92 age-matched patients with PD were followed for 2 years. All patients received 1200 IU ergocalciferol daily. The number of falls per person and incidence of hip fractures were compared between the two groups. RESULTS:At baseline, serum 25-hydroxyvitamin D (25-OHD) levels were in the deficient range (<25 nmol/L) in all patients, and vitamin D treatment enhanced serum 25-OHD and 1,25-dihydroxyvitamin D levels in both groups. Improved muscle strength of lower extremities was observed in both groups. There was significant difference between the two groups in the number of falls per subject during the 2 years (1.9 ± 0.5 in the PD group and 0.8 ± 0.4 in the VP group, P < 0.001). Hip fractures occurred in seven of 88 in the PD group and one in 90 of the VP group during the 2-year study period (P = 0.035). CONCLUSION:It is suggested that vitamin D decreases falls and hip fractures in VP by increasing muscle strength but not in PD.
Bone mineral density and vitamin D status in Parkinson's disease patients.
van den Bos F,Speelman A D,van Nimwegen M,van der Schouw Y T,Backx F J G,Bloem B R,Munneke M,Verhaar H J J
Journal of neurology
Bone loss is more common in Parkinson's disease (PD) than in the general population. Several factors may be involved in the development of bone loss, including malnutrition, immobilization, low body mass index, decreased muscle strength, vitamin D deficiency and medication use. This study investigates the prevalence of osteoporosis and possible risk factors associated with bone loss in early stage PD. In 186 PD patients (Hoehn and Yahr stage 1-2.5, mean age 64.1 years, 71 % men) bone mineral density (BMD) measurements were performed with DEXA. T- and Z-scores were calculated. Univariate linear regression analysis was performed to identify variables that contributed to BMD. 25-OH-vitamin D status of PD patients was compared with 802 controls (mean age 63.3 years, 50 % men) using linear regression analysis. Osteoporosis (11.8 %) and osteopenia (41.4 %) were common in PD patients. Mean Z-score for the hip was 0.24 (SD 0.93), and for the lumbar spine 0.72 (SD 1.91). Female gender, low weight, and low 25-OH-vitamin D were significantly correlated with BMD of the hip and lumbar spine. PD patients had lower 25(OH)D serum levels than controls (B = -10, p = 0.000). More than half of the patients with early stage PD had an abnormal BMD. Female gender, low weight, and low vitamin D concentration were associated with bone loss. Furthermore, vitamin D concentrations were reduced in PD patients. These results underscore the importance of proactive screening for bone loss and vitamin D deficiency, even in early stages of PD.
The relationship between balance control and vitamin D in Parkinson's disease-a pilot study.
Peterson Amie L,Mancini Martina,Horak Fay B
Movement disorders : official journal of the Movement Disorder Society
BACKGROUND:Balance problems and falls are a major source of morbidity and mortality in patients with Parkinson's disease. Vitamin D supplementation reduces falls and sway in neurologically intact elderly fallers, but effects in Parkinson's disease are not established. METHODS:To study this relationship and select outcome measures for a vitamin D intervention study, balance function and vitamin D concentration were quantified in a series of Parkinson's patients in a cross-sectional, observational study. Participants underwent a battery of 5 balance tests. RESULTS:Serum vitamin D concentrations were correlated inversely with Parkinson's severity, as measured by the motor Unified Parkinson's Disease Rating Scale. Among the balance measures, vitamin D concentrations were correlated with automatic posture responses to backwards translation, specifically with response strength and stance weight asymmetry. CONCLUSIONS:These findings support the hypothesis that vitamin D plays a role in balance among patients with Parkinson's disease and identify specific outcome measures for detecting effects of vitamin D upon balance.
Association of vitamin D receptor gene polymorphisms and Parkinson's disease in Hungarians.
Török Rita,Török Nora,Szalardy Levente,Plangar Imola,Szolnoki Zoltan,Somogyvari Ferenc,Vecsei Laszlo,Klivenyi Peter
Vitamin D receptor (VDR) gene encodes a transcription factor that influences calcium homeostasis and immunoregulation, and may play a role in neurological disorders including Parkinson's disease (PD). The investigations of the association between VDR and PD in different populations revealed various results. In a present study 100 PD patients and 109 healthy controls from the Hungarian population were genotyped for four polymorphic sites (BsmI, ApaI, FokI and TaqI) in the VDR gene. The polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Our results demonstrate an association between the FokI C allele and PD; the frequency of the C allele was significantly higher in PD patients than in controls, suggesting that this polymorphism may have a role in the development of PD in these patients.
Vitamin D: preventive and therapeutic potential in Parkinson's disease.
Liu Yan,Li Yan-Wu,Tang Ya-Lan,Liu Xin,Jiang Jun-Hao,Li Qing-Gen,Yuan Jian-Yong
Current drug metabolism
Vitamin D is one of the important nuclear steroid transcription regulators that controls transcriptions of a large number of genes. Vitamin D supplement is commonly recommended for the elderly to prevent bone diseases. Amounting new evidence has indicated that vitamin D plays a crucial role in brain development, brain function regulation and neuroprotection. Parkinson's disease (PD) is a degenerative disorder commonly seen in the elderly, characterized by movement disorders including tremor, akinesia, and loss of postural reflexes. The motor symptoms largely result from the continued death of dopaminergic neurons in the substantia nigra, despite use of current therapeutic interventions. The cause and mechanism of neuron death is currently unknown. Vitamin D deficiency is common in patients with PD suggesting its preventive and therapeutic potential. Vitamin D may exert protective and neurotropic effects directly at cellular level, e.g. protection of dopamine system, and/or by regulating gene expression. This review summarizes the epidemiological, genetic and translational evidence implicating vitamin D as a candidate for prevention and treatment for PD.
The role of vitamin D levels and vitamin D receptor polymorphism on Parkinson's disease in the Faroe Islands.
Petersen Maria Skaalum,Bech Sára,Christiansen Debes Hammershaimb,Schmedes Anna Vibeke,Halling Jónrit
The role of vitamin D in Parkinson's disease (PD) has been proposed and both low serum 25-hydroxyvitamin D levels (25(OH)D) and vitamin D receptor polymorphisms (VDR) have been linked to PD. The aim of this study is to investigate the associations among 25(OH)D and three VDR polymorphisms and PD in the Faroese population where the prevalence of PD is high. We conducted a case-control study where 121 cases were studied for 25(OH)D levels and VDR polymorphisms against 235 randomly selected controls, matched by gender and age. No significant difference was observed in 25(OH)D levels between PD cases and controls (P=0.49), although cases had slightly lower values than controls. As well, no differences were found in genotype frequencies between cases and controls in the VDR polymorphisms studied (ApaI, BsmI, TaqI) (P=0.70, P=0.56 and P=0.54, respectively). However, we found that VDR ApaI/AC genotype was significantly associated with 25(OH)D levels (P=0.01). Although our results indicate no association between PD and vitamin D polymorphisms and/or 25(OH)D levels, the study cannot exclude a weak association. However, the known doubling in PD prevalence in the Faroe Islands cannot be explained by the polymorphisms examined in the VDR gene or the 25(OH)D levels and has to be explored further.
Vitamin D receptor genetic variants and Parkinson's disease in a Taiwanese population.
Lin Chin-Hsien,Chen Kai-Hsiang,Chen Meng-Ling,Lin Han-I,Wu Ruey-Meei
Neurobiology of aging
Patients with Parkinson's disease (PD) have hypovitaminosis D status and genetic variants of vitamin D receptor (VDR) gene are recently shown to be associated with PD in a large-scale genome-wide association study in a Caucasian population. Few studies examined VDR genetic variants in large-scale Asian patients with PD. We therefore genotyped 6 VDR genetic variants in a total of 1492 Taiwanese subjects, including 700 patients with PD and 792 age and/or gender matched control subjects. We did not observe any significant associations between the studied genetic variants of VDR and the risk of PD. Our data suggest that genetic variations of the VDR gene did not play a major role in a Taiwanese PD population. Further studies of VDR and its interaction with serum vitamin D levels are warranted to clarify the potential role of vitamin D in PD pathogenesis.
A review of vitamin D and Parkinson's disease.
Peterson Amie L
The role of vitamin D in bone health has been known for over a century. More recent research has suggested that vitamin D may play a role in the muscular, immune, endocrine, and central nervous systems. Animal research suggests that vitamin D may have some protective effects against toxic insults that are known to damage dopamine cells, the primary cells to degenerate in PD. Persons with PD tend to have lower vitamin D levels than persons of similar ages without PD. Vitamin D levels are generally associated with bone mineral density (BMD) in persons with PD, but simply giving vitamin D does not appear to improve BMD. Results of genetic studies examining polymorphism of the vitamin D receptor and PD risk, severity, or age at onset have shown variable results, with FokI CC seeming to possibly carry some increased risk of PD. Amount of sun exposure and vitamin D levels in earlier life may influence the risk of developing PD. Cross-sectional research suggests a relationship between vitamin D levels and severity of PD symptoms. A single intervention study did show some improvement in PD with vitamin D supplementation. Vitamin D may have effects on PD symptoms and perhaps even on the risk of disease development or disease progression. More well designed intervention studies are needed to confirm the effect of vitamin D on PD symptoms. Human neuroprotection studies are needed, but probably not feasible until better biomarkers are established.
Association between vitamin D receptor gene polymorphisms and susceptibility to Parkinson's disease: a meta-analysis.
Zhang Zi-Teng,He Yi-Chuan,Ma Xiu-Juan,Li Dian-You,Lu Guo-Cai
Previous studies have reported an association between vitamin D receptor (VDR) gene polymorphisms and Parkinson's disease (PD), but the results were controversial. To explore whether VDR gene polymorphisms have an effect on PD risk, we performed this meta-analysis to evaluate the association between three VDR gene polymorphisms (Bsml, Apal, Taql) and PD susceptibility. We performed a systematic literature search for articles published up to February 2014 in multiple databases and selected seven eligible studies. Four studies were included for each polymorphism. Odds ratios (ORs) as well as their corresponding 95% confidence intervals (CIs) were used to estimate the association between VDR gene polymorphisms and PD risk in four phenotype models. Subgroup analysis and publication bias were also performed. Heterogeneity analysis and sensitivity analysis were performed if necessary. We failed to detect any association between Apal, Bsml, Taql polymorphisms and PD susceptibility in all four genetic models. In subgroup analysis grouped by ethnicity, no significant association was detected. The present meta-analysis indicates that the VDR genetic polymorphisms Bsml, Apal and Taql are not associated with susceptibility to PD. Because of the limited number of included studies, the results should be cautiously interpreted. More carefully designed studies are needed to verify our results.
Inverse associations of outdoor activity and vitamin D intake with the risk of Parkinson's disease.
Zhu Dan,Liu Gui-you,Lv Zheng,Wen Shi-rong,Bi Sheng,Wang Wei-zhi
Journal of Zhejiang University. Science. B
Early studies had suggested that vitamin D intake was inversely associated with neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis. However, the associations of vitamin D intake and outdoor activities with Parkinson's disease (PD) are still unclear, so this study is to evaluate these relationships from a case-control study in elderly Chinese. The study population involved 209 cases with new onsets of PD and 210 controls without neurodegenerative diseases. The data on dietary vitamin D and outdoor activities were collected using a food-frequency questionnaire and self-report questionnaire. Multivariable logistic regressions were used to examine the associations between dietary outdoor activities, vitamin D intake and PD. Adjustment was made for sex, age, smoking, alcohol use, education, and body mass index (BMI). Adjusted odds ratios (ORs) for PD in quartiles for outdoor physical activity were 1 (reference), 0.739 (0.413, 1.321), 0.501 (0.282, 0.891), and 0.437 (0.241, 0.795), respectively (P=0.002 for trend). Adjusted ORs for PD in quartiles for total vitamin D intake were 1 (reference), 0.647 (0.357, 1.170), 0.571 (0.318, 1.022), and 0.538 (0.301, 0.960), respectively (P=0.011 for trend). Our study suggested that outdoor activity and total vitamin D intake were inversely associated with PD, and outdoor activity seems to be more significantly associated with decreased risk for PD.
Vitamin D status and Parkinson's disease: a systematic review and meta-analysis.
Lv Zheng,Qi Huiping,Wang Le,Fan Xiaoxue,Han Fei,Wang Hong,Bi Sheng
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
To estimate the associations between vitamin D status and Parkinson's disease (PD). We searched electronic databases of the human literature in PubMed, EMBASE and the Cochrane Library up to February, 2014 using the following keywords: 'vitamin D' or '25(OH)D' and 'status' or 'deficiency' or 'insufficiency' and 'Parkinson's disease'. A systematic review and meta-analysis were conducted on observational studies that reported the association between blood vitamin D levels and PD. Seven studies met the inclusion criteria. 1,008 patients and 4,536 controls were included. Results of our meta-analysis show that PD patients had lower mean levels of 25-hydroxyvitamin D [25(OH)D] than healthy controls [weighted mean difference (MD), -16.9, 95 % confidence interval (CI)], -33.5 to -0.2). Patients with vitamin D insufficiency [25(OH)D level <75 nmol/l] had an increased risk of PD (OR 1.5, 95 % CI 1.1-2.0). Patients with vitamin D deficiency [25(OH)D level <50 nmol/l] experienced a twofold increased risk of PD (OR 2.2, 95 % CI 1.5-3.4). Low vitamin D levels are associated with an increased risk of PD.
Vitamin D receptor polymorphisms and susceptibility to Parkinson's disease and Alzheimer's disease: a meta-analysis.
Lee Young Ho,Kim Jae-Hoon,Song Gwan Gyu
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
The goal of this study was to examine whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to Parkinson's disease (PD) and Alzheimer's disease (AD). A meta-analysis was performed to investigate the association between VDR FokI, BsmI, TaqI, ApaI, rs4334089, or rs11568820 polymorphism and susceptibility to PD or AD. Thirteen studies, including seven on PD and six on AD, were included in this meta-analysis. The meta-analysis revealed an association between the BB + Bb genotype and PD in the Asian population (OR 0.478, 95 % CI 0.259-0.884, p = 0.018). We also observed a significant association between PD and the FokI F allele (OR 1.413, 95 % CI 1.144-1.746, p = 0.001). Meta-analysis of the A allele, the AA vs. Aa + aa, and the AA vs. aa for the ApaI polymorphism revealed significant associations with AD (OR 0.729, 95 % CI 0.0.591-0.900, p = 0.034; OR 0.591, 95 % CI 0.431-0.810, p = 0.001; OR 0.580, 95 % CI 0.361-0.931, p = 0.024, respectively). This meta-analysis demonstrates that the VDR BsmI polymorphism is associated with PD susceptibility in Asians, and the FokI polymorphism is associated with PD. Furthermore, we identified associations between the VDR TaqI and ApaI polymorphisms and AD susceptibility.
Vitamin D receptor gene polymorphisms and the risk of Parkinson's disease.
Li Chunlei,Qi Huiping,Wei Shuqin,Wang Le,Fan Xiaoxue,Duan Shurong,Bi Sheng
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
The effect of vitamin D receptor (VDR) gene polymorphisms on Parkinson's disease (PD) has recently gained interest. However, evidence on this relationship is controversial. We searched PubMed, EMBASE and the Cochrane Library database targeted all studies that evaluated VDR gene polymorphisms and PD up to April 2,014. A meta-analysis was conducted on the association between VDR ApaI, BsmI, TaqI and FokI polymorphisms and PD using (1) allelic contrast, (2) dominant, (3) recessive, and (4) additive models. A total of five relevant studies involving PD patients (n = 1,266) and controls (n = 1,649) were included in the analysis. There was a significant association between FokI polymorphism and PD. In the pooled allelic analysis, the F allele was associated with increased risk of PD (OR 1.41, 95% CI 1.14-1.75). In the genotype analysis, FF + Ff versus ff showed a significant association with PD in the dominant model (OR 2.32, 95% CI 1.49-3.61, P = 0.0002). FF versus ff showed a significant association with PD in the additive model (OR 2.45, 95% CI 1.52-3.93, P = 0.0002). There was also a statistically significant association between VDR BsmI polymorphisms in the recessive model, BB versus Bb + bb showed a significant increased risk of PD (OR 1.37, 95% CI 1.01-1.87, P = 0.04). No significant associations were observed between VDR ApaI and TaqI polymorphisms and PD. To sum up, VDR BsmI and FokI polymorphisms were associated with increased risk of PD.
Vitamin D receptor gene polymorphisms and Parkinson's disease in a population with high ultraviolet radiation exposure.
Gatto Nicole M,Sinsheimer Janet S,Cockburn Myles,Escobedo Loraine A,Bordelon Yvette,Ritz Beate
Journal of the neurological sciences
INTRODUCTION:A high prevalence of vitamin D deficiency has been reported in Parkinson's disease (PD). Epidemiologic studies examining variability in genes involved in vitamin D metabolism have not taken into account level of exposure to ultraviolet radiation (UVR). We examined whether exposure to UVR (as a surrogate for vitamin D levels) and variations in the vitamin D receptor gene (VDR) are associated with PD. METHODS:Within a geographical information system (GIS) we linked participants' geocoded residential address data to ground level UV data to estimate historical exposure to UVR. Six SNPs in VDR were genotyped in non-Hispanic Caucasian subjects. RESULTS:Average lifetime UVR exposure levels were >5000 Wh/m(2), which was higher than levels for populations in previous studies, and UVR exposure did not differ between cases and controls. Homozygotes for the rs731236 TT (major allele) genotype had a 31% lower risk of PD risk (OR=0.69; 95% CI=0.49, 0.98; p=0.04 for TT vs. TC+CC). The rs7975232 GG (minor allele) genotype was also associated with decreased risk of PD (OR=0.63; 95% CI=0.42, 0.93; p=0.02 for GG vs. TG+TT). The association between PD risk and a third locus, rs1544410 (BsmI), was not statistically significant after adjustment for covariates, although there was a trend for lower risk with the GG genotype. CONCLUSIONS:This study provides initial evidence that VDR polymorphisms may modulate risk of PD in a population highly exposed to UVR throughout lifetime.
Associations between Vitamin D Status, Supplementation, Outdoor Work and Risk of Parkinson's Disease: A Meta-Analysis Assessment.
Shen Liang,Ji Hong-Fang
The present study aimed to quantitatively assess the associations between vitamin D and Parkinson's Disease (PD) risks, which include: (i) risk of PD in subjects with deficient and insufficient vitamin D levels; (ii) association between vitamin D supplementation and risk of PD; and (iii) association between outdoor work and PD risk, through meta-analyzing available data. An electronic literature search supplemented by hand searching up to March 2015 identified seven eligible studies comprising 5690 PD patients and 21251 matched controls. Odds ratio (OR) and 95% confidence interval (CI) of PD risk were assessed through pooling the collected data from eligible studies using Stata software. Pooled data showed that subjects with deficient and insufficient vitamin D levels had increased PD risks compared with matched-controls according to the corresponding OR: 2.08, 95% CI: 1.63 to 2.65, and 1.29, 95% CI: 1.10 to 1.51. Vitamin D supplementation was associated with significantly reduced risk of PD (OR: 0.62, 95% CI: 0.35 to 0.90). Outdoor work was also related to reduced risk of PD (OR: 0.72, 95% CI: 0.63 to 0.81). The findings may stimulate larger, well-designed studies to further verify the associations between vitamin D and PD risk.
ApaI, BsmI, FokI, and TaqI Polymorphisms in the Vitamin D Receptor Gene and Parkinson's Disease.
Niu Meng-Yue,Wang Lei,Xie An-Mu
Chinese medical journal
BACKGROUND:The vitamin D receptor (VDR) gene has been identified as a candidate gene for susceptibility to Parkinson's disease (PD), but results from genetic association studies to date are inconsistent. Here, we conducted a meta-analysis of published case-control studies to evaluate the association of the extensively studied VDR ApaI (G/T), BsmI (G/A), FokI (C/T), and TaqI (T/C) gene polymorphisms with risk of PD. METHODS:Electronic search at PubMed, EMBASE, EBSCO, China National Knowledge Infrastructure, Weipu database, and Wanfang database was conducted to identify all relevant studies. Odds ratio (OR) with 95% confidence interval (CI) values was applied to evaluate the strength of the association. RESULTS:A total of seven studies with 2034 PD cases and 2432 controls were included in the meta-analysis following the inclusion and exclusion criteria. Overall, no significant association between ApaI, BsmI, and TaqI gene polymorphisms and PD susceptibility in all four genetic models was found (T vs. G: OR = 1.00, 95% CI: 0.89-1.12, P = 0.97; A vs. G: OR = 0.94, 95% CI: 0.77-1.15, P = 0.53; C vs. T: OR = 1.03, 95% CI: 0.85-1.25, P = 0.77) while a significant association between FokI (C/T) and PD risk was observed (C vs. T: OR = 1.41, 95% CI: 1.14-1.75, P = 0.001; CC vs. TT: OR = 2.45, 95% CI: 1.52-3.93, P = 0.0002; CT vs. TT: OR = 2.21, 95% CI: 1.38-3.52, P = 0.0009, CC vs. CT+TT: OR = 2.32, 95% CI: 1.49-3.61, P = 0.0002). CONCLUSIONS:Polymorphisms of ApaI, BsmI, and TaqI may not be associated with the susceptibility to PD while the FokI (C/T) polymorphism is possibly associated with increased PD risk. However, conclusions should be cautiously interpreted due to the relatively small number of studies included.
Vitamin D deficiency in Parkinson's disease patients with orthostatic hypotension.
Jang W,Park J,Kim J S,Youn J,Oh E,Kwon K Y,Jo K D,Lee M K,Kim H-T
Acta neurologica Scandinavica
OBJECTIVES:The purpose of our study was to investigate the associations between serum vitamin D3 levels and orthostatic hypotension (OH) in patients with Parkinson's disease (PD). MATERIALS AND METHODS:Fifty-five patients with PD were enrolled in this study. Blood pressure (BP) measurements were gathered while the patients were in the supine position and while standing up. Then, the patients were divided into two groups: PD patients with and without OH. We compared the levels of serum 25-hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 (calcitriol) between the two groups. RESULTS:Serum 25-hydroxyvitamin D and calcitriol levels were significantly decreased in patients with OH compared with those without OH. The systolic and diastolic BPs and symptom severities significantly negatively correlated with the serum 25-hydroxyvitamin D and calcitriol levels. CONCLUSIONS:Although the underlying mechanism for this association is not fully understood, our results suggest that low vitamin D status is associated with OH in patients with PD.
Vitamin D deficiency and its relationship with endothelial dysfunction in patients with early Parkinson's disease.
Yoon Jung Han,Park Dong Kyu,Yong Seok Woo,Hong Ji Man
Journal of neural transmission (Vienna, Austria : 1996)
Increasing evidence has shown that individuals with Parkinson's disease (PD) have lower levels of 25-hydroxyvitamin D (25[OH]D) than healthy controls. Low vitamin D has been associated with endothelial dysfunction which may play a role in the pathogenesis and progression of PD. Flow-mediated dilation (FMD) is widely used as a clinical marker of overall endothelial function. We evaluated the relationship between serum 25(OH)D levels and FMD in PD. We enrolled 81 patients with early PD and 52 healthy controls, and we evaluate endothelial function based on vitamin D status and identify the association between FMD and vitamin D status in patients with early PD. The mean serum 25(OH)D levels were significantly lower in the PD patients than in the controls (21.8 ± 9.5 vs. 25.2 ± 9.3 ng/mL, p < 0.05). FMD was significantly lower in the PD patients (7.1 ± 1.8 %) than in the controls (8.1 ± 2.1 %, p < 0.05). The serum 25(OH)D was significantly associated with FMD independently of age, cardiovascular disease risk factors, body mass index, motor Unified PD Rating Scale status and homocysteine levels (adjusted R (2) = 0.331, β = 0.494, p < 0.001). These findings provide evidence of a possible association between endothelial dysfunction as assessed by FMD and low vitamin D status in patients with early PD.
Systematic Review of the Relationship between Vitamin D and Parkinson's Disease.
Rimmelzwaan Lisanne M,van Schoor Natasja M,Lips Paul,Berendse Henk W,Eekhoff Elisabeth M W
Journal of Parkinson's disease
BACKGROUND:Although vitamin D may have both protective and symptomatic effects in Parkinson's disease (PD), the evidence is scarce and not well understood. Also, 25-hydroxyvitamin D (vitamin D) is suggested to play a neuroprotective and neurotrophic role in the brain. Therefore, this review investigates the relationship between vitamin D and PD. OBJECTIVE:Investigate the evidence for a relationship between vitamin D and PD by summarizing observational and interventional studies in humans, as well as relevant experimental studies. METHODS:A systematic search was made in the Medline, Cochrane and Embase databases (from inception to March 2014). All identified titles were independently evaluated by two reviewers. Articles were selected based on the presence of PD-related outcome data. Included were observational studies (including genetic studies) and interventional studies in humans, as well as relevant animal studies. RESULTS:A total of 20 studies (14 observational, 1 interventional and 5 rodent studies) were selected for analysis. Eight observational studies showed that serum 25(OH) D levels tend to be low in PD. One observational study indicated that low serum 25(OH) D may worsen automatic postural responses and one interventional study suggested that vitamin D supplementation can prevent worsening (based on the Hoehn and Yahr rating scale). Studies in rodent models of PD showed a protective effect of vitamin D treatment on dopaminergic neurons in the substantia nigra. Results of genetic studies on the association between vitamin D receptor polymorphisms and the risk of PD were contradictory. CONCLUSION:The literature supports possible protective and symptomatic effects of vitamin D in PD. However, more observational and interventional studies in humans are needed to confirm and further elucidate the suggested beneficial effect of vitamin D on PD.
Low Serum Vitamin D Levels May Contribute to Gastric Dysmotility in de novo Parkinson's Disease.
Kwon Ki Young,Jo Kwang Deog,Lee Moon Kyu,Oh Minyoung,Kim Eyu Nyong,Park Jinse,Kim Ji Sun,Youn Jinyoung,Oh Engseok,Kim Hee-Tae,Oh Mi Young,Jang Wooyoung
BACKGROUND AND OBJECTIVES:Gastrointestinal dysfunction is a common non motor symptom in Parkinson's disease (PD). However, the potential association between vitamin D and gastroparesis in PD has not been previously investigated. The aim of this study was to compare vitamin D levels between drug-naive de novo PD patients with normal gastric emptying and those with delayed gastric emptying. METHODS:Fifty-one patients with drug-naive de novo PD and 20 age-matched healthy controls were enrolled in this study. Gastric emptying time (GET) was assessed by scintigraphy, and gastric emptying half-time (T1/2) was determined. The PD patients were divided into a delayed-GET group and a normal-GET group. RESULTS:The serum 25-hydroxyvitamin D3 levels were decreased in the delayed-GET group compared with the normal-GET and control groups (11.59 ± 4.90 vs. 19.43 ± 6.91 and 32.69 ± 4.93, respectively, p < 0.01). In the multivariate model, the serum 25-hydroxyvitamin D3 level was independently associated with delayed gastric emptying in PD patients. CONCLUSIONS:Vitamin D status may be an independent factor for gastric dysmotility in PD. Although the underlying mechanism remains to be characterized, vitamin D status may play a role in the pathogenesis of delayed gastric emptying in drug-naive PD.
Vitamin D and Sunlight Exposure in Newly-Diagnosed Parkinson's Disease.
Wang Juan,Yang Deyu,Yu Yu,Shao Gaohai,Wang Qunbo
Circulating vitamin D has previously been found to be lower in patients with Parkinson's disease (PD), while the effects of sunlight exposure have not yet been fully investigated. Therefore, we evaluated the associations between serum vitamin D, vitamin D intake, sunlight exposure, and newly-diagnosed PD patients in a Chinese population. This case-control study measured serum 25-hydroxyvitamin D (25(OH)D) levels and sunlight exposure in 201 patients with newly-diagnosed PD and 199 controls without neurodegenerative diseases. Data on vitamin D intake and sunlight exposure were obtained using a self-report questionnaire. Multivariable logistic regressions were employed to evaluate the associations between serum 25(OH)D levels, sunlight exposure, and PD. Adjustments were made for sex, age, smoking, alcohol use, education, BMI, and vitamin D intake. There were significantly lower levels of serum 25(OH)D (20.6 ± 6.5 ng/mL), daily vitamin D intake (8.3 ± 3.7 g/day), and sunlight exposure (9.7 ± 4.1 h/week) in patients with PD compared to healthy controls (p < 0.05). Crude odds ratios (ORs) for PD in the quartiles of serum 25(OH)D were 1 (reference), 0.710 (0.401, 1.257), 0.631 (0.348, 1.209), and 0.483 (0.267, 0.874), respectively. Crude ORs for PD in quartiles of sunlight exposure were 1 (reference), 0.809 (0.454, 1.443), 0.623 (0.345, 1.124) and 0.533 (0.294, 0.966), respectively. A significant positive correlation between serum 25(OH)D and sunlight exposure was found, but serum 25(OH)D was not correlated with daily vitamin D intake. This study indicates that lower levels of serum 25(OH)D and sunlight exposure are significantly associated with an increased risk for PD.
Bone mass and vitamin D levels in Parkinson's disease: is there any difference between genders?
Ozturk Erhan Arif,Gundogdu Ibrahim,Tonuk Burak,Kocer Bilge Gonenli,Tombak Yasemin,Comoglu Selcuk,Cakci Aytul
Journal of physical therapy science
[Purpose] The aim of this study was to determine the bone mineral density, vitamin D level, and frequencies of osteopenia and osteoporosis in patients with Parkinson's disease and to compare male and female patients with the controls separately. [Subjects and Methods] One hundred fifteen Parkinson's disease patients (47 males, 68 females; age range: 55-85 years) and 117 age- and gender-matched controls (47 males, 70 females) were enrolled in the study. Bone mineral density measured by dual-energy X-ray absorptiometry and serum D vitamin levels of each participant were recorded. [Results] The mean lumbar spine, femur neck, and total femur bone mineral density levels, T-scores, and vitamin D levels were found to be significantly lower in Parkinson's disease patients in both genders. Furthermore, osteoporosis rates were found be significantly higher only in female Parkinson's disease patients compared with female controls. [Conclusion] Data from the present study revealed that while osteoporosis was significantly higher only in female Parkinson's disease patients, all Parkinson's disease patients had lower bone mineral density scores and vitamin D levels compared with the controls regardless of gender, suggesting that clinicians should pay attention to the osteoporosis risk in Parkinson's disease and that adequate preventive measures should be taken in order to limit the future risk due to osteoporotic fractures.
Vitamin D receptor polymorphisms and Parkinson's disease in a Korean population: Revisited.
Kang Seo Young,Park Suyeon,Oh Eungseok,Park Jinse,Youn Jinyoung,Kim Ji Sun,Kim Jeong-Uk,Jang Wooyoung
Recently, the effect of genetic variants in the Vitamin D receptor (VDR) gene on Parkinson's disease (PD) has gained interest. However, the precise relationship between VDR polymorphisms and PD remains unclear. In Korea, one study reported an association between VDR gene polymorphisms and PD. However, this study was conducted with a small sample size, and only the Bsml locus was evaluated. Therefore, further investigations about the relationship between VDR polymorphisms and PD are necessary in a Korean population. A total of 300 subjects were included in this study. One hundred and forty-six PD patients were diagnosed according to the United Kingdom Parkinson's Disease Society Brain Bank (UKPDBB) criteria with abnormal dopamine transporter imaging, and 154 healthy control subjects were also enrolled. We used a TaqMan genotyping assay to identify four SNPs of the VDR gene, including BsmI, FokI, ApaI, and TaqI (rs731236, rs2228570, rs7976091, and rs731236). A significant association was not noted between the risk of PD and genetic polymorphisms in the four loci in a Korean population. However, when the genetic variants of the VDR gene were analyzed after adjusting for the serum 25-OH vitamin D3 level, the TaqI and BsmI minor allele increased the risk of PD. Our data suggest no correlation between PD and the VDR polymorphisms, including BsmI, FokI, ApaI, and TaqI, in a Korean population; however, the results should be interpreted carefully because gene-environment interactions may exist. Further investigations of the VDR and its relationship with PD are required to identify the role of vitamin D in the pathogenesis of PD.
Vitamin D receptor gene polymorphisms and cognitive decline in Parkinson's disease.
Gatto Nicole M,Paul Kimberly C,Sinsheimer Janet S,Bronstein Jeff M,Bordelon Yvette,Rausch Rebecca,Ritz Beate
Journal of the neurological sciences
We and others have suggested that vitamin D receptor gene (VDR) polymorphisms influence susceptibility for Parkinson's disease (PD), Alzheimer's disease (AD), mild cognitive impairment (MCI) or overall cognitive functioning. Here we examine VDR polymorphisms and cognitive decline in patients with PD. Non-Hispanic Caucasian PD patients (n=190) in the Parkinson Environment Gene (PEG) study were successfully genotyped for seven VDR polymorphisms. Cognitive function was assessed with the Mini-Mental State Exam (MMSE) at baseline and at a maximum of three follow-up exams. Using repeated-measures regression we assessed associations between VDR SNP genotypes and change in MMSE longitudinally. PD cases were on average 67.4years old at diagnosis and were followed for an average of 7.1years into disease. Each additional copy of the FokI A allele was associated with a 0.115 decrease in the total MMSE score per year of follow-up (β=-0.115, SE(β)=0.05, p=0.03) after adjusting for age, sex, education and PD duration. The effect on MMSE by the FokI A allele was comparable in absolute magnitude to the effect for disease duration in years prior to first interview (β=-0.129 per year, SE(β)=0.08, p=0.13), and years of education (β=0.118 per year, SE(β)=0.03, p<0.001). When LD/LED use and PD subtype were added to the model, the effect of the FokI A allele on total MMSE score was magnified (β=-0.141, SE(β)=0.05, p=0.005). Results point to Fokl, a functional VDR polymorphism, as being associated with cognitive decline in PD. Future studies examining the contributions of the vitamin D metabolic pathway to cognitive dysfunction in PD are needed.
The Role of Vitamin D in Disease Progression in Early Parkinson's Disease.
Sleeman Isobel,Aspray Terry,Lawson Rachael,Coleman Shirley,Duncan Gordon,Khoo Tien K,Schoenmakers Inez,Rochester Lynn,Burn David,Yarnall Alison
Journal of Parkinson's disease
BACKGROUND:Previous cross-sectional studies have shown that Parkinson's disease (PD) patients have lower serum 25-hydroxy vitamin D (25(OH)D) concentrations than controls. Vitamin D deficiency was associated with increased disease severity and cognitive impairment in prevalent PD patients. OBJECTIVE:The aim of the study was to determine 25(OH)D in newly diagnosed PD and age-matched controls and to assess if there was an association with clinical outcomes (disease severity, cognition and falls) over the 36-month follow up period. METHODS:A prospective observational study of newly diagnosed PD patients in the North East of England with age-matched controls (PD, n = 145; control, n = 94). Serum 25(OH)D was assessed at baseline and 18 months. Participants underwent clinical assessment at baseline, 18 and 36 months. One hundred and ten participants with PD also took part in a prospective falls study. RESULTS:Mean serum 25(OH)D concentrations were lower in PD than control participants at baseline (44.1±21.7 vs. 52.2±22.1 nmol/L, p < 0.05) and 18 months (44.2±23.6 vs. 55.7±28.8 nmol/L, p < 0.05). Baseline serum 25(OH)D concentration, age, motor score and dosage of dopaminergic medication were significant predictors of variance of motor severity at 36 months ((ΔR2 = 0.039, F = 6.6, p < 0.01). Serum 25(OH)D was not associated with cognition or falls during the follow up period. CONCLUSIONS:Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls, which may have implications in terms of bone health and fracture risk. There was a small but significant association between vitamin D status at baseline and disease motor severity at 36 months.
Vitamin D receptor gene polymorphisms, smoking, and risk of sporadic Parkinson's disease in Japan.
Tanaka Keiko,Miyake Yoshihiro,Fukushima Wakaba,Kiyohara Chikako,Sasaki Satoshi,Tsuboi Yoshio,Oeda Tomoko,Shimada Hiroyuki,Kawamura Nobutoshi,Sakae Nobutaka,Fukuyama Hidenao,Hirota Yoshio,Nagai Masaki,Nakamura Yoshikazu,
Epidemiological evidence on the relationships between the vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), and rs2228570 (FokI) and Parkinson's disease (PD) is inconsistent. We investigated these relationships in 229 sporadic PD patients within six years of onset in Japan. Controls were 357 patients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, and smoking. A significant inverse association was found between SNP rs2228570 and the risk of sporadic PD under the additive but not the co-dominant or dominant model (P=0.048); however, this fell below significance after adjustment for multiple comparisons (adjusted P=0.46). No significant relationships were found between SNPs rs731236, rs7975232, or rs1544410 and the risk of sporadic PD in any genetic model. VDR haplotypes inferred in the current study were not associated with sporadic PD. Compared with subjects with the GA or AA genotype of SNP rs2228570 who had ever smoked, those with the GG genotype who had never smoked had a 3.78-fold increased risk of sporadic PD; however, no significant interaction was observed. VDR SNP rs2228570 may be associated with sporadic PD in Japan. Smoking did not significantly modify the relationship between SNP rs2228570 and sporadic PD.
GC and VDR SNPs and Vitamin D Levels in Parkinson's Disease: The Relevance to Clinical Features.
Gezen-Ak Duygu,Alaylıoğlu Merve,Genç Gençer,Gündüz Ayşegül,Candaş Esin,Bilgiç Başar,Atasoy İrem L,Apaydın Hülya,Kızıltan Güneş,Gürvit Hakan,Hanağası Haşmet,Ertan Sibel,Yılmazer Selma,Dursun Erdinç
Vitamin D deficiency is suggested to be associated with Parkinson's disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hundred eighty-two PD patients and 242 healthy subjects were included in this study. The serum 25OHD levels were investigated by CLIA, and GC and VDR SNPs were evaluated with LightSnip. Our results indicated a strong relationship between low serum 25OHD levels and PD (p < 0.001). rs7041 of GC and ApaI of VDR were associated with the PD risk (p < 0.05). Minor allele carriers for BsmI of VDR gene in both PD patients and healthy subjects had significantly higher levels of serum 25OHD (p < 0.05). The homozygous major allele carriers for rs2282679, rs3755967 and rs2298850 of GC gene in PD patients with slower progression had significantly higher levels of serum 25OHD (p < 0.05). Minor allele carriers for FokI of VDR gene were more frequent in patients with advanced-stage PD (p < 0.05). Consequently, this is the first study demonstrating GC gene as a risk factor for PD. The relationship between PD's clinical features and low 25OHD or risk genotypes might have effects on PD independently.
Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson's Disease, Shifting M1 to M2 Microglia Responses.
Calvello Rosa,Cianciulli Antonia,Nicolardi Giuseppe,De Nuccio Francesco,Giannotti Laura,Salvatore Rosaria,Porro Chiara,Trotta Teresa,Panaro Maria Antonietta,Lofrumento Dario Domenico
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
Microglia-mediated neuroinflammation has been described as a common hallmark of Parkinson's disease (PD) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. Current therapies are unable to prevent the disease progression. A significant association has been demonstrated between PD and low levels of vitamin D in patients serum, and vitamin D supplement appears to have a beneficial clinical effect. Herein, we investigated whether vitamin D administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced preclinical animal model of PD protects against glia-mediated inflammation and nigrostriatal neurodegeneration. Vitamin D significantly attenuated the MPTP-induced loss of tyrosine hydrlase (TH)-positive neuronal cells, microglial cell activation (Iba1-immunoreactive), inducible nitric oxide synthase (iNOS) and TLR-4 expression, typical hallmarks of the pro-inflammatory (M1) activation of microglia. Additionally, Vitamin D was able to decrease pro-inflammatory cytokines mRNA expression in distinct brain areas of the MPTP mouse. Importantly, we also assessed the anti-inflammatory property of vitamin D in the MPTP mouse, in which it upregulated the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) mRNA expression as well as increasing the expression of CD163, CD206 and CD204, typical hallmarks of alternative activation of microglia for anti-inflammatory signalling (M2). Collectively, these results demonstrate that vitamin D exhibits substantial neuroprotective effects in this PD animal model, by attenuating pro-inflammatory and up-regulating anti-inflammatory processes.
No clear support for a role for vitamin D in Parkinson's disease: A Mendelian randomization study.
Larsson Susanna C,Singleton Andrew B,Nalls Mike A,Richards J Brent,
Movement disorders : official journal of the Movement Disorder Society
BACKGROUND:Observational studies have found that relative to healthy controls, patients with Parkinson's disease have lower circulating concentrations of 25-hydroxyvitamin D, a clinical biomarker of vitamin D status. However, the causality of this association is uncertain. We undertook a Mendelian randomization study to investigate whether genetically decreased 25-hydroxyvitamin D concentrations are associated with PD to minimize confounding and prevent bias because of reverse causation. METHODS:As instrumental variables for the Mendelian randomization analysis, we used 4 single-nucleotide polymorphisms that affect 25-hydroxyvitamin D concentrations (rs2282679 in GC, rs12785878 near DHCR7, rs10741657 near CYP2R1, and rs6013897 near CYP24A1). Summary effect size estimates of the 4 single-nucleotide polymorphisms on PD were obtained from the International Parkinson's Disease Genomics Consortium (including 5333 PD cases and 12,019 controls). The estimates of the 4 single-nucleotide polymorphisms were combined using an inverse-variance weighted meta-analysis. RESULTS:Of the 4 single-nucleotide polymorphisms associated with 25-hydroxyvitamin D concentrations, one (rs6013897 in CYP24A1) was associated with PD (odds ratio per 25-hydroxyvitamin D-decreasing allele, 1.09; 95% confidence interval, 1.02-1.16; P = 0.008), whereas no association was observed with the other 3 single-nucleotide polymorphisms (P > 0.23). The odds ratio of PD per genetically predicted 10% lower 25-hydroxyvitamin D concentration, based on the 4 single-nucleotide polymorphisms, was 0.98 (95% confidence interval, 0.93-1.04; P = 0.56). CONCLUSIONS:This Mendelian randomization study provides no clear support that lowered 25-hydroxyvitamin D concentration is causally associated with risk of PD. © 2017 International Parkinson and Movement Disorder Society.
Effect of Vitamin D in HN9.10e Embryonic Hippocampal Cells and in Hippocampus from MPTP-Induced Parkinson's Disease Mouse Model.
Cataldi Samuela,Arcuri Cataldo,Hunot Stéphane,Mecca Carmen,Codini Michela,Laurenti Maria E,Ferri Ivana,Loreti Elisabetta,Garcia-Gil Mercedes,Traina Giovanna,Conte Carmela,Ambesi-Impiombato Francesco S,Beccari Tommaso,Curcio Francesco,Albi Elisabetta
Frontiers in cellular neuroscience
It has long been proven that neurogenesis continues in the adult brains of mammals in the dentatus gyrus of the hippocampus due to the presence of neural stem cells. Although a large number of studies have been carried out to highlight the localization of vitamin D receptor in hippocampus, the expression of vitamin D receptor in neurogenic dentatus gyrus of hippocampus in Parkinson's disease (PD) and the molecular mechanisms triggered by vitamin D underlying the production of differentiated neurons from embryonic cells remain unknown. Thus, we performed a preclinical study by inducing PD in mice with MPTP and showed a reduction of glial fibrillary acidic protein ( in the dentatus gyrus of hippocampus. Then, we performed an study by inducing embryonic hippocampal cell differentiation with vitamin D. Interestingly, vitamin D stimulates the expression of its receptor. Vitamin D receptor is a transcription factor that probably is responsible for the upregulation of microtubule associated protein 2 and neurofilament heavy polypeptide genes. The latter increases heavy neurofilament protein expression, essential for neurofilament growth. Notably N-cadherin, implicated in activity for dendritic outgrowth, is upregulated by vitamin D.
A randomized, controlled pilot study of the effects of vitamin D supplementation on balance in Parkinson's disease: Does age matter?
Hiller Amie L,Murchison Charles F,Lobb Brenna M,O'Connor Susan,O'Connor Morgan,Quinn Joseph F
OBJECTIVES:To explore if short term, high dose vitamin D supplementation is safe and improves balance in persons with Parkinson's disease (PD). METHODS:A pilot randomized, double-blind intervention trial to measure the effects of 16 weeks of high dose vitamin D (10,000 IU/day) on balance as well as other motor and non-motor features of PD. We measured balance, gait, strength, falls, cognition, mood, PD severity, and quality of life before and after 16 weeks of high dose vitamin D supplementation or placebo. All participants also received 1000 mg calcium once daily. RESULTS:Fifty-one randomized participants completed sixteen weeks of high dose vitamin D supplementation or placebo. The intervention resulted in a rise in serum concentrations of vitamin D (25-OH) (30.2 ng/ml to 61.1 ng/ml) and was well tolerated with no serious adverse events. Serum vitamin D (25-OH) levels rose steadily and did not suggest a leveling off at the end of the 16 weeks. There was not an improvement in the primary endpoint, balance as measured by the Sensory Organization Test (p = 0.43). A post hoc analysis examining treatment effects in younger (ages 52-66) versus older (ages 67-86) participants found a significant improvement in the SOT of 10.6 points in the younger half of the cohort (p = 0.012). CONCLUSIONS:Short term, high dose vitamin D supplementation appears safe in persons with PD, but did not significantly improve balance as measured with the Sensory Organization Test in this pilot study population. A post hoc analysis suggests that vitamin D may have potential for improving balance in a younger population with PD. High dose vitamin D supplementation in PD needs further study especially in light of new research suggesting that mega doses and even moderate doses (as low as 4000IU a day) may increase falls in an older populations. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01119131.
Characterization of vitamin D supplementation and clinical outcomes in a large cohort of early Parkinson's disease.
Luthra Nijee S,Kim Soeun,Zhang Yunxi,Christine Chadwick W,
Journal of clinical movement disorders
Background:Vitamin D (VitD) deficiency is common in Parkinson's disease (PD) and has been raised as a possible PD risk factor. In the past decade, VitD supplementation for potential prevention of age related conditions has become more common. In this study, we sought to characterize VitD supplementation in early PD and determine as an exploratory analysis whether baseline characteristics or disease progression differed according to reported VitD use. Methods:We analyzed data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term study (LS-1), a longitudinal study of 1741 participants. Subjects were divided into following supplement groups according to subject exposure (6 months prior to baseline and during the study): no VitD supplement, multivitamin (MVI), VitD ≥400 IU/day, and VitD + multivitamin (VitD+MVI). Clinical status was followed using the Unified Parkinson's Disease Rating Scale, Symbol Digit Modalities Test, total daily levodopa equivalent dose, and Parkinson's Disease Questionnaire. Results:About 5% of subjects took VitD alone, 7% took VitD+MVI, 34% took MVI alone, while 54% took no supplement. Clinical outcomes at 3 years were similar across all groups. Conclusion:This study shows VitD supplementation ≥400 IU/day was not common in early PD and that its use was similar to that seen in the US population. At 3 years, there was no difference in disease progression according to vitamin D supplement use.
Association Between Serum Vitamin D Levels and Parkinson's Disease: A Systematic Review and Meta-Analysis.
Luo Xiaoyue,Ou Ruwei,Dutta Rajib,Tian Yuan,Xiong Hai,Shang Huifang
Frontiers in neurology
Vitamin D is an important secosteroid which is involved the development and regulation of brain activity. Several studies have focused on exploring the relationship between serum vitamin D levels and Parkinson's disease (PD), but the conclusion remains ambiguous. We searched observational studies that explored the association between serum vitamin D levels and PD based on PubMed, EMBASE and Cochrane library from inception through to January 2018. The quality of included studies was evaluated by using Newcastle-Ottawa Scale (NOS). Statistical analysis of this meta-analysis was performed by Stata version 12.0 and R software. Twenty studies with a total of 2,866 PD patients and 2,734 controls were included. Compared with controls, PD patients had lower serum vitamin D levels (WMD -3.96, 95%CI -5.00, -2.92), especially in higher latitude regions (WMD -4.20, 95%CI -5.66, -2.75). Assay methods contributed significantly to high heterogeneity. Furthermore, PD patients with deficient vitamin D levels had advanced risk (OR 2.08, 95%CI 1.35, 3.19) than those patients with insufficient ones (OR = 1.73, 95%CI 1.48, 2.03). In addition, serum vitamin D levels were also related to the severity of PD (WMD -5.27, 95%CI -8.14, -2.39) and the summary correlation coefficient showed strongly negative correlation ( = -0.55, 95%CI -0.73, -0.29). Moreover, the pooled correlation coefficient revealed that serum vitamin D levels were also negatively correlated to the Unified Parkinson's Disease Rating Scale III (UPDRS III) ( = -0.36, 95%CI -0.53, -0.16), but did not correlate with the duration of PD ( = 0.37) and age of patients ( = 0.49). Serum vitamin D levels are inversely associated with the risk and severity of PD. Our results provided an updated evidence of association between low vitamin D levels and PD and prompt the adjunctive therapeutic decisions about vitamin D replacement in PD.
The Association Between Vitamin D Status, Vitamin D Supplementation, Sunlight Exposure, and Parkinson's Disease: A Systematic Review and Meta-Analysis.
Zhou Zonglei,Zhou Ruzhen,Zhang Zengqiao,Li Kunpeng
Medical science monitor : international medical journal of experimental and clinical research
BACKGROUND This literature review and meta-analysis aimed to determine the association between deficiency of vitamin D, or 25-hydroxyvitamin D, and Parkinson's disease, and whether vitamin D from supplements and sunlight improves the symptoms of Parkinson's disease. MATERIAL AND METHODS A literature review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Systematic literature review was performed using databases that included the Web of Science, PubMed, the Cochrane Library, and Embase. The Jadad scale (the Oxford quality scoring system) and the Newcastle-Ottawa scale (NOS) were used to evaluate the quality of the studies. RESULTS Eight studies were included in the meta-analysis. Both 25-hydroxyvitamin D insufficiency (<30 ng/mL) (OR, 1.77; 95% CI, 1.29-2.43; P<0.001) and deficiency (<20 ng/mL) (OR, 2.55; 95% CI, 1.98-3.27; P<0.001) were significantly associated with an increased risk of Parkinson's disease when compared with normal controls Sunlight exposure (³15 min/week) was significantly associated with a reduced risk of Parkinson's disease (OR, 0.02; 95% CI, 0.00-0.10; P<0.001). The use of vitamin D supplements was effective in increasing 25-hydroxyvitamin D levels (SMD, 1.79; 95% CI, 1.40-2.18; P<0.001), but had no significant effect on motor function (MD, -1.82; 95% CI, -5.10-1.45; P=0.275) in patients with Parkinson's disease. CONCLUSIONS Insufficiency and deficiency of 25-hydroxyvitamin D and reduced exposure to sunlight were significantly associated with an increased risk of Parkinson's disease. However, vitamin D supplements resulted in no significant benefits in improving motor function for patients with Parkinson's disease.
Vitamin D receptor polymorphisms and the susceptibility of Parkinson's disease.
Wang Xiong,Shen Na,Lu Yanjun,Tan Kun
Epidemiological evidence concerning the association between vitamin D receptor (VDR) polymorphisms, including rs2228570, rs731236, rs7975232, rs1544410 and Parkinson's disease (PD) risk is inconsistent. A meta-analysis was performed to evaluate these associations via searching PubMed and EMBASE databases up to Jan 4, 2019. Odds ratio (OR) with 95% confidence interval (CI) were applied to assess the strength of these associations. 6 studies with 1391 PD cases and 1570 controls for rs2228570, 7 studies with 1881 PD cases and 2135 controls for rs731236, 5 studies with 1298 PD cases and 1536 controls for rs7975232, and 6 studies with 932 PD cases and 1377 controls for rs1544410 were included in this meta-analysis. Significant associations between rs2228570 and PD risk were found in allelic, dominant, and additive models but not in recessive model. Stratified study revealed that rs2228570 was associated with PD susceptibility in Asian population, while no significant association was observed in Caucasian population. Sensitivity analysis showed stable results for rs2228570 and no publication bias existed. Rs731236 was associated with increased PD risk in dominant model, however, this result was unstable. No significant association was found between rs7975232 or rs1544410 and PD.
Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer's disease and Parkinson's disease.
Bivona Giulia,Lo Sasso Bruna,Iacolino Giorgia,Gambino Caterina Maria,Scazzone Concetta,Agnello Luisa,Ciaccio Marcello
Clinica chimica acta; international journal of clinical chemistry
The current review provides an overview on the development of 25(OH)D measurement standardization tools over the last three decades and clarifies whether there is a role as a serum biomarker for vitamin D in neurological diseases. In the past, a lack of internationally recognized 25(OH)D reference measurement procedures and reference standard materials led to unstandardized serum total 25(OH)D results among research and clinical care laboratories. The vitamin D Standardization Program (VDSP) has been introduced in 2010 to address this problem, however, vitamin D External Quality Assessment Scheme (DEQAS) reports still show substantial sample- to- sample variability. Further, immunoassays, which are mainly used in clinical care laboratories, display analytical issues, including matrix-effects interferences, which cannot be overcome by the standardization process. Hence, liquid chromatography-tandem mass spectrometry (LC/MS-MS) methods should be used to measure 25(OH)D. Low vitamin D serum levels have been found in patients affected by Alzheimer's disease and Parkinson's disease, suggesting a role for vitamin D as a serum biomarker in these diseases. However, few studies reported 25(OH)D standardized results, thus, no clear evidence on the potential role of 25(OH)D serum levels in these diseases exists.
Vitamin D receptor rs2228570 polymorphism and Parkinson's disease risk in a Chinese population.
Hu Weihong,Wang Lu,Chen Bo,Wang Xiong
Epidemiological evidence of the relationship between vitamin D receptor (VDR) rs2228570 (FokI) polymorphism and the susceptibility of Parkinson's disease (PD) is inconsistent, partially due to between-study variations in sample size, age, male/female ratio, and 25-OH vitamin D3 levels. Here, we examined the association between VDR rs2228570 polymorphism and PD risk in a Chinese population. A total of 940 subjects were included in this study, which consisted of 470 patients with sporadic PD (mean age: 62.65 ± 9.34 years) and 470 healthy control subjects (mean age: 62.70 ± 9.42 years). A TaqMan genotyping assay was applied to identify VDR rs2228570 polymorphism. The Hardy-Weinberg Equilibrium (HWE) was calculated for both groups with a Chi-square (χ2) test. The sample power was calculated with Power V3.0. The crude odds ratios (ORs) and 95 % confidence intervals (CIs) for sporadic PD in relation to VDR rs2228570 polymorphism were calculated using a logistic regression analysis. The minor A allele frequency was 0.42 and 0.48 in the control and PD groups, respectively. A allele carriers of rs2228570 were associated with an increased overall risk of PD as well as early-onset PD (EOPD) in the allele and additive genetic models. Stratification analyses showed similar results in male subjects in the allele and additive genetic models, but only in the additive genetic model in female subjects. In conclusion, our study suggests that the VDR rs2228570 A allele is associated with an increased risk of PD in a Chinese population. Further investigations with larger sample sizes with consideration of gene-gene and gene-environment interaction are needed to further elucidate the role of vitamin D receptors in the development of PD.
Association between vitamin D receptor polymorphisms and susceptibility to Parkinson's disease: An updated meta-analysis.
Gao Jinzhao,Teng Jijun,Liu Zongchao,Cai Min,Xie Anmu
The relationships between vitamin D receptor (VDR) gene polymorphisms, particularly ApaI, BsmI, FokI, and TaqI, and Parkinson's disease (PD) has received increasing attention in the research community. However, as the results yielded by this increased research have hitherto conflicted, we performed an updated meta-analysis of reports on the relationships between VDR polymorphisms and PD published before October 2019 that we collected from the PUBMED, EMBASE, EBSCO, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The ten articles that met our screening criteria included 2782 patients and 3194 healthy controls. All the data that we received were analyzed with Stata 12.0 statistical software. The odds ratio (OR) and 95 % confidence intervals (CIs) were used to determine the relationship between VDR gene diversity and PD. While we did not find a significant correlation between the ApaI, BsmI, and TaqI polymorphisms and the risk of PD in any of the considered genetic models, we found a clear association between the FokI polymorphism and susceptibility to PD (C vs. T: OR = 1.246, 95 % CI: 1.101-1.411, P = 0; CC vs. TT: OR = 1.630, 95 % CI: 1.243-2.139, P = 0; CT vs. TT: OR = 1.382, 95 % CI: 1.059-1.804, P = 0.017; CC + CT vs. TT: OR = 1.491, 95 % CI: 1.159-1.919,P = 0.002; CC vs. CT + TT: OR = 1.261, 95 % CI: 1.062-1.496, P = 0.008). Our subgroup analysis performed according to ethnicity revealed that FokI increased the risk of PD in Asian populations (C vs. T: OR = 1.261, 95 % CI: 1.080-1.472, P = 0.003; CC vs. TT: OR = 1.664, 95 % CI: 1.189-2.330, P = 0.003; CT vs.TT: OR = 1.387, 95 % CI: 1.000-1.925, P = 0.05; CC + CT vs. TT: OR = 1.497, 95 % CI: 1.098-2.042, P = 0.011; CC vs. CT + TT: OR = 1.285, 95 % CI: 1.036-1.593, P = 0.022). Overall, the gene polymorphism of FokI only increases the risk of PD among Asian populations. Given the limited sample size of this study, the findings should be carefully explained.
Bone mineral density and serum vitamin D status in Parkinson's disease: Are the stage and clinical features of the disease important?
Ozturk Erhan Arif,Gundogdu Ibrahim,Tonuk Burak,Umay Ebru,Kocer Bilge Gonenli,Cakci Aytul
Background:Although it is well known that patients with Parkinson's disease (PD) have low bone mineral density (BMD) and serum vitamin D level, there are no studies evaluating their relationship with the stage and clinical features of the PD. Objective:The purpose of this study was to evaluate the relationship between BMD and serum vitamin D level and stage or clinical features of the PD. Materials and Methods:One hundred twenty-four patients with PD recruited from Movement Disorders Outpatient Clinic and age- and sex-matched 116 healthy controls were included in the study. BMD and serum vitamin D level of all participants were measured. After patients had been divided into four groups according to Hoehn and Yahr (H and Y) staging, a total of 5 groups with controls, BMD (lumbar and femoral) and serum vitamin D level were compared between groups. The relationship between the clinical features of the PD [disease duration, medication history, Unified Parkinson's Disease Rating Scale (UPDRS) part II and III, and subscores of UPDRS part III] and BMD or vitamin D was investigated. Results:Lumbar and femoral BMD values and serum vitamin D level were significantly lower in patients with PD compared to controls. Low BMD and low serum vitamin D level were identified in the early stages of the disease (H and Y stage 1 and 1.5) and were marked by the progress of the stage of the disease. There was a negative relationship between the clinical features of the PD and both BMD and serum vitamin D level. Conclusion:All patients with PD should be screened for developing osteoporosis and for sufficient vitamin D level in the early stages of the disease. Preventive methods for bone quality should be taken into consideration at the onset of PD.
Nocturnal blood pressure changes in Parkinson's disease: correlation with autonomic dysfunction and vitamin D levels.
Arici Duz Ozge,Helvaci Yilmaz Nesrin
Acta neurologica Belgica
Nocturnal blood pressure (BP) changes are an indicator of autonomic dysfunction. We aim to investigate the correlation between nocturnal blood pressure (BP) variability, vitamin D levels and Parkinson's disease severity (PD) in this study. Thirty-five patients with PD participated in the study. Disease severity was evaluated by United Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr Scale (HYS). Equivalent levodopa dose was calculated and 25-hydroxyvitamin D levels were measured. The Non-Motor Symptom Questionnaire (NMSQ) was applied to all patients. Ambulatory BP monitoring for 24 h was established. Patients were divided into three groups according to nocturnal BP results: dippers (normal finding-a decline in mean nighttime BP of more than 10%); non-dippers (pathological-a decline in mean nighttime BP of less than 10%); reverse dippers (pathological-an increase in mean nighttime BP) .The mean score of the NMSQ was higher in the group with HYS > 2 (p = 0.050). Four patients were dipper, 17 patients were non-dipper and 16 patients were reverse dipper. There was no significant difference between the three groups in terms of age, gender, disease duration, age of the disease onset, disease stage, disease duration, dopamine agonist usage, levodopa equivalent dose, vitamin D level and NMSQ scores. NMSQ scores are high in advanced PD. Ambulatory BP monitoring is useful in detecting autonomic dysfunction. The number of patients with non-dipping and reverse dipping is high in PD, independent from PD severity, drug dose, vitamin D and the other NMS symptoms.
The Relationship Among Bone Mineral Density, Bone Biomarkers and Vitamin D Levels in Patients with Parkinson's Disease.
Can Nimet U,Alagöz Aybala N
BACKGROUND:Idiopathic Parkinson's disease (IPD) is the most common age-related neurodegenerative movement disorder. It causes a decrease and deceleration in movements. It may also lead to loss of bone mineral density, vi-tamin D deficiency, falls and fractures due to various factors. As indicated in our study, determining the prevalence of osteopenia and osteoporosis in IPD is important to determine complications. METHODS:Thirty patients with IPD and 30 age-matched control subjects were included in the study. The bone mineral density (BMD) measurements of the participants were taken from the lumbar spine (L1-4) and double femur regions using the dual energy X-ray absorptiometry device. Serum 25 (OH) vitamin D, alkaline phosphatase, parathormone, osteocalcin, prolidase and urine hydroxyproline levels were measured. RESULTS:The femur total BMD and serum 25 (OH) vitamin D levels were lower in the patients with IPD than in the control group (p > 0.05). The serum prolidase and urinary hydroxyproline levels were higher in the IPD group relative to the control group (p < 0.05). The frequency of osteoporosis and osteopenia was significantly higher in the IPD group than in the control group (p < 0.05). CONCLUSIONS:Patients with Parkinson's disease tend to have lower vitamin D levels than those with a similar age without Parkinson's disease. Vitamin D levels are usually associated with BMD in people with Parkinson's disease, but administering vitamin D does not improve BMD. Cross-sectional studies suggest a correlation between vitamin D levels and the severity of symptoms of Parkinson's disease. Decreased exposure to sunlight due to immobilisation and reduced vitamin D intake by diet may lead to vitamin D deficiency and low BMD. There is a negative correlation among the duration of disease, disease severity, number of falls, parathormone level and serum vitamin D level in people with Parkinson's disease. Consequently, vitamin D levels may be low in Parkinson's disease patients. Therefore, patients with Parkinson's disease should be checked for vitamin D and osteoporosis by considering the risk of hip fracture, fall from a height and high risk of osteoporosis.
The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson's disease.
Lv Lingling,Tan Xuling,Peng Xinke,Bai Rongrong,Xiao Qile,Zou Ting,Tan Jieqiong,Zhang Hainan,Wang Chunyu
In recent years, many studies have investigated the correlations between Parkinson's disease (PD) and vitamin D status, but the conclusion remains elusive. The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms from PubMed, Web of Science, Cochrane Library, and Embase databases. We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity. Furthermore, higher vitamin D concentrations are linked to better cognitive function and mood in PD patients. Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent, but the FokI (C/T) polymorphism is significantly linked with PD. The occurrence of FokI (C/T) gene polymorphism may influence the risk, severity, and cognitive ability of PD patients, while also possibly influencing the effect of Vitamin D supplementation in PD patients. In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission, interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.
Genetic variants of vitamin D metabolism-related locus and gene are associated with clinical features of Parkinson's disease.
Alaylıoğlu Merve,Dursun Erdinç,Genç Gençer,Şengül Büşra,Bilgiç Başar,Gündüz Ayşegül,Apaydın Hülya,Kızıltan Güneş,Gürvit Hakan,Hanağası Haşmet,Öztop Çakmak Özgür,Ertan Sibel,Yılmazer Selma,Gezen-Ak Duygu
The International journal of neuroscience
PURPOSE/AIM OF THE STUDY:Parkinson's disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor () and vitamin D binding protein () genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 () locus and vitamin D 25-hydroxylase () gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features. MATERIALS AND METHODS:Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the locus and gene. RESULTS:There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the locus and gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease. CONCLUSIONS:In conclusion, genetic variants of the locus and the gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients.
Brain Endothelial P-Glycoprotein Level Is Reduced in Parkinson's Disease via a Vitamin D Receptor-Dependent Pathway.
Kim Hyojung,Shin Jeong-Yong,Lee Yun-Song,Yun Seung Pil,Maeng Han-Joo,Lee Yunjong
International journal of molecular sciences
The progressive neurodegeneration in Parkinson's disease (PD) is accompanied by neuroinflammation and endothelial vascular impairment. Although the vitamin D receptor (VDR) is expressed in both dopamine neurons and brain endothelial cells, its role in the regulation of endothelial biology has not been explored in the context of PD. In a 6-hydroxydopamine (6-OHDA)-induced PD mouse model, we observed reduced transcription of the VDR and its downstream target genes, and . The 6-OHDA-induced transcriptional repression of these genes were recovered after the VDR ligand-1α,25-dihydroxyvitamin D (1,25(OH)D) treatment. Similarly, reduced vascular protein expression of P-glycoprotein (P-gp), encoded by , after 6-OHDA administration was reversed by 1,25(OH)D. Moreover, marked reduction of endothelial P-gp expression with concomitant α-synuclein aggregation was found in a combinatorial /αSyn preformed fibril (PFF) injection mouse model and postmortem PD brains. Supporting the direct effect of α-synuclein aggregation on endothelial biology, PFF treatment of human umbilical vein endothelial cells (HUVECs) was sufficient to induce α-synuclein aggregation and repress transcription of the VDR. PFF-induced P-gp downregulation and impaired functional activity in HUVECs completely recovered after 1,25(OH)D treatment. Taken together, our results suggest that a dysfunctional VDR-P-gp pathway could be a potential target for the maintenance of vascular homeostasis in PD pathological conditions.