Effects of vitamin B12, folate, and entacapone on homocysteine levels in levodopa-treated Parkinson's disease patients: A randomized controlled study.

INTRODUCTION: Previous studies have suggested a significant increase in plasma homocysteine (Hcy) levels in levodopa-treated Parkinson's disease (PD) patients, and vitamin B12 and folate supplementation may decrease Hcy levels. However, the effects of catechol-O-methyltransferase inhibitors on levodopa-induced increase in Hcy levels were conflicting. The aim of this study was to evaluate whether Hcy levels are increased in levodopa-treated PD patients and to evaluate the effects of vitamin B12 and folate or entacapone on Hcy levels in levodopa-treated PD patients. METHODS: We analyzed and compared plasma Hcy levels in 20 levodopa-naïve PD patients and 42 levodopa-treated PD patients, followed by randomized assignment of 42 levodopa-treated patients to treatment groups with either vitamin B12 and folate, entacapone, or no medication. RESULTS: Plasma Hcy levels in levodopa-treated PD patients were higher than those in the control group, but the difference was not statistical significant (15.25 ± 6.70 and 13.13 ± 4.68, P = 0.216). Patients treated with vitamin B12 and folate had a significant decrease in plasma Hcy levels (P < 0.001). In the entacapone group, Hcy levels were mildly decreased, but the change did not reach statistical significance. CONCLUSION: Levodopa-treated PD patients had higher plasma Hcy than levodopa-naive PD patients. Unlike entacapone, combination supplementation with vitamin B12 and folate was associated with significantly decreased plasma Hcy. We suggest that plasma Hcy levels should be monitored during levodopa treatment, and supplementation with inexpensive vitamin B12 and folate is beneficial for levodopa-treated patients.

Selenium level does not differ in blood but increased in cerebrospinal fluid in Parkinson's disease: a meta-analysis.

Objective: Recent studies have found that selenium (Se) levels were associated with the risk of Parkinson's disease (PD), but the results were contradictory. Therefore, this meta-analysis was conducted to investigate the correlation between Se levels and PD.Methods: PubMed, Embase and Web of Science were searched published up to 28 October 2019. The differences between groups were analyzed by forest plots and results were pooled and assessed using a random-effect model. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to assess the association between Se levels and the risk of PD. Subgroup analysis, meta-regression, and sensitivity analysis were also conducted. Publication bias was estimated using Begg's regression asymmetry test.Results: Finally, 12 articles involving 601 PD patients and 749 controls were included in this meta-analysis. The meta-analysis revealed a significantly higher cerebrospinal fluid (CSF) Se level in PD patients than those in controls (SMD = 1.22; 95%CI [0.05, 2.39]; p = 0.000). No publication bias was found.Conclusion: The meta-analysis indicated that CSF Se levels in PD patients were significantly higher than those in controls.

The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson's disease.

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 D3 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.

Sestrin2 as Serum Protein Marker and Potential Therapeutic Target for Parkinson's Disease.

Sestrin2 (Sesn2) appears to mediate neuroprotection against Parkinson's disease (PD)-associated pathophysiology, however, the mechanism is unknown. This pilot study examines serum Sesn2 level in PD patients and older adult control and also interrogates the rescue effect of Syzygium aromaticum extract on the neurotoxicity by paraquat in neuroblastoma cells. The blood sample was collected from 36 PD patients and 54 older adult control and concentration of serum Sesn2 was measured by surface plasmon resonance and western blot. A significantly elevated level of Sesn2 (p < .0001) was observed in sera of PD group (15.96 ± 2.428 ng/µL) than the control (13.65 ± 2.125 ng/µL) which was further confirmed by western blotting. The receiver operating characteristic (ROC) curve (0.76) determined the threshold value of ≥14.58 ng/µL for differentiating PD from control. The S aromaticum extract exhibited the rescue effect from paraquat induced toxicity in SH-SY5Y cells. Further, these cells showed dose-dependent downregulation of p53, Sesn2, and phosphorylated-AMPK with concomitant increase in phosphorylated-p70S6K level than paraquat-treated cells. The differential level of Sesn2 in study subjects proposes its utility as one of the potential serum markers in PD. The ethanolic extract of S aromaticum may serve as a novel platform for management of PD-associated neurotoxicity.

Efficacy of oral administration of licorice as an adjunct therapy on improving the symptoms of patients with Parkinson's disease, A randomized double blinded clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice preparations are used as neuroprotective remedies in Persian ethnomedicine, in order to prevent from disabilities in neurodegenerative conditions like Parkinson's disease (PD). AIM OF THE STUDY: This study was designed to determine the licorice (root of Glycyrrhiza glabra L.) effectiveness as an adjunct treatment in the PD management. MATERIAL AND METHODS: In this double-blinded trial, 128 patients were assessed for eligibility criteria. Seventy-eight patients were ineligible and 11 of them refused from participating. Thirty-nine PD patients (YAHR staging ≤ 3) were divided into two groups by random. The patients received oral licorice or placebo syrups with a dose of 5 cc, twice a day for 6 months. High-performance liquid chromatography and spectrophotometric instruments determined licorice syrup constituents. The patients' situation for Unified Parkinson's rating scale (UPDRS) was assessed every 6 weeks for the duration of six months. In addition, patients' blood pressure, blood glucose, sodium and potassium levels, quality of life and dizziness were determined. RESULTS: Six weeks after intervention, total UPDRS, daily activities and tremor were significantly improved with a considerable effect size. A significant better motor test and rigidity scores were observed 4 months after licorice intake (p > 0.05). No electrolyte abnormality, significant changes in blood pressure or blood glucose levels were observed during the study. Each 5cc of syrup contained 136 mg of licorice extract with 12.14 mg glycyrrhizic acid, and also 136 µg of polyphenols. CONCLUSION: The licorice intake could improve the symptoms in PD patients without serious adverse events.

Pharmacogenetics of Atremorine-Induced Neuroprotection and Dopamine Response in Parkinson's Disease.

Atremorine is a novel bioproduct with neuroprotective effects on dopaminergic neurons and a natural L-DOPA donor in Parkinson's disease (PD). In the present study, we show the effects of a single dose of Atremorine (5 g, p. o.) on plasma dopamine (DA) response and brain function in PD (n = 183) and the influence that pathogenic (LRRK2), metabolic (CYP2D5, CYP2C9, CYP2C19, CYP3A5, NAT2), transporter (ABCB1), pleiotropic (APOE), and detoxifying genes (CYP1B1, GSTT1, GSTP1, GSTM1, SOD2) involved in the pharmacogenetic network exerts on Atremorine-induced DA response. Over 90% of PD patients at diagnosis show plasma DA levels below 20 pg/mL. Atremorine induces DA synthesis causing a significant increase in plasma DA levels 1 h after administration in practically 100% of patients. Females tend to show lower basal DA levels than males and the response of DA to Atremorine is stronger in males than in females. Atremorine-induced DA response is pharmacogenotype-specific and lasts from 6 - 12 h depending upon the pharmacogenetic profile of each patient. Genetic variants in pathogenic genes, metabolic genes, and genes involved in the detoxification processes affect the response of DA to Atremorine in a genotype-specific manner. Atremorine or any of its bioactive components can cross the blood-brain barrier and improve brain function and motor function, as revealed by the reduction in slow wave activity in brain mapping and psychometric assessment, respectively. Atremorine is a selective neuroprotective agent for dopaminergic neurons with prophylactic and therapeutic potential in PD.

Relationship between 25-Hydroxyvitamin D, bone density, and Parkinson's disease symptoms.

OBJECTIVES: Vitamin D deficiency is widespread in patients with Parkinson's disease (PD). Our aim was to determine whether serum vitamin D levels correlated with bone mineral density (BMD) and non-motor symptoms in patients with PD. MATERIALS & METHODS: A consecutive series of 182 patients with PD and 185 healthy controls were included. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured by immunoassay, while BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Associations between serum vitamin D levels and clinical data were evaluated using partial correlation analysis. RESULTS: Patients with PD had significantly lower serum 25(OH)D levels relative to healthy controls (49.75 ± 14.11 vs 43.40 ± 16.51, P < 0.001). Furthermore, PD patients with lower vitamin D levels had a significantly higher frequency of falls (P = 0.033) and insomnia (P = 0.015). They also had significantly higher scores for the Pittsburgh Sleep Quality Index (PSQI; P = 0.014), depression (P = 0.020), and anxiety (P = 0.009). Finally, patients with PD also had a significantly lower mean BMD of the lumbar spine (P = 0.011) and femoral neck (P < 0.001). After adjusting for age, sex, and body mass index, vitamin D levels significantly correlated with falls, insomnia, and scores for the PSQI, depression, and anxiety. CONCLUSIONS: In patients with PD, vitamin D levels significantly correlated with falls and some non-motor symptoms. However, no associations were found between BMD and the serum 25(OH)D levels in patients with PD. Thus, vitamin D supplementation is a potential therapeutic for non-motor PD symptoms.

Mineral Nutrition and the Risk of Chronic Diseases: A Mendelian Randomization Study.

We applied Mendelian randomization analyses to investigate the potential causality between blood minerals (calcium, magnesium, iron, copper, and zinc) and osteoporosis (OP), gout, rheumatoid arthritis (RA), type 2 diabetes (T2D), Alzheimer's disease (AD), bipolar disorder (BD), schizophrenia , Parkinson's disease and major depressive disorder. Single nucleotide polymorphisms (SNPs) that are independent (r² < 0.01) and are strongly related to minerals (p < 5 × 10-8) are selected as instrumental variables. Each standard deviation increase in magnesium (0.16 mmol/L) is associated with an 8.94-fold increase in the risk of RA (p = 0.044) and an 8.78-fold increase in BD (p = 0.040) but a 0.10 g/cm² increase in bone density related to OP (p = 0.014). Each per-unit increase in copper is associated with a 0.87-fold increase in the risk of AD (p = 0.050) and BD (p = 0.010). In addition, there is suggestive evidence that calcium is positively correlated (OR = 1.36, p = 0.030) and iron is negatively correlated with T2D risk (OR = 0.89, p = 0.010); both magnesium (OR = 0.26, p = 0.013) and iron (OR = 0.71, p = 0.047) are negatively correlated with gout risk. In the sensitivity analysis, causal estimation is not affected by pleiotropy. This study supports the long-standing hypothesis that magnesium supplementation can increase RA and BD risks and decrease OP risk and that copper intake can reduce AD and BD risks. This study will be helpful to address some controversial debates on the relationships between minerals and chronic diseases.

Dissociation between urate and blood pressure in mice and in people with early Parkinson's disease.

BACKGROUND: Epidemiological, laboratory and clinical studies have established an association between elevated urate and high blood pressure (BP). However, the inference of causality remains controversial. A naturally occurring antioxidant, urate may also be neuroprotective, and urate-elevating treatment with its precursor inosine is currently under clinical development as a potential disease-modifying strategy for Parkinson's disease (PD). METHODS: Our study takes advantage of a recently completed phase II trial evaluating oral inosine in de novo non-disabling early PD with no major cardiovascular and nephrological conditions, and of three lines of genetically engineered mice: urate oxidase (UOx) global knockout (gKO), conditional KO (cKO), and transgenic (Tg) mice with markedly elevated, mildly elevated, and substantially reduced serum urate, respectively, to systematically investigate effects of urate-modifying manipulation on BP. FINDINGS: Among clinical trial participants, change in serum urate but not changes in systolic, diastolic and orthostatic BP differed by treatment group. There was no positive correlation between urate elevations and changes in systolic, diastolic and orthostatic BP ((p = .05 (in inverse direction), 0.30 and 0.63, respectively)). Between UOx gKO, cKO, or Tg mice and their respective wildtype littermates there were no significant differences in systolic or diastolic BP or in their responses to BP-regulating interventions. INTERPRETATION: Our complementary preclinical and human studies of urate modulation in animal models and in generally healthy early PD do not support a hypertensive effect of urate elevation or an association between urate and BP. FUND: U.S. Department of Defense, RJG Foundation, Michael J. Fox Foundation LEAPS program, National Institutes of Health, American Federation for Aging Research, Parkinson's Disease Foundation Advancing Parkinson's Therapies initiative.

Proposition of zinc supplementation during levodopa-carbidopa intestinal gel treatment.

OBJECTIVES: Levodopa-carbidopa intestinal gel (LCIG) infusion is a useful therapy for the wearing-off phenomenon of advanced Parkinson's disease (PD) patients. Recently, we found three PD patients that may have had a zinc deficiency after the LCIG infusion, possibly due to the zinc-chelating action of levodopa. This study aims to evaluate changes in serum zinc levels in three patients that received LCIG treatment and to determine possible remedies for zinc deficiency during treatment. MATERIALS AND METHODS: We performed a prospective blood analysis of serum zinc levels before, when possible, and after LCIG treatment in our three PD patients. RESULTS: The serum zinc levels of the first patient before treatment and 4 months after beginning LCIG treatment were 69 and 58 µg/dl, respectively. For the second patient, serum zinc levels before treatment and two months after starting LCIG treatment were 87 and 46 µg/dl, respectively. The baseline serum zinc level for the third patient was not examined, but was 48 µg/dl 5 months after starting the LCIG infusion. CONCLUSIONS: Levodopa-carbidopa intestinal gel infusion might have caused a zinc deficiency through levodopa zinc chelation. Zinc deficiency with LCIG infusion has not yet been reported, though preventing zinc deficiency may be an important factor in future LCIG treatment strategies.

Supplementation of Blackcurrant Anthocyanins Increased Cyclic Glycine-Proline in the Cerebrospinal Fluid of Parkinson Patients: Potential Treatment to Improve Insulin-Like Growth Factor-1 Function.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) function is impaired in Parkinson disease. Cyclic glycine-proline (cGP), a metabolite of IGF-1, is neuroprotective through improving IGF-1 function. Parkinson disease patients score lower on Hospital-associated Anxiety and Depression Scale after supplementing blackcurrant anthocyanins (BCA), which may be associated with IGF-1 function. We evaluated the changes of cGP and IGF-1 before and after the supplementation. METHODS: Plasma and cerebrospinal fluid (CSF) were collected from 11 male patients before and after 28 day supplementation of BCA. The concentrations of IGF-1, IGF binding protein (IGFBP)-3, and cGP were measured using ELISA and HPLC-MS assays. The presence of cGP in the BCA was evaluated. RESULTS: cGP presented in the BCA. BCA supplementation increased the concentration of cGP (p < 0.01), but not IGF-1 and IGFBP-3 in the CSF. CSF concentration of cGP was correlated with plasma concentration of cGP (R = 0.68, p = 0.01) and cGP/IGF-1 molar ratio (R = 0.66, p = 0.01). The CSF/plasma ratio was high in cGP and low in IGF-1 and IGFBP-3. CONCLUSION: cGP is a natural nutrient to the BCA. The increased CSF cGP in Parkinson disease patients may result from the central uptake of plasma cGP. Given neurotrophic function, oral availability, and effective central uptake of cGP, the BCA has the potential to be developed to treat neurological conditions with IGF-1 deficiency.

Plantar stimulation in parkinsonians: From biomarkers to mobility - randomized-controlled trial.

BACKGROUND: The decrease of Brain-Derived Neurotrophic Factor (BDNF) serum levels has been related to the pathophysiology of several neurodegenerative diseases as well as to neural plasticity and rehabilitation. Automated Mechanical Peripheral Stimulation (AMPS) has been investigated as a complementary therapy for Parkinson Disease (PD). OBJECTIVES: (1) to investigate the effects of AMPS on BDNF and Cortisol serum levels of subjects with PD; (2) to evidence the interplay between BDNF and Cortisol serum levels and the functional mobility improvement after AMPS treatment. METHODS: Thirty-three subjects with PD were randomized into two groups: effective stimulation (AMPS, n = 16) or placebo stimulation (AMPS SHAM, n = 17). Fourteen healthy aged-matched subjects were included as a reference group. Each AMPS group received eight sessions of treatment using a commercial medical device (Gondola™). BDNF and Cortisol serum levels, spatiotemporal gait parameters and TUG test were assessed at baseline and after eight sessions of treatment. RESULTS: After the treatment, AMPS group showed significantly higher levels of BDNF and lower levels of Cortisol compared to AMPS SHAM. AMPS group also showed a positive effect on gait pattern as a higher improvement on gait velocity, stride length, and TUG performance was shown. CONCLUSION: Effective AMPS treatment increased BDNF and decreased Cortisol serum levels and produced improvements in functional mobility.

Vitamin B12 and Homocysteine Levels Predict Different Outcomes in Early Parkinson's Disease.

BACKGROUND: In moderately advanced Parkinson's disease (PD), low serum vitamin B12 levels are common and are associated with neuropathy and cognitive impairment. However, little is known about B12 in early PD. OBJECTIVE: To determine the prevalence of low vitamin B12 status in early PD and whether it is associated with clinical progression. METHODS: We measured vitamin B12 and other B12 status determinants (methylmalonic acid, homocysteine, and holotranscobalamin) in 680 baseline and 456 follow-up serum samples collected from DATATOP participants with early, untreated PD. Borderline low B12 status was defined as serum B12 <184 pmol/L (250 pg/mL), and elevated homocysteine was defined as >15 µmol/L. Outcomes included the UPDRS, ambulatory capacity score (sum of UPDRS items 13-15, 29&30), and MMSE, calculated as annualized rates of change. RESULTS: At baseline, 13% had borderline low B12 levels, 7% had elevated homocysteine, whereas 2% had both. Elevated homocysteine at baseline was associated with worse scores on the baseline MMSE. Analysis of study outcomes showed that compared with the other tertiles, participants in the low B12 tertile (<234 pmol/L; 317 pg/mL) developed greater morbidity as assessed by greater annualized worsening of the ambulatory capacity score. Elevated homocysteine was associated with greater annualized decline in MMSE (-1.96 vs. 0.06; P = 0001). Blood count indices were not associated with B12 or homocysteine status. CONCLUSIONS: In this study of early PD, low B12 status was common. Low B12 at baseline predicted greater worsening of mobility whereas elevated homocysteine predicted greater cognitive decline. Given that low B12 and elevated homocysteine can improve with vitamin supplementation, future studies should test whether prevention or early correction of these nutritionally modifiable conditions slows development of disability. © 2018 International Parkinson and Movement Disorder Society.

Preclinical and clinical assessment of inhaled levodopa for OFF episodes in Parkinson's disease.

Inhaled drugs offer advantages, such as rapid onset of action, but require formulations and delivery systems that reproducibly and conveniently administer the drug. CVT-301 is a powder formulation of levodopa delivered by a breath-actuated inhaler that has been developed for treating OFF episodes (motor fluctuations between doses of standard oral levodopa) in patients with Parkinson's disease (PD). We present preclinical, phase 1, and phase 2 results for CVT-301. In dogs insufflated with a levodopa powder, plasma levodopa peaked in all animals 2.5 min after administration; in contrast, in dogs dosed orally with levodopa plus carbidopa, plasma levodopa was not detected until 30 min after administration. In 18 healthy persons, comparisons between inhaled CVT-301 and oral carbidopa/levodopa showed analogous differences in pharmacokinetics. Among 24 PD patients inhaling CVT-301 as a single 50-mg dose during an OFF episode, 77% showed an increase in plasma levodopa (>400 ng/ml) within 10 min versus 27% for oral dosing with carbidopa/levodopa at a 25-mg/100-mg dose. Improvements in timed finger tapping and overall motor function (Part III of the Unified Parkinson's Disease Rating Scale) were seen 5 and 15 min after administration, the earliest assessment time points. For average and best change, the improvements were statistically significant compared to placebo. The most common adverse event was cough; all cough events were mild to moderate, occurred at the time of inhalation, resolved rapidly, and became less frequent after initial dosing. These results support further development of CVT-301 for better management of PD.

Biochemical and clinical effects of Whey protein supplementation in Parkinson's disease: A pilot study.

BACKGROUND: Parkinson's disease (PD) is an oxidative stress-mediated degenerative disorder. Elevated plasma homocysteine (Hcy) is frequently found in the levodopa-treated PD patients, is associated with disease progression and is a marker of oxidative stress. Whey protein is a rich source of cysteine, and branched-chain amino acids (BCAA). It has been shown that supplementation with Whey protein increases glutathione synthesis and muscle strength. OBJECTIVES AND METHODS: In this study, we conducted a placebo-controlled, double-blind study (NCT01662414) to investigate the effects of undenatured Whey protein isolate supplementation for 6months on plasma glutathione, plasma amino acids, and plasma Hcy in PD patients. Clinical outcome assessments included the unified Parkinson's disease rating scale (UPDRS) and striatal L-3,4-dihydroxy-6-(18)F-fluorophenylalanine (FDOPA) uptake were determined before and after supplementation. 15 patients received Whey protein, and 17 received Soy protein, served as a control group. RESULTS: Significant increases in plasma concentration of reduced glutathione and the ratio of reduced to oxidized glutathione were found in the Whey-supplemented patients but not in a control group. This was associated with a significant decrease of plasma levels of Hcy. The plasma levels of total glutathione were not significantly changed in either group. Plasma BCAA and essential amino acids (EAA) were significantly increased in the Whey-supplemented group only. The UPDRS and striatal FDOPA uptake in PD patients were not significantly ameliorated in either group. However, significant negative correlation was observed between the UPDRS and plasma BCAA and EAA in the pre-supplemented PD patients. CONCLUSION: This study is the first to report that Whey protein supplementation significantly increases plasma reduced glutathione, the reduced to oxidized glutathione ratio, BCAAs and EAAs in patients with PD, together with a concomitant significant reduction of plasma Hcy. However, there were no significant changes in clinical outcomes. Long-term, large randomized clinical studies are needed to explore the benefits of Whey protein supplementation in the management of PD patients.

Mucuna pruriens for Parkinson's disease: Low-cost preparation method, laboratory measures and pharmacokinetics profile.

BACKGROUND: Parkinson's disease (PD) is a progressive neurological condition. Levodopa (LD) is the gold standard therapy for PD patients. Most PD patients in low-income areas cannot afford long-term daily Levodopa therapy. The aim of our study was to investigate if Mucuna pruriens (MP), a legume with high LD content that grows in tropical regions worldwide, might be potential alternative for poor PD patients. METHODS: We analyzed 25 samples of MP from Africa, Latin America and Asia. We measured the content in LD in various MP preparations (dried, roasted, boiled). LD pharmacokinetics and motor response were recorded in four PD patients, comparing MP vs. LD+Dopa-Decarboxylase Inhibitor (DDCI) formulations. RESULTS: Median LD concentration in dried MP seeds was 5.29%; similar results were obtained in roasted powder samples (5.3%), while boiling reduced LD content up to 70%. Compared to LD+DDCI, MP extract at similar LD dose provided less clinical benefit, with a 3.5-fold lower median AUC. CONCLUSION: Considering the lack of a DDCI, MP therapy may provide clinical benefit only when content of LD is at least 3.5-fold the standard LD+DDCI. If long-term MP proves to be safe and effective in controlled clinical trials, it may be a sustainable alternative therapy for PD in low-income countries.

Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease.

BACKGROUND: Recent studies have suggested that melatonin-a hormone produced by the pineal gland under circadian control-contributes to PD-related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We compared hypothalamic volumes in PD patients with matched controls and determined whether volume loss correlated with reduced melatonin output in the PD group. METHODS: A total of 12 PD patients and 12 matched controls underwent magnetic resonance imaging to determine hypothalamic volume. In addition, PD patients underwent 24-hour blood sampling in a controlled environment to determine serum melatonin concentrations using enzyme-linked immunosorbent assays. RESULTS: PD patients had significantly reduced hypothalamic gray matter volume when compared with matched controls. Melatonin levels were significantly associated with hypothalamic gray matter volume and disease severity in PD patients. CONCLUSION: Melatonin levels are associated with hypothalamic gray matter volume loss and disease severity in PD patients. This provides anatomical and physiological support for an intrinsic sleep and circadian phenotype in PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Vitamin D deficiency and its role in neurological conditions: A review.

This review exposes recent advances on the role of vitamin D, cholecalciferol, a secosteroid, in the central nervous system. In humans, vitamin D arises from cutaneous transformation of 7-dehydrocholesterol under the effect of UVB exposure or from food intake. Vitamin D has an immunomodulatory role through its anti-inflammatory and anti-autoimmune actions. In the nervous system, vitamin D is involved in the regulation of calcium-mediated neuronal excitotoxicity, in the reduction of oxidative stress, and in the induction of synaptic structural proteins, neurotrophic factors and deficient neurotransmitters. Reduced exposure to sunlight and low food intake can lead to vitamin D deficiency. Increasing evidence highlights the impact of vitamin D deficiency as a favoring factor in various central or peripheral neurological diseases, especially multiple sclerosis and several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. Recently, several clinical trials on vitamin D supplementation stressed the role of vitamin D as a protective and/or prognostic factor in the onset and progress of such neurological conditions.

Systematic Review of the Relationship between Vitamin D and 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.

Associations between Vitamin D Status, Supplementation, Outdoor Work and Risk of Parkinson's Disease: A Meta-Analysis Assessment.

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.