vitamin-b-12 and Parkinson-Disease

This umbrella review aimed to systematically review the available literature and assess the association of dietary intake or serum levels of different vitamins and the risk of PD, to help find out more efficient treatments for PD patients by replenishing the deficiency of vitamins.. Pubmed/Medline, Scopus, Google Scholar and hand searching bibliographies of retrieved articles in duplicate, were used to detect all relevant meta-analyses investigating the relationship between vitamins and PD. After study selection, data were extracted from previously published meta-analyses and pooled by Review Manager version 5.4 and CMA software version 2.2.064 to achieve effect sizes. Level of statistical significance was set at P ≤ 0.05.. 14 meta-analyses were included in the meta-review. Serum vitamin D and B12 levels were significantly lower in PD (SMD = -0.67 and SMD = -0.40 respectively). Homocysteine (Hcy) levels were significantly higher in PD patients (SMD = 1.26). Also the odds ratio for highest vs. lowest vitamin E intake was 0.73 which was significant. However, there was no significant difference between vitamin A, C and B6 intake or serum levels in PD vs. control groups.. Serum vitamin D and B12 levels were significantly lower in PD in comparison to healthy individuals, while Hcy level was significantly higher in PD patients. Also higher vitamin E intake was associated with significantly lower risk of development of PD in comparison to lower vitamin E intake. However, there was no significant difference between risk of PD and higher vitamin A, C and B6 intake or serum levels of folate.

Topics: Humans; Parkinson Disease; Systematic Reviews as Topic; Vitamin A; Vitamin B 12; Vitamin D; Vitamin E; Vitamin K; Vitamins

Hyperhomocysteinemia is considered an independent risk factor for cognitive impairment.. To study the correlation between homocysteine levels and cognitive impairment in patients with PD.. We conducted a case-control study that included 246 patients with PD, of whom 32 were cognitively impaired. The levels of homocysteine, folate, and vitamin B12 were measured in peripheral blood. Multivariate logistic regression analysis was applied to determine differences in homocysteine levels between PD patients with and without cognitive impairment. A meta-analysis was performed to clarify the role of Hcy levels in PD with cognitive decline. Five polymorphisms in genes involved in Hcy metabolism, including MTHFR rs1801133 and rs1801131, COMT rs4680, MTRR rs1801394, and TCN2 rs1801198, were genotyped.. Our case-control study showed that homocysteine levels were associated with cognitive impairment in PD after adjusting for possible confounding factors such as levodopa equivalent daily dose. The results of our meta-analysis further supported the positive association between homocysteine levels and cognition in PD. We found that the MTHFR rs1801133 TT genotype led to higher homocysteine levels in PD patients, whereas the MTHFR rs1801131 CC genotype resulted in higher folate levels. However, the polymorphisms studied were not associated with cognitive impairment in PD.. Increased homocysteine levels were a risk factor for cognitive decline in PD. However, no association was found between polymorphisms in genes involved in homocysteine metabolism and cognitive impairment in PD. Large-scale studies of ethnically diverse populations are required to definitively assess the relationship between MTHFR and cognitive impairment in PD.

Topics: Case-Control Studies; Cognitive Dysfunction; Folic Acid; Genetic Background; Genotype; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Parkinson Disease; Vitamin B 12

Elevated circulating homocysteine levels have been associated with cognitive impairment and cardio-cerebro-vascular events. Levodopa treatment of Parkinson's disease tends to further elevate circulating homocysteine levels due to the metabolism of levodopa via catechol-O-methyltransferase (COMT). COMT co-factors are vitamins B12, B6 and folic acid. Accumulating deficiencies of these vitamins are presumed to be the substrate for the homocysteine elevation. B-vitamin therapy reduces homocysteine levels. This begs the question of whether Parkinson's disease patients on levodopa should be concurrently treated with ongoing B-vitamin therapy (versus long-term monitoring of B-vitamins/homocysteine). There is a substantial literature on this topic that has accumulated over the last quarter-century, and this topic is still debated. This review summarizes the relevant literature with the aim of approximating closure on this issue. Also, noteworthy is that Parkinson's disease patients with renal insufficiency may not tolerate cyanocobalamin, the standard oral B12 supplement due to facilitation of renal decline; alternatives are discussed.

Topics: Antiparkinson Agents; Catechol O-Methyltransferase; Homocysteine; Humans; Levodopa; Parkinson Disease; Vitamin B 12; Vitamin B Complex

The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable. Potential contributors to abnormal B6 levels in PwPD include age, dietary habits, vitamin supplement misuse, gastrointestinal dysfunction and complex interactions with levodopa. The literature on the potential consequences of abnormal B6 levels in PwPD is limited by a small number of observational studies focused on polyneuropathy and epilepsy. Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa. In almost all studies reporting low B6 in PwPD receiving oral levodopa-carbidopa, the dose of levodopa was ≥1000 mg/day. Rigorous epidemiological studies will clarify the prevalence, natural history and clinical relevance of abnormal serum levels of vitamin B6 in PwPD. These studies should account for diet, vitamin supplement use, gastrointestinal dysfunction, concurrent levels of vitamin B12, folate, homocysteine and methylmalonic acid, formulations and dosages of levodopa and other medications commonly used in PwPD.

Topics: Aged; Antiparkinson Agents; Carbidopa; Epilepsy; Humans; Levodopa; Parkinson Disease; Polyneuropathies; Vitamin B 12; Vitamin B 6; Vitamins

Emerging studies suggest a correlation between elevated plasma homocysteine (hcy) levels and the risk of atherosclerosis, vascular disorders, and neurodegenerative diseases, including Parkinson's disease (PD). This narrative review delves into the intricate relationships between Hcy, vitamin B metabolites, dopamine-substituting compounds, and various symptoms of PD. Patients undergoing a long-term L-dopa/dopa-decarboxylase inhibitor (DDI) regimen, especially without a concurrent catechol-O-methyl transferase (COMT) inhibitor or methyl group-donating vitamin supplementation, such as vitamins B6 and B12, exhibit an elevation in Hcy and a decline in vitamin B metabolites. These altered concentrations appear to be associated with heightened risks of developing non-motor symptoms, including peripheral neuropathy and cognitive disturbances. The review underscores the impact of levodopa metabolism via COMT on homocysteine levels. In light of these findings, we advocate for the supplementation of methyl group-donating vitamins, notably B6 and B12, in patients undergoing a high-dose L-dopa/DDI regimen, particularly those treated with L-dopa/carbidopa intestinal gel (LCIG) infusion.

Topics: Antiparkinson Agents; Catechol O-Methyltransferase; Dopamine; Homocysteine; Humans; Levodopa; Parkinson Disease; Vitamin B 12; Vitamins

Many studies have shown that the levels of homocysteine (Hcy), vitamin B12 (Vit B12), and folate (FA) are abnormal in patients with Parkinson's disease (PD), but the results have not been consistent. Therefore, we conducted this meta-analysis to summarize the features of Hcy, Vit B12, and FA in PD patients.. A systematic literature search was conducted on PubMed, Cochrane Library, Web of Science, and Embase databases.. A total of 71 studies were included. The analysis showed the following. (1) PD patients had significantly increased Hcy level (standardized mean difference [SMD] 0.80, 95% confidence interval [CI] [0.61, 0.99];. In conclusion, PD patients may have higher Hcy levels and lower Vit B12 and FA levels than the healthy population. Thus, Hcy, Vit B12, and FA may play a role in cognitive impairment and neuropathy in PD patients.

Topics: Cognitive Dysfunction; Folic Acid; Homocysteine; Humans; Parkinson Disease; Vitamin B 12

Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise unpredictable motor fluctuations and other complications. Counteracting these complications with other pharmacological therapies may prompt a vicious circle of side effects, and here, nutritional therapy may have great potential. Knowledge about the role of diet in PD is emerging and multiple studies have investigated nutritional support specifically with respect to levodopa therapy. With this systematic review, we aim to give a comprehensive overview of dietary approaches to optimize levodopa treatment in PD. A systematic search was performed using the databases of PubMed and Scopus between January 1985 and September 2020. Nutritional interventions with the rationale to optimize levodopa therapy in human PD patients were eligible for this study and their quality was assessed with the Cochrane risk-of-bias tool. In total, we included 22 papers that addressed the effects of dietary proteins (n = 10), vitamins (n = 7), fiber (n = 2), soybeans (n = 1), caffeine (n = 1), and ketogenic diets (n = 1) on levodopa therapy. Interventions with protein redistribution diets (PRDs), dietary fiber, vitamin C, and caffeine improved levodopa absorption, thereby enhancing clinical response and reducing motor fluctuations. Furthermore, supplementation of vitamin B-12, vitamin B-6, and folic acid successfully reduced high homocysteine concentrations that emerged from levodopa metabolism and promoted many metabolic and clinical complications, such as neuropathology and osteoporosis. In conclusion, dietary interventions have the potential to optimize levodopa efficacy and control side effects. Nutrition that improves levodopa absorption, including PRDs, fiber, vitamin C, and caffeine, is specifically recommended when fluctuating clinical responses appear. Supplements of vitamin B-12, vitamin B-6, and folic acid are advised along with levodopa initiation to attenuate hyperhomocysteinemia, and importantly, their potential to treat consequent metabolic and clinical complications warrants future research.

Topics: Antiparkinson Agents; Diet; Humans; Levodopa; Parkinson Disease; Vitamin B 12

Epidemiological studies evaluating the associations of plasma homocysteine (Hcy), folate and vitamin B12 levels with Parkinson's disease (PD) in China have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize the relationships. PubMed, Cochrane Library, Elsevier Science Direct, Springer, CNKI (China National Knowledge Infrastructure), and Wanfang (Chinese) databases were searched for eligible studies from January 2000 to November 2018. The pooled standardized mean difference (SMD), Fisher's Z and corresponding 95% confidence interval (95% CI) were calculated with fix-effects or random-effects model. In total, 26 case-control studies and 1 cross-sectional study were included in this meta-analysis. The results showed that: (1) PD patients had a higher Hcy level than the control individuals (P <0.05). After stratification subgroup, significant differences of plasma Hcy level between PD patients and controls were found in subgroup with sample size< 100, sample size ≥100, as well as in the subgroup analysis by levodopa therapy. (2) Both plasma folate and vitamin B12 levels were lower in the PD patients compared with the control group (P <0.05). (3) Plasma Hcy level was negatively correlated with plasma levels of folate and vitamin Bl2 in PD patients (P <0.05). (4) The relevant influential factors of plasma Hcy level in PD patients were clinical types, Hoehn & Yahr stage, cognitive impairment, or levodopa therapy (P <0.05). In conclusion, PD patients had a higher Hcy level in China. Multiple factors were associated with Hcy levels of Chinese PD patients.

Topics: Case-Control Studies; China; Folic Acid; Homocysteine; Humans; Parkinson Disease; Vitamin B 12

Peripheral neuropathy (PN) is a common neurological problem defined as a dysfunction of sensory, motor, and autonomic nerves. The presence of peripheral neuropathy has recently been noticed in Parkinson's disease (PD) This comorbidity is concerning as it increases the burden on patients whose motor functions are previously compromised. A comprehensive computer-based literature review utilizing multiple peer-reviewed databases (e.g., Embase, PsycINFO, CINAHL, etc.) was conducted. There is evidence for the utility of robust diagnostic criteria to distinguish between large fiber neuropathy (LFN) and small fiber neuropathy (SFN). Some studies have established links between prolonged L-DOPA exposure and prevalence with increased levels of homocysteine (HCY) and methylmalonic acid (MMA) as pathological underlying mechanisms. PN in PD patients with relatively truncated exposure to L-DOPA therapy may have underlying mutations in the Parkin and MHTFR gene or separate mitochondrial disorders. Vitamin B12 and cobalamin deficiencies have also been implicated as drivers of PN. Accumulation of phosphorylated α-synuclein is another central feature in PN and deems urgent exploration via large cohort studies. Importantly, these underlying mechanisms have been linked to peripheral denervation. This review delves into the potential treatments for PN targeting B12 deficiencies and the use of COMT inhibitors along with other novel approaches. Avenues of research with powerful randomized controlled and long-term cohort studies exploring genetic mechanisms and novel treatment pathways is urgently required to alleviate the burden of disease exerted by PN on PD.

Topics: Humans; Levodopa; Methylmalonic Acid; Parkinson Disease; Peripheral Nervous System Diseases; Vitamin B 12

Topics: Acetylcholine; Cognition Disorders; Humans; Parkinson Disease; Severity of Illness Index; Vitamin B 12

Hyperhomocysteinemia has been associated with cognitive disorders such as mild cognitive impairment, Alzheimer's disease and vascular dementia. Previous studies showed that levodopa-treated Parkinson's disease (PD) patients were likely to have elevated homocysteine levels. In addition, epidemiological evidence found that cognitive impairment presented in the vast majority of PD patients. However, what role homocysteine played in cognitive function of PD patients remained debated. Therefore, we conducted this meta-analysis to investigate the possible correlations among cognitive function, homocysteine, folate and vitamin B12 levels in PD patients. A structured literature search was carried out on Pubmed, Springer, EMbase, Cochrane library, CNKI, VP and Wanfang database up to April 2016 using strict inclusion criteria. Data on demographic information, levodopa equivalent dosage, homocysteine, folate and vitamin B12 levels and Mini Mental Scale Examination scores were collected and pooled. The mean difference (MD) with 95% confidence intervals (CIs) was used as the effect size. Of 75 articles identified, 15 were eligible for inclusion. The results suggested that PD patients with cognitive dysfunction were likely to have higher homocysteine levels(MD=5.05, 95%CI [4.03, 6.07]), lower folate(MD=-0.21, 95%CI [-0.34, -0.08]) and vitamin B12 levels(MD=-47.58, 95%CI [-72.07, -23.09]). We again verified a close relationship between hyperhomocysteinemia and PD (MD=5.67, 95%CI [4.40, 6.94]). We concluded that hyperhomocysteinemia was related to cognitive impairment of PD patients, and further studies should focus on the intervention to lower homocysteine level, hopefully to provide useful advice for clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Cognition; Cognition Disorders; Female; Folic Acid; Homocysteine; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Treatment Outcome; Vitamin B 12

Patients with Parkinson's disease (PD) treated with oral levodopa have a higher prevalence of chronic, prevalently sensory, usually mild axonal polyneuropathy (PNP). Several studies showed a positive association among PNP, cumulative levodopa dosage, low serum B12 and high-homocysteine and methylmalonic acid level. Anecdotal severe acute or subacute PNPs thought to be Guillain-Barré syndrome have been reported in patients receiving continuous intraduodenal infusion of levodopa/carbidopa intestinal gel (LCIG). We report an additional acute case and by a systematic literature search we also reviewed the clinical and laboratory features of 13 other acute and 21 subacute PNP cases occurring during LCIG treatment. In series with at least nine patients, the mean frequency of acute and subacute PNP is 13.6% and the mortality rate at 6 months in acute cases is 14%. The great majority of PNP cases displayed axonal sensory-motor and reduced vitamin B12 levels, and alterations of metabolites of 1-carbon pathway were found in most patients. We discuss the possible role of high-levodopa dosage, vitamin B12, B6 and folate deficiency and accumulation of homocysteine and methylmalonic acid in the pathogenesis to conclude that there is enough, although circumstantial, evidence that alterations of 1-carbon pathway are implicated also in acute and subacute PNP during LCIG usage. There is no solid proof for a dysimmune pathogenesis and in our opinion acute, subacute and chronic PNP, either after oral levodopa or LCIG, represent a continuum. Finally, we propose recommendations for prevention and management of PNP occurring during LCIG treatment.

Topics: Administration, Oral; Carbidopa; Drug Combinations; Female; Gels; Humans; Levodopa; Parkinson Disease; Polyneuropathies; Vitamin B 12

B vitamins may correlate with Parkinson's disease (PD) through regulating homocysteine level. However, there is no comprehensive assessment on the associations between PD and B vitamins. The present study was designed to perform a meta-analytic assessment of the associations between folate, vitamin B6, and vitamin B12 and PD, including the status of B vitamins in PD patients compared with controls, and associations of dietary intakes of B vitamins and risk of PD. A literature search using Medline database obtained 10 eligible studies included in the meta-analyses. Stata 12.0 statistical software was used to perform the meta-analysis. Pooled data revealed that there was no obvious difference in folate level between PD patients and healthy controls, and PD patients had lower level of vitamin B12 than controls. Available data suggested that higher dietary intake of vitamin B6 was associated with a decreased risk of PD (odds ratio (OR) = 0.65, 95% confidence intervals (CI) = (0.30, 1.01)), while no significant association was observed for dietary intake of folate and vitamin B12 and risk of PD. PD patients had lower level of vitamin B12 and similar level of folate compared with controls. Dietary intake of vitamin B6 exhibited preventive effect of developing PD based on the available data. As the number of included studies is limited, more studies are needed to confirm the findings and elucidate the underpinning underlying these associations.

Topics: Case-Control Studies; Diet; Folic Acid; Humans; Odds Ratio; Parkinson Disease; Protective Factors; Risk Assessment; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Elevated concentration of total homocysteine (Hcy) in plasma (> 12 micromol/l) is a risk factor for several diseases of the central nervous system. Epidemiological studies have shown a dose-dependent relationship between concentrations of Hcy and the risk for neurodegenerative diseases. Hcy is a marker for B-vitamin deficiency (folate, B12, B6). Hyperhomocysteinemia (HHcy) causes hypomethylation which is an important mechanism that links Hcy to dementia. Supplementation with vitamins B aims at reducing the risk of neurodegenerative diseases. Current evidence suggests that Hcy-lowering treatment has a positive effect for the secondary and primary prevention of stroke. HHcy is very common in patients with Parkinson disease particularly those who receive L-dopa treatment. Furthermore, a positive association has been reported between HHcy and multiple sclerosis. Moreover, HHcy and vitamin B deficiency are reported to have a causal role in depression, and epilepsy. In addition several anti-epileptic drugs cause secondary HHcy. Therefore, sufficient intakes of the vitamins are recommended for patients who have already developed neuropsychiatric diseases. Vitamin B deficiency should be suspected in children with development disorders, failure to thrive and unexplained neurological manifestations. Elderly people are also an important at-risk group where vitamin B deficiency and HHcy have been linked to neurodegenerative diseases. Treatment with folate, B12, and B6 can improve cerebral function. Preventive vitamin B supplementation and sufficient intake seem very important for secondary and primary prevention of neuropsychiatric disorders, especially in subjects with a low intake or status of the vitamins.

Topics: Aged; Central Nervous System; Child; Dietary Supplements; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Mental Disorders; Nervous System Diseases; Parkinson Disease; Risk Factors; Vitamin B 12; Vitamin B Deficiency

To assess the effects, associations, mechanisms of action, and safety of B vitamins and, separately, berries and their constituents on age-related neurocognitive disorders-primarily Alzheimer's (AD) and Parkinson's disease (PD).. MEDLINE and CAB Abstracts. Additional studies were identified from reference lists and technical experts.. Vitamins B1, B2, B6, B12, and folate, and a dozen types of berries and their constituents were evaluated. Human, animal, and in vitro studies were evaluated. Outcomes of interest from human studies were neurocognitive function or diagnosis with AD, cognitive decline, PD, or related conditions. Intervention studies, associations between dietary intake and outcomes, and associations between B vitamin levels and outcomes were evaluated. Specific mechanisms of action were evaluated in animal and in vitro studies. Studies were extracted for study design, demographics, intervention or predictor, and neurocognitive outcomes. Studies were graded for quality and applicability.. In animal studies, deficiencies in vitamins B1 or folate generally cause neurological dysfunction; supplementation with B6, B12, or folate may improve neurocognitive function. In animal experiments folate and B12 protect against genetic deficiencies used to model AD; thiamine and folate also affect neurovascular function and health. Human studies were generally of poor quality. Weak evidence suggests possible benefits of B1 supplementation and injected B12 in AD. The effects of B6 and folate are unclear. Overall, dietary intake studies do not support an association between B vitamin intake and AD. Studies evaluating B vitamin status were mostly inadequate due to poor study design. Overall, studies do not support an association between B vitamin status and age-related neurocognitive disorders. Only one study evaluated human berry consumption, finding no association with PD. Animal studies of berries have almost all been conducted by the same research group. Several berry constituents have been shown to affect brain and nerve tissue function. Blueberry and strawberry extract were protective of markers of disease, although effects on neurocognitive tests were less consistent. Berry extracts may protect against the deleterious effects of compounds associated with AD. Reporting of adverse events was uncommon. When reported, actual adverse events from B vitamins were rare and minor.. The current research on B vitamins is largely inadequate to confidently assess their mechanisms of action on age-related neurocognitive disorders, their associations with disease, or their effectiveness as supplements. B vitamin supplementation may be of value for neurocognitive function, but the evidence is inconclusive.

Topics: Aging; Alzheimer Disease; Animals; Blueberry Plants; Cognition; Disease Models, Animal; Folic Acid; Fragaria; Fruit; Humans; Neurodegenerative Diseases; Parkinson Disease; Plant Extracts; Riboflavin; Thiamine; Vitamin B 12; Vitamin B 6; Vitamin B Complex

The author presents an overview of the current literature on homocysteine as a risk factor for neuropsychiatric disorders. The databases MEDLINE, Current Contents and EMBASE were searched (between 1966 and 2002) for English language publications with the key words 'Homocysteine' and 'Stroke'; 'Alzheimer Disease'; 'Cognitive Impairment'; 'Epilepsy'; 'Depression'; or 'Parkinson's disease'. Individual articles were hand searched for relevant cross-references. It is biologically plausible that high homocysteine levels may cause brain injury and neuropsychiatric disorders. Homocysteine is proatherogenic and prothrombotic, thereby increasing the risk of cerebrovascular disease, and may have a direct neurotoxic effect. Evidence for homocysteine as a risk factor for cerebral microvascular disease is conflicting but warrants further study. Cross-sectional and some longitudinal studies support increased prevalence of stroke and vascular dementia in hyperhomocysteinemic individuals. The evidence of increased neurodegeneration is accumulating. The relationship with depression is still tentative, as it is with epilepsy. Currently, treatment studies are necessary to place the evidence on a stronger footing, and maybe high-risk patients should be screened for hyperhomocysteinemia and this should be treated with folic acid. More research evidence is necessary before population screening can be recommended.

Topics: Alzheimer Disease; Dementia, Vascular; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Mental Disorders; Parkinson Disease; Risk Factors; Stroke; Vitamin B 12; Vitamin B 6

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.. 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.. 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.. 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.

Topics: Aged; Antiparkinson Agents; Catechols; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Research Design; Vitamin B 12

The manuscript is a commenting on the article "Effects of vitamin B12, folate, and entacapone on homocysteine levels in levodopa-treated Parkinson's disease patients: A randomized controlled study", recently published by Anamnart and Kitjarak (2021), in this prestigious journal. The authors demonstrated that combination supplementation with vitamin B12 and folate was associated with significantly decreased plasma homocysteine (Hcy), suggesting that plasma Hcy levels should be monitored during levodopa treatment, and supplementation with inexpensive vitamin B12 and folate is beneficial for levodopa-treated PD patients. Considering some evidences - i) that it has to be indicated that dietary and supplemental thiamine intake has a protective effect on various medical conditions, including PD; ii) that several studies highlighted a possible relationship between PD low levels of thiamine in the serum, suggesting that elevated thiamine levels might protect against PD; iii) that thiamine deficiency is not just a common finding in patients with cardiovascular dysfunctions, but it might also have a role in the development and prognosis of PD - our research group believes that some comprehensive cardiovascular screening protocols should be developed for PD patients in order to reduce fatal events in these individuals.

Topics: Folic Acid; Homocysteine; Humans; Levodopa; Parkinson Disease; Thiamine Deficiency; Vitamin B 12

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.. To determine the prevalence of low vitamin B12 status in early PD and whether it is associated with clinical progression.. 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.. 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.. 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.

Topics: alpha-Tocopherol; Antioxidants; Antiparkinson Agents; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Homocysteine; Humans; Male; Mental Status Schedule; Middle Aged; Parkinson Disease; Predictive Value of Tests; Selegiline; Treatment Outcome; Vitamin B 12

The progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.. A 1-year phase I proof-of-concept study.. The Department of Psychiatry and Psychotherapy at the University of Cologne.. We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent.. Bilateral low-frequency DBS of the nucleus basalis of Meynert.. Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.. With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = -0.829, p = 0.042).. Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.

Topics: Aged; Alzheimer Disease; Basal Nucleus of Meynert; Body Composition; Body Weight; Cognition; Deep Brain Stimulation; Diet Records; Female; Folic Acid; Humans; Male; Middle Aged; Nutritional Status; Parkinson Disease; Pilot Projects; Vitamin B 12

We tested the hypothesis that mood, clinical manifestations and cognitive impairment of levodopa-treated Parkinson's disease (PD) patients are associated with vitamin B12 and folate deficiency. To this end, we performed this cross-sectional study by measuring serum folate and vitamin B12 blood levels in 111 consecutive PD patients. Levodopa-treated PD patients showed significantly lower serum levels of folate and vitamin B12 than neurological controls, while depressed patients had significantly lower serum folate levels as compared to non-depressed. Cognitively impaired PD patients exhibited significantly lower serum vitamin B12 levels as compared to cognitively non-impaired. In conclusion, lower folate levels were associated with depression, while lower vitamin B12 levels were associated with cognitive impairment. The effects of vitamin supplementation merit further attention and investigation.

Topics: Affect; Aged; Aged, 80 and over; Analysis of Variance; Antiparkinson Agents; Case-Control Studies; Cognition; Enzyme-Linked Immunosorbent Assay; Female; Folic Acid; Humans; Levodopa; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Vitamin B 12

Serum folate and vitamin B12 levels were measured in 67 consecutive Parkinson's disease patients treated either with levodopa + dopa decarboxylase inhibitor (DDC-i) plus catechol-O-methyltransferase inhibitors (COMT-i) or only with levodopa + DDC-i. The data were compared to 67 age-matched controls. Our findings show that levodopa-treated Parkinson's disease patients have low folate (p < 0.0007) and vitamin B12 levels (p < 0.0003). They also demonstrate that the addition of a COMT-i to levodopa + DDC-i treatment causes lower serum vitamin B12 (p < 0.03) and folate levels (p < 0.005) than levodopa + DDC-i treatment alone. We suggest supplementary treatment with vitamin B12 and folic acid in these situations.

Topics: Aged; Analysis of Variance; Antiparkinson Agents; Case-Control Studies; Catechols; Female; Folic Acid; Humans; Immunoassay; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Vitamin B 12

Elevated homocysteine is associated with increased risk of heart disease, stroke, and dementia. Therapy of Parkinson disease (PD) with levodopa elevates homocysteine. The authors conducted a 6-week, multicenter, randomized, double-blind, placebo-controlled trial to test whether folate 1 mg/vitamin B(12) 500 microg or entacapone reduced serum homocysteine in 35 levodopa-treated PD patients. Levodopa initiation caused a small elevation in homocysteine. Vitamin therapy, but not entacapone, resulted in a decrease in homocysteine compared to placebo.

Topics: Aged; Antiparkinson Agents; Canada; Catechols; Double-Blind Method; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Placebo Effect; Treatment Outcome; United States; Vitamin B 12; Vitamins

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson disease (PD), through neurotoxic effects. Higher dietary intakes of folate, vitamin B12, and vitamin B6 (cofactors in homocysteine metabolism) might decrease the risk of PD through decreasing plasma homocysteine. Moreover, vitamin B6 might influence the risk of PD through antioxidant effects unrelated to homocysteine metabolism and through its role in dopamine synthesis.. In the Rotterdam Study, a prospective, population-based cohort study of people aged 55 years and older, the authors evaluated the association between dietary intake of folate, vitamin B12, and vitamin B6 and the risk of incident PD among 5,289 participants who were free of dementia and parkinsonism and underwent complete dietary assessment at baseline. PD was assessed through repeated in-person examination and continuous monitoring by computer linkage to medical records. Data were analyzed using Cox proportional hazards regression analysis.. After a mean follow-up of 9.7 years, the authors identified 72 participants with incident PD. Higher dietary intake of vitamin B6 was associated with a significantly decreased risk of PD (hazard ratio per SD, 0.69 [95% CI 0.50 to 0.96]; for highest vs lowest tertile, 0.46 [0.22 to 0.96]). Stratified analyses showed that this association was restricted to smokers. No association was observed for dietary folate and vitamin B(12).. Dietary vitamin B6 may decrease the risk of Parkinson disease, probably through mechanisms unrelated to homocysteine metabolism.

Topics: Administration, Oral; Cohort Studies; Diet Therapy; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Male; Middle Aged; Netherlands; Parkinson Disease; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin B 12; Vitamin B 6

The aim of this study was to determine whether hyperhomocysteinemia caused by levodopa used in idiopathic Parkinson's disease (IPD) is associated with cognitive or physical impairments. The role of folate and vitamin B12 levels in this context was also ascertained.. Thirty-nine patients who had been followed with the diagnosis of IPD in our clinic for > 2 years and 28 healthy control subjects with similar demographic features were included in the study. The homocysteine, folic acid and vitamin B12 levels and the results of the short test of mental status (STMS) and the clock drawing test of IPD patients were compared with those of the controls. Subsequently, the patients with a homocysteine level of >14 micromol/l were compared with those having a homocysteine level of <14 micromol/l by means of detailed neuropsychometric test batteries.. Homocysteine levels were significantly higher in the patient group in comparison with the controls. There was a negative correlation between hyperhomocysteinemia and the levels of vitamin B12 and folate. On the other hand, a positive correlation between hyperhomocysteinemia and the levodopa dose was detected. There was a positive correlation between hyperhomocysteinemia and unified Parkinson's disease rating scale (UPDRS) motor section. The critical dose of levodopa was observed to be 300 mg/d. In terms of cognitive and frontal functions, no significant difference was detected between the patients and control group. The subgroup with a homocysteine level of >14 micromol/l had a significantly poorer performance in frontal and memory tests.. In patients with IPD who are detected to have hyperhomocysteinemia, the assessment of the cognitive performance, folic acid and vitamin B12 levels and the supplementation of folic acid and vitamin B12 to the treatment regimen might be appropriate.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Case-Control Studies; Cognition; Enzyme-Linked Immunosorbent Assay; Female; Folic Acid; Homocysteine; Humans; Levodopa; Male; Middle Aged; Motor Activity; Neuropsychological Tests; Parkinson Disease; Statistics, Nonparametric; Vitamin B 12

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment, and dementia. Elevated plasma concentrations of Hcy have been found recently in Parkinson's disease (PD) patients treated with levodopa, suggesting that levodopa is a cause of hyperhomocysteinemia (HHcy). The mechanism underlying HHcy in PD is the O-methylation of levodopa catalyzed by catechol-O-methyltransferase (COMT) that produces S-adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. COMT inhibitors (COMT-I) are used currently in the treatment of PD; however, no study has assessed the effects of COMT-I administration on Hcy concentrations in PD patients. We compared plasma levels of Hcy, B12, and folate in 26 PD patients treated with levodopa, 20 PD patients treated with levodopa + COMT-I, and 32 controls. No significant differences were found in vitamin B12 levels, whereas folate concentrations were significantly lower in the levodopa-treated group. Plasma Hcy was increased significantly in the two groups of PD patients and was significantly lower in the group treated with levodopa + COMT-I. Statistical analysis showed that the difference in mean Hcy levels observed among PD patients was related to the addition of COMT-I, rather than to folate concentrations. We conclude that levodopa treatment increases plasma Hcy and the addition of COMT-I effectively reduces HHcy.

Topics: Aged; Antiparkinson Agents; Case-Control Studies; Catechols; Chromatography, High Pressure Liquid; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Levodopa; Linear Models; Male; Middle Aged; Nitriles; Parkinson Disease; Vitamin B 12

Elevated plasma homocysteine (Hcy) concentrations have been reported in L-dopa treated Parkinson's disease (PD) patients, suggesting that L-dopa treatment is an acquired cause of hyperhomocysteinemia. Aim of this study is to evaluate the effects of different antiparkinsonian drugs on Hcy concentrations. We compared Hcy, B(12) and folate levels in 45 PD patients (15 treated with dopamine-agonists, 15 with L-dopa and 15 with L-dopa plus a catechol-O-methyltransferase-inhibitor (COMT-I) and in 15 controls. Analysis of data revealed that L-dopa administration significantly increases Hcy concentrations and that the addition of COMT-I effectively reduces the homocysteinemia.

Topics: Aged; Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Dopamine Agonists; Enzyme Inhibitors; Female; Folic Acid; Homocysteine; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Vitamin B 12

The antiparkinsonian drug L-dopa causes increased cellular synthesis of homocysteine and consequent hyperhomocysteinemia in rats. This effect of L-dopa on plasma homocysteine is accentuated under conditions of impaired homocysteine metabolism such as folate deficiency.. To investigate the effect of L-dopa administration and B-vitamin status on plasma homocysteine concentrations in humans with PD.. Plasma homocysteine, folate, vitamin B(12), and pyridoxal-5'-phosphate (PLP) concentrations were determined in 40 individuals diagnosed with idiopathic PD who were being treated as outpatients at the Boston University Medical Center Neurology Clinic. Twenty of the patients were on L-dopa therapy (treatment group) and 20 were L-dopa-naive (control group).. The mean plasma homocysteine concentration was higher in the treatment group than in the controls (p = 0.018). Plasma homocysteine was correlated with plasma folate, vitamin B(12), and PLP concentrations in the treatment group (p

Topics: Antiparkinson Agents; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Linear Models; Male; Middle Aged; Parkinson Disease; Pyridoxal Phosphate; Risk Factors; Vitamin B 12; Vitamin B Complex

Parkinson's disease (PD) is a common disease whose pathophysiological mechanism is not well understood. Recent research studies have shown that PD patients have low serum levels of vitamins B12 and D. Therefore, in this study, the effects of supplementation with vitamins B12 and D on PD female mice as well as their fetuses were studied. After preparation of female mice and induction of Parkinson's by rotenone administration for 19 days, rotarod test was used to confirm PD induction. During this time, supplementations with vitamins B12 and D were performed. On day 19, after confirmation of PD induction, half of the mice were killed and the other half were allowed to mate with males. Viability was measured by the MTT method, and apoptosis and necrosis of cerebellar neurons were measured by flow cytometry. The RT-PCR technique was used to evaluate the relative expressions of the bax, bcl-2, miR-211, and circRNA 0,001,518 genes. Data analysis was performed by the GraphPad Prism V.8 software. Co-administration of vitamins B12 and D resulted in highest viability percentage and greatest reduction in apoptosis and necrosis of cerebellar neurons in the female mice as well as their fetuses compared to the PD females. A decrease in the relative expression of the bax and miR-211 genes and an increase in bcl-2 expression were observed in the cerebellar tissue of PD mice receiving both vitamins. Vitamins B12 and D have neuroprotective effects on PD conditions. Therefore, co-administration of these two vitamins is recommended in PD patients during pregnancy.

Topics: Animals; bcl-2-Associated X Protein; Female; Male; Mice; MicroRNAs; Necrosis; Neuroprotective Agents; Parkinson Disease; Pregnancy; Proto-Oncogene Proteins c-bcl-2; Vitamin B 12; Vitamins

Folate and vitamins B6 and B12 have been proposed as protective against the development of Parkinson's disease (PD). Two prior longitudinal studies were inconclusive.. The aim was to examine the association of long-term intake of folate, vitamin B6, and vitamin B12 with the incidence of PD.. The study population comprised 80,965 women (Nurses' Health Study, 1984-2016) and 48,837 men (Health Professionals Follow-up Study, 1986-2016) followed prospectively for the development of PD. Intake of B vitamins was measured at baseline and every 4 years thereafter using food frequency questionnaires. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of PD based on quintiles of cumulative average intake adjusting for potential confounders. Secondary analyses considered different lagged exposure periods as well as baseline and recent intakes.. In separate analyses of cumulative average intake, total folate, B6, and B12 were not associated with the risk of PD. Results from 8-, 12-, and 16-year lag analyses were consistent with these findings. Results for baseline intake of folate and B6 also pointed toward a null association. In contrast, a lower PD risk was observed among individuals with higher baseline total intake of B12 (pooled HR top vs. bottom quintile: 0.80; 95% CI: 0.67-0.95; P-trend = 0.01); results from 20-year lag analyses were consistent with this finding.. Our results do not support the hypothesis that a higher intake of folate or vitamin B6 would reduce PD risk in this population. Our results provide moderate support for a possible protective effect of vitamin B12 on the development of PD. © 2023 International Parkinson and Movement Disorder Society.

Topics: Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Humans; Incidence; Male; Parkinson Disease; Risk Factors; Vitamin B 12; Vitamin B 6

Topics: Folic Acid; Humans; Hyperhomocysteinemia; Parkinson Disease; Vitamin B 12

Parkinson's disease (PD) is characterized by a range of motor signs, but cognitive dysfunction is also observed. Supplementation with folic acid and vitamin B12 is expected to prevent cognitive impairment. To test this in PD, we promoted a lesion within the substantia nigra

Topics: Animals; Disease Models, Animal; Folic Acid; Parkinson Disease; Rats; Rotenone; Vitamin B 12

Topics: Humans; Parkinson Disease; Peripheral Nervous System Diseases; Vitamin B 12

Previous evidence has suggested roles for α-synuclein propagation and vitamin B12 (VitB12) deficiency in the pathogenesis of Parkinson's disease (PD). We investigated whether gastric cancer (GC) patients who underwent gastrectomy had a lower risk of PD and whether VitB12 supplementation modified the risk.. GC patients aged ≥50 years who underwent curative gastrectomy between 2007 and 2012 (n = 72,216) and matched comparison groups (n = 211,389) were identified from the Korean National Health Insurance database. The risks of PD were analyzed by Cox regression.. Compared to their matched comparison groups, GC patients who underwent gastrectomy showed a decreased risk of PD (adjusted HR [aHR] 0.86; 95% confidence interval [CI] 0.75-0.98), but the significance disappeared after further adjustment with smoking and body mass index (BMI). To elaborate, subtotal gastrectomy (STG) was associated with decreased risk of PD (aHR 0.85; 95% CI 0.74-0.99) while total gastrectomy (TG) was not (aHR 0.89; 95% CI 0.66-1.19), although the risk reduction was not significant when further adjusted for smoking and BMI. Among the patients who underwent TG, their risk of PD was markedly lower when they had VitB12 supplementation after surgery (aHR 0.36; 95% CI 0.17-0.76), while the risk was higher when they did not have any (aHR 1.55; 95% CI 1.03-2.32).. GC patients who underwent gastrectomy and received uninterrupted VitB12 supplementation had a decreased incidence of PD. This study provides indirect epidemiological evidence for the potential roles of gastrectomy and VitB12 in the pathogenesis of PD.

Topics: Aged; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Parkinson Disease; Republic of Korea; Risk; Stomach Neoplasms; Vitamin B 12

With the aging population and increasing life expectancy, Parkinson's disease (PD), a neurological disorder rapidly increasing in morbidity and mortality, is causing a huge burden on society and the economy. Several studies have suggested that one-carbon metabolites, including homocysteine, vitamin B6, vitamin B12 and folate acid, are associated with PD risk. However, the results remain inconsistent and controversial. Thus, we performed a two-sample Mendelian randomization (MR) study to detect the causality between one-carbon metabolites and PD susceptibility as well as age at PD onset. We collected several genetic variants as instrumental variables from large genome-wide association studies of one-carbon metabolites (homocysteine: N = 14, vitamin B6: N = 1, vitamin B12: N = 10, folate acid: N = 2). We then conducted MR analyses using the inverse variance-weighted (IVW) approach and additional MR-Egger regression, weighted median and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods to further test causality. The results showed no causal association between circulating homocysteine levels and PD risk (p = 0.868) or age at PD onset (p = 0.222) with the IVW method. Meanwhile, similar results were obtained by three complementary analyses. In addition, we did not observe any evidence that the circulating levels of vitamin B6, vitamin B12 and folate acid affected the risk of PD or age at onset of PD. Our findings implied that lowering homocysteine levels through vitamin B6, vitamin B12 or folate acid supplementation may not be clinically helpful in preventing PD or delaying the age at PD onset.

Topics: Age of Onset; Dietary Supplements; Disease Susceptibility; Folic Acid; Genome-Wide Association Study; Homocysteine; Mendelian Randomization Analysis; Negative Results; Parkinson Disease; Risk; Vitamin B 12; Vitamin B 6

To determine whether vitamin B12 level at Parkinson's disease (PD) diagnosis predicts time to develop dementia.. We utilized a population-based cohort of Parkinsonism patients to examine the relationship between serum vitamin B12 at the time of PD diagnosis and dementia risk. Receiver operating curves were calculated for vitamin B12 cutoffs maximizing sensitivity and specificity for determining who developed dementia. Time from Parkinsonism diagnosis to dementia, death, or censoring was calculated utilizing Kaplan-Meier analysis and Cox-proportional hazard models.. PD patients who did not develop dementia had higher baseline levels of vitamin B12 at PD diagnosis (648.5 ng/L vs 452 ng/L, p < 0.05) than those who developed dementia. Dementia risk was significantly lower in the 3rd tertile compared with 2nd tertile and trended towards significance compared to the 1st tertile. Each 100 unit increase in vitamin B12 level had a hazard ratio of 0.31 (95% CI 0.44-0.95) for future dementia (p < 0.05). Vitamin B12 cutoff of <587 ng/L was 87% sensitive and 70% specific (AUC 0.79, 95% CI 0.60-0.98) distinguishing patients with dementia. PD patients with vitamin B12 levels <587 ng/L were 5.4 times more likely to develop dementia, with 50% having dementia within 5 years of PD diagnosis compared with 11% in those with a vitamin B12 level of ≥587 ng/L (p < 0.05).. Higher levels of serum vitamin B12 at PD diagnosis correlate with lower risk of future dementia. The role of vitamin B12 in the development of dementia among PD patients deserves further evaluation.

Topics: Aged; Aged, 80 and over; Cognitive Dysfunction; Cohort Studies; Dementia; Female; Humans; Male; Middle Aged; Parkinson Disease; Prognosis; Risk; Sensitivity and Specificity; Time Factors; Vitamin B 12

Using blood specimens from untreated early Parkinson's disease (PD) patients from the DATATOP trial, we found that subjects in the low serum vitamin B12 tertile experienced greater annualized change in ambulatory capacity score, whereas those with moderately elevated (>15 μmol/L) total homocysteine had greater annualized declines in the Mini-Mental State Exam.. In this this study we sought to determine whether levels of cerebrospinal fluid (CSF) B12 markers were also associated with progression of PD.. The annualized change in the UPDRS "walking" item, a component of the ambulatory capacity score, was worse in the low B12 tertile. No association with change in the Mini-Mental State Exam was seen for those 7% with the highest baseline CSF total homocysteine.. In these untreated early-PD subjects, low CSF B12 predicted greater worsening of the UPDRS "walking" item, whereas CSF total homocysteine was not associated with progression of cognitive impairment. These findings extend and partially support our findings in serum. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Topics: Biomarkers; Disease Progression; Humans; Mental Status and Dementia Tests; Parkinson Disease; Vitamin B 12

This study aimed to investigate the prevalence of peripheral neuropathy (PNP) and its related serum metabolites in. This study included 105 drug-naïve. We found abnormal nerve conduction velocity findings in 24 out of 105 total patients. Among them, 20 patients showed a type of combined motor-sensory, while three were a type of pure sensory and one was a pure motor. Nine patients had carpal tunnel syndrome. PD with PNP group demonstrated higher serum levels of Hcy and UA compared to PD without PNP group.. Our data demonstrated a potential role of Hcy and UA on PNP in

Topics: Adult; Aged; Case-Control Studies; Female; Homocysteine; Humans; Levodopa; Male; Middle Aged; Neural Conduction; Parkinson Disease; Peripheral Nervous System Diseases; Prevalence; Risk Factors; Uric Acid; Vitamin B 12

Missense mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) cause the majority of familial and some sporadic forms of Parkinson's disease (PD). The hyperactivity of LRRK2 kinase induced by the pathogenic mutations underlies neurotoxicity, promoting the development of LRRK2 kinase inhibitors as therapeutics. Many potent and specific small-molecule LRRK2 inhibitors have been reported with promise. However, nearly all inhibitors are ATP competitive-some with unwanted side effects and unclear clinical outcome-alternative types of LRRK2 inhibitors are lacking. Herein we identify 5'-deoxyadenosylcobalamin (AdoCbl), a physiological form of the essential micronutrient vitamin B

Topics: Allosteric Regulation; Animals; Caenorhabditis elegans; Cobamides; Disease Models, Animal; Drosophila melanogaster; Drug Repositioning; HEK293 Cells; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Parkinson Disease; Rats; Vitamin B 12; Vitamin B Complex

Topics: Allosteric Regulation; Humans; Neuroprotection; Parkinson Disease; Phosphorylation; Vitamin B 12

Vitamin B12 (VB12) is a necessary micronutrient for growth and the development of the nervous system. Severe deficiencies of VB12 have been linked to damage of learning and memory ability and cognitive decline, along with several neurological diseases. Misfolding and aggregation of α-synuclein (αSN) into insoluble fibrils is associated with the onset and progression of Parkinson's disease (PD), which affects tens of millions of elderly patients all over the world. Developing novel inhibitors to obstruct the aggregation of αSN has become a topic of intense research. In this study, the inhibitory effect of VB12 against the fibrillogenesis and cytotoxicity of αSN was systematically analyzed using thioflavin T (ThT) fluorescence, atomic force microscopy (AFM), circular dichroism (CD) spectroscopy and cytotoxicity assays. Both ThT and AFM results showed that VB12 could inhibit αSN fibrillogenesis in a dose-dependent manner. CD data suggested that VB12 delays the conformational conversion of αSN to β-sheet rich structures, especially to the parallel β-sheet conformation. As a result, VB12 greatly alleviated the cytotoxicity of αSN aggregates. Moreover, VB12 was also found to disassemble preexisting mature αSN fibrils and attenuate the consequent cytotoxicity. These findings not only provide a comprehensive understanding of the inhibitory effect of VB12 on αSN fibrillogenesis, but also identify a valuable nutrient source that possesses great potential to be developed as a new functional food ingredient to help alleviate PD.

Topics: alpha-Synuclein; Amyloid beta-Peptides; Humans; Parkinson Disease; Protein Aggregates; Protein Conformation; Vitamin B 12

Topics: Case-Control Studies; Humans; Levodopa; Parkinson Disease; Vitamin B 12

Recent studies have shown a relatively higher prevalence of peripheral neuropathy in idiopathic Parkinson's disease (IPD). The hypothesis is that prolonged levodopa exposure causes vitamin B12 deficiency, which leads to peripheral neuropathy. The aim of our study was to find the relationship between vitamin B12 and its precursor methylmalonic acid (MMA) in IPD patients with neuropathic pain. We performed a cross-sectional study by enrolling consecutive 43 patients who were clinically tested positive for F-18 FP-CIT PET and 15 patients were diagnosed with peripheral neuropathy according to the Toronto clinical scoring system (TCSS). The severity of neuropathic pain was evaluated using total neuropathy scale, revised (TNSr), and Korean Neuropathic Pain Questionnaire (KNPQ). The correlations between age, IPD duration, levodopa equivalent dose (LED), UPDRS III, vitamin B12, MMA, and homocysteine levels were assessed. The prevalence rate of peripheral neuropathy in IPD patients was 35%. Among the serums assessed, MMA levels showed a positive correlation to TNSr and KNPQ in the IPD patients with peripheral neuropathy (TNSr r = 0.882, p < 0.001, KNPQ r = 0.710, p = 0.004), while Vitamin B12 and homocysteine showed no statistically significant correlation. Our study showed a prevalence of peripheral neuropathy in 35% of Korean IPD patients. The serum MMA positively correlated with the severity of neuropathic pain and this can be used as a useful marker in assessment of peripheral neuropathy in Parkinson's disease.

Topics: Aged; Antiparkinson Agents; Biomarkers; Cross-Sectional Studies; Female; Homocysteine; Humans; Levodopa; Male; Methylmalonic Acid; Middle Aged; Neural Conduction; Neuralgia; Pain Measurement; Parkinson Disease; Prevalence; Severity of Illness Index; Vitamin B 12

Recent reports suggest increased frequency of peripheral neuropathy (PN) in Parkinson's disease (PD) patients on levodopa compared with age-matched controls particularly during continuous levodopa delivery by intestinal infusion (CLDII). The aim of this study is to compare frequency, clinical features, and outcome of PN in PD patients undergoing different therapeutic regimens.. Three groups of consecutive PD patients, 50 on intestinal levodopa (CLDII), 50 on oral levodopa (O-LD) and 50 on other dopaminergic treatment (ODT), were enrolled in this study to assess frequency of PN using clinical and neurophysiological parameters. A biochemical study of all PN patients was performed.. Frequency of PN of no evident cause was 28% in CLDII, 20% in O-LD, and 6% in ODT patients. Clinically, 71% of CLDII patients and all O-LD and ODT PN patients displayed a subacute sensory PN. In contrast, 29% of CLDII patients presented acute motor PN. Levodopa daily dose, vitamin B12 (VB12) and homocysteine (hcy) levels differed significantly in patients with PN compared to patients without PN.. Our findings support the relationship between levodopa and PN and confirm that an imbalance in VB12/hcy may be a key pathogenic factor. We suggest two different, possibly overlapping mechanisms of PN in patients on CDLII: axonal degeneration due to vitamin deficiency and inflammatory damage. Whether inflammatory damage is triggered by vitamin deficiency and/or by modifications in the intestinal micro-environment should be further explored. Proper vitamin supplementation may prevent peripheral damage in most cases.

Topics: Aged; Antiparkinson Agents; Cross-Sectional Studies; Electromyography; Female; Folic Acid; Homocysteine; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Peripheral Nervous System Diseases; Prevalence; Vitamin B 12

Continuous jejunal levodopa infusion is an increasingly used therapy option in patients with Parkinson's disease who experience severe fluctuations from oral levodopa. In a number of recent reports polyneuropathy in patients receiving jejunal levodopa infusion was referenced to cobalamin (vitamin B12) deficiency. We describe one of three cases from our hospital with severe subacute polyneuropathy that developed during jejunal levodopa infusion, and occurred despite vitamin substitution therapy and normal vitamin B12 and holotranscobalamin serum levels.

Topics: Aged; Antiparkinson Agents; Carbidopa; Drug Combinations; Humans; Infusions, Parenteral; Jejunum; Levodopa; Male; Parkinson Disease; Polyneuropathies; Vitamin B 12

The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥ 3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037-1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130-5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical-neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa.

Topics: Aged; Antiparkinson Agents; Female; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Logistic Models; Male; Middle Aged; Neural Conduction; Parkinson Disease; Peripheral Nervous System Diseases; Prevalence; Risk; Vitamin B 12

Higher prevalence of neuropathy has been described in patients with Parkinson's disease (PD) in comparison with age and gender-matched controls. The cause of neuropathy may be levodopa-induced impairment of vitamin B12 metabolism, suggesting levodopa-naïve subjects should be unaffected. There may, however, be other yet unidentified determinants of neuropathy in PD. We screened 33 consecutive levodopa-naïve PD patients for neuropathy. Demographics, vitamin B12 and folate levels were studied. Findings were analyzed in the light of our previous available data on levodopa-treated PD patients. Four of 33 (12.1 %) levodopa-naïve PD patients were diagnosed with neuropathy. This compared to 13/36 (36.1 %) previously evaluated levodopa-treated patients (p = 0.027) and 3/37 controls (p = 0.7). Analysis of our whole PD cohort consisting of a total of 70 subjects, including levodopa-naïve and levodopa-treated patients, revealed that neuropathy correlated with use of levodopa (p = 0.041), cumulative levodopa exposure (p = 0.046), age at time of study (p = 0.005) and serum folate levels <10 μg/L (p = 0.003). There was no association of neuropathy with PD duration. Multivariate regression analysis showed that neuropathy was only independently associated with age (p = 0.016) and serum folate levels <10 μg/L (p = 0.012). We conclude that this study confirms the roles of levodopa usage and cumulative levodopa exposure in the neuropathy of PD. However, the effects of levodopa only appear contributory and are surpassed by age and lower folate levels. In view of the independent implication of lower folate levels, the need for preventative/protective supplementation including folate in addition to vitamin B12, probably irrespective of levodopa use, may deserve consideration in patients with PD.

Topics: Adult; Aged; Aging; Antiparkinson Agents; Cross-Sectional Studies; Female; Folic Acid; Humans; Levodopa; Male; Middle Aged; Nervous System Diseases; Parkinson Disease; Vitamin B 12

The presence of Helicobacter pylori (HP) in the gastrointestinal tract may limit the absorption of levodopa. The objectives of this study were to investigate whether HP infection may affect the clinical response to levodopa as well as levodopa dose requirement in patients with Parkinson's disease (PD) as well as to investigate whether HP infection may affect plasma levels of vitamin B12, folic acid, and homocysteine. Seventy-five patients with PD diagnosed at least 4 years ago were included. Symptom fluctuations were assessed by UPDRS-IV and the WOQ9 wearing-off-scale. Plasma levels of vitamin B12, folic acid, and homocysteine were analyzed. Screening for HP was performed with a 13C-labeled urea breath test (Diabact UBT). A propensity-matched analysis was made where each patient in the HP-infected group was matched with one patient in the non-infected group with respect to age and gender. Of the 75 included patients, 20 were HP infected (27 %). Median Hoehn & Yahr scores were 3 in both HP infected patients and the matched group (n = 20). HP-infected patients had decreased "complications of therapy" with average total UPDRS-IV score of 4.8 ± 3.0 vs. 7.7 ± 3.8 (p < 0.05), despite no significant difference in levodopa equivalent dose. Wearing-off and sleep disturbance were significantly less common in the HP group (p < 0.05). There were no differences regarding vitamin B12, folic acid, or homocysteine values. HP infection in patients with PD may result in a decreased occurrence of symptom fluctuations according to this small study. This finding may be due to altered absorption of levodopa in the gastrointestinal tract in patients with HP infection, but further studies are required.

Topics: Aged; Antiparkinson Agents; Breath Tests; Female; Folic Acid; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Absorption; Levodopa; Male; Parkinson Disease; Treatment Outcome; Vitamin B 12

Some heavy metals are suspected to be pathogenic to both Parkinson's disease (PD) and depression. Common background may exist in them.. Subjects comprised PD patients with depression, PD patients without depression and controls recruited from the outpatient clinic in China. Morning blood and urine samples were used to measure concentrations of metals and vitamins.. Whole-blood manganese was significantly higher in the PD patients without depression than in both the PD patients with depression and the controls. Serum iron was significantly higher in the PD patients without depression than in the controls. Urine iron was also significantly higher in the PD patients without depression than in the controls. Serum copper was significantly lower in the PD patients with depression than in both the PD patients without depression and the controls.. Excessive intake of iron and accumulation of manganese seemed to be involved in the etiology of non-depressive PD.

Topics: Aged; Depression; Female; Humans; Male; Metals, Heavy; Middle Aged; Parkinson Disease; Vitamin B 12; Vitamin E

The prevalence of restless legs syndrome (RLS) has been studied extensively in Parkinson's disease (PD), with conflicting findings. More recently, both neuropathy and leg motor restlessness (LMR) have been found to be significantly more prevalent in PD patients than in controls.. Our objective was to determine whether RLS or LMR may be secondary to neuropathy, or its currently postulated determinants, cumulative levodopa usage and vitamin B(12) metabolism, in patients with PD.. We compared prevalence of RLS, LMR and neuropathy in 37 PD patients and 37 age- and gender-matched controls. Correlations between RLS/LMR and neuropathy and symptomatic neuropathy, cumulative levodopa usage and vitamin B(12) levels were ascertained.. RLS prevalence was comparable in PD patients and controls (16.2% vs 10.8%; P = 0.30). LMR was significantly more common in PD patients than in controls (40.5% vs 16.2%; P = 0.038), as was neuropathy (37.8% vs 8.1%; P = 0.005). Neither RLS, nor LMR correlated with neuropathy or symptomatic neuropathy, cumulative levodopa exposure or serum vitamin B(12) levels in patients with PD. There was a non-significant trend for a correlation between LMR and earlier age of onset of PD (P = 0.069).. RLS and LMR appear unrelated to neuropathy or symptomatic neuropathy, cumulative levodopa usage, or serum vitamin B(12) levels in patients with PD. The occurrence of LMR may relate to the earlier onset of PD, raising the possibility of common pathophysiological mechanisms for PD and RLS, of which LMR may be an early manifestation in some patients.

Topics: Antiparkinson Agents; Female; Humans; Levodopa; Male; Parkinson Disease; Peripheral Nervous System Diseases; Prevalence; Restless Legs Syndrome; Vitamin B 12

There is evidence that increased homocysteine (Hcy) levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects. Homocysteine neurotoxicity mainly relies on redox state alterations. The present work was aimed at investigating the relationships between plasma Hcy concentrations and percent content of oxidized versus total Coenzyme Q10 (%CoQ10) in 60 PD patients and 82 healthy subjects. Both groups were screened for plasma levels of Hcy, vitamin B12, folate, %CoQ10 and C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism. The MTHFR TT677 mutated genotype was found more frequently in patients than in controls (p = 0.01). In a multivariate analysis, Hcy levels and %CoQ10 were associated with the case/control category (p < 0.0001), MTHFR genotype (p < 0.0001) and their interaction term (p = 0.0015), even after adjusting for age, sex, folate and vitamin B12. Patients carrying the TT677 genotype exhibited the highest values of Hcy and %CoQ10 (p < 0.0001). Structural equation modelling evidenced that the TT677 genotype and levodopa daily dose were independently and directly correlated with Hcy (p < 0.0001, and p = 0.003, respectively), which, in turn, showed a significant correlation (p < 0.0001) with the %CoQ10 in PD patients. Our results suggest that increased Hcy levels act as mediator of the systemic oxidative stress occurring in PD, and %CoQ10 determination might be regarded as a predictor of toxic Hcy effects.

Topics: Aged; Antiparkinson Agents; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Parkinson Disease; Polymorphism, Genetic; Ubiquinone; Vitamin B 12

We aimed to investigate possible associations between systemic iron metabolism deficiency and Parkinson's disease, and also to research any possible correlations between stage of the disease and vitamin B12 and folic acid levels. 33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and 22 male and 20 female age- and sex-matched controls were enrolled in the study. Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and for the females, not being in the menopausal stage were considered as exclusion criteria. Recordings of blood samples of both groups collected after 8 h fasts were assessed in terms of serum iron, ferritin levels and iron-binding capacity, vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine the stage of the disease. No statistically significant difference was found with respect to mean serum iron, median serum ferritin levels and median serum iron-binding capacity between the groups. A statistically significant but inverse correlation was found between symptoms' duration and serum iron and ferritin levels. There was no statistically significant difference between the groups with respect to vitamin B12 and folic acid levels. However, a statistically significant but inverse correlation was determined between the patients' vitamin B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses, serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of these parameters may be the cause of the progression or may be the result of it.

Topics: Aged; Case-Control Studies; Female; Folic Acid; Humans; Iron; Male; Middle Aged; Parkinson Disease; Vitamin B 12

Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial.. The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A).. A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging, and the Schwab-England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1).. The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41-0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42-0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 μmol/l) as compared with the controls (14.0±9.6 μmol/l, P=10(-8)) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients.. The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations.

Topics: Catechol O-Methyltransferase; Cognition Disorders; Female; Folic Acid; Genetic Association Studies; Genetic Predisposition to Disease; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Parkinson Disease; Polymorphism, Genetic; Reduced Folate Carrier Protein; Vitamin B 12

Patients with Parkinson's disease (PD) and chronically treated with L-DOPA exhibit, in a percentage of 10-30%, supra-physiological levels of plasma total homocysteinemia (tHcy). In this study, we have investigated, in a group of hyper-homocysteinemic PD patients, the time of hyper-tHcy recurrence after discontinuation of 1-month folate supplementation given to normalize plasma tHcy levels.. Plasma tHcy, cobalamin and folate were assayed before and after 1-month folate supplementation (5 mg/day), and after 2 and 4 months after folate discontinuation in 29 PD patients (16M/13F, mean age 69.4 +/- 6.9 years) stabilized on a mean L-DOPA dose of 509.4 +/- 312.1 mg/day.. After folate supplementation, plasma tHcy levels fell within the normal range in all patients. At the 2-month control after folate discontinuation, plasma tHcy remained within physiological values in 25 out of 29 patients. Conversely, 4 months after folate discontinuation, all patients exhibited hyper-tHcy.. One-month intake of 5 mg/day folate normalizes plasma tHcy levels in all hyper-homocysteinemic PD patients. Following folate discontinuation, hyper-tHcy recurs in all patients within 4 months. Knowledge of this time interval is useful to optimize pulses of folate therapy in hyper-homocysteinemic patients with PD.

Topics: Aged; Cross-Sectional Studies; Dopamine Agents; Female; Genetic Predisposition to Disease; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Middle Aged; Parkinson Disease; Prospective Studies; Secondary Prevention; Treatment Outcome; Vitamin B 12

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects; thus, increasing intake of B vitamins involved in the regulation of homocysteine metabolism might decrease the risk of PD through decreasing plasma homocysteine. However, epidemiological evidence for the association of dietary B vitamins with PD is sparse, particularly in non-Western populations. We conducted a hospital-based case-control study in Japan to examine associations between dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and the risk of PD. Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n 249) and controls without neurodegenerative diseases (n 368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semi-quantitative, comprehensive diet history questionnaire. After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0.87, 0.70 and 0.11, respectively). However, low intake of vitamin B6 was associated with an increased risk of PD, independent of potential dietary and non-dietary confounders. Multivariate OR (95 % CI) for PD in the first, second, third and fourth quartiles of vitamin B6 were 1 (reference), 0.56 (0.33, 0.94), 0.69 (0.38, 1.25) and 0.48 (0.23, 0.99), respectively (P for trend = 0.10). In conclusion, in the present case-control study in Japan, low intake of vitamin B6, but not of folate, vitamin B12 or riboflavin, was independently associated with an increased risk of PD.

Topics: Aged; Case-Control Studies; Diet; Diet Surveys; Female; Folic Acid; Humans; Japan; Male; Middle Aged; Odds Ratio; Parkinson Disease; Riboflavin; Risk Factors; Surveys and Questionnaires; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Increasing evidence suggests that elevated levels of homocysteine (Hcy) and methylmalonate (MMA) may be involved in the pathogenesis of neurodegenerative diseases.. The urine levels of MMA and serum levels of Hcy as well as folic acid and vitamin B(12) were measured in patients suffering from the distinct neurodegenerative diseases progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), and compared to age- and gender-matched control subjects.. We found significantly elevated concentrations of Hcy (PD 15.1, PSP 15.8, ALS 13.9, control 11.2 micromol/l) and MMA (PD 3.7, PSP 3.1, ALS 3.7, control 1.8 mg/g) in all patient groups in comparison with controls. Levels of Hcy and MMA did not differ significantly between the neurodegenerative diseases.. Our findings might imply that Hcy and MMA are released as a consequence of neurodegeneration regardless of the underlying cause and serve as surrogate markers of neurodegeneration. Alternatively they might be directly implicated in the pathogenesis of these diseases. Since elevated levels of both Hcy and MMA are neurotoxic, further studies might investigate the effect of vitamin therapy on disease progression.

Topics: Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Case-Control Studies; Female; Folic Acid; Homocysteine; Humans; Male; Matched-Pair Analysis; Methylmalonic Acid; Middle Aged; Parkinson Disease; Reference Values; Supranuclear Palsy, Progressive; Vitamin B 12

We describe two patients who developed subacute axonal peripheral neuropathy under duodopa treatment. Comprehensive diagnostic workup including muscle and sural nerve biopsy revealed that the most probable cause of subacute axonal peripheral neuropathy was cobalamin and vitamin B6 deficiency in both the patients.

Topics: Aged; Antiparkinson Agents; Dihydroxyphenylalanine; Drug Administration Routes; Female; Humans; Male; Parkinson Disease; Peripheral Nervous System Diseases; Vitamin B 12; Vitamin B 6 Deficiency; Vitamin B Complex

In the present work we measured blood levels of total homocysteine ((t)Hcy), vitamin B(12) and folic acid in patients with Parkinson s disease (PD) and in age-matched controls and searched for possible associations between these levels with smoking, alcohol consumption, L-DOPA treatment and disease duration in PD patients. We initially observed that plasma (t)Hcy levels were increased by around 30 % in patients affected by PD compared to controls. Linear correlation, multiple regression and comparative analyses revealed that the major determinant of the increased plasma concentrations of (t)Hcy in PD patients was folic acid deficiency, whereas in controls (t)Hcy levels were mainly determined by plasma vitamin B(12) concentrations. We also observed that alcohol consumption, gender and L-DOPA treatment did not significantly alter plasma (t)Hcy, folic acid and vitamin B(12) levels in parkinsonians. Furthermore, disease duration was positively associated with (t)Hcy levels and smoking was linked with a deficit of folic acid in PD patients. Considering the potential synergistic deleterious effects of Hcy increase and folate deficiency on the central nervous system, we postulate that folic acid should be supplemented to patients affected by PD in order to normalize blood Hcy and folate levels, therefore potentially avoiding these risk factors for neurologic deterioration in this disorder.

Topics: Analysis of Variance; Case-Control Studies; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Matched-Pair Analysis; Middle Aged; Nerve Degeneration; Parkinson Disease; Reference Values; Statistics, Nonparametric; Vitamin B 12

The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Aged; Aged, 80 and over; Brain; Carbon-Nitrogen Ligases; Case-Control Studies; Cognition Disorders; Cystathionine beta-Synthase; Depression; Female; Folic Acid; Homocysteine; Humans; Immunoassay; Logistic Models; Magnetic Resonance Imaging; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Parkinson Disease; Polymorphism, Genetic; Severity of Illness Index; Vitamin B 12; Vitamin B 6

Vitamin B12 is indispensable for proper brain functioning and cytosolic synthesis of S-adenosylmethionine. Whether its deficiency produces effects on viability and apoptosis of neurons remains unknown. There is a particular interest in investigating these effects in Parkinson disease where Levodopa treatment is known to increase the consumption of S-adenosylmethionine. To cause deprivation of vitamin B12, we have recently developed a cell model that produces decreased synthesis of S-adenosylmethionine by anchoring transcobalamin (TCII) to the reticulum through its fusion with Oleosin (OLEO).. Gene constructs including transcobalamin-oleosin (TCII-OLEO) and control constructs, green fluorescent protein-transcobalamin-oleosin (GFP-TCII-OLEO), oleosin-transcobalamin (OLEO-TCII), TCII and OLEO were used for expression in N1E-115 cells (mouse neuroblastoma) and in substantia nigra of adult rats, using a targeted transfection with a Neurotensin polyplex system. We studied the viability and the apoptosis in the transfected cells and targeted tissue. The turning behavior was evaluated in the rats transfected with the different plasmids.. The transfection of N1E-115 cells by the TCII-OLEO-expressing plasmid significantly affected cell viability and increased immunoreactivity of cleaved Caspase-3. No change in propidium iodide uptake (used as a necrosis marker) was observed. The transfected rats lost neurons immunoreactive to tyrosine hydroxylase. The expression of TCII-OLEO was observed in cells immunoreactive to tyrosine hydroxylase of the substantia nigra, with a superimposed expression of cleaved Caspase-3. These cellular and tissular effects were not observed with the control plasmids. Rats transfected with TCII-OLEO expressing plasmid presented with a significantly higher number of turns, compared with those transfected with the other plasmids.. In conclusion, the TCII-OLEO transfection was responsible for apoptosis in N1E-115 cells and rat substantia nigra and for Parkinson-like phenotype. This suggests evaluating whether vitamin B12 deficit could aggravate the PD in patients under Levodopa therapy by impairing S-adenosylmethionine synthesis in substantia nigra.

Topics: Animals; Apoptosis; Behavior, Animal; Cell Line, Tumor; Cell Survival; Humans; Intracellular Space; Methamphetamine; Mice; Necrosis; Parkinson Disease; Plant Proteins; Plasmids; Protein Transport; Rats; Recombinant Fusion Proteins; Substantia Nigra; Transcobalamins; Transfection; Transgenes; Vitamin B 12

The presence and potential etiologies of peripheral neuropathy (PN) in patients with Parkinson's Disease (PD) is unknown. We examined for presence of PN in patients with PD. From a PD patient population of 500 patients screened for features of symptomatic PN, patients were further selected for clinical, electrophysiological, and laboratory studies related to PN. This PD patient population with idiopathic PN (PD-IPN) was compared to a group of PD patients without PN (PD-only), and a large group of patients without PD with idiopathic PN (IPN) for abnormalities in Cbl, fasting homocysteine (Hcy), and fasting methylmalonic acid (MMA) levels. PD-IPN and IPN patients identified with abnormalities in Cbl, Hcy, or MMA levels were treated with intramuscular Cbl for 1 to 2 years. Of 49 PD patients with symptomatic PN, 34 patients (69%) had PD-IPN, and 32/34 (94%) had abnormal Hcy or MMA levels as compared to 26/258 (10%) of IPN patients. Cumulative lifetime L-dopa dosage and fasting MMA levels were associated with PN severity. Cbl therapy led to improvements in Hcy and MMA levels in all groups, and PN in PD-IPN patients stabilized during therapy. PN in PD patients may be associated with iatrogenic Cbl metabolic abnormalities. Alternatively PN may be a peripheral nervous system manifestation of PD.

Topics: Analysis of Variance; Antiparkinson Agents; Female; Homocysteine; Humans; Levodopa; Male; Methylmalonic Acid; Parkinson Disease; Peripheral Nervous System Diseases; Retrospective Studies; Vitamin B 12

Total plasma homocysteine (tHcy) may be a risk factor for vascular diseases and is associated with renal failure or deficiency of vitamin B12 or folate. Recently, elevated tHcy concentrations were observed in patients with Parkinson's disease (PD), particularly those under levodopa treatment. Our objective was to determine whether changes in tHcy are also found in patients with restless legs syndrome (RLS) in relation to levodopa treatment and whether folate and vitamins B6 and B12 play a role in RLS.. In a total of 228 subjects, tHcy and B vitamin status (vitamins B6 and B12, folate) were studied: 97 patients with idiopathic RLS (40 under levodopa therapy), 39 with PD (25 under levodopa therapy), and 92 healthy controls adjusted for age and gender.. No significant differences were observed in tHcy levels between RLS patients and controls or between the RLS groups without treatment or with levodopa or dopamine agonist treatment. Mean tHcy was significantly higher in PD patients (13.8 micromol/l) than in either RLS patients (11.7 micromol/l) or controls (11.0 micromol/l; p<0.001). There was an inverse association between tHcy and vitamin B12 in each group.. RLS and, in particular, levodopa treatment in RLS are not associated with hyperhomocysteinemia. Elevated tHcy could, however, be confirmed in PD patients.

Topics: Aged; Antiparkinson Agents; Catechols; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Reference Values; Restless Legs Syndrome; Vitamin B 12; Vitamin B 6

Topics: Antiparkinson Agents; Carbon; Catechol O-Methyltransferase Inhibitors; Catechols; Folic Acid; Humans; Hyperhomocysteinemia; Levodopa; Nitriles; Parkinson Disease; Randomized Controlled Trials as Topic; S-Adenosylmethionine; Time Factors; Vitamin B 12; Vitamin B 6

High plasma homocysteine levels have been observed in Parkinson's disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with L-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 L-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 +/- 5.7 vs. 11.7 +/- 2.7 micromol/l, P < 0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P < 0.05), but not associated with an increased risk for PD (OR = 2.3, CI = 1.0-5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 +/- 4.9 micromol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 +/- 1.6 micromol/l; OR = 0.19, CI = 0.06-0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 +/- 3.6 micromol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.

Topics: Aged; Antiparkinson Agents; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Parkinson Disease; Polymorphism, Genetic; Vitamin B 12

Elevated levels of homocysteine have been observed in Parkinson's disease (PD) patients treated with levodopa. However, it is not studied if duration of PD or PD per se is associated with hyperhomocysteinemia. In the present study, the levels of homocysteine in 99 levodopa-treated PD patients, 15 untreated PD patients and 100 controls were examined. We focused on the influence of levodopa dose, duration of therapy and disease as well as genetic (C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism) and environmental factors. We found that levodopa-treated PD patients had elevated homocysteine plasma levels as compared to controls (p < 0.05), but the levels did not depend on levodopa doses. Another factor influencing homocysteine level was the duration of PD (p < 0.001). The frequency of allele C677T of MTHFR gene did not differ between PD and controls. In conclusion, hyperhomocysteinemia is associated with the duration of PD and levodopa treatment and possibly also with PD per se.

Topics: Adult; Aged; Aged, 80 and over; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Parkinson Disease; Polymorphism, Single Nucleotide; Reference Values; Vitamin B 12

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment and dementia. L-dopa treatment may represent an acquired cause of hyperhomocysteinemia (HHcy), as evidenced by studies in rats as well as in Parkinson's disease (PD) patients. Folate and cobalamin status also seems to influence the effects of L-dopa on plasma Hcy levels; therefore B-vitamins supplementation has been proposed to reduce the HHcy in L-dopa treated PD patients. Plasma Hcy, folate, and cobalamin levels were evaluated in 20 PD patients treated with L-dopa in the baseline condition and following a 5-week period of treatment with cobalamin and folate; results were compared with 35 controls. Analysis of data revealed that Hcy levels were higher in L-dopa treated PD patients when compared with age- and sex-matched controls and that supplementation of the diet with cobalamin and folate is effective in reducing Hcy concentrations; these findings may have important implications in the treatment of PD patients who are potentially at risk for vascular diseases and cognitive impairment or dementia.

Topics: Aged; Antiparkinson Agents; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Middle Aged; Parkinson Disease; Vitamin B 12

Hyperhomocysteinemia is not only a major risk factor for atherothrombotic disease, but is also strongly associated with an increased risk of dementia and cognitive impairment, both of which are common in the course of Parkinson's disease (PD). Previous work has found that levodopa increases plasma homocysteine concentrations. Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. The objective of our study was to assess the impact of entacapone, a COMT inhibitor, on plasma levels of homocysteine, serum folate, and vitamin B12 in levodopa-treated PD patients. Nineteen PD patients receiving only levodopa and 21 PD patients on a combination of levodopa and entacapone participated in the cross-sectional study. The control group consisted of 17 subjects on dopamine agonists. The mean plasma homocysteine concentration in the subjects on only levodopa was higher than that in the subjects on a combination of levodopa and entacapone (P=0.001) or in the control group (P=0.0001). Concentrations of serum vitamin B12 and serum folate were on average normal in all groups, but levodopa-treated subjects (with or without entacapone therapy) were more prone to have hypovitaminosis B12 (45%) than controls on dopamine agonists (6%). We suggest that the COMT inhibition may play a promising role in successfully controlling levodopa-induced hyperhomocysteinemia and in reducing the risk of pathologies probably linked to it. These preliminary findings and postulated hypotheses must now be confirmed in prospective studies.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Catechols; Cross-Sectional Studies; Drug Therapy, Combination; Enzyme Inhibitors; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Vitamin B 12

Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (Abeta) metabolism, implicated in neurodegenerative diseases.. To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD).. Plasma tHcy, folate, vitamin B(12), creatinine, and Abeta levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n = 88).. The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p < 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma Abeta levels even after adjustments for age and creatinine (p < 0.0001).. Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma Abeta levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Amyloid beta-Peptides; Brain; Causality; Cerebral Amyloid Angiopathy; Cognition Disorders; Creatinine; Female; Folic Acid; Homocysteine; Humans; Levodopa; Male; Memory Disorders; Middle Aged; Neurodegenerative Diseases; Parkinson Disease; Predictive Value of Tests; Vitamin B 12

In clinical studies, individuals with Parkinson's disease have had higher concentrations of plasma homocysteine than did controls, and experimental evidence suggests that folate deficiency or focal administration of homocysteine sensitizes dopaminergic neurons to the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The authors thus prospectively investigated whether higher intake of folate, vitamin B(6), or vitamin B(12) was related to a lower risk of Parkinson's disease in the Health Professionals Follow-up Study (1986-2000) and the Nurses' Health Study (1980-1998). They documented Parkinson's disease diagnoses in 248 men and 167 women during the follow-up. Folate intake was not associated with the risk of Parkinson's disease; the relative risks for the highest compared with the lowest quintiles were 1.0 (95% confidence interval: 0.7, 1.5) in men and 1.3 (95% confidence interval: 0.8, 2.3) in women. Neither did they find significant associations in analyses stratified by age, smoking, alcohol consumption, or lactose intake. Intake of vitamin B(6) or vitamin B(12) also was not related to the risk of Parkinson's disease. The current study does not support the hypothesis that higher intake of folate or related B vitamins lowers the risk of Parkinson's disease.

Topics: Adult; Cohort Studies; Diet; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Multivariate Analysis; Parkinson Disease; Prospective Studies; Reference Values; Risk Factors; United States; Vitamin B 12; Vitamin B 6

Levodopa, typically ingested chronically at high daily doses, is predictably methylated by means of a series of reactions using B vitamins, which convert methionine to homocysteine. Elevated total plasma homocysteine (tHcy), a risk factor for dementia, has been found in PD patients using levodopa. We prospectively measured the effects on plasma tHcy and B vitamins of levodopa initiation, and measured the effects of dose changes and of treatment with dopamine agonists and entacapone. We collected paired plasma samples, at baseline and again after several months treatment, from patients initiating levodopa (n = 30), from patients whose levodopa dose was doubled (n = 15), halved or stopped (n = 14), from patients starting or stopping entacapone (n = 15) and from patients initiating or doubling dopamine agonist monotherapy (n = 16). Vitamin B12, folate, and tHcy concentrations were measured. Baseline tHcy concentration of 8.7 (2.8) micromol/L increased to 10.1 (3.1) micromol/L (P = 0.004) an average of 94 (range 36 to 200) days after initiation of 604 (240 to 1050) mg/day of L-dopa. Average concentration of vitamin B12 fell from 380 to 291 pmol/ L (P = 0.01). Patients who doubled their daily levodopa dose experienced tHcy elevations from 9.5 to 11.1 micromol/L (P = 0.05). Levodopa reduction, agonist treatment, and entacapone treatment did not have significant effects. Levodopa elevates tHcy and lowers vitamin B12 concentration to modest degrees. The clinical implications, if any, have not yet been determined.

Topics: Aged; Antiparkinson Agents; Folic Acid; Humans; Hyperhomocysteinemia; Levodopa; Middle Aged; Parkinson Disease; Prospective Studies; Vitamin B 12

Hyperhomocysteinemia is a risk factor for vascular disease and potentially for dementia and depression. The most common cause of elevated homocysteine levels is deficiency of folate or vitamin B(12). However, patients with Parkinson disease (PD) may have elevated homocysteine levels resulting from methylation of levodopa and dopamine by catechol O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl donor and yields S-adenosylhomocysteine. Since S-adenosylhomocysteine is rapidly converted to homocysteine, levodopa therapy may put patients at increased risk for vascular disease by raising homocysteine levels.. To determine whether elevations in plasma homocysteine levels caused by levodopa use are associated with increased prevalence of coronary artery disease (CAD), and to determine what role folate and vitamin B(12) have in levodopa-induced hyperhomocysteinemia.. Subjects included 235 patients with PD followed up in a movement disorders clinic. Of these, 201 had been treated with levodopa, and 34 had not. Blood samples were collected for the measurement of homocysteine, folate, cobalamin, and methylmalonic acid levels. A history of CAD (prior myocardial infarctions, coronary artery bypass grafting, or coronary angioplasty procedures) was prospectively elicited. We analyzed parametric data by means of 1-way analysis of variance or the t test, and categorical data by means of the Fisher exact test or chi(2) test.. Mean +/- SD plasma homocysteine levels were significantly higher in patients treated with levodopa (16.1 +/- 6.2 micro mol/L), compared with levodopa-naïve patients (12.2 +/- 4.2 micro mol/L; P<.001). We found no difference in the plasma concentration of folate, cobalamin, or methylmalonic acid between the 2 groups. Patients whose homocysteine levels were in the higher quartile (>or=17.7 micro mol/L) had increased prevalence of CAD (relative risk, 1.75; 95% confidence interval, 1.08-2.70;P=.04).. Levodopa therapy, rather than PD, is a cause of hyperhomocysteinemia in patients with PD. Deficiency of folate or vitamin B(12) levels does not explain the elevated homocysteine levels in these patients. To our knowledge, this is the first report that levodopa-related hyperhomocysteinemia is associated with increased risk for CAD. These findings have implications for the treatment of PD in patients at risk for vascular disease, and potentially for those at risk for dementia and depression.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Coronary Artery Disease; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Middle Aged; Parkinson Disease; Risk Factors; Vitamin B 12

Moderate hyperhomocysteinaemia has been linked to an increased risk for cardiovascular diseases. Increased homocysteine concentrations may follow folate depletion due to insufficient dietary intake of the vitamin, but there is also some indication that immune activation could play a role. In this preliminary study, homocysteine, folate, and vitamin B(12) concentrations were measured in 19 patients with Parkinson's disease, 61-90 years of age, and compared to a healthy control group of similar age and to neopterin concentrations as an indicator of immune activation. A subgroup of patients presented with increased homocysteine and low folate concentrations. Homocysteine levels correlated inversely with vitamins folate and B(12) and positively with neopterin concentrations. Disturbed homocysteine metabolism in Parkinson's disease may be associated with vitamin deficiency and with immune system activation which may underlie folate depletion.

Topics: Aged; Aged, 80 and over; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Neopterin; Parkinson Disease; Vitamin B 12

Topics: Adult; Aged; Blood Pressure; Body Weight; Drug Tolerance; Female; Folic Acid; Humans; Hyperkinesis; Male; Middle Aged; Niacinamide; Parkinson Disease; Pulse; Pyridoxine; Testosterone; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Parkinson Disease; Vitamin B 12

Topics: Corrinoids; Hematinics; Humans; Parkinson Disease; Parkinsonian Disorders; Vitamin B 12