Vitamin B12 and Parkinson’s Disease

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Low Vitamin B12 and Parkinson Disease – May 2019

Potential Link to Reduced Cholinergic Transmission and Severity of Disease
Mayo Clinic COMMENTARY, ISSUE 5, P757-762, MAY 01, 2019 DOI:https://doi.org/10.1016/j.mayocp.2019.01.039

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by prominent motor dysfunction including rest tremor, bradykinesia, and rigidity responsive to levodopa. However, postural instability, freezing of gait, and cognitive impairment are important non–levodopa-responsive symptoms of PD and are significant risk factors for falls, leading to hospitalization, disability, and death.1 Treatments for key nonmotor symptoms of PD that might improve cognitive decline and postural instability are currently a major gap in PD therapeutics.
Dysfunction of the cholinergic systems in PD is thought to possibly play a contributory role in postural instability and cognitive impairment. Therefore, modulation of cholinergic transmission could improve balance and cognition in these patients.1 Vitamin B12 is lower in patients with PD compared with controls, and low levels have been associated with peripheral neuropathy, cognitive impairment, and more rapid rate of disease progression in PD.2, 3, 4 Although this relationship does not necessarily mean causality, there are several hypothetical mechanisms by which reduced vitamin B12 may lead to reduced availability of choline as a substrate for cholinergic transmission. Here we will review the proposed pathophysiology of nonmotor symptoms in PD and the potential relationship between vitamin B12 and acetylcholine metabolism. We propose that vitamin B12 supplementation could be considered as an adjuvant approach to improve cholinergic transmission and, potentially, motor and cognitive function in patients with PD.
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Taking B12 slowed the progression of PD March 2018

Vitamin B12 and homocysteine levels predict different outcomes in early Parkinson's disease.
Mov Disord. 2018 Mar 6. doi: 10.1002/mds.27301. [Epub ahead of print]
Christine CW1, Auinger P2, Joslin A3, Yelpaala Y3, Green R3; Parkinson Study Group-DATATOP Investigators.

BACKGROUND: In moderately advanced Parkinson's disease (PD), low serum vitamin B12 levels are common and are associated with neuropathy and cognitive impairment. However, little is known about B12 in early PD.

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

METHODS:
We measured vitamin B12 and other B12 status determinants (methylmalonic acid, homocysteine, and holotranscobalamin) in 680 baseline and 456 follow-up serum samples collected from DATATOP participants with early, untreated PD. Borderline low B12 status was defined as serum B12 <184 pmol/L (250 pg/mL), and elevated homocysteine was defined as >15 µmol/L. Outcomes included the UPDRS, ambulatory capacity score (sum of UPDRS items 13-15, 29&30), and MMSE, calculated as annualized rates of change.

RESULTS:
At baseline, 13% had borderline low B12 levels, 7% had elevated homocysteine, whereas 2% had both. Elevated homocysteine at baseline was associated with worse scores on the baseline MMSE. Analysis of study outcomes showed that compared with the other tertiles, participants in the low B12 tertile (<234 pmol/L; 317 pg/mL) developed greater morbidity as assessed by greater annualized worsening of the ambulatory capacity score. Elevated homocysteine was associated with greater annualized decline in MMSE (-1.96 vs. 0.06; P = 0001). Blood count indices were not associated with B12 or homocysteine status.

CONCLUSIONS:
In this study of early PD, low B12 status was common. Low B12 at baseline predicted greater worsening of mobility whereas elevated homocysteine predicted greater cognitive decline. Given that low B12 and elevated homocysteine can improve with vitamin supplementation, future studies should test whether prevention or early correction of these nutritionally modifiable conditions slows development of disability. © 2018 International Parkinson and Movement Disorder Society.

PMID: 29508904 DOI: 10.1002/mds.27301

Vitamin B12 and Parkinson's disease: What is the relationship? – Editorial March 2018

Mov Disord. 2018 Mar 6. doi: 10.1002/mds.27366. [Epub ahead of print]
Cardoso F1. PMID: 29508925 DOI: 10.1002/mds.27366

Association of plasma homocysteine, vitamin B12 and folate levels with cognitive function in Parkinson's disease: A meta-analysis. – Jan 2017

Neurosci Lett. 2017 Jan 1;636:190-195. doi: 10.1016/j.neulet.2016.11.007. Epub 2016 Nov 10.
Xie Y1, Feng H1, Peng S1, Xiao J1, Zhang J2.
1 Dept of Neurology, Zhongnan Hospital, Wuhan University, No. 169, Donghu Road, 430071 Hubei, China.
2 Dept of Neurology, Zhongnan Hospital, Wuhan University, No. 169, Donghu Road, 430071 Hubei, China. wdsjkx at 163.com.

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
• (lower) 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.

PMID: 27840145 DOI: 10.1016/j.neulet.2016.11.007

Associations between B Vitamins and Parkinson's Disease – Aug 2015

Nutrients. 2015 Aug 27;7(9):7197-208. doi: 10.3390/nu7095333.
Shen L Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo 255049, China. shen at sdut.edu.cn.

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.

PMID: 26343714 PMCID: PMC4586528 DOI: 10.3390/nu7095333
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See also VitaminDWiki

• Vitamin B12

Overview Parkinson's and Vitamin D contains the following summary

• Vitamin D associated with Parkinson’s Disease in 55 studies, more studies needed- March 2022
• Parkinson's category has 117 studies
• Parkinson’s Disease and Vitamin D – review of 52 studies – May 2022
• Parkinson patients: 60 % taking Vitamin D – Dec 2019
• Low Vitamin D increases Parkinson's by 3X– July 2010 "only" a 30 year test, need more study
• Parkinson's disease prevented by Vitamin D, but small doses do not treat it - Aug 2023
• 10 clinical trials for PD with vitamin D intervention as of June 2023
• Parkinson’s Disease Summer School – alternative therapies included 60-80 ng of Vitamin D – Sept 2019
• Associated with PD are: Meta-analyses (12 ), Cognition (24 studies), Multiple Sclerosis (18 studies), VIRUS (4 studies), Omega-3 (3 studies), Vitamin D Receptor (11 studies)
• Note by the Founder of VitaminDWiki: I have twice recommended lots of Vitamin D to treat PD. Both got much better, but one had his doctor him cut back to just 2,000 IU. All of his recovery got reversed. With lots of vitamin D he could sing and bike, but now he can barely talk or walk

The articles in both Parkinson's and Meta-analysis

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Google Scholar: B12 parkinson's - 18,000 items March 2022

b12 parkinson's

• Gastrectomy, vitamin B12 supplementation and the risk of Parkinson's disease: A nationwide cohort study - Feb 2021. https://doi.org/10.1016/j.parkreldis.2020.12.026
• Role of Vitamins in Advanced Therapy for Parkinson’s Disease: Decoding the Paradox May 2021 PDF