Research
Featured article for March 2025
Parkinson’s disease (PD) is a complex neurodegenerative disorder that affects movement and a wide range of motor and non-motor functions. Among the various factors studied in relation to PD, vitamins—particularly vitamin B12—have garnered significant attention. Recent research suggests that vitamin B12 deficiency not only exacerbates the symptoms of PD but may also play a role in its progression. This article explores the intricate relationship between vitamin B12 and Parkinson’s disease, including its potential mechanisms, clinical manifestations, and therapeutic implications.
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Given the strong association between B12 deficiency and PD symptoms, supplementation has been proposed as a potential therapeutic strategy. Studies suggest that vitamin B12 supplementation may:
1. Improve gait and balance in PD patients with neuropathy.
2. Reduce homocysteine levels, potentially slowing cognitive decline.
3. Support nerve regeneration and reduce the risk of neuropathy.
4. Enhance overall well-being and quality of life in PD patients.
However, it is important to note that while B12 supplementation can address deficiency-related symptoms, it is not yet proven to modify the course of PD itself. More research is needed to determine whether B12 therapy can alter disease progression in a meaningful way.
For PD patients, regular monitoring of vitamin B12 levels is recommended, especially for those undergoing long-term Levodopa therapy. If a deficiency is detected, supplementation should be considered to prevent further complications. Physicians may also recommend dietary adjustments to include more B12-rich foods or prescribe injectable forms of the vitamin for better absorption.
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Link: https://link.springer.com/article/10.1007/s00702-024-02769-z
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Featured article for February 2025
In this exciting new study, the authors (several of them being CluB-12 members) enrolled 231 healthy elderly volunteers (median age 71.2 years old) with a median B12 blood concentration of 414.8 pmol/L (as measured by automated chemiluminescence assay). They performed a variety of evaluations, including multifocal visual evoked potential testing, processing speed testing, and magnetic resonance imaging to assess neurological status. They also measured serum biomarkers of neuroaxonal injury, astrocyte involvement, and amyloid pathology.
Their main findings were:
Low B12, especially decreased holo-transcobalamin (sometimes called 'active B12', as this is the form of B12 that can be taken up into the brain), was associated with visual evoked potential latency delay, processing speed impairment (in an age-dependent manner), and larger volumes of white matter hyperintensities on MRI. High levels of holo-haptocorrin (the biologically inactive fraction of B12) correlated with serum levels of Tau, a biomarker of neurodegeneration.
In a press release, the authors wrote: "The current threshold to consider B12 deficiency as a diagnosis and to supplement with vitamin B12, is currently set at 148 pmol/L and is successful at treating most cases of B12-related anaemia. However, a significant amount of people with B12 levels above that threshold have complained of neurological symptoms which improved when getting B12 supplementation. We show that in an older population, lower B12 levels (but above the current threshold of 148 pmol/L) are associated with impaired myelination (slower mfVEPs), neurological function (slower processing speed) and structure (higher WMH lesions on MRI). However, serum biomarkers for neurodegeneration (Tau and UCHL-1) were elevated in people with higher inactive B12 levels." Remember, dear readers, inactive B12 can not be taken up into the brain. It may be a mere marker, and not a cause of higher Tau levels.
The authors have drawn a number of important conclusions:
• The current threshold that defines B12 deficiency must be revisited.
• Clinicians should consider B12 supplementation in older patients with neurological complaints even if B12 levels are higher than 148 pmol/L. But, how do we select these individual;s, and what follow-up do we provide for them?
• Both low active B12 levels and high inactive B12 levels should be considered in future studies about the impact of B12 on neurological function;
• We must invest in more research about the underlying biology of B12 insufficiency since it may impact brain ageing and can be a preventable cause of cognitive decline.
Research grant providers should prioritize research in the aforementioned areas.
Link to the article: https://onlinelibrary.wiley.com/doi/10.1002/ana.27200
Featured article for January 2025
This article from 2023 explores how genetic variations in the gene for the transcobalamin receptor (CD320) affect vitamin B12 uptake into the brain in elderly individuals. Vitamin B12 is vital for producing red blood cells, maintaining the nervous system, and other critical processes. The study found that certain gene variants are linked to higher levels of a specific form of B12 in the blood (holotranscobalamin or holo-TC), which might suggest altered cellular uptake.
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Key findings include:
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Gene Variants Detected: Four specific changes in the CD320 gene were found. About 12% of elderly individuals carry at least one of these variations.
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Impact on B12 Measurement: People with these variants had higher holo-TC levels. Holo-TC is a marker used to measure B12 availability in the body, but this study suggests it might not always reflect true B12 status.
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Clinical Implications: Since B12 status is often assessed using multiple markers like holo-TC, total B12, and methylmalonic acid, these findings suggest that genetic variations could lead to misleading test results in some individuals.
This study highlights the need to adjust current diagnostic tools for B12 deficiency to account for genetic variations in the CD320 gene. Without these adjustments, some individuals might be misdiagnosed as having normal B12 levels despite potential deficiency.
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Link: https://www.clinicalnutritionespen.com/article/S2405-4577(23)00116-X/fulltext
Featured article for December 2024
The article by Pluvinage et al (published in Sci. Transl. Med. 2024; 16:eadl3758) explores a novel autoimmune cause of vitamin B12 deficiency in the central nervous system (CNS), termed "Autoimmune B12 Central Deficiency" (ABCD). Researchers from San Francisco discovered autoantibodies targeting the transcobalamin receptor (CD320), a key protein in vitamin B12 transport, impairing B12 uptake into the brain despite normal serum B12 levels.
The authors have used phage display technology, and demonstrated the presence of a specific autoantibody against the CD320 receptor in a patient with poorly understood progressive neurological symptoms (e.g., tremor, ataxia, speech issues). It was observed that the autoantibody blocks B12 uptake into the brain, causing B12 deficiency in nervous tissue and leading to a variety of neurological symptoms.
CD320 antibodies were also found in other patients with unexplained neurological deficits, neuropsychiatric lupus (21.4% prevalence), and some healthy controls (6% prevalence).
A genome-wide CRISPR screen revealed that an alternate pathway via LDL receptors compensates for CD320 loss in hematopoietic cells but not in the CNS, explaining the tissue-specific effects.
In the index patient, high-dose systemic vitamin B12 supplementation and immunosuppressive therapy showed improvements in CSF B12 levels and clinical symptoms. Larger studies are needed to explore the prevalence and long-term effects of these autoantibodies in people with symptoms suggestive of B12 deficiency, and the therapeutic role of B12 in neuropsychiatric disorders.
Our paper on diagnostics and therapeutics of vitamin B12 deficiency, with emphasis on patient experiences, written on request of the BMJ Editorial Board
Vitamin B12 Deficiency in Clinical Practice: Scientific Insights at the Bookends of Life-Proceedings of the First International B12 Conference, June 2023, Rotterdam'
The supplement consists of 88 pages and 14 peer-reviewed manuscripts published by the Food and Nutrition Bulletin 2024/ Supplement June 2024.
It can be found here:
https://journals.sagepub.com/toc/fnba/45/1_suppl
The congress organisers and authors hope that these publications will lead to a better understanding and knowledge of the complex spectrum of B12 deficiencies.
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