Tag: vitamin b12

Explaining the Parallels between Vitamin B12 Deficiency and Multiple Sclerosis

This is a pseudo-colored image of high-resolution gradient-echo MRI scan of a fixed cerebral hemisphere from a person with multiple sclerosis. Credit: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health

For decades, scientists have noted an intriguing similarity between a deficiency in vitamin B12 – an essential nutrient that supports healthy development and functioning of the central nervous system (CNS) – and multiple sclerosis (MS), a chronic disease in which the body’s immune system attacks the CNS and which can produce neurodegeneration.

Both vitamin B12 deficiency and MS produce similar neurological symptoms, including numbness or tingling in hands and feet, vision loss, difficulty walking or speaking normally and cognitive dysfunction, such as problems with memory.

In a new study, published in Cell Reports, researchers at Sanford Burnham Prebys, with collaborators elsewhere, describe a novel molecular link between vitamin B12 and MS that takes place in astrocytes – important non-neuronal glial cells in the brain.

The findings by senior study author Jerold Chun, MD, PhD, professor and senior vice president of neuroscience drug discovery, and Yasuyuki Kihara, PhD, research associate professor and co-corresponding author, and colleagues suggest new ways to improve the treatment of MS through CNS-B12 supplementation.

“The shared molecular binding of the brain’s vitamin B12 carrier protein, known as transcobalamin 2 or TCN2, with the FDA-approved MS drug fingolimod provides a mechanistic link between B12 signaling and MS, towards reducing neuroinflammation and possibly neurodegeneration,” said Chun.   

“Augmenting brain B12 with fingolimod or potentially related molecules could enhance both current and future MS therapies.”

In their paper, the team at Sanford Burnham Prebys, with collaborators at University of Southern California, Juntendo University in Japan, Tokyo University of Pharmacy and Life Sciences and State University of New York, focused on the molecular functioning of FTY720 or fingolimod (Gilenya®), a sphingosine 1-phosphate (S1P) receptor modulator that suppresses distribution of T and B immune cells errantly attacking the brains of MS patients.

Working with an animal model of MS as well as human post-mortem brains, the researchers found that fingolimod suppresses neuroinflammation by functionally and physically regulating B12 communication pathways, specifically elevating a B12 receptor called CD320 needed to take up and use needed B12 when it is bound to TCN2, which distributes B12 throughout the body, including the CNS.  This known process was newly identified for its interactions with fingolimod within astrocytes. Importantly, the relationship was also observed in human MS brains.

Of particular note, the researchers reported that lower levels of CD320 or dietary B12 restriction worsened the disease course in an animal model of MS and reduced the therapeutic efficacy of fingolimod, which occurred through a mechanism in which fingolimod hitchhikes by binding to the TCN2-B12 complex, allowing delivery of all to the astrocytes via interactions with CD320, with component losses disrupting the process and worsening disease.

These new findings further support to the use of B12 supplementation – especially in terms of delivering the vitamin to astrocytes within the brain – while revealing that fingolimod can correct the impaired astrocyte-B12 pathway in people with MS. 

The scientists said it is possible that other S1P receptor modulators on the market, such as Mayzent®, Zeposia® and Ponvory®, may access at least parts of this CNS mechanism.  The study supports B12 supplementation with S1P receptor modulators with the goal of improving drug efficacy for this class of medicines.

The study also opens new avenues on how the B12-TCN2-CD320 pathway is regulated by sphingolipids, specifically sphingosine, a naturally occurring and endogenous structural analogue of fingolimod, toward improving future MS therapies, Chun said. 

“It supports creating brain-targeted B12 formulations. In the future, this mechanism might also extend to novel treatments of other neuroinflammatory and neurodegenerative conditions.”

Source: Sanford-Burnham Prebys

Vitamin B12 Plays a Key Role in Cellular Reprogramming and Tissue Regeneration

Photo by National Cancer Institute on Unsplash

Vitamin B12 is a well-known micronutrient that has long been acknowledged for its essential role in maintaining nerve function, supporting red blood cell production, and facilitating DNA synthesis, all vital processes for overall health. Researchers have now discovered that vitamin B12 also plays a pivotal role in cellular reprogramming and tissue regeneration. The findings have been published in the journal Nature Metabolism.

The research was focused on an experimental process known as cellular reprogramming which is thought to mimic the early phases of tissue repair. The IRB team found that cellular reprogramming in mice consumes large amounts of vitamin B12. Indeed, the depletion of vitamin B12 becomes a limiting factor that delays and impairs some aspects of the reprogramming process. Considering the abundance of vitamin B12 in the normal diet of mice, the investigators were surprised to observe that the simple supplementation of vitamin B12 significantly enhanced the efficiency of reprogramming.

Therapeutic potential in ulcerative colitis

The researchers validated their findings in a model of ulcerative colitis, demonstrating that the intestinal cells initiating repair undergo a process similar to cellular reprogramming and also benefit from vitamin B12 supplementation. Patients with intestinal bowel disease could potentially benefit from vitamin B12 supplementation.

“Our research uncovers a critical role of vitamin B12 in cellular reprogramming and tissue repair. These findings hold promise for regenerative medicine, with the potential to benefit patients through an improved nutrition,” says lead researcher Dr Manuel Serrano at IRB.

Understanding the role of vitamin B12 in cellular reprogramming

In this study, the researchers delved into the metabolic requirements of cellular reprogramming and found that vitamin B12 is a limiting factor for a particular branch of metabolism involved in a reaction known as methylation. Precisely, the DNA of the cells initiating reprogramming or tissue repair require very high levels of this methylation reaction and therefore of vitamin B12. The researchers discovered that vitamin B12 insufficiency during reprogramming or tissue repair resulted in significant epigenetic changes, leading to errors in the function of multiple genes.

“Supplementation with vitamin B12 corrected this imbalance, resulting in enhanced gene function fidelity and overall improved reprogramming efficiency,” confirms Dr. Marta Kovatcheva, first author of the study and a postdoctoral researcher in the same laboratory. Dr. Kovatcheva will open a new laboratory in 2024 at the Istituto Fondazione di Oncologia Molecolare ETS (IFOM) in Milan, Italy, which will be focused on the study of partially reprogrammed cells in vivo.

Separate study links vitamin B12 to lower inflammation

The group led by Dr. Serrano has recently published another study, in collaboration with the laboratory of Dr. Rosa Lamuela-Raventós at the University of Barcelona (UB), and Dr. Ramon Estruch at the Hospital Clínic of Barcelona, in which they concluded that people with higher levels of vitamin B12 in blood had lower levels of inflammatory markers (IL-6 and CRP). The researchers also observed a similar relationship in aged mice. These observations suggest that vitamin B12 exerts anti-inflammatory action by reducing these markers in the body and they provide valuable insights into the potential health benefits of vitamin B12.

Source: Institute for Research in Biomedicine (IRB Barcelona)