Researchers have identified a novel molecular link between vitamin B12 and the chronic disease multiple sclerosis (MS) in astrocytes — non-neuronal glial cells in the brain. Based on a new study, its authors suggest new ways to improve the treatment of MS through supplementing with vitamin B12.
Using an animal model that mimics MS and human post-mortem brains, the researchers determined that fingolimod — the first FDA-approved therapy to treat relapsing or remitting MS — suppresses neuroinflammation by functionally and physically regulating vitamin B12 communication pathways.
“The shared molecular binding of the brain’s vitamin B12 carrier protein, known as transcobalamin 2 or TCN2, with the MS drug fingolimod, provides a mechanistic link between vitamin B12 signaling and MS, toward reducing neuroinflammation and possibly neurodegeneration,” says senior study author Jerold Chun, professor and SVP of neuroscience drug discovery at Sanford Burnham Prebys.
“Augmenting brain vitamin B12 with fingolimod or potentially related molecules could enhance current and future MS therapies.”
Suppressing neuroinflammation
In the study, published in Cell Reports, the researchers focused on the molecular functioning of the medication fingolimod — a sphingosine 1-phosphate (S1P) receptor modulator — which suppresses the distribution of immune cells that attack the brains of MS patients. They note that the identified pathway is “essential for the mechanism of action” of this drug.
Vitamin B12 is bound to a carrier protein, TCN2, to distribute it throughout the body, including the central nervous system. Fingolimod elevates a vitamin B12 receptor — called CD320 — that is needed to absorb and use the vitamin when it is bound to TCN2.
The drug also binds to this TCN2-vitamin B12 complex, delivering all components to the astrocyte cells in the brain. The researchers report that lower levels of the CD320 receptor or dietary vitamin B12 restriction worsened MS in an animal model and reduced the efficacy of fingolimod.
Researchers found a new molecular pathway between vitamin B12 and MS that occurs in brain cells.Moreover, the researchers observed the same pathway in human MS brains. They also note that the CD320 receptor was reduced in MS patients.
The new molecular link potentially explains the relationship between vitamin B12 deficiency and MS, as scientists have long noted a similarity. Both produce similar neurological symptoms, including numbness or tingling in hands and feet, vision loss, difficulty walking or speaking normally and cognitive dysfunction, such as memory problems.
Vitamin B12 supplementation
The study’s findings support supplementation with vitamin B12 and the need to deliver the vitamin to the astrocytes within the brain, where the pathway occurs. In addition, the researchers suggest that fingolimod can correct the impaired pathway of MS.
According to the researchers, other S1P receptor modulator medications on the market may also access at least part of this mechanism in the central nervous system.
Moreover, the study suggests how sphingolipids, specifically sphingosine — a naturally occurring and endogenous structural analog of the fingolimod drug — regulate the same identified pathway, opening avenues for improving future MS therapies.
“It supports creating brain-targeted vitamin B12 formulations. This mechanism might extend to novel treatments of other neuroinflammatory and neurodegenerative conditions in the future,” says Chun.
Research on nutrition for MS
The publication joins other research identifying links between diets, nutrients and MS symptoms.
For example, a study published last month suggests that reducing calorie intake by 19% may alleviate fatigue in people who battle MS, specifically focusing on reducing fat intake.
Moreover, researchers suggest that diet modification may help to manage MS symptoms. Earlier this year, a study revealed that MS patients following a specific diet for 2.5 years had a 20% lower risk of depression than people who did not. The high-quality “overcoming MS” diet included fruits, vegetables, whole grains and fish and was low in refined sugars, processed meat and saturated fat.
Meanwhile, a US-based team designed a probiotic that can suppress autoimmunity in the brain, a cause of diseases such as MS. The probiotic could target brain inflammation more effectively than standard therapies.
At the same time, researchers caution that micronutrient deficiencies, including insufficient intake of vitamin B12, affect people worldwide. As animal-based foods are important sources of this vitamin, plant-based focused diets may hold significant nutrient gaps.