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Medically reviewed by Dr. Samuel Sarmiento, M.D., MPH on August 3, 2023

Vitamin D has been found to exert numerous neuroprotective effects in multiple sclerosis, according to a recent review.

Vitamin D deficiency in childhood and adolescence is a multiple sclerosis (MS) risk factor. The mechanism of vitamin D-mediated anti-inflammatory and immunomodulatory activity in MS is well-established in the literature. However, its potential neuroprotective benefits for preventing initial myelin loss or promoting remyelination require further investigation.

A study in the journal Nutrients reviewed the latest research findings regarding the mechanism of vitamin D-mediated neuroprotection in MS.

Vitamin D Enhances Remyelination in Multiple Sclerosis

Oligodendrocyte dystrophy and apoptosis are significant features in MS demyelinating lesions. Oligodendrocytes are myelin-producing glial cells that support central nervous system (CNS) neurons. While they can remyelinate CNS axons during tissue injury, this ability diminishes in the later stages of MS due to the reduced regenerative capacity of neural stem cells (NSCs) and oligodendrocyte progenitor cells (OPCs) to give rise to oligodendrocytes. Increased vitamin D (1,25(OH)2D3) exposure promoted NSC proliferation and differentiation into OPCs and oligodendrocytes in animal models, potentially enhancing remyelination in MS.

Neurotrophin Secretion and Its Impact on Neuroprotection in Multiple Sclerosis

Another factor contributing to inadequate neuroprotection in MS is reduced neurotrophin secretion. Neurotrophins are proteins secreted by various cells, including NSCs, neurons, and glial cells. They are involved in NSC proliferation and differentiation and the growth, survival, and functioning of neuronal and glial cells. Vitamin D enhances neurotrophin expression, potentially contributing to CNS repair and regeneration by stimulating oligodendrogenesis and neurogenesis.

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Attenuation of Pro-Inflammatory Microglia and Their Role in Multiple Sclerosis

Microglia play a crucial role in CNS development and immune surveillance. In MS, activated microglia contribute to disease progression through M1 (pro-inflammatory) microglia-associated inflammation and neurotoxicity. Vitamin D exposure induces a phenotypic shift from M1 to M2 (anti-inflammatory) microglia, resulting in reduced pro-inflammatory cytokines and reactive oxygen species (ROS) and increased anti-inflammatory cytokines and neurotrophins, leading to enhanced myelin repair.

The Role of Vitamin D in Reducing Astrocyte Activation

Astrocytes become reactive and divide rapidly in response to CNS injury, known as astrogliosis. Reactive astrocytes can become detrimental due to the release of pro-inflammatory cytokines and ROS. Vitamin D administration in animal models reduced astrocyte activation, which could create a more favorable environment for repair processes.

Vitamin D’s Role in Stabilizing the Blood–Brain Barrier in Multiple Sclerosis

The blood–brain barrier (BBB), which maintains CNS stability, becomes hyperpermeable in MS due to pro-inflammatory cytokines from immune cells and reactive astrocytes. Vitamin D stabilizes the BBB by upregulating tight junctions, downregulating cell-adhesion molecules, reducing matrix metalloproteinase-9 expression, and reducing endothelial cell apoptosis, thus limiting immune cell entry into the CNS and promoting neuroprotection.

Vitamin D’s Role in Reducing Oxidative Stress

Oxidative stress is another significant contributor to MS pathogenesis, with ROS causing cell injury and death. Vitamin D decreases oxidative stress by restoring antioxidant enzyme expression, reducing ROS production, and promoting Nrf2 activation to enhance antioxidant synthesis, thereby promoting neuroprotection.


Sangha, A., Quon, M., Pfeffer, G., & Orton, S. (2023). The role of vitamin D in neuroprotection in multiple sclerosis: an update. Nutrients, 15(13), 2978. https://doi.org/10.3390/nu15132978