Neuro(b)log for Patients

The first mention of vitamin D dates back to the early 19th century thanks to observations by Sir Edward Mellanby in Scotland, where he encountered an increased incidence of rickets. McCollum later linked vitamin D deficiency specifically to this disease. In 1932 Askew and colleagues isolated vitamin D₂, and Windaus and Rock described the structure of vitamin D₃ in 1937.

Vitamin D belongs to the calciferols, and as most informed laypeople know, it is a fat‑soluble vitamin. It is best known for its role in calcium and phosphate metabolism and in bone mineralization. However, it is not only a vitamin but also a steroid hormone, and besides supporting bone mineralization it contributes to muscle development and immunity, and is believed to help protect the body against cardiovascular disease and cancer.

Let us now consider what effect vitamin D has on the nervous system. Recent studies have attempted to clarify the varied effects of vitamin D supplementation on the course of progressive neurological diseases.

How does the body obtain vitamin D?

Sunlight is essential for vitamin D production, especially UVB, which enables conversion of 7‑dehydrocholesterol in the skin to vitamin D₃. It is released into the bloodstream up to three days after skin exposure. Therefore, when sunlight is scarce, in people with darker skin or in those using UV protection, less vitamin D₃ is produced.

Dietary sources include fatty fish, eggs, fortified foods and supplements containing vitamin D₂ or D₃. In these forms vitamin D is inactive. To become active it must be converted in the liver (a process that requires magnesium and enzymes) into calcidiol (25‑hydroxyvitamin D). Magnesium acts as a cofactor, so low magnesium levels can halt vitamin D activation. The kidneys then convert calcidiol into the active hormone calcitriol, a step that also depends on magnesium and iron.

Other cofactors matter: vitamin K2 is needed to increase calcium uptake into bone by activating proteins (e.g., osteocalcin) that direct calcium into bone rather than arteries. Zinc and vitamin A are required for vitamin D to bind effectively to its receptors.

The active form of vitamin D regulates calcium and phosphate balance, supports bone strength, helps the pancreas release insulin and participates in immune system regulation.

Vitamin D‑binding receptors occur in neurons and glial cells, for example in the substantia nigra, hippocampus, hypothalamus, thalamus and subcortical nuclei. Vitamin D likely influences neuronal differentiation and maturation and regulates growth factors and neurotransmitters such as acetylcholine, dopamine and GABA.

Recommended daily intake and deficiency

Vitamin D deficiency is commonly defined as serum levels below 30 nmol/L. Recommended daily doses vary, but average guidance is about 400–800 IU per day. Some countries (USA, Canada, Finland) fortify foods with vitamin D. A single vitamin D measurement does not reflect only diet; it is influenced by physical activity, body mass index (BMI) and other factors.

How does vitamin D affect the immune system?

Vitamin D enables monocytes to differentiate into macrophages, increasing antimicrobial activity against pathogens such as Mycobacterium tuberculosis. It enhances phagocytosis and modulates cytokine production: increasing anti‑inflammatory IL‑10 while reducing proinflammatory cytokines (IL‑1β, IL‑6, TNF‑α) and COX‑2 in macrophages. Similar immunomodulatory effects occur in dendritic cells and other neural immune cells. Vitamin D also influences B‑lymphocyte and NK cell function. Its effects on immunity are complex and multifaceted.

Vitamin D and neurological diseases

Alzheimer's disease Alzheimer's is a neurodegenerative disorder with proposed mechanisms including amyloid deposition, tau pathology, mitochondrial dysfunction and inflammation. Evidence suggests vitamin D may help preserve cognitive function by promoting clearance of amyloid plaques via phagocytosis and immune cells (macrophages). Vitamin D also participates in biochemical and signaling pathways involved in protein synthesis, regulation of amyloid precursor protein (APP) and control of inflammation, oxidative stress and mitochondrial function — all relevant to Alzheimer's pathogenesis. Epidemiological studies show mixed results due to methodological differences, but generally higher vitamin D levels are associated with lower Alzheimer's risk in people over 60. Whether supplementation benefits patients with cognitive impairment requires further clinical trials.

Parkinson's disease Parkinson's is characterized by loss of dopaminergic neurons in the substantia nigra and alpha‑synuclein deposition. A Finnish cohort study suggested low vitamin D as a risk factor, but larger pooled data have not consistently confirmed this. Conflicting results may reflect vitamin D receptor polymorphisms, geographic and lifestyle differences across populations. One randomized, placebo‑controlled trial (Suzuki et al.) reported promising results: Parkinson's patients taking 1200 IU daily of vitamin D had better outcomes over a 2‑year follow‑up.

ALS (amyotrophic lateral sclerosis) ALS is a progressive neurodegenerative disease with multifactorial causes (genetic, environmental, aging). Pathogenic mechanisms include oligodendrocyte degeneration, inflammation and mitochondrial dysfunction. The relationship between vitamin D and ALS is controversial; current data are insufficient to confirm benefit from supplementation.

Multiple sclerosis (MS) MS is an immune‑mediated CNS disease. Strongest evidence for vitamin D's role exists in MS: incidence rises with latitude, and populations consuming vitamin D‑rich diets (e.g., fatty fish) show lower rates. Lower sun exposure in childhood and adolescence appears to increase MS risk. There is broad agreement on testing and monitoring vitamin D in MS patients because low levels are common and because vitamin D supplementation helps prevent bone fragility (osteopenia/osteoporosis) and fractures. Target serum levels for MS patients are often >100 nmol/L, with dosing adjusted by latitude (higher doses recommended in northern Europe and North America than in southern regions).

Migraine Some studies link low vitamin D to migraine and tension‑type headache in adults and children. Supplementation has reduced migraine attack frequency in some trials, though pain intensity was not consistently affected.

Diabetic neuropathy

As the population ages and diabetes prevalence rises, diabetic polyneuropathy becomes more common. Vitamin D deficiency has been identified as a risk factor for diabetic polyneuropathy, and supplementation is recommended in many cases. Mechanisms may include vitamin D receptor expression in neurons and glia, modulation of gene expression, growth factors (neurotrophins), inflammatory pathways and oxidative stress — all supporting neuronal survival, remyelination and neurogenesis. In small‑fiber neuropathy, vitamin D deficiency affects nociceptive and parasympathetic fibers, particularly in younger type‑2 diabetic patients; supplementation is therefore expected to reduce neuropathic pain and other neuropathy symptoms, though precise mechanisms and optimal regimens need further study.

Conclusion

Lately I increasingly meet patients who are very interested in a healthy lifestyle, improving their health and, ultimately, longevity. I also understand that the general public is practically bombarded with advertisements for various dietary and nutritional supplements, to which some people cling uncritically. I see patients taking many supplements in various appropriate and inappropriate combinations, often with amounts of certain vitamins far exceeding the recommended daily doses. For this reason I always try to review with patients which supplements (vitamins) they are taking, and I emphasize that their diet should be varied and rich in minerals and vitamins that the body can use effectively.

Conversely, a monotonous diet and limited food choices can lead to deficiencies of certain vitamins and minerals, which may contribute to neurological problems, as this article has partly addressed. Low consumption of vitamin‑D‑rich foods, such as fish, a sedentary lifestyle and reduced sun exposure in the Czech population contribute to low vitamin D levels.

Vitamin D supplementation should be started when a low blood level is detected. If you have had blood tests done privately, you should discuss the results with your primary care physician. Always consult a pharmacist about any dietary supplements or herbs you plan to take. This is especially important for patients on long‑term medication, since both supplements and herbs can interact with prescribed drugs.

Finally, further research is needed to clarify whether and how vitamin D affects conditions such as dementia or other neurodegenerative diseases. Low vitamin D levels have been found in about 13% of the European population, so clinical studies of various diseases will likely identify subgroups with vitamin D deficiency. In older adults—some of whom are less mobile, spend less time outdoors or have poor appetite (or an unvaried diet)—vitamin D levels are often low. It is therefore not possible to claim unequivocally that this single vitamin alone causes a specific disease. The human body is highly complex, and the development of many diseases usually involves multiple risk factors and biochemical and genetic processes at cellular and molecular levels.

Every research finding must be interpreted in the context of current knowledge, available methods and, importantly, the limitations of different methodologies, technical equipment, laboratory techniques and study populations. Some research results can only be speculative—for example, when they involve small patient groups or when findings across studies contradict each other—so conclusions may remain controversial. 

MUDr. Petra Mištríková, MBA

References for further study:

Plantone D, Primiano G, Manco C, Locci S, Servidei S, De Stefano N. Vitamin D in Neurological Diseases. Int J Mol Sci. 2022 Dec 21;24(1):87. doi: 10.3390/ijms24010087. PMID: 36613531; PMCID: PMC9820561.