Vitamin D and neurodegenerative diseases
Heliyon Volume 9, Issue 1, January 2023, e12877 https://doi.org/10.1016/j.heliyon.2023.e12877
Neurodegenerative diseases, featured by progressive loss of structure or function of neurons, are considered incurable at present. Movement disorders like tremor and postural instability, cognitive or behavioral disorders such as memory impairment are the most common symptoms of them and the growing patient population of neurodegenerative diseases poses a serious threat to public health and a burden on economic development. Hence, it is vital to prevent the occurrence of the diseases and delay their progress. Vitamin D can be transformed into a hormone in vivo with both genomic and non-genomic actions, exerting diverse physiological effects.
Cumulative evidence indicates that vitamin D can ameliorate neurodegeneration by
- regulating pertinent molecules and signaling pathways including maintaining Ca2+ homeostasis,
- reducing oxidative stress,
- inhibiting inflammation,
- suppressing the formation and aggregation of the pathogenic protein, etc.
This review updates discoveries of molecular mechanisms underlying biological functions of vitamin D in neurodegenerative diseases including
- Alzheimer’s disease,
- Parkinson’s disease,
- multiple sclerosis, and
- vascular dementia.
Clinical trials investigating the influence of vitamin D supplementation in patients with neurodegenerative diseases are also summarized. The synthesized information will probably provoke an enhanced understanding of the neuroprotective roles of vitamin D in the nervous system and provide therapeutic options for patients with neurodegenerative diseases in the future.
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Top 10 Neurolocial Disease and Vitamin D - Perplexity AI Aug 2025
| Rank | Neurological Disease | Prevalence/Burden | Vitamin D Likelihood | Evidence Quality | Key Research Findings |
| 1 | Stroke | Leading cause of death and DALYs from neurological conditions | Moderate | Mixed - observational shows benefit RCTs show no prevention effect | Low vitamin D associated with increased stroke risk; supplementation doesn't prevent strokes but may aid rehabilitation |
| 2 | Migraine/Tension-Type Headache | Most prevalent neurological condition (1.16 billion people globally) | High | Strong - multiple RCTs show reduced frequency and severity | Vitamin D supplementation (1000-4000 IU/day) reduces headache frequency by ~2.7 attacks/month |
| 3 | Alzheimer's Disease and Other Dementias 56.9 million cases globally | 4th highest DALYs | Moderate-High | Strong observational weak RCT - deficiency doubles risk supplementation trials mixed | Deficiency increases dementia risk by 53-125%; brain tissue contains vitamin D linked to cognitive function" |
| 4 | Parkinson's Disease | 8.5 million cases globally rapid increase in incidence | Moderate | Strong observational weak RCT - consistent association | limited supplementation studies Consistent inverse relationship between vitamin D levels and motor symptom severity |
| 5 | Epilepsy | 50+ million cases worldwide 7th highest contributor to DALYs | Moderate | Moderate - some studies show seizure reduction meta-analysis shows no significant effect | Some studies show 30-40% seizure reduction with supplementation; mixed results in controlled trials |
| 6 | Multiple Sclerosis | 2.8 million cases globally higher in northern latitudes | High | Strong observational strong RCT - recent major trial shows significant disease activity reduction D-Lay MS trial: 100,000 IU every 2 weeks reduced disease activity by 34% vs placebo | |
| 7 | Diabetic Neuropathy | 206 million cases globally (tripled since 1990) | Low-Moderate | Limited evidence for neuroprotection effects | Mainly benefits related to diabetes management rather than direct neuroprotection |
| 8 | Motor Neuron Disease/ALS | Progressive neurodegenerative disease 5th leading cause of neurological deaths | Low | Very limited evidence mainly theoretical neuroprotective mechanisms Very limited clinical data; mainly preclinical neuroprotective mechanisms | |
| 9 | Autism Spectrum Disorder | 61.8 million cases globally 9th highest contributor to DALYs | Low-Moderate | Limited evidence mainly developmental and genetic factors Vitamin D important for brain development; deficiency may worsen behavioral symptoms | |
| 10 | Traumatic Brain Injury | High incidence major cause of disability | Low-Moderate | Limited evidence mainly related to bone health and falls prevention Benefits mainly related to bone health and fall prevention rather than brain injury prevention | |
High Likelihood (Strong Evidence) MS, Headache
Multiple Sclerosis emerges as the condition with the strongest evidence for vitamin D benefits. The landmark D-Lay MS randomized clinical trial published in 2025 demonstrated that high-dose vitamin D (100,000 IU every 2 weeks) significantly reduced disease activity by 34% compared to placebo in early multiple sclerosis patients. This represents the most robust clinical evidence available for vitamin D's therapeutic potential in neurological disease. thelancet
Migraine and Headache Disorders show compelling evidence across multiple randomized controlled trials. Meta-analyses consistently demonstrate that vitamin D supplementation at doses of 1,000-4,000 IU daily reduces headache frequency by approximately 2.7 attacks per month, decreases headache days, and lowers disability scores. The mechanism involves vitamin D's role in regulating serotonin neurotransmission and reducing neuroinflammation. jamanetwork+2
Moderate-High Likelihood
Alzheimer's Disease and Other Dementias present strong observational evidence but mixed results from intervention trials. Vitamin D deficiency increases dementia risk by 53-125%, with the risk markedly increasing below 50 nmol/L. Importantly, vitamin D has been found in brain tissue for the first time, with higher concentrations associated with 25-33% lower odds of cognitive impairment. However, supplementation trials have shown limited success in improving cognitive function once dementia develops. wfneurology+3
Moderate Likelihood: Stroke, PD, Epilepsy
Stroke shows a complex relationship with vitamin D. While observational studies consistently link low vitamin D levels to increased stroke risk, multiple meta-analyses of randomized controlled trials demonstrate that vitamin D supplementation does not prevent stroke occurrence. However, supplementation may aid rehabilitation and recovery after stroke. clevelandclinic+3
Parkinson's Disease demonstrates consistent inverse relationships between vitamin D levels and motor symptom severity across multiple studies. Patients in the highest vitamin D quartile show 65% lower risk of developing Parkinson's disease. Limited supplementation studies suggest potential benefits for motor function, but larger randomized trials are needed. centromedicoabc+2
Epilepsy presents mixed evidence. Some studies report 30-40% seizure reduction with vitamin D supplementation, particularly in children. However, a recent meta-analysis found no statistically significant effect of vitamin D supplementation on seizure frequency, indicating the need for more rigorous controlled trials. michiganneurologyassociates+3
Low-Moderate Likelihood
Diabetic Neuropathy, while rapidly increasing globally, shows limited direct evidence for vitamin D neuroprotection. Benefits appear primarily related to diabetes management rather than direct neural protection.
Autism Spectrum Disorder has limited evidence, mainly focused on vitamin D's role in brain development and the observation that deficiency during pregnancy may increase autism risk.
Traumatic Brain Injury shows minimal direct evidence for vitamin D's neuroprotective effects, with benefits mainly related to bone health and fall prevention.
Low Likelihood – ALS
Motor Neuron Disease/ALS has very limited clinical evidence, despite theoretical neuroprotective mechanisms. The evidence remains largely preclinical with minimal human intervention data.
Key Mechanisms of Action
Vitamin D exerts its neurological effects through several mechanisms: neurology+2
- Neuroprotection: Reduces neuronal apoptosis and supports neuronal survival
- Anti-inflammatory: Inhibits NF-κB activation and reduces neuroinflammation
- Neurotransmitter regulation: Modulates serotonin, dopamine, and GABA systems
- Calcium homeostasis: Essential for synaptic transmission and plasticity
- Gene expression: Regulates thousands of genes important for brain function
- Immune modulation: Reduces autoimmune responses in conditions like multiple sclerosis
Clinical Implications
The evidence suggests that vitamin D deficiency assessment should be routine in neurological practice, particularly for conditions showing moderate to high likelihood of benefit. While supplementation shows promise for several conditions, optimal dosing and treatment duration require further investigation through well-designed randomized controlled trials.
For conditions with strong evidence (multiple sclerosis, migraine), vitamin D supplementation appears to offer meaningful clinical benefits as adjunctive therapy. For conditions with moderate evidence, supplementation may be considered given the favorable safety profile and potential benefits, while recognizing the need for additional research to establish definitive efficacy.
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